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)

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!

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.

Intel’s ninth-generation Core has now begun to spread out gradually, and it has launched a comprehensive fight with AMD’s Ruilong.

The performance is quite powerful, but the corresponding power consumption and price are also amazing, soRelatively speaking, many students will pay more attention to the i7-9700K. After all, it is more balanced in terms of specifications, performance and price.

Today, I will bring the test report of the first i7 processor without hyper-threading technology.

Description of product specifications: The appearance of i7-9700K is exactly the same as that of i9-9900K, so I won’t repeat it here. Here is a brief look at the product specifications.

Compared with i9-9900K, the obvious difference is that the core scale has changed from 8 cores and 16 threads to 8 cores and 8 threads, and the hyper-threading technology has been cancelled. In fact, except i9-9900K, all the nine generations of Core have no hyper-threading.

The core frequency drops slightly,The dual-core turbo frequency is 4.9GHz and the full-core turbo frequency is 4.6GHz.

Introduction of test platform:

This time, the motherboard is Huaqing Z390-TAICHI, which is also a product with high attention at present. After careful disassembly, it is found that this product is quite different from Gigabyte Asustek’s design idea, which is very interesting.

The CPU base is still LGA1151, Intel’s ancestral base, which will be used in 2020.

A set of filter capacitors can be seen on the back of the CPU base, and Huaqing also added two additional polymer capacitors to improve the stability of the motherboard current.

The power supply socket of CPU is 8+4PIN, mainly to cope with i9-9900K.

The power supply of CPU is 10+2+2 phases, and heat pipe fins are used to assist heat dissipation, that is to say, the CPU core supplies 10 phases, the centralized display supplies 2 phases and the bus supplies 2 phases.

There is also a R67161PY chip next to the CPU base, which is used to unlock the CPU external frequency adjustment limit from the wiring point of view.

There are still four memory slots, which support dual-channel DDR4.

There are five expansion slots on the motherboard, which are arranged as X1X16NAX1X8NAX4 according to the PCI location, among which the slots of PCI-EX1 are all designed with notches, which can be compatible with high-bandwidth PCI-E expansion cards, such as SATA cards of PCI-E X4.

There are three M.2 SSD expansion slots on the motherboard, all of which can support PCI-E X4 and SATA channels. However, the slots on the left (M2_1) and the right (M2_3) in the figure occupy two SATA interfaces, which are mutually exclusive. The slot in the middle (M2_2) will eat a SATA interface when using the SSD of SATA channel. The M2_3 slot of the motherboard is covered with a metal heat sink.

There is a 24PIN power supply interface and two USB 3.0 front sockets on the side of the motherboard near the memory slot, one of which is horizontal.

The front USB 3.1 Type-C socket can be seen between the memory slot and the SATA interface. The ASM1074 chip next to it is the channel for two USB 3.0 sockets on the motherboard.

The chip of USB Type-C is on the back of the motherboard, and it is an ASM1543. It seems that the mode of chipset direct connection USB 3.1 Type-C used by Huaqing in the past is not very effective, and this time an extra bridge chip is added.

There are 8 SATA interfaces on the motherboard, of which 6 are provided by the chipset natively, 2 are extra bridges, and the bridge chip is ASM1061.

At the bottom of the motherboard is a row of expansion slots. From the chipset side, from right to left, they are SYS FAN, chassis front control pin, BIOS test pin, BIOS cleaning pin, 80 debug lamp, front USB 2.0 and front USB 2.0 (single interface 4PIN). The single-port USB 2.0 pin is a bit strange. This interface is because a USB 2.0 was eaten by wireless Bluetooth, so the general motherboard will not let go directly, because the wires of the chassis are now in groups of two. It’s ok to control the cold headlight group inside the chassis.

Close to the audio system, from right to left in the figure are TPM, SYS FAN, lightning extension pin, RGB 4PIN lamp strip pin *2, digital LED strip pin and front audio pin.

In addition to the two SYS FAN pins at the bottom of the motherboard, the motherboard has three pins between CPU power supply and memory slot, two pins next to PCI-E X1, and one pin between memory slot and M.2 SSD slot. The number of fan pins is still sufficient.

The rear window interfaces of the motherboard are, from the left in the figure, clear COMS button, Wi-Fi antenna interface, USB 3.0*2+PS2, HDMI+DP, USB 3.0*2, USB 3.1*2+LAN, USB 3.1 A+C +LAN, and 3.5 audio *5+ digital fiber.

The main chip of the audio part is ALC1220 of Little Crab, and the power amplification effect of the audio interface in the rear window of the main board is provided by ALC1220 chip. The front audio provides power amplification effect through N5532 chip.

The motherboard adopts dual Gigabit network cards and the mainstream Intel i211+i219 scheme.

The motherboard is integrated with a wireless network card, and the model is Intel’s 3168N.

You can see an ASM1562 chip next to the motherboard chipset, which is two USB 3.1 TYPE-A interfaces corresponding to the motherboard rear window. The three bridge chips behind the SATA interface at the top of the picture are used to switch with the M.2 SSD slot.

The two P13EQX chips in the rear window of the motherboard are used for signal relay of ASM1562 chip and two USB 3.1 TYPE-A interfaces in the rear window of the motherboard.

The ASM1543 on the back of the motherboard provides a bridge for USB 3.1 A+C on the rear window of the motherboard.

There are two L04083B chips at the end of PCI-E X16 slot on the motherboard, which are used to bridge the bandwidth of the graphics card slot to support the 8+8 dual card mode of the graphics card.

Next, the motherboard was disassembled, and the number of armor of Huaqing motherboard was not particularly exaggerated.

The power supply of the motherboard is 10+2+2 phases, the CPU core part is 10 phases, and the centralized display part is 2 phases, both of which share the same scheme. The PWM chip is IR 3520, which is a 6+2-phase control chip, and the DRIVER is extended to 10+2-phase power supply through IR 3598; The input capacitance is 8 solid-state capacitors of Nijikang FP12K, 16V 172 microfarads; MOS adopts one TI 87350D drMOS for each phase, and one MOS can achieve the function of bridge. The inductance is a closed inductor with one inductance R47 per phase; The output capacitors are 10 in the CPU core part and 3 in the display part. The capacitors are all Nijikang FP12K solid-state capacitors with 6.3V 561 microfarads.

The other two items on the motherboard are for the power supply of VCCSA and VCCIO, and the materials used in this part have been reduced. The input capacitance is shared by one Nijikang FP12K solid-state capacitor, with 16V 101 microfarads; MOS is 1 7341EH； per phase; The output capacitor is 1 Nijikang FP12K solid capacitor per phase, 2.5V 821 microfarads.

Memory power supply is a luxury, using 2-phase power supply directly. The PWM chip is UP1674P；; The input capacitance is 2 solid-state capacitors of Nijikang FP12K, 6.3V 561 microfarads; MOS is 87350D drMOS with one TI per phase, which is the same as CPU power supply; The inductance is a closed inductor with one inductance R30 per phase; The output capacitor is 4 solid-state capacitors of Nijikang FP12K, 6.3V 561 microfarads.

There is also a hardware monitoring chip of nuvoTon NCT6791D and a super IO chip of Nuvoton NCT 5567d on the motherboard. The integration level is still a little low.

There is also an ASM1184 chip on the motherboard, which is used to switch PCI-E channels and bridge one PCI-E 3.0 into four PCI-E2.0. Generally speaking, the design ideas of Huaqing and Gigabyte Asustek are quite different. Asustek Gigabyte prefers to use a lot of SWITCH switching and speed reduction to solve the problem of insufficient chipset channels. Huaqing, on the other hand, prefers to use more HUB chips for switching, so as to minimize the loss of PCI-E bandwidth. However, the cost is also obvious. More chips reduce the integration of the motherboard.

Introduction of test platform:

First, introduce the test platform.

The memory is DDR4 8G*4 of the pirate ship. The actual operating frequency is 2666C15.

There will be a test with a unique display in the middle, and the graphics card is the water-cooled version of VEGA 64 by Dylan Hengjin.

SSD is three pieces of Intel, and the system disk uses the mainstream 535 to ensure that the test is closer to the average user. 240G is used as the system disk, and 480G*2 is mainly used to play test games.

　　 The NVMe SSD test used Intel 750 400G.

The radiator is the cool ice god G360RGB.

The power supply is an Antaike HCG-X1000.

The test platform is BC1 of Streacom.

Introduction of performance test items:

For children’s shoes interested in further understanding the comparative performance, detailed test data will be provided here. If you don’t want to see it, you can skip to the last summary.

The test will be roughly divided into the following parts:

-CPU performance test: including system bandwidth, CPU theoretical performance, CPU benchmark test software, CPU rendering test software and 3DMARK physical score.

-Integrated graphics card test: including theoretical performance test, benchmark test software and professional software benchmark of integrated display.

-Matching stand-alone test: including stand-alone benchmark test software, stand-alone game test and stand-alone professional software benchmark.

-Power consumption test: Power consumption is measured under the platform of centralized display and single display.

－ Since this test, WBE3.0 and Android game simulator have been added, and the test items will be more and more abundant.

Performance test and analysis of CPU;

The system bandwidth test shows that the system bandwidth i9-9700K has been further improved, slightly lower than i9-9900K. Compared with i7-8700K, the improvement is mainly concentrated on L1 and L2, especially the bandwidth of L1 is increased by 40%. There is also a 10% improvement in the delay of L1L2.

The theoretical performance test of CPU is carried out with the built-in tools of AIDA64. Excluding memory bandwidth, other computing power is improved by about 40% compared with i7-8700K.

CPU performance test mainly tests some commonly used CPU benchmark software, and also includes some application software and CPU test items in the game. In this part, i7-9700K mainly has advantages in single-threaded testing, and can be close to i9-9900K. However, multithreading performance is relatively general, and some tests are not even as good as i7-8700K.

CPU rendering test, which tests the rendering ability of CPU.

The 3D physical performance test measures the physical scores in the 3DMARK test, which are mainly related to the CPU.

CPU performance test section comparison section:

According to the comprehensive statistics of CPU, i7-9700K and R7 2700X are basically on the same level, but there will be obvious gap with i9-9900K.

In fact, there is still a more tangled problem, that is, single thread and multi-thread, which has also been decomposed here.

-Single thread:Single thread is quite close to i9-9900K, about 5% behind and 5% stronger than i7-8700k.

-multithreading:Multithreading is a relatively weak part, which is about 35% behind I9-9900k, 8% behind R7 2700×8, and stronger than i7-8700K 4%.

Set display performance test:

The theoretical performance test of centralized display is carried out with the built-in tools of AIDA64. Due to the compatibility problem between Intel’s integrated display driver and WIN10 of 1709, i7-9700K did not collect data for integrated display 3D benchmark test, and mainly ran some benchmark test software.

Set display OpenGL benchmark test, and the professional software part is based on SPEC viewperf 12.1.

Set display performance test section:

Since the centralized display of i7-9700K is the same as that of i7-8700K, there is no substantial difference.

With a stand-alone test:

The graphics card is VEGA 64. Simply running i7-9700K is the highest, but the advantage is weak.

Unique 3D game test, i7-9700K will be slightly weaker than i9-9900K in the game test.

In terms of each generation, i7-9700K has a slight advantage over i9-9900K in DX9 & DX11, slightly weaker than i9-9900K in DX11, and has a great advantage in DX12, with the greatest advantage over i9-9900K.

There has always been a big controversy about the resolution in game testing, so I’ll break it down directly here. Because DX11 games account for more than half of my testing, it seems that i7-9700K will be slightly weaker than i9-9900K at both resolutions, but it will be significantly stronger than R7 2700X at 1080P.

OpenGL benchmark test alone. The OpenGL part is based on SPEC viewperf 12.1. This test is a professional operation test for graphics cards, and the gap is more related to CPU single thread.

With a separate test section:

According to the test results, the i7-9700K is quite close to the i9-9900K, which directly throws off other CPUs.

Disk performance test:

The disk test part uses CrystalDiskMark 5,1g data file to run 9 times, which can basically eliminate the test error. The tested SSDs are 535 480G and 750 400G, both of which are hung from the disk. Simply explain the concept in this test, SATA interface and PCI-E channel can be drawn from CPU or chipset (see how CPU manufacturers design). Here, for the sake of unification, all the tests are SATA from chipset and PCI-E from CPU.

Judging from the test results, i7-9700K is roughly equivalent to i9-9900K, and R5 2600X is relatively high in NVMe test mainly because some specific vulnerabilities are not fixed. Please refer to R7 2700X.

Platform power consumption test:

In terms of power consumption, the power consumption control of i7-9700K will be better. In the most extreme case, it is 40W more than i7-87000K, which is within the controllable range.

With the unique display, the overall power consumption of i7-9700K will be between i7-8700K and R5 2600X, which is well controlled.

Detailed statistics:

Summary of test results:

The comparison groups in this test are i9-9900X, R7 2700X, i7-8700K and R5 2600X. All products are close to the current positioning or price of i7-9700K.

Because the performance test environment of CPU has been changing dynamically (system, BIOS, driver), i9-9900K, i7-8700K and R7 2700X have been tested completely. The testing time of R5 2600X is in April 2018.

AMD RYZEN has undergone some changes after updating the BIOS and drivers. The problem of memory copy performance degradation found in the initial test of B450 has been fixed, but at the cost of CPU power consumption increase and NVME disk performance decline. Therefore, it can be confirmed that AMD’s microcode in 1.0.0.4 recently corrected some Spectre vulnerabilities. Overall, the CPU performance is basically unchanged (increased by 0.5%), and the NVMe performance is reduced by 5%. In the release test, the problem of current limiting of R7 2700X baking machine has also been solved, so the power consumption of R7 2700X will be revised and increased by about 15%.

As far as the performance of CPU is concerned, it is quite interesting.After synthesizing various usage scenarios, the i7-9700K and R7 2700X are on a par. Relatively speaking, the single-threaded performance of i7-9700K is more advantageous, while the multi-threaded performance of R7 2700X is more advantageous.

As far as the performance of Jixian is concerned, there is nothing to say because Jixian has not been updated.

With the unique part, the i7-9700K has become the strongest one without any accident, but it has not opened the decisive gap.

In terms of power consumption,I7-9700K is more balanced, a little higher than i7-8700K, and there will be no out-of-control situation like i9-9900K.

Here is a screenshot of the baking machine. i7-9700K can stably bake the FPU project of AIDA 64 in 4.6G.

Finally, the last horizontal comparison table is for your reference.

The performance part only compares the test items related to CPU, and does not include the results of the game performance test. Because the graphics card has been changed in the middle and the memory frequency has changed to some extent, this table can only be used for general reference for the time being. In the table, the results of previous tests (different graphics cards) are not included, and only the test results that are not affected by the graphics card are extracted. In the horizontal test, it is found that R7 2700X is slightly higher than i7-9700K. This is because the benchmark in the previous test is i7-8700K, and the reference benchmark in the horizontal test is i7-7700K all the time, so the CPU with a particularly close performance gap will be affected by the benchmark change, and its ranking will change.

Simple summary:

About CPU performance:

As far as CPU performance is concerned, i7-9700K is quite good by itself. Single-thread performance ensures the fluency of daily software use, and multi-thread performance reaches the level of i7-8700K.

On the performance of centralized display:

The display of i7-9700K has not been updated, so there is no change. With regard to the unique display: In the case of unique display, i7-9700K and i9-9900K are quite close, and they sit firmly in the first group, but relatively speaking, the influence of CPU on game performance is really not great, and there is no substantial difference above six cores.

About power consumption:

The power consumption control of i7-9700K is quite reasonable, even if the FPU is baked alone, it will not roll over. It seems that high frequency+hyper-threading is a poison to AVX instruction set. Accordingly, the B360 motherboard with solid power supply can be considered in the matching of i7-9700K, which can greatly reduce the budget of the whole machine. The motherboard suggests that the power supply of the CPU core should be greater than or equal to 6 phases.

About overclocking:

Because the power consumption control of i7-9700K is much better than that of i9-9900K, it should be easier to achieve super 5G.

Generally speaking, the performance of i7-9700K is relatively excellent, both single-threaded and multi-threaded. However, compared with other products in the market, the biggest embarrassment is that it can’t open the gap with R7 2700X, but there is a big gap in price. The boxed price difference in JD.COM exceeds that in 1000 yuan.

I7-9700K and R7 2700X are just two CPU optimization directions, i7-9700K has advantages in single thread, R7 2700X has advantages in multi-thread, and the two on the other end are also completely qualified, so in the use scenarios of these two CPUs, single-thread performance will be more important. If the price difference between i7-9700K and R7 2700X is below 15%, then i7-9700K will have obvious purchase value.

　　Cctv newsOn the evening of 25th local time, a snowstorm started from southern Wyoming and headed for central Colorado. At present, the snowfall has exceeded 30cm, and the gust speed has reached 72km/h.. Up to now, this winter storm has caused hundreds of flights to be cancelled at Denver International Airport in Colorado, and more than 1,000 passengers stayed overnight at the airport. Another interstate highway was closed due to snowstorm.

　　According to the National Weather Service, the storm will then cross Nebraska and Kansas eastward, bringing 15.2~30.5 cm of snowfall to the areas along the way. At the same time, the National Weather Service also said that another snowstorm, which started on the night of 26th local time, is expected to bring heavy snow to parts of the northwest Pacific coast and reach the snowstorm level in Oregon and northern California. As two snowstorms occurred during Thanksgiving, it is expected to disrupt the plans of tens of millions of Americans to travel during the Thanksgiving holiday. (CCTV reporter Xu Wei)

Nowadays, the first thing for consumers to buy a car is to see whether this car is rich in configuration, and it is no exception to nature. Let’s look down with Xiaobian.

Let’s take a look at Komik’s appearance first. Komuk’s front face looks very clean and refreshing as a whole, and the air intake grille uses a straight waterfall shape, which is very recognizable. Coupled with fashionable headlights, it has a great visual impact. The car is equipped with LED daytime running lights, automatic opening and closing, delayed closing and so on. Coming to the side of the car body, the size of the car body is 4409 mm * 1781 mm * 1606 mm. The car adopts fashionable and dynamic lines, and the side circumference looks very sharp. With large-sized thick-walled tires, the shape is quite simple. In the design of the rear end, the rear end looks very comfortable, the taillights look very simple, and with the unique exhaust pipe, it is very simple and fashionable.

Coming to Komuk, Komuk’s interior looks solid and the visual effect is very good. The car looks very good outside the steering wheel, made of plastic, and looks a little more unique. Let’s take a look at the central control. The design of the center console is reasonable, which makes the interior design quite layered and conforms to the mainstream aesthetics. The dashboard and seats are equally eye-catching, and the car is equipped with a stylish dashboard with excellent display effect. The car adopts imitation leather seats, which are wrapped in place, with exquisite materials and comfortable ride.

Komik is matched with an automatic manual transmission (AT) gearbox, with a maximum power of 80KW and a maximum torque of 141N.m, with good power performance.

The car is equipped with driving mode selection, remote control key, rear wiper, engine start and stop, traction control (ASR/TCS, etc.) and other configurations, which greatly improves the convenience of using the car.

The car introduced today is remarkable in terms of space, configuration and power, and home travel is also a good helper. If you are interested, you might as well experience it.

　　On the afternoon of March 30th, the 2022 excellent network audiovisual works selected by the State Administration of Radio and Television were announced at the 10th China Network Audiovisual Conference. As a comprehensive selection activity for the whole industry, the "National Excellent Network Audio-visual Works Selection Activity" aims to play a leading role in demonstrating excellent network audio-visual works, better meet the new expectations of the people for a better audio-visual life, and gather together the majestic power of struggling for a new era and forging ahead in a new journey.

　　中央广播电视总台央视网共10部作品入选，分别是特别节目《最高领袖与乡村振兴的故事》；网络综艺节目《中央广播电视总台2022网络春晚》；短视频《最高领袖擘画的现代版“富春山居图”》《家风世泽长》《跟着习主席看世界｜最高领袖“典”亮命运共同体》《2021年版清明上河图 藏了一年的彩蛋》《熊猫终极治愈行为大赏》《以梦为马》《好久不见！沉浸式重温70、80、90回不去的童年》;网络直播节目《“中国比利时两国共庆旅比大熊猫双胞胎三岁生日”主题直播》。

特别节目

《最高领袖与乡村振兴的故事》

　　党的二十大召开前夕，乡村振兴战略实施五周年之际，央视网策划推出系列时政微纪录片《最高领袖与乡村振兴的故事》(全5期)，以“山、河、湖、海”作题眼，立足中国版图，围绕最高领袖跨越山海、关心农业农村发展的足迹，展现新时代乡村振兴战略实践成果。尤其《在希望的田野上》一集，采用一镜到底的创意表达，带领观众展开一场穿越之旅，打开振兴之门，看见希望的田野。

Network variety show

CCTV 2022 Network Spring Festival Gala

　　With the theme of "youth is just right, when it is new", the 2022 Internet Spring Festival Evening at the reception desk vividly shows the youthful style and struggle story of the "net-born generation" with the expression of networking and youthfulness, and gathers youthful strength. The party will be broadcast simultaneously through CCTV-1 integrated channel and new media matrix of CCTV, CCTV news, CCTV video, CCTV finance, CCTV literature and art, etc., to achieve cross-circle communication effect.

　　The number of TV viewers reached 143 million, the number of live broadcasts of related content and new media matrix was 150 million, and the number of video broadcasts was 1 billion. It triggered 260 hot topics in the whole network, including 151 hot searches in Weibo.

short video

The modern version of "Fuchun Shan Jutu" painted by the Supreme Leader.

　　General Secretary of the Supreme Leader used the modern version of "Fuchun Shan Jutu" as a metaphor to describe the beautiful vision of rural revitalization in the new era. Based on Fuchun Shan Jutu, CCTV copied and innovated, drew a 6-meter long scroll of traditional Chinese painting, and launched a heavy micro-video, showing the rural butterfly changes under the guidance of the Supreme Leader’s New Era Socialism with Chinese characteristics Thought.

Family style is long.

　　Deze has a long history and a long family tradition. General Secretary of the Supreme Leader emphasized that "family is the first classroom in life, and parents are the first teachers of children". Xi’s family style, adhering to "keeping the family in order" and then "governing the country", comes down in one continuous line and is dedicated to the people. CCTV plans to launch "Family Style and Prosperity" and feel the general secretary’s fiery national conditions.

《跟着习主席看世界｜最高领袖“典”亮命运共同体》

　　2013年，最高领袖主席首次提出人类命运共同体的理念。如今，该理念已成为引领人类文明进步潮流的旗帜。央视网推出微视频，通过VR绘画，带领网友品读习主席阐释命运共同体理念时引用的典故，感悟其中蕴含的中国智慧。

《2021年版清明上河图藏了一年的彩蛋》

　　该片将2021年众多瞬间和元素以彩蛋的形式藏在全图，彩蛋包括人物形象、声音素材、关键物件等，据统计超过200个。彩蛋元素从二次元到三次元，从游戏、动漫、电影、热梗到时政新闻均有涵盖，正如网友评论这是最用心最贴近当代年轻人的一版年终盘点。

《熊猫终极治愈行为大赏》

　　2022年10月27日国际大熊猫日，央视网推出混剪短视频《熊猫终极治愈行为大赏》，记录整合萌宠界各大“顶流”熊猫高萌瞬间，画面更具喜感和萌感，广受海内外网友的喜爱。

《以梦为马》

　　香港回归25周年之际，央视网推出原创动画《以梦为马》，通过举世闻名的“人骑图”和“狮子玉”两匹马从北京南下香港的一路见闻，轻松幽默传播中华传统文化，进而增强文化自信，增进民族认同感。

The miniature scene freeze-frame short film | Long time no see!Immerse yourself in reliving the childhood that you can’t go back to in 70, 80 and 90.

　　The so-called growing up is a journey with no return. In order to welcome the arrival of Children’s Day in 2022, CCTV and the post-1995 miniature landscape creators spent two months recreating the childhood scenes of three generations with a scale of 1:20, and launched a creative miniature scene stop-motion short film "Long time no see! Immerse yourself in reliving the childhood that you can’t go back in 70, 80 and 90.

Webcast program

"China and Belgium celebrate the third birthday of the giant panda twins".

　　On the occasion of the 51st anniversary of the establishment of diplomatic relations between China and Belgium, CCTV Panda Channel, together with many authoritative organizations, launched the world’s first live broadcast of the theme of "China and Belgium celebrate the third birthday of the giant panda twins", and the overseas connection for the celebration of the giant panda’s birthday caused a topical discussion, which set a new high in the live broadcast effect of the overseas account of Panda Channel in 2022. This live link between China and Belgium shows a colorful and vivid image of China, and promotes cultural and cultural exchanges between China and Belgium.

　　Guided by the spirit of the 20th National Congress of the Communist Party of China, CCTV, the General Station of Central Radio and Television, will always take innovation as the main theme, vigorously promote the integrated communication of "thought+art+technology", and strive to create more excellent network audio-visual works with both positive energy and large flow, serving the country’s governance, a better life and economic and social development.

1905 movie network news Directed by Jin Zhencheng and starring Haoran Liu and Chen Douling, the youth suspense film released the finalized poster of "Falling in Love with Another Me" today, officially announcing the finalization on April 19th. At the same time, the role stills of Haoran Liu and Chen Douling also met the audience, and this much-anticipated film finally unveiled its mystery.

"Returning to the age of eighteen", Haoran Liu ushered in the biggest challenge of his film career.

Judging from the posters and role stills released this time, Haoran Liu’s role image is quite different from other works, which is mature, restrained and exudes artistic flavor. In Twins, he is no longer the talented boy who stands behind his brother and sister and is bent on solving the case, but has to face everything that happens around him alone. This was a big challenge for Haoran Liu, who was only eighteen at that time. In order to perform this role well, Haoran Liu devoted himself to the filming process. According to Haoran Liu, he was still immersed in the role for a long time after the filming, so he specially chose to go on vacation to release himself after the filming, which made people wonder what role Haoran Liu would present to everyone.

Since the film, every film that Haoran Liu starred in has had a very good box office performance. With his sunny image and excellent acting skills that are rare among his peers, he has been recognized and loved by the audience step by step. Now, after four years, Twins has finally been released, and the audience can see the 18-year-old Haoran Liu brother again, which is undoubtedly a belated surprise for the domestic youth film market and the audience who love Haoran Liu.

The first screen cooperation, the first encounter between the national school flower and the popular niche

The film Twins tells the story of Li Pin (played by Haoran Liu), an art school student, who got a one-month part-time job by chance. His job was to paint portraits of Tao (Chen Douling), a girl whose birthday is coming soon, so he came to a remote mansion. As a result, two young people who had never met each other became attached, and a youthful encounter began. However, in the process of getting along with each other, Li Pin gradually discovered that there seemed to be some unknown secrets hidden in this house, and the relationship between him and Tao gradually became subtle.

As the outstanding actors of the new generation, the first screen cooperation between Haoran Liu and Chen Douling can be described as very topical. One is a popular young actor who starred in the box office of nearly 5 billion, and his acting skills are first-class; One is a national school flower that stands out from countless competitors. The first film starring in it has achieved good box office results, and their youthful attributes perfectly match the temperament of the film. For the two leading actors, this cooperation is their "first encounter with youth" both inside and outside the play, which is of very special significance. Therefore, when the film has not yet been finalized, countless audiences have expressed their expectations for "Twins". The official announcement of the schedule this time is undoubtedly a reassurance to the audience.

　　[Press conference]

　　The diplomacy of a big country with China characteristics has opened up a new realm

　　— — The heads of relevant departments introduced the diplomatic situation of big countries with China characteristics.

　　Guangming Daily reporter Zhong Chao finishing

　　On the morning of October 20th, the 20th press center of the Party held the fourth press conference. Shen Beili, Vice Minister of the International Liaison Department of the Central Committee, and Ma Zhaoxu, Member of the Party Committee and Vice Minister of the Ministry of Foreign Affairs, introduced the relevant situation around the theme of "The diplomatic thought of the Supreme Leader guides the diplomatic development of a big country with China characteristics" and answered questions from reporters.

　　At Vientiane Station in China-Laos Railway, Laos, the flight attendants of Laozhong Railway Co., Ltd. greeted the passengers outside the "Lancang" EMU. Xinhua news agency

　　The China-Ma Youyi Bridge aided by China connects Malé, the capital of Maldives, with the airport island. Xinhua news agency

　　1. The supreme leader’s diplomatic thought has led us to open up a new diplomatic path for a big country with China characteristics.

　　Ma Zhaoxu:In the decade of the new era, the CPC Central Committee with the Supreme Leader as the core led China’s diplomacy as a big country with characteristics to forge ahead, overcome difficulties and achieve all-round and groundbreaking historical achievements.

　　First, the party’s centralized and unified leadership over foreign work has been comprehensively strengthened. The party’s overall situation and coordination of all parties’ external work have been continuously consolidated. Second, the all-round, multi-level and three-dimensional diplomatic layout is becoming more and more perfect. In the decade of the new era, the total number of countries that have established diplomatic relations has increased from 172 to 181, and the number of partnerships with countries and regional organizations around the world has increased from 41 to 113. Third, national sovereignty, security and development interests have been vigorously safeguarded. We have successively won nine so-called "countries of diplomatic relations" with the Taiwan Province authorities, and the international community’s adherence to the one-China policy has been further consolidated. Fourth, China’s international influence, appeal and shaping power have improved significantly. China’s image as a responsible big country is more deeply rooted in people’s hearts. Fifth, serving the country’s economic and social development is more powerful and effective. Nineteen free trade agreements were signed with 26 countries and regions to promote the entry into force and implementation of the Regional Comprehensive Economic Partnership Agreement.

　　The supreme leader’s diplomatic thought has led us to open up a new diplomatic path for a big country with China characteristics. The leadership of the Party is the foundation and soul of China’s diplomacy, the people are supreme is the source of strength for China’s diplomacy, independence is the fine tradition of China’s diplomacy, and the initial intention of China’s diplomacy is to care about the world. Fairness and justice are the persistence of China’s diplomacy, and courage to struggle is the spiritual character of China’s diplomacy.

　　2. The Party’s external work should be upright, innovative and pioneering.

　　Shen Beili:Since the 18th National Congress of the Communist Party of China, the General Secretary of the Supreme Leader has made a series of important expositions on the Party’s foreign work, which are an important part of the Supreme Leader’s diplomatic thoughts, profoundly answered a series of directional, fundamental and strategic questions about the Party’s foreign work in the new era, raised our Party’s regular understanding of foreign work to a new height, pointed out the direction of progress and injected strong impetus into the Party’s foreign work in the new era.

　　In recent years, the Party’s external work has been innovative and pioneering, holding a high-level dialogue meeting between the Communist Party of China (CPC) and the world’s political parties and a summit meeting between the Communist Party of China (CPC) and the world’s political party leaders, and advocating that political parties from all countries join hands to cope with the unprecedented changes in the world in the past century. We responded to the great concern of political parties in various countries and the international community for our party, and held various briefings and presentations in time after the conclusion of the party’s important meetings. Many foreign political party politicians said that the important meeting in the Communist Party of China (CPC) was "a major event that affects the world and concerns themselves".

　　We have promoted and deepened relations with the ruling parties in socialist countries, political parties in neighboring countries and developing countries, and political parties in developed countries, built various regional and global political party dialogue platforms, constantly consolidated and improved the global political party partnership, and helped deepen and expand the global partnership of equality, openness and cooperation. At present, our party maintains different forms of contact with more than 600 political parties and organizations in the world. We have provided nearly 400 foreign political parties with COVID-19 epidemic prevention, treatment and treatment programs, and provided medical materials and technical assistance to foreign political parties in need. These political parties have said that the Communist Party of China (CPC) was a timely help and "was our true friend".

　　3. Constantly create a new situation in diplomacy of a big country with China characteristics.

　　Ma Zhaoxu:The Party’s Report to the 20th CPC National Congress systematically summed up the historic achievements and changes in the cause of the Party and the state in the new era in the past ten years, scientifically sketched the grand blueprint for building a socialist modern country in an all-round way and promoting the great rejuvenation of the Chinese nation in an all-round way, and held high the banner of promoting world peace and development and building a community of human destiny, which was inspiring and inspiring.

　　The decade in which the supreme leader’s diplomatic thoughts led China’s diplomatic development was a decade in which China achieved a historic leap in its relations with the world and made a historic contribution to the international community. Under the guidance of the supreme leader’s diplomatic thought, we comprehensively promoted the diplomacy of a big country with China characteristics, firmly safeguarded international fairness and justice, promoted the construction of new international relations, actively participated in the reform and construction of the global governance system, won wide international praise, and significantly enhanced China’s international influence, appeal and shaping power.

　　On the new journey, the diplomatic front will unite more closely around the CPC Central Committee with the Supreme Leader as the core, thoroughly study and implement the spirit of the 20th Party Congress, be guided by the Supreme Leader’s Socialism with Chinese characteristics Thought in the new era, especially the Supreme Leader’s diplomatic thought, be confident and self-reliant, be upright and innovative, forge ahead courageously, constantly create a new diplomatic situation for a big country with China characteristics, and make new contributions to building a socialist modern country and promoting the great rejuvenation of the Chinese nation in an all-round way.

　　4. The international community pays close attention to the 20th Party Congress.

　　Shen Beili:The 20th National Congress of the Communist Party of China is not only an important event, an important event and a happy event in the political life of our party and country, but also highly concerned and continuously focused by the international community.

　　Political parties, politicians and people from all walks of life in various countries have sent us congratulatory letters, fully expressing their warm congratulations on the victory of the 20 th National Congress of the Communist Party of China.

　　From their congratulatory letters, we can see that they sincerely admire the style of the Supreme Leader General Secretary as a leader of a big party and a big country, and think that the Supreme Leader General Secretary "has keen insight and the spirit of taking responsibility for the times, and has made outstanding contributions to the development of China" and led China to "create the future in a way that benefits all mankind".

　　They earnestly expect the Communist Party of China (CPC) to make greater contributions to the world at a new historical starting point, and believe that the 20th National Congress of the Communist Party of China is "another important milestone in the extraordinary and magnificent historical process of the Communist Party of China (CPC)" and will surely "provide a more solid guarantee for the future development and prosperity of China and the people’s better life". The people of the Communist Party of China (CPC) and China will "continue to make greater contributions to world peace, progress and prosperity".

　　5. China actively participates in international economic cooperation.

　　Ma Zhaoxu:Since the 18th National Congress of the Communist Party of China, the General Secretary of the Supreme Leader has personally promoted the grand diplomacy of the head of state, raised the flag for the diplomacy of a big country with China characteristics, and guided the direction for a chaotic and intertwined world.

　　Not long ago, General Secretary of the Supreme Leader launched a "trip to Central Asia" and attended 31 events intensively within 48 hours, which effectively led China’s relations with relevant countries to a new level.

　　After the outbreak of the COVID-19 epidemic, General Secretary of the Supreme Leader actively carried out "cloud diplomacy", made 181 phone calls with foreign leaders and heads of international organizations, and attended 78 major foreign affairs activities by video, which gathered strong synergy for international anti-epidemic cooperation.

　　The 17th summit of G20 leaders will be held in Bali, Indonesia from November 15th to 16th this year. The G20 is the main forum for international economic cooperation. As an important member of the G20, China has always actively participated in international economic cooperation and global economic governance, and worked with all parties to promote strong, sustainable, balanced and inclusive growth of the world economy.

　　6. Promote the building of a community of human destiny with practical actions.

　　Ma Zhaoxu:The purpose and goal of China’s foreign policy is very clear, that is, to safeguard world peace, promote common development and promote the building of a community of human destiny. At present, changes in the world, times and history are unfolding in an unprecedented way. The historical trend of peace, development, cooperation and win-win is irresistible. At the same time, human society faces many unprecedented challenges. There are indeed some forces in the world who go against the historical trend, cling to the cold war mentality and zero-sum game, are keen to piece together small circles, fight a "new cold war", draw ideological lines, provoke camp confrontation, and engage in hegemony and bullying. This is the greatest threat to the world order. A divided world is not in anyone’s interest, and camp confrontation will only bring the world into a "dead end."

　　China insists on building a community of human destiny through practical actions. Under the personal leadership and promotion of the Supreme Leader General Secretary, substantial progress has been made in building a community of human destiny in all fields and directions from country to region and from bilateral to multilateral. China firmly upholds the international system with the United Nations at the core, the international order based on international law and the basic norms of international relations based on the purposes and principles of the United Nations Charter, and promotes the development of global governance in a more just and rational direction.

　　The global epidemic of COVID-19 and the Ukrainian crisis further demonstrate the true significance of the concept of building a community of human destiny. We will firmly stand on the right side of history, on the side of human civilization and progress, hold high the banner of peace, development, cooperation and win-win, seek our own development while firmly safeguarding world peace and development, and better safeguard world peace and development through our own development.

　　7. Work together to contribute to the development of human civilization.

　　Shen Beili:"Non-interference in each other’s internal affairs" and "mutual learning and mutual learning" are dialectical unity, which embodies our party’s consistent position of respecting the diversity of human political civilization and promoting the progress of human political civilization.

　　"Non-interference in each other’s internal affairs" is the general consensus of political parties in various countries and the basic norm of international relations, and it is the premise for different political parties to maintain their independence. Regardless of the length of history, the number of people, the strength, and whether they are in power or not, political parties should treat each other as equals and respect each other. The choice of political system and development path is a matter for political parties and people of all countries. Our Party will not dictate the internal affairs of political parties in other countries, nor will it "export" the China model and ask other countries and political parties to "copy" our practices. At the same time, we are determined not to accept condescending and bossy preaching, and we will never copy the political system of other countries.

　　"Learning from each other" is an important driving force for the prosperity and development of human political civilization. By other’s faults, wise men correct their own. Promoting the progress of human civilization is inseparable from seeking common ground while reserving differences and learning from each other. Our party has always attached importance to exchanges and dialogues with political parties in other countries, and actively learned from and absorbed all outstanding achievements of human civilization. In the future, our party will continue to carry out in-depth exchanges of experience in governing the country with foreign political parties, jointly strengthen its own construction, enhance its governance capacity, better benefit the people, and work together to contribute to the development of human civilization.