At 9: 30am on July 22nd, the first batch of 25 science and technology innovation board stocks started trading on the Shanghai Stock Exchange, and science and technology innovation board officially opened.

　　Chen kangliang

　　2019 is a "big year" for China’s capital market reform, including the establishment of science and technology innovation board and the pilot registration system, and many other heavy reforms have been carried out one after another, which not only achieved phased results, but also triggered the market’s expectation on how to "continue to reform" in the next step. In this regard, the Central Economic Work Conference, which closed in Beijing on December 12th, gave the answer.

　　The meeting proposed to speed up the reform of the financial system, improve the basic system of the capital market, improve the quality of listed companies, improve the exit mechanism, and steadily promote the reform of the Growth Enterprise Market and the New Third Board.

　　Dong Dengxin, director of the Institute of Finance, Wuhan University of Science and Technology, said that the Central Economic Work Conference made clear four requirements on how to reform the capital market in China in the next step, among which "improving the basic system of the capital market" was the first one, which was the requirement of clearly promoting the modernization of the capital market governance system and governance capacity from the height of top-level design, and was in line with the spirit of the Fourth Plenary Session of the 19th CPC Central Committee.

　　Dong Dengxin further pointed out that as far as the development of China’s capital market is concerned, in the past 30 years, it has focused on the expansion of scale, from scratch, from small to large, and paid relatively little attention to the improvement of the basic system. However, it should be noted that institutional advantage is the greatest advantage and institutional development is the greatest development. It is of great significance to improve the basic system of the capital market, especially considering that China’s capital market should achieve high-quality development.

　　"Relevant systems, including information disclosure system, IPO (initial public offering) system, delisting system, etc., all need to be further improved, and the direction is to realize the marketization, legalization and internationalization of the capital market." Dong Dengxin said.

　　In order to improve the quality of listed companies, Zhang Yuewen, director of the Corporate Finance Research Office of the Institute of Finance of China Academy of Social Sciences, said that listed companies are the foundation of the capital market, and the long-term healthy development of the capital market can only be guaranteed if there are high-quality listed companies. However, in the current China capital market, the quality of some listed companies is worrying, and there are still big problems, including the decline in comprehensive financial quality and the increase in asset-liability ratio; There are defects in corporate governance, and the relationship between controlling shareholders and minority shareholders is alienated; The quality of information disclosure is not high; The protection of investors’ rights and interests is not paid enough attention, and it needs to be reformed urgently.

　　To this, Dong Dengxin also agreed. He said that in the past, market players and regulators paid insufficient attention to improving the quality of listed companies, but this year, the attention of all parties has been continuously strengthened. A few days ago, the China Securities Regulatory Commission issued the "Action Plan to Promote the Quality Improvement of Listed Companies", striving to greatly improve the overall appearance of listed companies through three to five years’ efforts. This indicates that the special reform to improve the quality of listed companies has moved from blueprint planning to construction, and the next step is to implement it, including improving the delisting mechanism.

　　Zhang Lichao, a senior researcher at Guosen Securities, also said that improving the delisting system of listed companies and strengthening delisting efforts are important components of multi-level capital market construction, which plays an important role in optimizing resource allocation, promoting the survival of the fittest, improving the quality of listed companies and protecting the legitimate rights and interests of investors. The remarkable increase of delisting companies since this year shows that the export of A-share market is gradually smooth. Only by making the delisting channels smooth can the capital market become an organic system with normal metabolism, which will also objectively promote the improvement of the quality of listed companies.

　　Li Zhan, chief economist of zhongshan securities, believes that the diversified delisting mechanism of China’s capital market will be accelerated in the future, including both compulsory delisting and active delisting, as well as restructuring delisting methods such as absorption and merger, clearing assets replacement and selling shells, and gradually converge with developed capital markets such as the United States.

　　Pan Xiangdong, chief economist of New Era Securities, said that this is an important area for deepening the reform of China’s capital market, especially the conditions surrounding the reform of the pilot registration system of GEM have become more and more mature. Growth Enterprise Market will take over from science and technology innovation board and become the main battlefield of China’s registration system reform in the future.

　　In fact, the top-level design to promote the reform of the registration system of the Growth Enterprise Market was published nearly four months ago. In August, the Opinions of the Central Committee of the Communist Party of China and the State Council on Supporting Shenzhen to Build a Pilot Demonstration Zone in Socialism with Chinese characteristics proposed that we should study and improve the GEM listing, refinancing, mergers and acquisitions, and create conditions to promote the reform of the registration system.

　　Pan Xiangdong further pointed out that encouraging science and technology enterprises to list on the GEM will help to further lower the threshold for science and technology enterprises to enter the capital market; GEM and science and technology innovation board will form an organic supplement to further improve the construction of multi-level capital markets; The implementation of the registration system for GEM enterprises can encourage more high-quality operating assets such as small and medium-sized enterprises to enter the GEM, improve the capital market structure of the GEM, and promote the healthy development of China’s capital market.

　　General Secretary Supreme Leader’s important speech at the celebration meeting of the 40th anniversary of the establishment of Shenzhen Special Economic Zone spoke highly of the great achievements made in the construction of special economic zones, profoundly summed up the valuable experience of 40 years of reform, opening up and innovative development of special economic zones, and at the same time, focused on realizing the grand goal of the great rejuvenation of the Chinese nation and building a broad vision of a community of human destiny, clarified the fundamental requirements for the construction of special economic zones under the new situation, systematically expounded the historical mission entrusted to Shenzhen by the CPC Central Committee in the new era, and pointed out the way forward for the new era of special economic zones. Reality develops from history. At the important historical node of the 40th anniversary of the establishment of special economic zones, it is undoubtedly of special and important significance to review the background of the establishment of special economic zones, sort out the development process of special economic zones, and clarify the position of special economic zones in the practice of reform and opening up, so as to create a new situation in the work of special economic zones, promote the great practice of reform and opening up at a new higher starting point, and write a new chapter in the great cause of Socialism with Chinese characteristics.

　　Special economic zones are a great initiative to promote reform, opening up and socialist modernization.

　　The establishment of special economic zones has its profound historical background, which is not only a strategic choice made by the party and the country to actively conform to the new trend of world political and economic development under the new historical conditions, but also a great pioneering work carried out by the party and the country to promote reform, opening up and socialist modernization on the basis of profoundly summing up historical experience.

　　Since 1970s, profound changes have taken place in the world political and economic structure. On the one hand, the hegemony of great powers between the United States and the Soviet Union has gradually turned into a stalemate, and the danger and possibility of the outbreak of world war have been greatly reduced. It has become the universal will of most countries to strive for peace and development. The Communist Party of China (CPC) keeps pace with the changes of the times and actively carries out overseas inspection and exchange activities. On the other hand, with the rise of the third wave of scientific and technological revolution, the world economy has developed rapidly, and the exchanges between countries have become increasingly close. In order to get rid of the shadow of the economic crisis quickly, major capitalist countries are generally faced with the need to adjust industrial structure and open up emerging markets, which provides a good opportunity for China to accelerate the introduction of foreign capital, technology and management methods. The changes in the world political and economic situation since the 1970s have provided favorable external conditions for the establishment of special economic zones in China.

　　After the founding of New China, a complete national economic system was gradually established, which laid an important foundation for the economic development of contemporary China. After the end of the "Cultural Revolution", the broad masses of cadres and people urgently demanded to reverse the chaotic situation caused by ten years of civil strife and put the cause of socialist construction back on the right track. At this important historical juncture, the CPC Central Committee actively complied with the trend of the times and the wishes of the people, convened the Third Plenary Session of the Eleventh Central Committee of the Party, and made a great decision to shift the focus of the Party’s work to economic construction and implement reform and opening up. China’s reform and opening up is aimed at the disadvantages of the original system and mechanism. To promote the cause of reform, opening up and socialist modernization, we should not only clarify the crux, but also identify the breakthrough. Considering China’s vast territory, large population and complicated situation, the reform and opening-up can only be carried out from the point to the surface, starting from the local area and then gradually spreading to the whole country. This is the macro thinking and strategic consideration of the establishment of special economic zones by the CPC Central Committee. In June, 1985, when meeting with foreign guests, Deng Xiaoping said, "Shenzhen Special Economic Zone is an experiment. It remains to be seen whether we are on the right track. It is a new thing of socialism. Success is our wish, and failure is an experience. " It can be said that the establishment of special economic zones was carried out as a pioneer and experimental area of reform and opening up under the background of China’s reform and opening up and socialist modernization.

　　The establishment of China Special Economic Zone is the result of the interaction of international and domestic factors, history and reality. A clear understanding of the historical background of the establishment of special economic zones is helpful to understand the historical inevitability of the establishment of special economic zones and the arduous exploration and innovation in the process of their establishment.

　　Special economic zones are vivid epitome of the process of reform and opening up.

　　The establishment and development of special economic zones has gone through a process from brewing and putting forward to continuous improvement and upgrading, which is not only a microcosm of the historical process of reform and opening up, but also an interpretation of the path and strategy of reform and opening up from one side.

　　During the Central Working Conference in April 1979, Xi Zhongxun, the first secretary of the Guangdong Provincial Committee of the Communist Party of China, proposed at the meeting that he hoped the Central Committee would let Guangdong go first and let it go. Deng Xiaoping agreed with the Guangdong Provincial Committee of the Communist Party of China’s proposal to set up processing zones in Shenzhen, Zhuhai and Shantou, which are adjacent to Hong Kong and Macao, and said: It’s better to call it a special zone, since Shaanxi, Gansu and Ningxia started to call it a special zone! The central government has no money, so you can give some policies, and you can do it yourself and fight your way out. After the meeting, the Central Committee of the Communist Party of China and the State Council instructed Guangdong and Fujian provinces to further organize and demonstrate the pilot export special zones in Shenzhen, Zhuhai, Shantou and Xiamen, and put forward specific implementation plans and submit them to the Central Committee for examination and approval. After in-depth investigation and careful consideration, on July 15th, 1979, the Central Committee of the Communist Party of China and the State Council approved two reports of Guangdong Provincial Committee and Fujian Provincial Committee on implementing special policies and flexible measures for foreign economic activities, and agreed to pilot export special zones in Shenzhen and Zhuhai first, and then consider setting up special zones in Shantou and Xiamen after gaining experience. On August 26th, 1980, the 15th meeting of the 5th the National People’s Congress Standing Committee (NPCSC) decided to set aside certain areas to set up special economic zones in Shenzhen, Zhuhai, Shantou in Guangdong Province and Xiamen in Fujian Province, and approved the Regulations on Special Economic Zones in Guangdong Province. At this point, the construction of special economic zones was formally determined through legislative procedures.

　　In the early days of the establishment of special economic zones, with the correct leadership of the CPC Central Committee and the strong support of the people of the whole country, the broad masses of cadres and masses faced difficulties, forged ahead, fought bravely, resolutely implemented the decision-making arrangements of the CPC Central Committee, and made remarkable achievements in the fields of national economic growth, foreign export trade, economic management system reform, socialist spiritual civilization construction, and created many development miracles such as "Shenzhen Speed" that built a floor in three days. At the beginning of 1984, after witnessing the development achievements of special economic zones during his inspection in Guangdong, Deng Xiaoping wrote an inscription for Shenzhen Special Economic Zone: "The development and experience of Shenzhen have proved that our policy of establishing special economic zones is correct." The achievements made in the early days of the establishment of special economic zones have further strengthened the central government’s determination and belief in carrying out reform and opening up. On April 13, 1988, the first session of the Seventh National People’s Congress officially approved the establishment of Hainan Special Economic Zone, clearly demanding that the special economic zone play an important role as a window and demonstration for the national reform, opening up and modernization, thus creating a new situation for the development of special economic zones in China.

　　In the late 1980s and early 1990s, the political turmoil in the Soviet Union and the socialist countries in Eastern Europe continued to intensify, and the contradictions and problems accumulated in the process of reform and opening up began to stand out. At one time, there was a debate on the surnames of special economic zones, which caused considerable ideological resistance to the construction and development of special economic zones. In this regard, Deng Xiaoping pointed out in his southern talk: "The achievements of Shenzhen’s construction have clearly answered those who are worried about this or that. Last name of the SAR ‘ Society ’ No surname ‘ Capital ’ 。” This strongly refutes the doubts and questions about the construction of special economic zones and escorts the construction of special economic zones. With the publication of the Southern Talks and the convening of the 14th National Congress of the Communist Party of China, the construction of special economic zones has entered a new stage of "increasing innovative advantages" and leaping development. Focusing on the central government’s plan and requirements of "increasing innovation advantages and by going up one flight of stairs", the special economic zones have made new breakthroughs in ownership reform, state-owned enterprise reform and price reform, initially established the basic framework of the socialist market economic system, and led the cause of reform and opening up to the outside world.

　　Since the 21st century, the trend of world political multipolarization, economic globalization and social informatization has developed in depth, and the pattern of multi-level, multi-channel and all-round opening to the outside world has been accelerated. Special economic zones are shouldering more arduous tasks in the new historical stage, with opportunities and challenges coexisting, and pressure and motivation coexisting. In the critical period of deepening reform in an all-round way and realizing the great rejuvenation of the Chinese nation, special economic zones continue to be the vanguard of reform, opening up and modernization, and have made outstanding achievements in adhering to new development concepts, deepening reform in an all-round way, opening up to the outside world in an all-round way, promoting the overall layout of the "five in one" and coordinating the promotion of the "four comprehensive" strategic layout. They have not only made new explorations and provided new experiences for the development of Socialism with Chinese characteristics’s cause, but also made important contributions to building a socialist modern country in an all-round way.

　　The development of special economic zones is a vivid epitome of the great practice of reform and opening up, which embodies the efforts and painstaking efforts of generations of builders of special economic zones, and interprets the China road and China wisdom of reform and opening up.

　　The historical position of special economic zones in the practice of reform and opening up

　　Since the reform and opening-up, the special economic zones have written a magnificent chapter in the historical process of building Socialism with Chinese characteristics, not only playing the role of "experimental field" in the system reform, but also playing an important "window" role in the opening-up, and showing the bright future of Socialism with Chinese characteristics to the world with world-renowned development achievements.

　　China’s reform and opening-up is a process of continuous accumulation, which is first tested, then summarized and then popularized. The introduction of reform measures requires some regions to try first, sum up experience, give full play to the role of "experimental field", and explore the way for the national reform and opening up. The special economic zones have fully carried forward the spirit of being bold, pioneering and hard-working, and made active explorations in the fields of economic system reform, political system reform and cultural system reform, providing valuable experience for promoting reforms at the national level. Under the background of deepening reform in an all-round way, special economic zones should have the courage to take responsibility and try first in all aspects of institutional reform, especially in important areas and key links, so as to provide more replicable and scalable experiences for the whole country.

　　Special economic zones are the earliest areas opened to the outside world in China since the reform and opening up, and they are also the most active areas for foreign economic exchanges. With the support of the central policy, special economic zones have introduced foreign capital, technology and management experience on a large scale, and insisted on the combination of "bringing in" and "going abroad", which not only played a positive role in foreign exchanges, but also further promoted the formation and development of China’s opening-up pattern. In February 1984, after inspecting the special economic zones, Deng Xiaoping pointed out: "The special economic zones are a window, a window of technology, a window of management, a window of knowledge and a window of foreign policy." This is an image summary of the position and role of special economic zones in the practice of China’s reform and opening up in the early days of reform and opening up. With the globalization of the world economy and the development of China’s new pattern of comprehensive opening up, the "window" role of special economic zones in opening up will be further enhanced.

　　In the great practice of 40 years’ reform and opening-up, Shenzhen Special Economic Zone has achieved a historic leap from a backward border town to an international metropolis with global influence, from economic system reform to comprehensive deepening reform, from focusing on import and export trade to all-round and high-level opening-up, from economic development to coordinating the development of socialist material civilization, political civilization, spiritual civilization, social civilization and ecological civilization, and from solving food and clothing to a high-quality and comprehensive well-off society, creating a historic leap. Socialism with Chinese characteristics is the theme of all the Party’s theories and practices since the reform and opening up. The successful practice of special economic zones has fully proved that the line, principles and policies formed since the Third Plenary Session of the Eleventh Central Committee of the Party are completely correct, which will not only further strengthen Socialism with Chinese characteristics’s road confidence, theoretical confidence, institutional confidence and cultural confidence, but also show the world the bright future and vigorous vitality of Socialism with Chinese characteristics with eloquent facts.

　　Today, the world is experiencing a great change that has never happened in a hundred years, and China is in a critical period to realize the great rejuvenation of the Chinese nation. The 40-year reform and opening-up practice in Shenzhen and other special economic zones has created great miracles and accumulated valuable experience. The new situation needs new responsibilities and calls for new actions. The construction of special economic zones in the new era should always maintain the spirit of "pioneering", "creative" and "dry" style, take the 40th anniversary of the establishment of special economic zones as a new starting point and a new opportunity, and strive to write more "spring stories" and create new and greater miracles that make the world sit up and take notice.

　　(Author: Chen Jinlong and Zhang Penghui, both special researchers of the New Era Socialism with Chinese characteristics Thought Research Center, the supreme leader of the Ministry of Education)

Regulations of Shenzhen Special Economic Zone on Comprehensive Control of Anti-smuggling

　　On January 20, 2006, the fourth meeting of the Standing Committee of the Fourth Shenzhen Municipal People’s Congress passed the first amendment according to the Decision of the 15th meeting of the Standing Committee of the Fifth Shenzhen Municipal People’s Congress on April 27, 2012 on Amending the Regulations on Comprehensive Anti-smuggling in Shenzhen Special Economic Zone, and the 36th meeting of the Standing Committee of the Sixth Shenzhen Municipal People’s Congress on October 31, 2019 on Amending the Regulations on Human Organ Donation and Transplantation in Shenzhen Special Economic Zone.

Catalogue

　　Chapter I General Principles

　　Chapter II Duties and Responsibilities

　　Chapter III Precaution

　　Chapter iv investigation

　　Chapter V Handling

　　Chapter VI Reward and Punishment

　　Chapter VII Supplementary Provisions

Chapter I General Principles

　　Article 1 In order to effectively prevent and crack down on smuggling and maintain the order of socialist market economy, these Regulations are formulated in accordance with the Customs Law of People’s Republic of China (PRC) and the basic principles of relevant laws and administrative regulations, combined with the reality of Shenzhen Special Economic Zone.

　　Article 2 Anti-smuggling work adheres to the principle of combining crackdown with prevention and giving priority to prevention; Follow the principles of joint anti-smuggling, unified handling and comprehensive management.

　　Article 3 Customs, public security, frontier defense and market supervision departments shall perform their anti-smuggling duties according to law, and other state organs shall provide support and cooperation.

　　Article 4 The municipal and district people’s governments shall, in accordance with these regulations and the relevant provisions of the state, carry out comprehensive anti-smuggling management.

　　City and district anti-smuggling comprehensive management institutions (hereinafter referred to as comprehensive management institutions) are specifically responsible for the organization, guidance, coordination, supervision and inspection of comprehensive anti-smuggling management.

　　City comprehensive management agencies to conduct business guidance and supervision of the work of district comprehensive management agencies.

　　Article 5 The funds needed for the comprehensive control of anti-smuggling shall be included in the financial budget by the municipal and district people’s governments and guaranteed.

　　The special funds allocated by the state and the province for the comprehensive control of anti-smuggling shall be earmarked for special purposes and shall not be used for other purposes.

Chapter II Duties and Responsibilities

　　Article 6 The Customs is the national supervision and administration organ for entry and exit of customs territory, and independently performs the duties of smuggling investigation according to law.

　　The municipal and district people’s governments and their departments shall support the customs in exercising their functions and powers according to law and shall not interfere with the customs’ law enforcement activities.

　　Article 7 Public security organs shall perform the following duties:

　　(1) Investigating and handling non-tax-related smuggling crimes outside the customs supervision area according to law;

　　(2) Stop smuggling activities outside the customs supervision area in time and handle them according to the division of labor under the jurisdiction of the case;

　　(3) When encountering resistance in the performance of anti-smuggling duties by customs, frontier defense, market supervision and other departments, assisting them and handling them according to law;

　　(four) other duties as prescribed by laws and regulations.

　　The public security frontier defense department shall perform the duties of anti-smuggling work in accordance with the relevant provisions of the state.

　　Article 8 The market supervision department shall perform the following duties:

　　(a) to investigate and deal with the behavior of importing goods and articles without legal sources outside the customs supervision area;

　　(two) to cooperate with the relevant functional departments to investigate and deal with suspected smuggling in import and export enterprises and special industries;

　　(three) other duties as prescribed by laws and regulations.

　　Ninth comprehensive management institutions shall perform the following duties:

　　(1) Organizing the publicity of laws, regulations, guidelines and policies related to anti-smuggling;

　　(two) to formulate the comprehensive anti-smuggling control work plan, and organize the implementation after the approval of the people’s government at the same level;

　　(3) Organizing, guiding and coordinating relevant units to carry out the work of preventing smuggling;

　　(four) to organize and coordinate the relevant functional departments to carry out joint operations and special operations of comprehensive anti-smuggling management, coordinate and supervise the investigation of major and complex smuggling cases;

　　(five) to coordinate the relevant functional departments to deal with emergencies such as resisting and obstructing the investigation of smuggling;

　　(six) to supervise, inspect and assess the comprehensive anti-smuggling work of the relevant units;

　　(seven) to coordinate and deal with the relevant matters that need the cooperation of local departments in the customs investigation of smuggling;

　　(eight) to organize and carry out comprehensive anti-smuggling cooperation with the surrounding areas;

　　(nine) other duties as prescribed by laws and regulations.

　　Article 10 The relevant departments or units of industry and information technology, culture, radio, film, television, tourism and sports, marine fisheries, taxation, tobacco monopoly, liquor management, finance, etc. shall promptly notify the customs or comprehensive management agencies when they discover smuggling clues when performing their duties.

Chapter III Precaution

　　Eleventh comprehensive anti-smuggling management to implement the responsibility system. The relevant functional departments or units to carry out comprehensive anti-smuggling work should be included in the scope of performance appraisal.

　　The specific measures for the responsibility system for the comprehensive management of anti-smuggling shall be formulated separately by the Municipal People’s Government.

　　Article 12 The municipal comprehensive management institution shall regularly publish reports on the comprehensive management of anti-smuggling, summarize the comprehensive management of anti-smuggling in the whole city, analyze the characteristics and laws of smuggling activities, and put forward specific measures to prevent smuggling.

　　Article 13 The municipal comprehensive management organization shall guide the trade associations of import and export enterprises to establish an anti-smuggling credit system, and coordinate relevant departments to classify and manage import and export enterprises according to their credit ratings.

　　Fourteenth the establishment of anti smuggling monitoring and early warning mechanism, by the city comprehensive management agencies to coordinate the relevant departments, analysis and prediction of smuggling trends, to guide the relevant units to carry out preventive work.

　　Fifteenth the establishment of anti smuggling emergency response mechanism, by the city comprehensive management agencies to coordinate the relevant departments, formulate emergency response plans, do a good job in emergency preparedness.

　　Sixteenth comprehensive management institutions should strengthen anti-smuggling publicity and education, and relevant state organs, enterprises and institutions and other organizations should give support and cooperation.

　　Seventeenth news media should, according to the needs, strengthen the publicity and reporting of comprehensive anti-smuggling control.

Chapter iv investigation

　　Article 18 A joint meeting system for comprehensive management of anti-smuggling shall be established, and the municipal comprehensive management agency shall convene relevant departments to hold regular meetings to study and deal with the following matters:

　　(a) analysis of smuggling dynamics and situation;

　　(two) put forward specific measures for comprehensive management of anti-smuggling;

　　(3) Deploying joint actions and special actions for comprehensive anti-smuggling management;

　　(four) other matters that need to be coordinated.

　　Article 19 An anti-smuggling information exchange and processing mechanism shall be established, and the municipal comprehensive management agency shall coordinate with relevant departments such as customs, public security, frontier defense and market supervision to exchange information and realize information sharing.

　　Article 20 Comprehensive management institutions shall organize and coordinate relevant departments to carry out special treatment on areas with high smuggling incidence, key smuggling channels and smuggled hot commodities.

　　Twenty-first key areas shall, according to the needs, establish a grass-roots anti-smuggling inspection mechanism, organize patrol teams, and cooperate with relevant departments to strengthen comprehensive anti-smuggling management.

　　Specific measures for grassroots anti-smuggling inspections shall be formulated separately by the municipal comprehensive management agency.

　　Twenty-second to establish an incentive mechanism for anti-smuggling intelligence information, the relevant departments should strengthen the collection of intelligence information, timely handle the obtained intelligence information, and reward the intelligence information providers in accordance with relevant regulations.

　　The specific measures for the reward shall be formulated separately by the municipal comprehensive management institution in conjunction with the relevant departments.

Chapter V Handling

　　Article 23 When performing the duties of anti-smuggling work, the market supervision department may exercise the following functions and powers:

　　(a) ask the relevant parties;

　　(2) consulting and copying the contracts, invoices, account books and other materials related to the operation of imported goods and articles without legal sources;

　　(3) Conducting on-site inspection on the places where the parties are suspected of dealing in imported goods and articles without legal sources.

　　Twenty-fourth smuggling cases under the jurisdiction of the customs according to law, the relevant departments shall, in accordance with the relevant provisions of the state, transfer them to the customs anti-smuggling department for handling.

　　In case of smuggling cases with jurisdiction disputes or unclear jurisdiction, the relevant departments shall promptly submit them to the municipal comprehensive management agency for coordination and handling.

　　Twenty-fifth relevant functional departments in the process of law enforcement, seized suspected smuggled goods and articles, but the owner and the illegal facts of smuggling can not be ascertained, it shall hand over the goods and articles to the municipal comprehensive management agency; City comprehensive management institutions shall issue a claim announcement for a period of sixty days. If the announcement expires unclaimed, it shall be transferred to the municipal finance department for handling in accordance with relevant regulations. The specific measures shall be formulated separately by the municipal comprehensive management institution in conjunction with the relevant functional departments.

　　If the dangerous goods in the goods and articles mentioned in the preceding paragraph are fresh, perishable and ineffective, etc., which should not be preserved for a long time, the relevant departments shall hand them over to the municipal finance department within 24 hours after being seized, and the municipal finance department shall handle them in time in accordance with relevant regulations, and the proceeds shall be deposited into the account designated by the municipal finance department; If the announcement expires unclaimed, it shall be turned over to the state treasury.

　　Article 26 The means of transport specially or repeatedly used for smuggling shall be handled by the customs according to law; Other means of transport used for smuggling shall be registered and put on record by the municipal comprehensive management agency, and it is suggested that the relevant departments deal with it according to law.

　　For the means of transport used for smuggling that need to be destroyed centrally, the municipal comprehensive management organization shall organize relevant departments to destroy them in accordance with relevant regulations.

　　Article 27. Anyone who deals in imported goods and articles without legal sources outside the customs supervision area shall be confiscated by the market supervision department and be fined the same amount as the value of the goods and articles. Where laws and regulations provide otherwise, such provisions shall prevail. If a crime is constituted, criminal responsibility shall be investigated according to law.

Chapter VI Reward and Punishment

　　Twenty-eighth units and individuals that meet one of the following conditions shall be commended and rewarded by the municipal and district people’s governments:

　　(a) the implementation of the comprehensive anti-smuggling management responsibility system, with remarkable achievements;

　　(2) Having made outstanding contributions in investigating and handling major and extraordinarily serious smuggling cases;

　　(3) Actively assisting in the seizure of smuggling cases and making outstanding contributions;

　　(four) investigate and deal with reactionary, obscene, intellectual property infringement and other smuggled goods and articles, a large number;

　　(5) The research results or rationalization proposals of comprehensive anti-smuggling management have been adopted and achieved remarkable results;

　　(6) Having made other outstanding contributions to the anti-smuggling work.

　　The specific measures for recognition and reward shall be formulated separately by the municipal comprehensive management organization and implemented after being approved by the Municipal People’s government.

　　Twenty-ninth relevant units in any of the following circumstances, the comprehensive management agency shall order rectification, and shall be informed:

　　(1) Failing to effectively implement the responsibility system for comprehensive management of anti-smuggling, resulting in serious smuggling activities in the region and its jurisdiction or having a bad influence;

　　(2) Failing to properly handle emergencies such as violent resistance to anti-smuggling or obstruction of anti-smuggling in accordance with the emergency response plan;

　　(3) Failing to effectively perform other duties as stipulated in these Regulations.

　　Article 30 If the relevant departments fail to perform their duties in accordance with the provisions of these Regulations, if the circumstances are serious, the directly responsible person in charge and other directly responsible personnel shall be punished by the unit to which they belong or the supervisory organ shall give administrative sanctions to the directly responsible person in charge and other directly responsible personnel according to law.

　　If the staff of the relevant departments abuse their powers, neglect their duties or engage in malpractices for selfish ends, the unit to which they belong shall be punished according to law or the supervisory organ shall give administrative sanctions according to law; If a crime is constituted, criminal responsibility shall be investigated according to law.

Chapter VII Supplementary Provisions

　　Article 31 The term "imported goods and articles without legal sources" as mentioned in these Regulations refers to imported goods and articles that cannot provide proof of legal sources such as import procedures, invoices from legal distribution units or legal and effective administrative punishment decisions within ten working days from the date of investigation.

　　Article 32 These Regulations shall come into force as of March 1, 2006.

　　BEIJING, Beijing, May 15 (Wei Xianghui) On April 28 this year, the Organization Department of jiangsu provincial party committee issued a number of pre-service announcements for leading cadres in provincial administration. Among them, Zhang Mingkang, Pan Guoqiang and Liu Hao intend to recommend and nominate candidates as mayors of districts and cities. As of May 15th, the whereabouts of the above three people have been made clear.

The picture shows Zhang Mingkang Image source: WeChat WeChat official account "Suqian Release"

　　According to the website of the Organization Department of the CPC jiangsu provincial party committee, the 11th meeting of the Standing Committee of the Ninth Yancheng Municipal People’s Congress decided on May 15th to accept Zhou Bin’s request to resign as the mayor of Yancheng Municipal People’s Government and appointed Zhang Mingkang as the deputy mayor and acting mayor of Yancheng Municipal People’s Government.

　　On May 13th, the 9th meeting of the Standing Committee of the Ninth People’s Congress of Yangzhou decided to accept Wang Jinjian’s request to resign as mayor of Yangzhou Municipal People’s Government and appointed Pan Guoqiang as deputy mayor and acting mayor of Yangzhou Municipal People’s Government.

Pan Guoqiang took the constitutional oath. Image source: WeChat WeChat official account "Yangzhou Release"

　　On May 12th, the 10th meeting of the Standing Committee of the Sixth Suqian Municipal People’s Congress decided to accept Chen Zhongwei’s request to resign as mayor of Suqian Municipal People’s Government and appointed Liu Hao as deputy mayor and acting mayor of Suqian Municipal People’s Government.

　　According to the information published on the website of jiangsu provincial party committee Organization Department, all three are "post-70s".

　　Zhang Mingkang, male, Han nationality, born in July 1973, university, bachelor’s degree, party member, CPC.

　　Pan Guoqiang, male, Han nationality, born in October 1974, graduate student of Party School of Provincial Party Committee, bachelor’s degree, party member, CPC.

　　Liu Hao, male, Han nationality, born in May 1973, holds an in-service postgraduate degree, and holds an MBA in party member, CPC.

　　Zhang Mingkang has worked in Wuxi for a long time. He used to be the director of Wuxi Statistics Bureau, the party secretary, the director of Wuxi Development and Reform Commission and the party secretary.

　　In January 2019, Zhang Mingkang was appointed Secretary-General of Wuxi Municipal Government, a member of the party group, and concurrently served as the director of the research office of the municipal government. In July 2020, he served as the deputy mayor of Wuxi. In 2021, Zhang Mingkang was transferred to the Standing Committee of Suqian Municipal Committee and executive deputy mayor until this time in Yancheng.

　　Pan Guoqiang has worked in Suzhou for a long time. He used to be the director, office director and deputy researcher of the Research Office of the Organization Department of Suzhou Municipal Committee, the member of the Standing Committee of Wuzhong District Committee, the director of the United Front Work Department, the deputy secretary-general of Suzhou Municipal Committee and the director of the Municipal Reception Office.

　　In 2018, Pan Guoqiang was appointed as the acting mayor of Zhangjiagang City, and later as the mayor. In 2020, he was appointed as the secretary of the Zhangjiagang Municipal Party Committee. In 2021, he served as member of the Standing Committee and Secretary General of Suzhou Municipal Committee, and was transferred to Yangzhou this time.

　　Suqian City, Liu Hao, is the youngest prefecture-level city in Jiangsu Province. According to official website, the local government, Suqian, located in the north of Jiangsu Province, belongs to the cross-radiation area of Huaihai Economic Belt, Coastal Economic Belt and Riverside Economic Belt.

The picture shows Liu Hao Source: WeChat WeChat official account "Chongchuan Online"

　　Liu Hao once worked in the general office of jiangsu provincial party committee for a long time, and served as the secretary of the Economic Department of the General Office of the Provincial Party Committee, the deputy director and researcher of the Economic Department of the General Office of the Provincial Party Committee, the deputy director and director of the General Office, and the deputy inspector of the Research Office of the Provincial Party Committee.

　　In July 2017, Liu Hao was transferred to the Standing Committee of Nantong Municipal Committee and Minister of Propaganda Department. In 2018, he served as the Standing Committee of Nantong Municipal Committee and Secretary of Chongchuan District Committee. In 2021, Liu Hao became the Standing Committee of Taizhou Municipal Committee, Deputy Secretary of the Party Group and Executive Deputy Mayor of the Municipal People’s Government. Today, he goes to Suqian. (End)

The afterheat of The Knockout has not dissipated, because the supporting actors in the play are still enjoying the bonus through the heat of the drama. The two real protagonists in the play seem to be "completely uninterested" in money.

1, small five-go to the real estate.

Wu Jingli, who plays Xiao Wu in The Knockout, was originally a music teacher, and her sideline job was as a group actor. It’s better to play with a group of actors than with a group. If you stay in the group, you will have a fixed role, lines and more opportunities to appear than the flash of group performances.

The Knockout is Wu Jingli’s first play, because she plays a policeman in the play. She also accepted an activity to preach fire safety knowledge on campus, which should be public welfare.

Later, Wu Jingli went to participate in the opening activities of a real estate, and brought her role bonus to the extreme.

The netizen also left a message under her Weibo, telling her not to go to the real estate.

Wu Jingli is still young. Although she is not a trained actress, she may get some plays with the help of the east wind in The Knockout. Let’s take good care of her feathers.

2, Qisheng Gao-endorsement online games, go to the live room to bring goods.

Su Xiaowan, the actor of Qisheng Gao, is deeply attached to his brother Gao Qiqiang, and has gained a lot of audience’s love, so he has invited many brands.

Su Xiaowan first endorsed an advertisement for an online game. Although netizens thought it was a bit LOW, he did make money.

In addition, Su Xiaowan was invited by a certain tens of millions of online celebrity to go to the live broadcast room in online celebrity to bring goods and interact with online celebrity. It was awkward to watch.

Su Xiaowan is a child star born in the 1990s. He started acting at the age of 3, and officially entered the entertainment circle at the age of 7. He has acted in such hot TV dramas as Snow Leopard, Rouge and No Boundless Charmer, but he has been in a state of "nobody knows".

Maybe he wants to seize this opportunity and earn more money.

Su Xiaowan or Dong Xuan talked about love, probably in 2020, and later broke up and became her predecessor.

3, Lao Mo-live room with goods

Feng Bing, the actor of Lao Mo, has also been in the entertainment circle for many years. Last year, his "Picture Book of Hunting Crime" and "Glory of Special War" were broadcast one after another, but only The Knockout was the most popular.

Lao Mo also went to the live studio to bring goods, and he went to the same house as Su Xiaowan. For a supporting actor who has not been popular for many years, it is really rare to have a chance to be popular.

In March, Lao Mo went fishing and shared the news. Such a simple thing rushed to the hot search, which shows that the audience’s "sequela" of The Knockout has not been alleviated!

4. Secretary Wang-take the endorsement and take a photo.

Compared with selling goods in the live broadcast room, Zheng Jiabin, the actor of Secretary Wang, seems to be treated better, because he received a perfume advertisement, at least it looks very stylish, not fall in price.

Zheng Jiabin, born in the 1990s, walks in the elegant style of a handsome man. He not only has endorsements, but also has some photo shoots, which looks very advanced.

Although the role he plays is obscene, he is clean and handsome, and many viewers have studied his previous private service. It is found that his post-90 s actor is very scarce in the entertainment circle.

Maybe he has a longer-term plan than making quick money for a while.

5, Gao Ye-6 endorsements a month

Although Gao Ye, who plays the eldest sister-in-law, is a female partner, she is much stronger than the heroine and receives more advertisements than the heroine. She received six advertisements within one month.

However, it is said that Gaoye is connected with top brands, and it is very well-known for not looking for Gaoye to advertise.

The brand style is high enough, so Gao Ye won’t go to fall in price next, let alone "cut leeks", and she can make money herself.

Even if you take the endorsement, Gao Ye will not pick it up indiscriminately, which is still worthy of recognition.

In addition, she also rushed to attend the awards ceremony, and was able to sit in the same row with Rachel Momo, which shows that her popularity and coffee table have skyrocketed.

The above are advertisements and endorsements, but after The Knockout became popular, the two leading actors, Zhang Yi and Zhang Songwen, were not in a hurry to make money, so they kept a low profile.

6. Zhang Yi

Rumors about Zhang Yi’s disagreement with The Knockout’s cast have been discussed by netizens. In addition, since the beginning of the series, Zhang Yi hasn’t made any dynamic publicity, which seems to confirm this rumor.

But for the audience, it doesn’t matter whether to publicize or not, as long as the actors present excellent works.

Zhang Yi himself doesn’t deal with the "cast", and he is low-key, so he naturally doesn’t want to eat the bonus of the drama’s popularity. In addition, Zhang Yi didn’t even attend The Knockout’s celebration dinner.

At present, the ratings of Zhang Yi’s new drama "Who Is He" are also very bright, and some viewers even said that the drama has surpassed The Knockout!

As an actor, Zhang Yi is really excellent and successful!

7. Zhang Songwen

Although Zhang Songwen attended the celebration dinner and had a good relationship with The Knockout, he didn’t eat the bonus of exploding fire.

According to insiders, all business people in the circle want to find Zhang Songwen and cooperate with him, but all of them are rejected by Zhang Songwen. I feel that Zhang Songwen has "lost hundreds of millions"!

Not only did he not accept advertisements, but Zhang Songwen also rarely interviewed, and he remained "invisible".

Zhang Songwen refused, on the one hand, he really kept a low profile. A while ago, a few fans ran to the airport to pick up the plane. Zhang Songwen was a little troubled, but he didn’t blame the fans. First, he called everyone to take a photo together, and then he gently comforted the fans, hoping that they wouldn’t pick up the plane at the airport in the future. The fans are also very obedient.

Moreover, Zhang Songwen, who became popular, seems to be no different from before. She continues to shoot silently in the crew, share her interesting daily life in Weibo and interact with fans.

On the other hand, Zhang Songwen actually thinks that Gao Qiqiang, who he plays, is always a villain. In his essay, Zhang Songwen hopes that the three brothers and sisters can live a simple and peaceful life.

Zhang Songwen doesn’t want his negative role to be touted, so as not to bring bad influence and wrong effect.

The role is the role, the reality is the reality, and Zhang Songwen clearly distinguishes it. It is good for Zhang Songwen to reduce his sense of existence after The Knockout. He is too smart and sober.

Indeed, the positive characters are silent, but the villains are arrogant, which may, in a sense, have a bad guide to the audience who have not yet formed the three views.

Punishing evil and promoting good must be the most basic principle. I hope that the supporting actors in The Knockout will make money and don’t forget to guide them well!

China Banking and Insurance Regulatory Commission on printing and distributing financial assets investment companies

Notice of Measures for Capital Management (for Trial Implementation)

Yin Bao Jian Gui [2022] No.12

All banking insurance regulatory bureaus, Industrial and Commercial Bank of China, Agricultural Bank of China, China Bank, China Construction Bank, Bank of Communications, and all financial asset investment companies:

"Measures for Capital Management of Financial Asset Investment Companies (Trial)" has been adopted at the second ministerial meeting in China Banking and Insurance Regulatory Commission in 2022, and is hereby issued to you, please follow it.

China Banking and Insurance Regulatory Commission

June 17, 2022

Measures for capital management of financial asset investment companies (for Trial Implementation)

Chapter I General Principles

the first　In order to strengthen the capital supervision of financial asset investment companies and promote the stable operation of financial asset investment companies, these Measures are formulated in accordance with the Banking Supervision Law of the People’s Republic of China, the Administrative Measures for Financial Asset Investment Companies (Trial) (Order No.4 of the Bank of China Insurance Regulatory Commission in 2018) and other laws and regulations.

the second　These Measures shall apply to groups composed of financial asset investment companies and their subsidiaries.

The term "financial asset investment company" as mentioned in these Measures refers to a non-bank financial institution established within the territory of People’s Republic of China (PRC) with the approval of China Banking and Insurance Regulatory Commission, which is mainly engaged in bank debt-to-equity swap (hereinafter referred to as debt-to-equity swap) and supporting business. The term "affiliated institutions" as mentioned in these Measures refers to institutions that are directly or indirectly held by financial asset investment companies and should be included in the scope of consolidated capital supervision in accordance with the provisions of Section V of Chapter II of these Measures.

Article　A financial asset investment company shall ensure that the capital it holds can withstand the risks it faces, including group risks, individual risks and systemic risks.

Article 4　A financial asset investment company shall continuously meet the regulatory requirements and indicators of capital adequacy as stipulated in these Measures.

Article 5　The term "capital adequacy ratio" as mentioned in these Measures refers to the ratio between capital and risk-weighted assets held by financial asset investment companies that meet the requirements of these Measures.

Tier 1 capital adequacy ratio refers to the ratio between tier 1 capital and risk-weighted assets held by financial asset investment companies that meet the requirements of these Measures.

Core Tier 1 capital adequacy ratio refers to the ratio between core Tier 1 capital and risk-weighted assets held by financial asset investment companies that meet the requirements of these Measures.

Article 6　A financial asset investment company shall calculate the consolidated and non-consolidated capital adequacy ratio in accordance with the provisions of these Measures.

Article 7　The term "net capital" as mentioned in these Measures refers to the capital balance after deduction from all levels of capital held by financial asset investment companies and affiliated institutions that meet the provisions of these Measures.

Article 8　In addition to the above regulatory requirements for capital adequacy ratio, financial asset investment companies should also meet the regulatory requirements for leverage ratio.

The term "leverage ratio" as mentioned in these Measures refers to the ratio between the net Tier 1 capital held by a financial asset investment company and the adjusted balance of assets on the balance sheet and the balance of off-balance sheet items.

Article 9　A financial asset investment company shall establish a comprehensive risk management framework and internal capital adequacy management and evaluation procedures.

Article 10　China Banking and Insurance Regulatory Commission and its dispatched offices shall, in accordance with these Measures, conduct daily supervision and on-site inspection on the capital adequacy and capital management of financial asset investment companies, and may take corresponding supervision measures as appropriate.

Chapter II Capital Supervision Requirements

Section 1 Calculation of Capital Adequacy Ratio and Regulatory Requirements

Article 11　The formula for calculating the capital adequacy ratio of a financial asset investment company is:

Article 12　The total capital of a financial asset investment company includes core tier 1 capital, other tier 1 capital and tier 2 capital. A financial asset investment company shall calculate all levels of capital and deductions in accordance with the provisions of Section II of this chapter.

Article 13　The risk-weighted assets of financial asset investment companies include credit risk-weighted assets, market risk-weighted assets, operational risk-weighted assets and asset management business risk-weighted assets. A financial asset investment company shall separately measure credit risk-weighted assets, market risk-weighted assets, operational risk-weighted assets and asset management business risk-weighted assets in accordance with the provisions of Section III of this chapter.

Article 14　The capital adequacy ratio of financial asset investment companies at all levels shall not be lower than the following requirements:

(1) The core tier-one capital adequacy ratio shall not be less than 5%;

(2) The Tier 1 capital adequacy ratio shall not be less than 6%;

(3) The capital adequacy ratio shall not be less than 8%.

Article 15　Under certain circumstances, a financial asset investment company shall accrue countercyclical capital above the minimum capital requirement. The countercyclical capital requirement is 0-2.5% of risk-weighted assets, which is met by core Tier 1 capital. The countercyclical capital requirement is determined by China Banking and Insurance Regulatory Commission according to the actual situation.

Section 2 Definition of Capital

Article 16　Core Tier 1 capital includes:

(1) Paid-in capital or common stock;

(2) Capital reserve;

(3) Surplus reserve;

(4) General risk preparation;

(5) Undistributed profits;

(6) Other parts that can be included.

Article 17　Other Tier 1 capital includes:

(1) Other Tier 1 capital instruments;

(2) Premium of other Tier 1 capital instruments.

Article 18　Tier 2 capital includes:

(1) Tier 2 capital instruments;

(2) Premium of secondary capital instruments;

(3) Reserve for excess losses.

Financial asset investment companies should use the weight method to measure credit risk-weighted assets, and the excess loss reserve can be included in tier 2 capital, but it shall not exceed 1.25% of credit risk-weighted assets.

A financial asset investment company shall carry out impairment accounting treatment on financial instruments that need impairment accounting treatment in strict accordance with the requirements of accounting standards and confirm the loss reserve. The excess loss reserve mentioned in the preceding paragraph refers to the part of the loss reserve actually withdrawn by a financial asset investment company that exceeds the balance of non-performing assets.

Article 19　When calculating the capital adequacy ratio, a financial asset investment company shall fully deduct the following items from the core Tier 1 capital:

(1) Goodwill;

(2) Other intangible assets (except land use rights);

(3) Net deferred income tax assets caused by operating losses;

(4) The gap of loss provision for credit risk assets.

The gap of loss reserve refers to the part where the loss reserve actually accrued by a financial asset investment company is lower than the balance of non-performing assets.

Article 20　Capital instruments at all levels held by financial asset investment companies and other financial institutions through agreements, or capital investments at all levels identified by China Banking and Insurance Regulatory Commission and its dispatched offices as inflated capital, should be deducted from the corresponding regulatory capital.

Financial asset investment companies directly or indirectly hold capital instruments at all levels issued by the company, which should be deducted from the corresponding regulatory capital. Financial asset investment companies should deduct the capital investment in affiliated institutions from the capital at all levels when calculating the capital adequacy ratio without consolidation.

Corresponding deduction refers to a one-time full deduction from the corresponding capital of the financial asset investment company. If the net capital of a financial asset investment company at a certain level is less than the amount to be deducted, the gap shall be deducted from the net capital at a higher level.

Article 21　The small minority capital investment made by a financial asset investment company to financial institutions that are not included in the scope of capital supervision, which exceeds 30% of the company’s core tier-one net capital, shall be deducted from the supervision capital at all levels.

Small minority capital investment refers to the capital investment (including direct and indirect investment) of a financial asset investment company to all levels of financial institutions, which accounts for less than 10% (excluding) of the paid-in capital (common stock plus common stock premium) of the invested financial institution, and can be excluded from the scope of capital supervision according to the provisions of Section 5 of this chapter.

Article 22　Among the large minority capital investments made by financial asset investment companies to financial institutions that are not included in the scope of capital supervision, the part where the total core tier-one capital investment exceeds 30% of the company’s net core tier-one capital shall be deducted from the company’s core tier-one capital; Other tier-1 capital investments and tier-2 capital investments shall be fully deducted from the corresponding level of capital.

Large minority capital investment refers to the capital investment (including direct and indirect investment) made by a financial asset investment company to all levels of financial institutions, which accounts for more than 10% (inclusive) of the paid-in capital (common stock plus common stock premium) of the invested financial institution, and may not be included in the scope of capital supervision according to the provisions of Section 5 of this chapter.

Article 23　Except for the net deferred income tax assets specified in Article 19 of these Measures, other net deferred income tax assets that depend on the company’s future earnings, which exceed 10% of the company’s net core tier 1 capital, shall be deducted from the core tier 1 capital.

Article 24　According to the provisions of Article 22 and Article 23 of these Measures, the total amount of large minority capital investment in financial institutions and the corresponding net deferred income tax assets not deducted from the core tier 1 capital of a financial asset investment company shall not exceed 35% of the company’s net core tier 1 capital.

Section 3 Measurement of Risk-weighted Assets

Article 25　Financial asset investment companies use the weight method to measure credit risk-weighted assets.

Article 26　When measuring the risk-weighted assets of various on-balance-sheet assets, a financial asset investment company should first deduct the corresponding impairment reserve from the book value of the assets, and then multiply it by the risk weight.

A financial asset investment company shall measure the credit risk-weighted assets of various on-balance-sheet assets in accordance with the provisions of Annex 1 to these Measures.

Article 27　When a financial asset investment company uses the weighting method to measure credit risk-weighted assets, it may consider the risk mitigation effect of the risk mitigation clause in accordance with the provisions in Annex 1 of these Measures, and the calculation method is as follows:

Credit risk weighted assets = (book value of assets-impairment reserve-book value of risk mitigation tools) × risk weight of assets+book value of risk mitigation tools× risk weight of risk mitigation tools.

Article 28　Financial asset investment companies should adopt the standard method to measure the market risk capital requirements.

Article 29　A financial asset investment company shall formulate clear criteria for the division of trading books and bank books, specify the positions of financial instruments included in trading books and the conditions for transfer between trading books and bank books, and ensure the consistency of implementation.

Article 30　The market risk-weighted assets of financial asset investment companies are 12.5 times of the market risk capital requirements, that is, market risk-weighted assets = market risk capital requirements ×12.5.

Article 31　A financial asset investment company shall separately measure the capital requirements of various asset market risks in accordance with the provisions of Annex 2 to these Measures.

Article 32　Financial asset investment companies should adopt the basic index method to measure the operational risk capital requirements.

Article 33　The operational risk-weighted assets of financial asset investment companies are 12.5 times of the operational risk capital requirements, that is, operational risk-weighted assets = operational risk capital requirements ×12.5.

Article 34　A financial asset investment company shall measure the operational risk capital requirements based on the average total income in the last three years.

Total income shall be confirmed in accordance with the provisions of Annex 3 of these Measures, including investment income, net fee and commission income, net interest income, net income from disposal of non-performing assets and other income.

Operational risk capital shall be measured according to the following formula:

Among them:

KBIAIt is the operational risk capital requirement measured by the basic index method;

GI is the positive total income in each of the past three years;

N is the number of years with positive total income in the past three years;

α is 15%.

Article 35　Financial asset investment companies should measure the risk capital requirements of asset management business.

Article 36　The risk-weighted assets of the asset management business of a financial asset investment company are 12.5 times the risk capital requirement of the asset management business, that is, the risk-weighted assets of the asset management business = the risk capital requirement of the asset management business ×12.5.

Article 37　A financial asset investment company shall measure the risk capital requirements of asset management business in accordance with the provisions of Annex 4 of these Measures.

Article 38　A financial asset investment company shall carefully judge the risk situation faced by its asset management business and ensure that the capital can cover the risk of asset management business.

Section 4 Calculation of Leverage Ratio and Regulatory Requirements

Article 39　The formula for calculating the leverage ratio of a financial asset investment company is:

Leverage ratio = net Tier 1 capital/(adjusted balance of on-balance-sheet assets+balance of off-balance-sheet items) ×100%

Article 40　The adjusted balance of on-balance-sheet assets is the balance of on-balance-sheet assets after deducting Tier 1 capital deduction from the total assets in the table.

Article 41　Off-balance sheet items do not include asset management business. The balance of off-balance-sheet items is the risk exposure calculated by the off-balance-sheet business of financial asset investment companies according to the corresponding credit conversion coefficient, and the credit conversion coefficient of various off-balance-sheet items shall be implemented in accordance with Annex 5 of these Measures.

Article 42　The leverage ratio of a financial asset investment company shall not be less than 6%.

Section 5 Calculation Scope of Consolidated Capital Supervision Indicators

Article 43　The calculation scope of consolidated capital supervision indicators shall include financial asset investment companies and institutions that directly or indirectly invest in them in accordance with the provisions of these Measures.

Article 44　A financial asset investment company shall follow the principle of "substance is more important than form", take control as the basis, and take into account the risk correlation, and include the invested institutions that meet one of the following conditions into the consolidated calculation scope:

(1) The investee directly owned by the financial asset investment company or its affiliated institutions, or jointly owned by the financial asset investment company and its affiliated institutions with more than 50% of the voting rights.

(2) An investee whose financial asset investment company has less than 50% of the voting rights, but is under any of the following circumstances:

1. Having more than 50% of the voting rights of the institution through agreements with other investors;

2. According to the articles of association or agreement, have the right to decide the financial and operating policies of the institution;

3. Have the right to appoint or remove most members of the board of directors of the institution or similar authority;

4. Have a majority of voting rights in the board of directors of the institution or similar authority.

When determining the voting right of the invested institution, we should consider the potential voting factors such as the current convertible corporate bonds and current executable warrants held by the financial asset investment company. The potential voting rights that can be realized in the current period shall be included in the voting rights of the financial asset investment company to the invested institution.

(3) There is other evidence that the invested institution is actually controlled by the financial asset investment company.

Control means that the investor has the power over the investee, enjoys variable returns by participating in the related activities of the investee, and has the ability to influence the amount of returns by using the power over the investee.

Article 45　A financial asset investment company does not have the majority voting rights or control rights of the invested institution, and it shall be included in the calculation range of consolidated capital supervision indicators under any of the following circumstances:

(1) Although the asset size of a single institution accounts for a small proportion of the overall asset size of a financial asset investment company, according to the risk correlation, the overall risk of such institutions is enough to have a significant impact on the financial position and risk level of a financial asset investment company;

(2) The harm and loss caused by the compliance risk and reputation risk of the invested institution are sufficient to have a significant impact on the financial asset investment company.

Article 46　The following invested institutions may not be included in the calculation scope of consolidated capital supervision indicators:

(a) closed or declared bankrupt institutions;

(2) Institutions that have entered liquidation procedures due to termination;

(3) Invested institutions that have evidence to prove that they have decided to sell within three years, and the equity capital of financial asset investment companies or affiliated institutions is more than 50%;

(4) A subsidiary non-financial institution that meets any of the following conditions:

1. The proportion of financial assets in total assets is less than 50% (the scope of financial assets shall conform to the relevant provisions of Accounting Standards for Enterprises No.22-Recognition and Measurement of Financial Instruments);

2. The asset-liability ratio is lower than 70%;

3. It is recognized by China Banking and Insurance Regulatory Commission and its agencies that it has no investment and financing function.

The conditions stipulated in this paragraph are mainly judged according to the arithmetic average of the audited year-end financial statements of the affiliated non-financial institution in the last two years. If it is established less than two years, it can be judged according to the audited financial statements from the date of establishment to the latest period.

Article 47　If a financial asset investment company and its affiliated financial institutions provide long-term repayment guarantee to affiliated non-financial institutions, the non-financial institutions shall be included in the scope of capital supervision; If there is no repayment guarantee or the repayment guarantee can be unconditionally revoked, the financial asset investment company shall handle it according to the principle of prudence. Equity investment through structured entities such as asset management plans and funds should be managed according to the penetrating principle.

Article 48　A financial asset investment company shall strengthen the capital management of its subsidiaries, determine the management requirements for the capital adequacy of its subsidiaries at all levels according to its actual situation, and urge the subsidiaries to continuously meet the capital management and supervision requirements.

Article 49　China Banking and Insurance Regulatory Commission and its dispatched offices have the right to determine and adjust the scope of capital supervision according to the changes in equity structure and risk categories of financial asset investment companies and their investment institutions.

Chapter III Internal Capital Adequacy Assessment Procedures

Article 50　A financial asset investment company shall, in accordance with the regulatory requirements, establish a sound risk management framework and a robust internal capital adequacy assessment procedure, clarify the risk governance structure, carefully assess various risks, capital adequacy levels and capital quality, and formulate capital planning and capital management plans to ensure that capital can fully resist the risks it faces and meet the needs of business development.

Article 51　The board of directors of a financial asset investment company bears the primary responsibility for capital management of the company. The board of directors shall perform the following duties:

(1) Set the risk preference and capital adequacy target suitable for the company’s development strategy and external environment, and examine and approve the internal capital adequacy assessment procedures to ensure that the capital fully covers the major risks.

(2) Examining and approving the company’s capital management system, and ensuring that the capital management policies and control measures are effective.

(3) Examining and approving and supervising the implementation of capital planning. Examine and approve the capital management plan at least once a year, review the capital management report and the internal capital adequacy assessment report, and listen to the audit report on the implementation of the capital management and internal capital adequacy assessment procedures.

(4) Examining and approving the policies, procedures and contents of capital information disclosure, and ensuring the truthfulness, accuracy and completeness of the disclosed information.

(five) to ensure that financial asset investment companies have sufficient resources to independently and effectively carry out capital management.

Article 52　When making a capital plan, a financial asset investment company shall comprehensively consider the results of risk assessment, stress test, future capital demand, capital regulatory requirements and capital availability to ensure that the capital level continuously meets the regulatory requirements. Capital planning should set at least a three-year target of internal capital level.

Article 53　A financial asset investment company shall improve its reporting system, regularly monitor and report the changing trend of the company’s capital level and main influencing factors, and the report shall at least include the following contents:

(1) Assessing the impact of major risks and development trends, strategic objectives and external environment on the capital level;

(2) Assessing whether the capital actually held is sufficient to resist major risks;

(3) Put forward suggestions to ensure that capital can fully cover major risks.

According to the different importance and purpose of the report, a financial asset investment company shall specify the sending scope, contents and details of all kinds of reports, and ensure that the reporting information and frequency meet the needs of the capital management of the financial asset investment company.

A financial asset investment company shall submit a report on capital management and internal capital adequacy assessment to China Banking and Insurance Regulatory Commission within four months after the end of the year.

Chapter IV Supervision and Administration

Article 54　China Banking and Insurance Regulatory Commission and its agencies shall supervise and inspect the capital adequacy of financial asset investment companies to ensure that the capital can fully cover all kinds of risks.

Article 55　China Banking and Insurance Regulatory Commission and its dispatched offices have the right to put forward more prudent additional capital requirements according to the daily supervision and on-site inspection to ensure that the capital fully covers risks, including:

(a) according to the function orientation of a single financial asset investment company, the implementation of development strategy, the operation and development of debt-to-equity swap, etc., the additional capital requirements put forward;

(2) According to the judgment of the risk of a specific asset portfolio and its relevance to the main business, the additional capital requirements for a specific asset portfolio are put forward by adjusting the risk weight and other methods;

(3) According to the fact that a single financial asset investment company has not established an internal capital adequacy assessment procedure, or the internal capital adequacy assessment procedure fails to meet the relevant requirements, combined with the assessment results of the risk situation, the additional capital requirements are put forward for the financial asset investment company;

(4) According to the operational risk management level of a single financial asset investment company and the occurrence of operational risk events, the additional capital requirements for operational risk put forward by the financial asset investment company;

(five) according to the results of supervision and inspection, the additional capital requirements for financial asset investment companies.

Article 56　According to the capital adequacy, China Banking and Insurance Regulatory Commission and its agencies will be divided into three categories of financial asset investment companies:

(1) Class I financial asset investment companies: the capital adequacy ratio, tier 1 capital adequacy ratio and core tier 1 capital adequacy ratio all meet the capital requirements at all levels as stipulated in these Measures.

(2) Type II financial asset investment companies: the capital adequacy ratio, tier 1 capital adequacy ratio and core tier 1 capital adequacy ratio are not lower than the minimum capital requirements and countercyclical capital requirements, but any one of them fails to meet the additional capital requirements.

(3) Category III financial asset investment companies: any one of the capital adequacy ratio, tier 1 capital adequacy ratio and core tier 1 capital adequacy ratio fails to meet the minimum capital requirements and countercyclical capital requirements.

Article 57　For the first type of financial asset investment companies, in order to prevent the rapid decline of their capital adequacy level, China Banking and Insurance Regulatory Commission and its dispatched offices may put forward the following regulatory requirements:

(a) to strengthen the analysis and prediction of the reasons for the decline in the level of capital adequacy;

(2) Formulating a feasible capital adequacy management plan;

(3) Improve risk control capability.

Article 58　For the second kind of financial asset investment companies, in addition to the regulatory measures stipulated in Article 57 of these Measures, China Banking and Insurance Regulatory Commission can also take the following regulatory measures according to law according to different situations:

(1) Prudent talks with the board of directors and senior management of the financial asset investment company.

(2) Issuing supervision opinions, including: problems existing in capital management, corrective measures to be taken, and opinions on meeting the standards within a time limit, etc.

(3) Require financial asset investment companies to formulate feasible capital replenishment plans and plans to meet the standards within a time limit.

(4) Increase the frequency of supervision and inspection on the capital adequacy of financial asset investment companies.

(5) Require financial asset investment companies to take risk mitigation measures in specific risk areas.

Article 59　For the third kind of financial asset investment companies, in addition to the regulatory measures stipulated in Articles 57 and 58 of these Measures, China Banking and Insurance Regulatory Commission can also take the following regulatory measures according to law according to different situations:

(1) Restrict financial asset investment companies from distributing dividends and other income. Dividends and other income include: items that can be used for profit distribution, stock repurchase, independent income from other Tier 1 capital instruments and independent payment to employees.

(2) Restrict financial asset investment companies from offering any form of incentives to directors and senior managers.

(3) Restrict financial asset investment companies from making equity investments or repurchasing capital instruments.

(four) to limit the important capital expenditure of financial asset investment companies.

(5) Require financial asset investment companies to control the growth of risky assets.

When dealing with such financial asset investment companies, China Banking and Insurance Regulatory Commission can also take other necessary measures in consideration of external factors.

Article 60　For financial asset investment companies whose leverage ratio is lower than the minimum regulatory requirements, China Banking and Insurance Regulatory Commission can put forward the following regulatory requirements:

(1) Replenishing Tier 1 capital within a limited period;

(2) Controlling the growth rate of assets on and off the balance sheet;

(3) Reduce the scale of off-balance-sheet assets.

Chapter V Information Disclosure

Article 61　A financial asset investment company shall disclose information related to capital adequacy to investors and the public through open channels to ensure the centralization, accessibility and openness of information disclosure.

Article 62　The frequency of information disclosure of financial asset investment companies is divided into temporary, semi-annual and annual disclosures. Among them, temporary information shall be disclosed in a timely manner, and the semi-annual information disclosure time shall be within the last 60 working days and the annual information disclosure time shall be within four months after the end of the fiscal year. If it cannot be disclosed on time due to special reasons, it shall apply to China Banking and Insurance Regulatory Commission and its dispatched offices for delayed disclosure at least 15 working days in advance.

Article 63　A financial asset investment company shall disclose relevant information at the following frequency:

(1) Changes in paid-in capital or common stock and other capital instruments shall be disclosed in a timely manner.

(2) Important information such as net core tier-one capital, net tier-one capital, net capital, core tier-one capital adequacy ratio, tier-one capital adequacy ratio, capital adequacy ratio and leverage ratio shall be disclosed once every six months.

(3) Relevant important information such as the calculation range of capital adequacy related indicators, total credit risk exposure, total non-performing assets, provision for impairment of credit risk assets, risk exposure balance after slow release of credit risk portfolio, market risk, operational risk, asset management business risk and debt-to-equity swap business risk shall be disclosed once a year.

Article 64　With the consent of China Banking and Insurance Regulatory Commission, the content of information disclosure can be appropriately simplified on the basis of meeting the overall requirements of information disclosure.

Chapter VI Supplementary Provisions

Article 65　China Banking and Insurance Regulatory Commission is responsible for the interpretation of these measures.

Article 66　These Measures shall come into force as of the date of issuance.

Attachment: 1. Assets credit risk weight in the balance sheet and risk mitigation tools for qualified equity investment.

　　　2. Measurement rules of market risk standard method

　　　3. Measurement rules of basic index method of operational risk

　　　4. Risk capital measurement rules for asset management business

　　　5. Credit conversion coefficient of off-balance sheet items

(The above attachment is omitted, please visit the website of China Banking and Insurance Regulatory Commission for details.)

　 　 　 　Cctv news (Reporter Su Jin) On December 12, 2014, the first phase of the Middle Route of South-to-North Water Transfer Project was officially put into use. Up to now, more than 50 billion cubic meters of water has been transferred to the north, which is equivalent to transferring the Yellow River to the north for one year. The population benefited from the project exceeds 85 million.

The tunnel crosses the Yellow River for the first time, and the largest aqueduct in the world … … One project with world-class difficulty runs continuously and safely in Henan, making a clear water meander northward.

　　The Yellow River Crossing Project keeps the river from invading the river.

(Photo courtesy of China South-to-North Water Transfer Project)　　

　　Xingyang City, Zhengzhou City, Henan Province, from the air, the rushing "South Water" meets the Yellow River here, and the Yangtze River water in the north passes through two tunnels crossing the Yellow River and swoops down here, crossing the Yellow River in ancient times. This is the symbolic and controlling project of the middle route of the South-to-North Water Transfer Project-the Yellow River Crossing Project, which is called the "throat" of the middle route of the South-to-North Water Transfer Project. Its main task is to transport water from the south bank of the Yellow River to the north bank of the Yellow River safely and effectively.

　　"This is one of the most challenging parts in the construction of the middle route of the South-to-North Water Transfer Project." Wu Guoquan, director of the Yellow River Crossing Management Office of the Middle Route Company of China South-to-North Water Diversion Group, introduced that at the beginning of the design, two schemes were put in front of us. Some people proposed to fly across the channel, while others suggested to drill holes. "After repeated scientific argumentation and numerous mathematical model calculations, the technical difficulty, water quality safety, ecological protection and other factors were comprehensively considered, and finally the shield tunnel crossing yellow river scheme was selected."

　　The Yellow River Crossing Project is located about 30km upstream of the Beijing-Guangzhou Railway Bridge on the Yellow River in Zhengzhou City, Henan Province, with a total length of 19.30km. The most difficult project is the Yellow River Crossing Tunnel, with a single tunnel length of 4,250 m, of which the river crossing tunnel is 3,450 m long and the inner diameter of the tunnel is 7.0m m. The tunnel is arranged in parallel with two holes, and the center line spacing is 28m.

　　"Under the bed of the Yellow River, long deposits form various complex strata." Wu Guoquan still remembers the difficulties in construction. The shield machine moves forward slowly, and more than 100 cutters on the cutter head rotate and cut. The cutter head is worn, and it will continue to advance after replacement and repair; The geological conditions ahead are changeable, so the plan should be adjusted in time … …

　　A water diversion line is also a "scientific and technological innovation line". The breakthrough of technical problems has broken records: for the first time, a large-diameter tunnel was used to cross the bottom of the Yellow River, for the first time in China, a mud-water pressurized balanced shield machine was used for hydraulic tunnel construction, a 3.45-kilometer Yellow River channel was crossed at one time, and the accuracy error of the shaft reaching the south bank was successfully controlled within 3 cm.

　　According to reports, as of August 30, 2022, the tunnel crossing the Yellow River in the middle line has accumulated 35.75 billion cubic meters of water to the north, greatly alleviating the water shortage in Beijing, Tianjin and Hebei.

　　Shahe aqueduct, the first aqueduct in the world

(Photo courtesy of Shahe Aqueduct China South-to-North Water Transfer Group)

　　Lushan County, Pingdingshan City, Henan Province, Shahe Aqueduct is like a dragon flying across, entrenched in the Central Plains. This "overpass on the water" shocked the reporters of the online theme publicity campaign of the South-to-North Water Transfer Project, "Miracle China Tianhe Dreaming".

　　Shahe aqueduct project, with a total length of 11.9km, is one of the largest and most complicated control projects in the middle route of South-to-North Water Transfer Project, and the largest comprehensive aqueduct project in the world at present.

　　Zhang Peng, director of Lushan Management Office of China South-to-North Water Diversion Group Middle Line Company, introduced that the beam aqueduct of Shahe Aqueduct weighs 1,200 tons, and the integrated construction scheme of "lifting, transporting and erecting" was adopted to efficiently complete the project construction, which filled the technical gap in the design and construction of large-flow aqueduct in water conservancy industry at home and abroad.

In the economic field, debt economy is a common and complicated economic model. Simply put, debt economy is to obtain funds by borrowing and issuing bonds to promote economic development. This economic model is very common in the modern economic system, and many countries, enterprises and even individuals will use this method to meet their own capital needs.

At the national level, the government may issue treasury bonds to raise funds for infrastructure construction and social welfare. For example, some countries will build highways, railways and other transportation facilities on a large scale, and these projects need a lot of capital investment. The government will attract investors to buy them by issuing government bonds, thus obtaining funds to support the development of the projects. For enterprises, in order to expand production scale and carry out technological innovation, they will also borrow money from banks or issue corporate bonds. Like some emerging science and technology enterprises, in the process of developing new products, they need a lot of money for scientific research investment and equipment purchase, so they will choose debt financing to solve the funding problem.

Triangular debt is a special and thorny phenomenon in debt economy. Triangular debt refers to the debt chain formed by mutual arrears of payment between enterprises. In this case, enterprise A owes money to enterprise B, enterprise B owes money to enterprise C, and enterprise C may owe money to enterprise A, forming a complex debt cycle.

The influence of triangular debt is various. For enterprises, it will seriously affect the capital turnover of enterprises. When an enterprise’s payment is in arrears by other enterprises, its own funds cannot be withdrawn in time, which leads to the enterprise’s failure to pay the payment of raw material suppliers and the wages of employees on time, thus affecting the normal production and operation of the enterprise. In the long run, it may also lead to the reduction of the production scale of enterprises and even face the risk of bankruptcy.

From the macro-economic perspective, triangular debt will affect the operational efficiency of the whole economy. A large number of enterprises fall into the dilemma of triangular debt, which will make the capital flow in the market not smooth and hinder the rational allocation of resources. Debt disputes between enterprises may also trigger a series of legal proceedings and increase the transaction cost of society.

In order to understand the debt economy and triangular debt more intuitively, the following table is used for comparison:

In short, debt economy and triangular debt are both important issues that need to be paid attention to in economic operation. Correctly understanding and handling them is of great significance for maintaining economic stability and healthy development.

[Disclaimer] This article only represents the author’s own views and has nothing to do with Hexun. Hexun.com is neutral about the statements and opinions in this article, and does not provide any express or implied guarantee for the accuracy, reliability or completeness of the contents. Readers are requested for reference only, and please take full responsibility. Email: news_center@staff.hexun.com.

foreword　 　

At present, tumor immunotherapy is in the ascendant, and one of the most effective treatment strategies is adoptive cell transfer therapy (ACT). Chimeric antigen receptor (CAR) and engineered T cell receptor (TCR) are the main adoptive T cell immunotherapy in recent years. TCR engineering T cells express tumor antigen-specific receptors, and their α chains and β chains are produced by high-quality and high-affinity antigen-specific T cell clones.

TCR molecule belongs to a superfamily of immunoglobulin, which consists of two covalently bound polymorphic subunits, each of which is antigen-specific, and they are related to at least four different types of signal transduction chains. In order to activate T cells, there must be interaction between TCR and MHC.

The interaction between TCRs and pMHC(peptide-MHC) determines the fate of immature thymocytes, which is very important for the survival of naive T cells. Therefore, TCR-T immunotherapy technology activates the host’s immune system through effective interaction with MHC, especially class II molecules, which are specifically recognized by TCR-T cells and CAR-T cells. TCR-T cells can recognize tumor-specific antigens in cells, while CAR-T cells mainly recognize tumor-specific antigens on the surface. This makes TCR-T cells more effective in tumor treatment.

At present, some new technologies and tools are being applied to TCR-T, which is helpful to improve the efficacy and safety of TCR-T therapy. TCR-T cell therapy is showing great potential for anti-tumor therapy.

　 Comparison between CAR-T and TCR-T

In ACT therapy, TCR-T and CAR-T cells have been successfully used in the clinical treatment of solid tumors.

CAR contains single chain antibody targeting tumor antigen, transmembrane domain and intracellular activation domain of CD3ζ. In this way, the engineered CAR can recognize specific tumor-associated antigens, and CAR can bind untreated tumor surface antigens without MHC treatment.

The first generation of CAR-T cells showed limited expansion and relatively short persistence, and the "second generation" CAR-T added costimulatory receptors CD28, 4-1BB/CD137 and OX40. These costimulatory receptors are added to the CD3ζ domain of CAR-T cells, thus promoting a more powerful and lasting T cell response. The third generation CARs combines two co-stimulatory signals (CD28 and 4-1BB) at the same time, which has better amplification and longer persistence than the second generation CARs.

On the contrary, TCR is an α/β heterodimer that binds to MHC antigen complex. Compared with TCR, CARs has some disadvantages in identifying tumor antigens, such as extratumoral toxicity. Compared with CARs, TCRs has some structural advantages in T cell-based therapy, such as more subunits (10: 1) in its receptor structure, more tyrosine-based activation motifs (ITAMs) in immune receptors (10: 3), less dependence on antigens (1: 100), and more costimulatory receptors (CD3, CD4, CD28, etc.). TCR with a low MHC affinity range (104-106M-1) can effectively activate T cells, whereas CARs needs a higher affinity range (106-109M-1).

Therefore, CAR-mediated cytotoxicity depends on higher density of cell surface antigens. In addition, T-cell/antigen interaction IS initiated in the structure of immune synapse (IS), in which TCR presents an annular region with peripheral LFA-1 adhesion, while CAR presents a diffuse LFA-1 distribution without annular region. Therefore, TCR-IS is slower but lasts longer than CAR-IS. At the same time, CAR-T cells show faster killing function and migrate to the next tumor target (serial killing), which is in sharp contrast to TCR-T cells’ prolonged signal transduction and killing time.

Recombination TCRs 　

TCR is one of the most complex receptors in human body. It contains six different receptor subunits, which have a very wide range of functions in T cells. The change of TCR of tumor infiltrating lymphocytes (TILs) significantly affects tumor-specific T cells. Among them, the change of TCR is helpful to the proliferation of T cells, and the diversity of TCR is related to the anti-tumor effect.

TCR engineering of TIL is one of the best treatment methods for tumors. TCR consists of α chain and β chain bound to peptide -MHC ligand, signal subunits (,γ and δ) of CD3 complex and CD3ζ homodimer. Except CD3ζ, all subunits have extracellular immunoglobulin (Ig) domain. Based on these structures, new technologies using engineering TCR include ImmTAC, TRuCs and TAC.

Immune mobilization monoclonal t cell receptor (ImmTAC)

ImmTACs is designed using engineered, soluble and affinity-enhanced monoclonal TCRs(mTCRs). ImmTACs is basically a fusion protein, which combines the engineering TCR targeting system and single chain antibody fragment (scFv) effector function. In the construction of ImmTACs, TCR can recognize peptides from intracellular targets presented by human leukocyte antigen (HLA).

ImmTAC specifically targets HLA- peptide complexes on the surface of tumor cells, and promotes T cell-mediated effector function through the interaction between scFv antibody fragments and CD3. ImmTAC also activates CD8+T cells in a dose-dependent manner, and can effectively redirect and activate CD8+ and CD4+ cells. ImmTAC shows multifunctional reaction by secreting various cytokines, such as TNF-α, IFN-γ, IL-6, MIP1α-β and IFN-γ inducible protein 10.

In addition, selecting the appropriate target antigen is the key to ImmTACs, and mass spectrometry and MHC polymer technology are helpful to identify the appropriate antigen. It is worth noting that TCR engineered T cells also show unexpected targeted toxicity. Generally speaking, ImmTACs has been proved to enhance the anti-tumor response of TCR-T cells, but its safety needs further study.

T cell receptor fusion structure

T cell receptor fusion structure (TRuCs), an antibody binding domain fused with T cell receptor subunits, is designed to effectively recognize tumor surface antigens. TRuCs is composed of specific antibodies targeting tumor-associated antigens fused to the extracellular N- terminal of five TCR subunits (TCRα, TCRβ, CD3, CD3γ and CD3δ), which provides new targeting specificity and HLA-independent target cell clearance for engineered T cells and can be activated by corresponding target cells.

Compared with the second generation of CAR-T cells, this method shows better anti-tumor effect. In addition, TRuCs dominates all the signal mechanisms of TCR complex, while CARs only uses the limited signal of the isolated intracellular segment of CD3ζ.

T cell antigen coupling agent (TAC)

T cell antigen coupling agent is another engineered TCR cell, which can induce more effective anti-tumor response and reduce toxicity in an MHC-independent way. TAC chimeric protein can form TCR/CD3 complex and get more T cell responses by binding to CD3 domain.

The activity of TAC receptor is closely related to the selection of CD3 binding domain. For example, a single chain antibody from OKT3(muromonab-CD3) has lower cytokine production and cytotoxicity compared with UCHT1, which may lead to substantially different functional results. Compared with the second generation of CARs, T cells engineered with TAC gene are not only beneficial to the greater infiltration in solid tumors after adoption, but also reduce the expansion and extratumoral toxicity of T cells in healthy tissues expressing antigens.

Workflow of TCR-T cell therapy 　

In order to isolate therapeutic TCR, antigen-specific T cells must be isolated from the blood of patients or healthy blood donors and amplified in vitro with specific peptide antigens and cytokines (such as IL-2 and IL-15). This process needs to determine the specific tumor-related peptide targets that can be safely targeted to patients in advance. After selecting the target antigen, different methods can be used to screen TCR with the required high affinity and tumor specificity. Pre-clinical safety testing is also necessary to ensure the minimum off-target effect and cross-reactivity of isolated high affinity TCR. Viral vectors are usually used to genetically modify autologous patient T cells to express the proven therapeutic TCR, and then transfuse it back into patients.

Determine the target antigen

Melanoma antigen 1(MART-1) recognized by T cells is the first tumor-related antigen targeted in TCR-T clinical trials. After this breakthrough, TCR-T therapies for various tumor antigens have been developed, including TCR-T therapies for MAGE-A3, MAGE-A4, GD2, mesothelin, gp100, MART1, AFP, CEA, NY-ESO-1 and viral peptides derived from HPV and EBV. Among them, NY-ESO-1 has been proved to be one of the most promising targets of TCR-T cells, and it has achieved success in the treatment of synovial sarcoma, with an objective effective rate of 67%.

The ideal TCR-T target antigen shows the following characteristics: (1) the ability to induce immune response; (2) It is related to driving tumor phenotype (such as oncogene) to reduce the risk of antigen loss and tumor immune escape; And (3) expression on tumor stem cells to promote permanent tumor eradication.

Identification method of tumor-associated antigen

High-resolution mass spectrometry (MS) has been proved to be the most powerful Qualcomm method to promote the direct identification of HLA-I binding peptides from tumor cells. In this method, HLA-I/ peptide complexes are separated from tumor tissues or cell lines by immunoprecipitation (IP), and then the binding peptide antigens are separated from HLA-I molecules and antibodies for IP by fully washing and applying acidic elution buffer. This strategy allows each tumor sample to identify thousands of validated peptide targets, and has been used to identify HLA-I ligands of glioblastoma (GB), melanoma, renal cell carcinoma (RCC) and colorectal cancer (CRC).

Identification method of new tumor antigen

Although MS-based technology can be used to identify new antigens, it is more difficult to identify them, especially for tumor samples with limited size, because of their relatively low abundance and limited sensitivity of MS. However, the development of new generation sequencing technology is helpful to identify and locate such tumor targets. All-exon DNA sequencing, combined with computational prediction algorithm, allows to identify specific genetic changes in cancer cells, which can produce mutant peptides and present them on tumor HLA-I molecules.

All somatic mutant genes can be analyzed by computer to predict the potential high affinity epitopes that may bind to HLA-I molecules of patients, so as to be recognized by T cells. With the use of large MS elution peptide database, HLA-I peptide binding prediction algorithm is constantly updated and improved, and other prediction algorithms try to consider biological variables related to the complexity of intracellular processes.

Another commonly used method is tumor RNA sequencing, which allows the selection of new antigens with the highest transcriptional expression. It is worth noting that although these prediction methods usually show very good accuracy in identifying presented and highly immunogenic new antigens, the number of new antigen targets they usually predict is 1 to 2 orders of magnitude higher than the actual number of real targets.

Discovering new antigens by trogocytosis is a new method in recent years. Trogocytosis is a biological phenomenon in the process of cell combination, in which cells share and transfer membrane and membrane-related proteins. Li et al. found that T cell membrane proteins were specifically transferred to tumor target cells, which presented homologous HLA-I/ peptide complexes. Using these T cell-target cell interactions, they created a new antigen discovery system by incubating T cells expressing orphan TCR with homologous target cells. By transferring fluorescent markers from T cells to target cells, this method can isolate these target cells and sequence homologous TCR ligands, thus establishing a new antigen library.

Isolation of tumor-specific T cells and TCR

Using HLA-I polymer, single cell TCR sequencing or antigen-negative humanized mice, tumor-reactive T cells and TCR can be identified from autologous, allogeneic or xenogeneic cell banks.

Using HLA-I multimer method, antigen-specific CD8+T cells can be directly separated by multimer staining and flow cytometry. Before isolating the paired full-length TCR sequences, these polyclonal T cells were tested for homologous peptide recognition and anti-tumor function. TCR with high affinity and specificity can be obtained by using a highly sensitive PCR-based single cell TCR analysis method (TCR-SCAN).

Another method uses humanized mouse TCR gene bank, which will not cause T cell clone deletion or tolerance in humans. Therefore, Li et al. used the whole human TCRα/β gene locus and chimeric HLA-A2 transgene to construct transgenic mice to isolate human TCR against human TAA.

Single cell sequencing method represents a more promising method to isolate tumor-specific TCR coding genes by Qualcomm method. Using RNA bait libraries targeting each individual V and J element in TCRα and TCRβ loci, TCR coding genomic elements can be selectively isolated from excised genomic DNA(gDNA) fragments for subsequent paired terminal deep sequencing. This makes it possible to identify antigen-specific TCR from human materials or oligoclonal T cell populations of TCR humanized mice.

Infantile T cells can also be used as TCR sources for TCR-T therapy. TAA and new antigen-specific T cells can be derived and amplified from low-frequency precursors in peripheral blood of cancer patients, and can be reinfused or used as the source of antigen-specific TCR. Because cancer patients usually show immunosuppression or dominant T cell tolerance, the original sequence of HLA-I matched healthy donors also represents a reliable source, because it has a huge diversity of TCR sequences, and theoretically T cells have any antigen specificity, including new tumor antigens. A Qualcomm-quantity technology platform has been developed to find the original sequence, so as to quickly and effectively identify the rare but valuable TCR for personalized adoptive T cell therapy.

Cloning of TCR

Most TCR-based gene therapy methods rely on in vitro transduction of T cells with viral vectors, and adenovirus is the earliest vector used for gene therapy. However, due to their inability to integrate transgenes into the host genome, TCR expression will be lost during T cell proliferation. In addition, the immune genetic characteristics of adenovirus also limit its application as a gene therapy vector. In contrast, retroviruses show greater prospects as gene transfer vectors, because they can infect a variety of cells and have the ability to insert transgenes into the host genome, thus making the ectopic TCRα/β chain stably expressed.

Retroviral vectors derived from γ -retroviruses such as mouse leukemia virus (MLV) have been widely used for gene transfer into human T cells. This method has been used to transfer various genes, including suicide gene, TCR and CARs. The main disadvantage is that they cannot transduce non-proliferative target cells, which excludes the application of resting T cells in TCR-T therapy. In addition, retrovirus insertion mutation may cause potential side effects.

Recently, lentiviral vectors (LV) have attracted more attention as gene transfer vectors, because they can transfer genes into mitotic and non-splinter cell. Various techniques, such as Golden Gate cloning and LR cloning, are usually used to construct a vector for inserting TCRα/β gene.

Adeno-associated virus (AAV) is another widely used virus vector. Compared with adenovirus vector, AAV has lower immunogenicity and wider cell tropism, so it has been widely used in tumor gene therapy. In order to promote the integration of transgenes, people have developed self-complementary AAV vector (scAAV) to make AAV independent of the complementary strand synthesis of host cells. scAAV is more effective than traditional AAV in preclinical model.

At the same time, some non-viral gene editing methods have also been developed. MRNA electroporation has been proved to achieve transient expression of TCR and CAR, thus minimizing the risk of persistent virus components. Clinical data show that both TCR-T and CAR T cells modified by mRNA are feasible and safe, and there is no obvious evidence that they have non-targeted toxicity to normal tissues. However, the lack of continuous TCR expression may limit the curative effect and require repeated infusion. In addition, the non-viral sleeping beauty retrotransposon system is also used for the transduction of TCR and CARs.

Gene editing can insert large gene fragments into target cells specifically and efficiently through homologous directional repair (HDR). TCR-T cells developed by CRISPR/CAS9 have been proved to specifically recognize tumor antigens in vitro and induce a productive anti-tumor response in vivo.

Verification method of TCR

After TCR cloning, extensive preclinical verification is needed to prove the specificity and safety of engineered TCR-T cells. Verification includes evaluating the affinity of TCR by titration of homologous peptide antigens and measuring the killing effect of a group of HLA-I matched tumor cell lines. If there is no such tumor cell line, the target cells can transductively express related antigens and related HLA-I molecules. The new antigen can also be expressed in autologous antigen presenting cells to evaluate the antigen reactivity of TCR.

The safety test includes testing the ability of candidate TCR-T to identify HLA-I matching primary tissues, so as to ensure that there is no normal tissue as the target, which may lead to non-targeted toxicity. In at least two clinical trials of TCR-T cell therapy, there was a cross reaction between normal brain cells and heart cells, which led to the death of patients. These test results emphasize the importance of extensive safety tests before TCR enters clinical trials.

Safety of TCR-T 　

The ACT of TCR-T cells showed high tumor killing, but some serious adverse events also appeared in some clinical studies. It is very important to optimize TCR affinity in engineered T cells, and receptor affinity can determine the safety and effectiveness of T cell therapy. In terms of curative effect, affinity TCR interaction is enough to activate T cells, but strong affinity is needed to maintain the expansion of T cells.

In phase I/II ACT clinical trials, engineered T cells with low affinity show safer characteristics, but their anti-tumor response is weak. By identifying the TCR-pMHC interaction of T cells, engineered T cells can be divided into high affinity type and low affinity type. In addition, some technologies have been developed to improve the safety of TCR-T.

The safety switch mechanism based on engineered T cells is an attractive strategy. Thymidine kinase gene from herpes simplex virus type I (HSV-TK) is one of the most common suicide genes.

Although HSV-TK shows safety in cell-based immunotherapy, it is necessary to introduce phosphorylated nucleoside analogues. Another safer induced T cell safety switch is called inducible caspase-9(iC9). IC9 is a modified human FK binding protein, which can be activated by a small molecule compound AP1903, and this process depends on the mitochondrial apoptosis pathway.

The immunogenicity of iC9 suicide gene is low, and the immune response to transgenic cells is reduced. IC9-based safety switch has been proved to be more potential for cell therapy than previous suicide genes.

Clinical status of TCR-T cell therapy 　

As of August 9, 2021, there are 175 studies using TCR-T therapy in ClinicalTrials, 71 of which are specific TCR for specific TAA or new antigen, and 32 studies have been completed. NY-ESO-1 is the most common targeted antigen, which is expressed in many cancers, including myeloma and melanoma. Other tumor testis-associated antigens, such as PRAME and MAGE proteins, melanoma differentiation antigens MART-1 and gp100, and recent cancer drivers, such as WT1, KRAS and TP53, are also popular TCR-T targets.　 　 　 　 　 　 　 　 　 　 　

A total of 83 sponsors/collaborators initiated or participated in the research of TCR-T cell therapy, including the National Institutes of Health (NIH), government organizations, industries and universities/academic institutions. At present, the National Cancer Institute (NCI) has supported 53 TCR-T projects, accounting for 20% of all ongoing projects.

Among the 29 pharmaceutical companies developing TCR-T therapy, GlaxoSmithKline and Adaptimunime initiated the most clinical trials, with 11 and 7 respectively. Recently, a phase 1 clinical trial (NCT02858310) of TCR-T cells targeting human papillomavirus (HPV)-16 E7 protein in the treatment of metastatic human papillomavirus-related epithelial cancer was reported. In this study, 6 of the 12 patients who received treatment showed objective clinical response and observed steady tumor regression. This is a landmark clinical trial of TCR-T cell therapy, which proves that targeted virus antigen has good clinical effect on patients with virus-related cancer. Other viral antigens explored as TCR targets include HPV-E6 protein, antigens from Epstein-Barr virus (EBV) and human endogenous retrovirus (HERV) targets, such as Herv-E.

MART-1 and NY-ESO-1 TCR-T therapy targeting TAAs also showed clinical efficacy in advanced melanoma, myeloma and non-small cell lung cancer. The total effective rate (ORR) of TCR-T clinical trial is between 0 and 60%. It is worth noting that most of these TCR-T clinical trials only enrolled a small number of patients (2 to 25), so ORR may not be statistically accurate. Therefore, larger-scale phase II and III clinical trials are needed to confirm the actual clinical efficacy of these TCR-T therapies.

Challenges and potential solutions of TCR-T cell therapy 　

Although immunotherapy based on TCR-T cells has shown certain clinical efficacy in most patients receiving treatment, it still faces many challenges in many fields. These challenges include: (1) Immunotoxicity caused by targeting normal tissues; (2) The expression of TCR in engineered T cells is insufficient or transient; (3)T cell exhaustion and dysfunction; (4) tumor immune escape, and (5) most cancer patients lack effective tumor-specific antigens as targets. Overcoming these challenges will be the key to greater clinical success in the future.　 　 　 　 　 　　

Discovery of new targets

At present, the target of peptide antigen for effective and safe immunotherapy of TCR-T is very limited. At present, most of the targets used are TAA. Although it is up-regulated in tumor tissues, it still maintains a low level of expression in normal tissues, which may lead to autoimmune toxicity. Therefore, the new antigen seems to be the safest target for TCR-T cancer treatment. However, the main challenges of developing new antigens in TCR-T clinic include: (1) the mutation of new antigens is individualized to a great extent, and there are differences among cancer patients, so it is difficult to develop widely used immunotherapy products; (2) The expression of new antigens in tumor tissues is often heterogeneous.

Nevertheless, recent reports have highlighted the emergence of new immunogenic antigens widely shared by tumor cells, including mutated KRAS and TP53. Many other studies have also demonstrated the immunogenicity of shared new antigens that can be used to generate potential therapeutic tumor-specific TCR. With the development of next generation sequencing technology, especially single cell DNA sequencing, transcriptome sequencing and mature in vitro verification methods, TCR-T immunotherapy targeting personalized new antigens may become a popular cancer treatment method in the next few years. In addition, the emerging TAA class, such as carcinoembryonic antigen, may also constitute a feasible target for the future development of TCR-T.

Maximize therapeutic TCR expression

The correct pairing of transgenic α and β chains is one of the main challenges that hinder the development of TCR-T cells. Since each transduced T cell includes two endogenous TCR chains and two transformed TCR chains, heterodimers with unknown specificity can lead to potential autoimmune consequences. Another related problem is that improper α/β chain TCR pairing will compete for CD3 complex, thus reducing the surface expression and signal transduction of therapeutic TCR.

There are several methods to properly pair the transduced TCR chains, including: (1) the constant region of partially murine TCR; (2) adding cysteine residues to promote the introduction of disulfide bonds in TCR chains; (3) changing the secondary structure of the constant region of endogenous TCR; (4) adding a signal domain to the intracellular part transduced with TCR; (5) Introducing TCR-α/β chain into substitute effector cells or constructing single-stranded TCR.

Methods to enhance the expression of therapeutic TCR include: (1) codon optimization of TCR-α and TCR-β chain transgene, and (2) changing the configuration of TCR-α/TCR-β vector to optimize expression.

Reduce adverse events

Usually, targeting non-tumor toxicity is the main key obstacle of TAA, and this risk urges researchers to study common new antigens more carefully. At present, several oncogene hot spot mutations are being studied as potential TCR targets, such as phosphoinositide -3- kinase (PI3K), KRAS and TP53. In addition, genetically engineered TCR-T cells with suicide genes are an important safety measure. Obviously, it is very important to develop reliable, identifiable, personalized, highly specific and immunogenic tumor antigen targets to reduce adverse events related to TCR-T cell therapy.

Graft-versus-host disease of allogeneic T cells

Using allogeneic T cells is a very promising scheme, which can overcome manufacturing problems, patient-related immune cell defects and treatment delays. In order to use allogeneic T cells, it is necessary to control graft-versus-host disease caused by transduced allogeneic reactive lymphocytes and rejection of engineered lymphocytes by host immune system.

The deletion of endogenous TCR gene, HLA-I locus or CD52 molecule is one of the strategies to avoid the failure of TCR-T transplantation, which can be achieved by many methods, such as gene editing or using siRNA. In addition, pluripotent stem cell technology is also considered as a potential solution.

　 summarize

In recent years, engineered T cells have shown excellent curative effect in the treatment of hematological tumors. TCR regulation is very important for T cell reactivation, immune response and its clinical effect on foreign antigens. TCR-T cells have incomparable advantages over CAR-T cells, and show great potential in preclinical and clinical research.

However, there are still several key challenges to improve the anti-tumor efficacy of TCR-T immunotherapy, including how to safely increase the affinity of therapeutic TCR, how to identify the common tumor-specific antigen and TCR in the patient population, and how to regulate the expression of TCR and achieve the best function. The solution of these problems will help to give full play to the potential of TCR-T cell therapy and bring hope to cancer patients to relieve their pain.

References:

1.Engineered TCR-T CellI mmunotherapy in Anticancer Precision Medicine: Pros and Cons. Front Immunol.　2021; 12: 658753.

2. Evolution of CD8+　T Cell Receptor(TCR) Engineered Therapies for the Treatment of Cancer. Cells.　2021 Sep; 10(9): 2379.

　　
The People’s Liberation Army (PLA) has accumulated rich operational experience after a year and a half of fighting, especially since it turned to a strategic offensive. Mao Zedong made a systematic and scientific summary of these experiences. From December 25th to 28th, 1947, the Central Committee of the Communist Party of China held an enlarged meeting in Yangjiagou, Mizhi County, northern Shaanxi, at which Mao Zedong made a report on "Current Situation and Our Tasks". In this report, the famous "Ten Military Principles" were put forward. The main contents are: fight scattered and isolated enemies first, and then fight concentrated and powerful enemies; Take small cities, medium-sized cities and vast villages first, and then take big cities; The main goal is to annihilate the enemy’s effective forces, not to preserve or seize cities and places; Concentrate absolute superior forces in each battle, surround the enemy on all sides, and strive to wipe out the enemy, so as not to escape the net; Don’t fight unprepared battles, don’t fight uncertain battles; Carry forward the style of fighting bravely, not afraid of sacrifice, not afraid of fatigue and continuous fighting; Strive to annihilate the enemy in the movement, while paying attention to position attack tactics; On the issue of siege, all enemy strongholds and cities with weak defenses are firmly seized, all enemy strongholds and city cameras with medium defenses are seized, and all enemy strongholds and cities with strong defenses are seized when conditions are ripe; Replenish ourselves by capturing all the enemy’s weapons and most of their personnel. The source of our army’s manpower and material resources is mainly at the front. Be good at using the gap between the two campaigns to rest and train troops.
The full text of the top ten military principles is 593 words. In incisive language, Mao Zedong made the strategic and tactical principles of the People’s Liberation Army clear, which is both easy to understand and easy to remember. It is completely different from his opponent Chiang Kai-shek’s long speech. In the later stage of strategic decisive battle and strategic pursuit, the People’s Liberation Army flexibly applied ten military principles, further enriched and developed this theoretical treasure, and finally relied on this treasure to completely defeat eight million Kuomintang troops.
From the sixteen-character formula to the ten military principles, it marks the improvement of the strategic and tactical theory of the people’s army, and marks that Mao Zedong’s military thought reached an unprecedented height during the War of Liberation. Therefore, it is not difficult for people to understand why Chiang Kai-shek, who was an excellent cadet studying in the Japanese military academy and the president of the Whampoa Military Academy, was finally defeated by Mao Zedong, who had never been to a military academy for a day. Batman, a British military expert, commented: "Mao Zedong is an era figure who holds all the keys to unlock the military mysteries of this era." (Xinhua News Agency)

Editor: Cao Jin