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Test drive and experience China Zunchi 1.8T automatic manual integration (multiple pictures)

  3.23 I received a phone call in the morning, and the new 1.8T Zunchi test drive car has arrived. I started a test drive at the weekend and invited old users to participate!


  I didn’t have time to go on Saturday, but I went with my brother-in-law at 9 o’clock on Sunday morning! As soon as I entered the gate of the 4S shop, I saw a row of Junjie, and there was a red bracelet in the silver and blue hall, which was very attractive to female friends! It is estimated that the car came with 1.8T. The owner hasn’t had time to take it away, but only a black 1.8T Zunchi waited alone and looked around him first, which is roughly the same as what I saw on the Internet!



  When I entered the hall, there was actually a new 1.8T car in it, next to the red Junjie mentioned just now. Because I just went to work, there were few people in the hall, only two salesmen, and I didn’t care to say hello to the two, so I sat in Zunchi directly. At this moment, one of the two came to ask me if I wanted to buy a car. I said I had already bought it, and I came to test drive, plugged in the key and ignited it. I felt that the engine was not loud and the direction was not right. It’s a bit astringent to put the D gear on, and the foot is lifted slightly. The car moves slowly, and the throttle feels better than the old car. The heavy body feels very relaxed. When you go out, turn left and go on a straight road. When the throttle is stepped down slightly, the car jumps out. When you are moving, you feel that the car is very stable, the brakes are still so reassuring, and the car is relatively quiet. The whole test drive process lasts about 10 minutes.


  Disadvantages:


  1. I am mainly dissatisfied with the interior, and those round air outlets are the first to bear the brunt.


  2. The dashboard looks uncomfortable and I don’t like it.


  3. The storage box of the co-pilot has poor texture.


  4. The design of the front armrest is so poor that it seems to resist, including the big hole at the bottom of the center console.


  5. The revision of the door lock was not very successful.


  Advantages:


  1. Strong motivation, needless to say.


  2. The rearview mirror is much bigger and has a wider field of vision.


  3. The direction, brakes and throttle are all lighter than before.








The appearance of China Zunchi 1.8T

> > Click to view more pictures.<<

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Tengshi’s first sports car spy photos exposure! Two-door four-seat layout, performance comparable to 911?

A few days ago, the spy photos of Tengshi sports car were exposed on the Internet. This car was originally a production version of Equation Leopard Super 9, and now it has been changed to Tengshi. It is reported that the new car will be available in both hardtop and convertible versions, and its performance is comparable to that of Porsche 911. It is expected to be unveiled at the Shanghai Auto Show in 2025, and the price is expected to exceed 300,000 yuan.

From the spy photos, the car is covered with a blue camouflage sticker that is common in Tengshi. The body is low and smooth, and the size of the whole car is not expected to be too large. It adopts a two-door four-seat layout. It is also equipped with large-size wheels.

Equation Leopard’s first sports car, SUPER 9, was unveiled at the press conference in April. It is a pure electric two-compartment racing car with an open roof design, equipped with suspended double-wing doors, integrated carbon fiber seats, carbon fiber matrix skeleton and racing steering wheel.

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Scientifically grasp the connotation, characteristics and path of high-quality economic development

  Theoretical connotation of high-quality economic development

  The report of the 19th National Congress of the Communist Party of China pointed out that China’s economy has shifted from a high-speed growth stage to a high-quality development stage. This is a major judgment made by the CPC Central Committee with the Supreme Leader as the core according to the changes in the international and domestic environment, especially the changes in China’s development conditions and stages. The core of high-quality economic development is quality first and benefit first, which has profound theoretical connotation and great practical guiding significance.

  Looking at the history of world economic development, the understanding of the law of economic development evolution and quality and efficiency is deepening with the development of social productive forces. From the early use of "efficiency" or "efficiency" to express the pursuit of the quality of economic development, to the economic growth theory in western economics that technological progress is the decisive factor to achieve sustainable economic development. With the deepening and development of theoretical research, the research on the quality of economic development has gradually expanded to institutional system, social equity, environmental protection and so on.

  With regard to the current high-quality economic development in China, the central authorities stressed that high-quality development is a development that can well meet the people’s growing needs for a better life and embodies the new development concept. This thesis clarifies the purpose and means of high-quality development. Described by personal capital, high-quality economic development is an economic development that provides high-quality products and services to the whole society in a sustained and fair way with high efficiency and high efficiency, and it is a high-quality, high-efficiency and high-stability supply system in the specific economic form.

  First, the quality of the supply system is high. The supply system includes three links: factor input, intermediate input and final output. The quality of the three links of the supply system is closely related. The high quality of the supply system means that the quality of all three links should be high. The high quality of factor input refers to the high quality of labor, capital, technology, energy resources, data, information and other factors put into the supply system, which is manifested in the high quality of labor, the high degree of automation, data and informatization of production materials, the high degree of greening of energy resources, the high technical level put into the production process, and the large scale, quality and value of information and data resources. The high quality of intermediate products means that the intermediate products in the production process, such as the quality and precision of parts, can meet the production needs well, which requires the continuous improvement of industrial division of labor and specialization, the continuous optimization and upgrading of industrial structure, and the formation of an effective collaborative and mutually supportive supply chain system. High quality of final output is an important connotation of high-quality development, that is, what we usually call high quality of products and services means that we can provide high-quality products and services to meet the diversified, personalized and escalating high-grade needs of consumers and better meet the growing needs of people for a better life. High-quality supply system is characterized by high quality and high performance of products and services at the level of specific output forms; At the industrial level, it is manifested as a rational and advanced industrial structure.

  The second is the high efficiency of the supply system. From a static point of view, the high efficiency of the supply system is manifested in the unity of high technical efficiency and good economic benefits. Technical efficiency determines that under the given resource conditions, production possibility frontier, in the reality of scarce resources, promoting high-quality development inevitably requires the efficient and intensive development of the potential of existing resource elements, maximizing the input-output efficiency of various production factors, and achieving a fairly high level of capital efficiency and human resource efficiency. Economic benefits emphasize the rationality of resource allocation and combination, which represents the degree of allocation efficiency and reasonable distribution. High-quality development requires the rational allocation of resources between different uses, so that the marginal productivity of all kinds of factors can reach the highest, and marginal return of all kinds of factors can reach the highest. From a dynamic point of view, the high efficiency of the supply system is also manifested in the continuous improvement of efficiency, which has become the driving force for sustained and strong economic development, that is, economic growth has shifted from mainly relying on factor input to relying more on the improvement of total factor productivity, and the contribution of total factor productivity in the driving force of economic growth has been continuously improved. In this sense, the transformation process of economic growth momentum is also a process of promoting output efficiency, and power transformation and efficiency improvement are unified.

  Third, the stability of the supply system is high. High-quality economic development should also be reflected in maintaining a relatively high level of stability in the supply system. From the time dimension, high stability is characterized by stable economic operation in a reasonable range in the short term and strong sustainability of output in the medium and long term. From the spatial dimension, high stability requires not only the health and stability of the economic system itself, but also the coordination of the economic system with society and environment. At the same time, economic development can provide development opportunities for all members of society, and the results will be shared by all people. In terms of resources and environment, rational utilization of natural resources and effective protection of ecological environment can bear long-term sustainable economic growth. In short, high stability of economic development means stable economic operation, controllable major risks, bearable resources and environment, and shared development achievements.

  It should be emphasized that the high quality, efficiency and stability of the supply system are the core essence of high-quality economic development. Only when these characteristics are simultaneously possessed, and these characteristics are mutually supportive rather than conflicting, can they be called high-quality economic development.

  High-quality development is a gradual and systematic development process

  Summarizing the past development experience at home and abroad, high-quality development shows obvious stage characteristics. With the transformation of economic development stage, some aspects related to development quality, such as product and service quality, technical efficiency and economic benefit, economic growth power transformation, environmental quality, income distribution, etc., will change in trend at a certain time. It mainly shows that with the economic development, the quality of production factors such as capital and labor has been continuously improved, the quality of output has been continuously improved, the labor productivity has been continuously improved, and the industrial added value rate has been continuously improved. The driving force of economic development has shifted from factor-driven to efficiency-driven and innovation-driven, and the industrial structure has been continuously upgraded. What needs special attention is that these trend changes do not happen naturally, which are not only the embodiment of objective laws, but also the result of institutional policies.

  By analyzing the changes of main quality indicators in different development stages, we can find that the transition to high-quality development presents the following typical characteristics: First, it is gradual. High-quality development is a process of constant change and slow evolution, and it is also a process from small accumulation to big change, from quantitative change to qualitative change. In this development process, factors, product and industrial quality, output efficiency, economic growth momentum, as well as the stability of economic growth and the sustainability of development have gradually changed. The improvement of output quality usually starts from the improvement of micro-factor quality, and then the driving force of economic growth shifts from factor-driven to efficiency-driven and innovation-driven. At the same time, the use efficiency of micro-factor and macro-total factor productivity are constantly improved, which lays the foundation for the improvement of output quality. The gradual development of high quality is also the result of the gradual improvement of demand level. The high quality of supply cannot exist in isolation from the fundamental purpose of meeting demand, and it needs to meet the low-level demand first and then change to meet the high-level demand. The second is systematic. High-quality development is an all-round and systematic process of change, and high-quality development in various fields is both a prerequisite and a result. In this development process, systematic changes have taken place at both ends of supply and demand, input and output, micro and macro fields. This includes both the optimization of industrial structure on the supply side and the upgrading and shifting of consumption on the demand side; It includes not only the improvement of labor, capital and other factors at the input end and the quality of intermediate inputs, but also the improvement of product quality and performance at the output end; Including the improvement of the use efficiency of micro-elements,It also includes the improvement of macro total factor productivity; It includes not only the transformation of short-term growth momentum, but also the fairer and more sustainable long-term development. What needs to be seen is that high-quality development is a spiral upward process, which is not only an objective and inevitable law that quantity accumulation will inevitably turn to quality improvement at a certain stage, but also the result of policy efforts to overcome difficulties and take the initiative. The two work together to better promote high-quality economic development.

  An important path to promote high-quality economic development

  Promoting quality change, efficiency change and power change of economic development is the key to realize high-quality economic development. Among them, quality change is the main body, efficiency change is the main line, and power change is the foundation. The three depend on each other and are an organic whole. Generally speaking, the core of promoting the three major changes is to improve the quality of factors and increase the total factor productivity, and the fundamental driving force lies in scientific and technological innovation and institutional innovation.

  First, to improve the quality of the supply system as the main direction to promote quality change.

  Improving the quality of the supply system is to promote the all-round reform of ideas, objectives, systems and work details in specific fields. It is a systematic project, and the quality reform should be promoted from three aspects: the quality of factor input, the quality of intermediate input and the quality of final output.

  The first is to improve the quality of factor input. Factor input is the foundation, and its quality directly affects the quality of intermediate input and final output. From the perspective of labor factors, the higher the health status, years of education and skill level, the higher the output quality. From the perspective of capital factors, the output quality of different levels of factories, machinery and equipment will also be significantly different. From the perspective of technical factors, adopting higher-level science and technology and technology will also help to improve the quality of output. It can be said that the quality of factor input largely determines the quality of output and is the starting point for improving the quality of supply system. At the same time, recent studies show that the improvement of factor quality in developed countries has made an increasingly significant contribution to economic development, and the improvement of factor quality also has spillover effect on productivity improvement.

  The second is to improve the input quality of intermediate products. The refinement and specialization of socialized division of labor constitute the industrial chain form of all walks of life. The quality of products in each chain will affect the quality of final output, and the input of intermediate products in key links can even directly determine whether the final output can be produced and the quality of production. China has been deeply embedded in the global industrial chain, but there are still many bottlenecks in the intermediate products of key links. Therefore, improving the input quality of intermediate products is the key to improve the quality of supply system, which requires building a mid-to high-end industrial structure and forming an effective industrial synergy supporting system.

  The third is to improve the quality of final output. Starting from better meeting people’s growing needs for a better life, high quality products and services is the core and foothold of high quality supply system. The final product and service quality is related to the quality of residents’ consumption and the international competitiveness of a country’s products. We must speed up the improvement of China’s product and service quality by adjusting the quality standard system and promoting the quality brand action, so as to better promote the quality improvement of the supply system.

  Second, promote efficiency change with improving total factor productivity as the core.

  Improving output efficiency is the eternal theme of economics. The key to promoting efficiency change is to improve total factor productivity, so that economic growth depends more on total factor productivity. Total factor productivity is the "residual" contribution excluding the contribution of factor input. To improve the total factor productivity, we must vigorously promote the efficiency reform, constantly improve the technical efficiency and improve the efficiency of factor allocation.

  The first is to improve technical efficiency. Technical efficiency corresponds to production possibility frontier, and improving technical efficiency means pushing production possibility frontier outward, which means the maximum output increase caused by the same scale of investment. From the essence of economic development, technical efficiency is the most important connotation of total factor productivity, and it should also occupy the most important position in total factor productivity, because it has broken through the original capacity boundary and reached a new and higher level. Promoting technical efficiency and continuously increasing the contribution of total factor productivity to economic growth is an important way to break the constraints of resources and environment and an important driving force to maintain long-term sustainable economic growth.

  The second is to improve the efficiency of factor allocation. The efficiency of factor allocation affects the distance between actual output and production possibility frontier. If only the technical efficiency is improved and the factor allocation efficiency is low, the actual output will be far away from production possibility frontier, and the potential of technological progress to promote economic development will not be fully released. Under the dual economic structure, promoting the transfer of production factors from low-productivity departments to high-productivity departments and improving the allocation of factors have a significant effect on improving the total factor productivity. In addition, other factors that affect the efficiency of factor allocation include system and management. Good system and high-level management can also provide effective incentives, thus improving the supply and use efficiency of factors and improving the total factor productivity.

  Third, focus on scientific and technological innovation and system reform to promote dynamic change.

  From a deeper perspective, the driving force of economic development is to expand the input and output drive of existing resources and factors under the established technical level, which is an extension expansion on the original path. The other is to expand the scope of resources, improve the efficiency of resource elements and create new output drivers through technological and institutional innovation, which is a structural change of the economy. The change of the driving force of economic development, from relying mainly on the former to relying mainly on the latter, is an important manifestation of the economy turning to high-quality development.

  First, scientific and technological innovation is the key driving force for economic development. Without technological innovation, with the increase of resource scarcity and the law of diminishing factor returns, economic development will come to a standstill. Through technological innovation, we can expand the scope of available resources and break the bottleneck of resources; Improve the use efficiency of resources and elements, and create more output with less input; It provides a technical basis for the configuration and combination of elements in a larger space; Create new diversified and high-quality products and services to better attract and meet the demand; Solve the negative effects of economic development on the environment and enhance the sustainability of economic development. It can be said that all aspects of the connotation of high-quality development are closely related to scientific and technological innovation, so scientific and technological innovation must be the first driving force for high-quality development.

  Second, institutional innovation is also an important driving force to promote high-quality economic development. Institutional changes affect all dimensions of economic development. Reasonable institutional arrangements can continuously improve the quality and efficiency of economic development in a country or region, improve the total factor productivity and better promote high-quality economic development. For example, reasonable property right system and price system arrangement are helpful to promote the recombination of production factors, improve the efficiency of factor allocation, and are conducive to economic and efficient development; Effective market competition mechanism and intellectual property protection system can accelerate innovation and technological progress and promote economic innovation and development; Scientific management of resources and environment and system of ecological civilization can promote the improvement and sustainability of resources and environment; Wait. At present and in the future, we should make more efforts to deepen the reform of institutional mechanisms, so as to better stimulate the creativity and development vitality of the whole society and promote higher quality, more efficient, fairer and more sustainable economic development.

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No bid, no sales, no raw materials! How do pharmaceutical companies that are "holding their throats" survive?

No bid, no sales; There is no raw material in the bid. Can pharmaceutical companies with "involuntary fate" survive in the cracks?

Recently, Zhejiang Pharmaceutical Machinery Purchasing Center issued a notice on suspending the online trading of cefmetazole sodium for injection of Suzhou Dongrui Pharmaceutical Co., Ltd. (hereinafter referred to as Dongrui Pharmaceutical).

Description of the announcement: The cefmetazole sodium for injection produced by Suzhou Dongrui Pharmaceutical Co., Ltd. failed to fulfill the obligation of selecting the first batch of drugs in our province, and said that the raw materials of cefmetazole sodium for injection could not be purchased and the normal supply of the drug could not be guaranteed. After research, the online trading of cefmetazole sodium for injection (specifications: 0.5g and 1.0g) produced by Suzhou Dongrui Pharmaceutical Co., Ltd. will be suspended from now on.

According to the description in the announcement, the reason why Dongrui Pharmaceutical fulfilled the obligation of winning the bid was related to the inability to purchase raw materials.

01 or withdraw from the network due to the supply of raw materials.

In November, 2020, Zhejiang Medical Machinery Procurement Center issued the Procurement Document for Centralized Procurement of Some Drugs in Zhejiang Province, announcing that eight drugs, such as Rabeprazole Oral Constant Release Dosage, Ursodeoxycholic Acid Oral Constant Release Dosage and Cefemetazole Injection, will be purchased with quantity, and the procurement cycle will be 12 months. Among them, the agreed purchase quantity of cefmetazole injection (specification 1.0g) is 2,502,800 pieces.

In January this year, Zhejiang Medical Machinery Purchasing Center announced the results of the selection, involving 10 varieties. According to the principle of winning the bid in Zhejiang Province, if there are more than two bidding enterprises, the lowest quotation will be selected, and only one enterprise can be selected. Dongrui Pharmaceutical beat 17 other competitors, such as Harbin Pharmaceutical Group, Fuan Qingyutang, Beite Pharmaceutical, etc. The company’s cefmetazole sodium for injection (powder injection, packaging specification: 1.0g/ bottle) was selected by 8.2 yuan. The successful result will be implemented from March 15th.

However, on April 14th, Zhejiang Pharmaceutical Machinery Purchasing Center released another report on the purchasing results of cefmetazole sodium injection. According to the circular, because Dongrui Pharmaceutical refused to fulfill its bid-winning obligations, it did not complete the work of signing the purchase and sale agreement and establishing the distribution relationship, which affected the normal implementation of the bid-winning results. As for the lack of cefmetazole sodium in centralized drugs due to Dongrui Pharmaceutical’s failure to fulfill the obligation of selection, the processing method of Zhejiang Medical Machinery Purchasing Center is that the purchase of cefmetazole sodium injection with quantity is treated as no selected product, and all medical and health institutions temporarily purchase it according to the original method.

Dongrui Pharmaceutical may also be defended for failing to fulfill its obligations as required and causing losses to medical and health institutions.

For enterprises with dishonesty, Zhejiang Medical Equipment Purchasing Center has also implemented notification measures while reminding medical and health institutions to choose carefully and avoid purchasing products from untrustworthy enterprises.

When pharmaceutical companies participate in centralized procurement declaration, they will be required to provide the Commitment Letter of Drug Declaration Enterprise. Among them, it includes the requirement of credibility: there is no serious illegal record in the two years before the declaration, such as disturbing the order of centralized procurement, maliciously violating the contract and other acts contrary to honesty and credit. The requirement for production capacity is that the annual production capacity of the declared varieties should reach 2 times or more of the agreed purchase quantity. If it is untrue, it is willing to accept the treatment including canceling the qualification for winning the bid and including bad records.

Under normal circumstances, the punishment result of the successful company’s failure to fulfill the obligation of successful selection will be more serious, while the punishment result of Dongrui Pharmaceutical this time is notification, which is relatively light. This result may be related to the inability of Dongrui Pharmaceutical to purchase APIs.

According to the company’s official website, Dongrui Pharmaceutical is mainly engaged in the development, manufacture and sales of cephalosporin antibiotics and system specialized drugs. According to the information of domestic drugs in National Medical Products Administration, there are currently 28 pharmaceutical companies in China with a total of 65 registered production approvals of Cefmetazole Sodium for Injection. Suzhou Dongrui has registered production approval documents of 1.0g and 0.5g cefmetazole sodium for injection.

According to media reports, it was learned from interviews with several regional sales leaders of Suzhou Dongrui that raw materials could not be purchased because the upstream raw material enterprises were unwilling to supply Suzhou Dongrui. "At first, we were told to raise prices substantially, but we accepted it. But then the manufacturer said that it could not be supplied. " Informed employees of the company revealed.

In China, only six pharmaceutical companies, including Harbin Pharmaceutical Group, Fuan Pharmaceutical Group, Chongqing Bosheng Pharmaceutical and Chongqing Gisrui Pharmaceutical, have registered production approval documents for cefmetazole sodium raw materials.

According to Health Network, in February this year, the price of rare varieties of cephalosporin raw materials doubled, and the most concerned small product was cefmetazole sodium raw material. The recent price increase was caused by the price increase of raw materials and the lack of manufacturers. The original price of domestic manufacturers was about 4,000 yuan /kg, and now it is quoted at 8,000 yuan /kg.

The supply cut-off incident of Dongrui Pharmaceutical further highlights the "dilemma" faced by pharmaceutical companies whose raw materials are not in their own hands: if a large number of raw materials are hoarded before the election, but the results are not selected, the pharmaceutical companies will face the risk of unsalable products and broken capital chains at any time; If you don’t hoard a large number of APIs, but the result is selected, you will face the current problem of Dongrui Pharmaceutical, "you can’t buy APIs with money", which will eventually lead to the suspension of drug supply.

02 API monopoly, who is controlling it?

Since the procurement with quantity was carried out at the end of 2018, the supply interruption of selected products has occurred from time to time.

In 2019, the supply of Fosinopril sodium tablets of Bristol-Myers Squibb (BMS) was cut off due to insufficient supply, which became the first cut-off event after centralized procurement, and was finally supplemented by Huahai Pharmaceutical. At the end of last year, two selected products, Penglai Nuokang Pharmaceutical Metformin Tablets and Nanjing Changao Pharmaceutical Pivastatin Calcium Tablets, were unable to be supplied in sufficient quantities in a short period of time, so the transition period was increased by three months.

There are many reasons for drug supply interruption, and the shortage and price increase of raw materials are very important factors. In recent years, many API companies have also been issued "sky-high fines" for alleged monopoly.

At the beginning of this month, Tianyao Co., Ltd. was punished by Tianjin Municipal Market Supervision and Management Committee for allegedly reaching a monopoly agreement on fluoxetine bulk drug, with a fine of 44.02 million yuan.

In April, 2020, the State Administration of Market Supervision made an administrative penalty decision on the illegal acts of abusing the dominant market position of three calcium gluconate raw material drug distribution enterprises, namely Shandong Kanghui Medicine, Weifang Taiyangshen Medicine and Weifang Puyunhui Medicine, and confiscated a total of 325.5 million yuan. This is also the biggest fine for the monopoly of APIs since the implementation of the Anti-Monopoly Law.

In November 2020, Wanbangde Pharmaceutical was fined 2.474 million yuan for abusing its dominant market position and attaching unreasonable trading conditions to the production and sale of bromhexine hydrochloride.

According to the Annual Report on Anti-monopoly Law Enforcement in China (2019) issued by the State Administration of Market Supervision at the end of 2020, there were 6 monopoly cases in the API industry in 2019. According to incomplete statistics, since 2016, a total of 15 companies, including Tianyao Co., Ltd., have been subject to administrative penalties for monopolistic behavior of APIs.

Why monopoly events frequently occur in the field of APIs?

There may be "passive" and "active" reasons for this.

"More registered pieces, less actual production". China holds 8482 valid API approval documents, and there are 1699 pharmaceutical companies with API production license qualifications. However, there are few companies that can actually produce and actually produce.

According to the information released by the Price Supervision, Inspection and Anti-monopoly Bureau of the National Development and Reform Commission, there are about 1,500 kinds of APIs in China, but their production is in the hands of a few manufacturers, of which only one enterprise can produce 50 kinds of APIs, only two enterprises can produce 44 kinds of APIs and only three enterprises can produce 40 kinds of APIs. Some people in the industry have also analyzed that many enterprises are unwilling to produce low-priced drugs because of their low prices and low profits, which is more likely to lead to monopoly.

"Environmental protection costs are under great pressure". On January 1, 2018, the "Environmental Protection Tax Law" was officially implemented, and the collection of sewage charges was changed to the collection of environmental protection fees, which greatly increased the cost for API manufacturers that needed a large amount of sewage discharge. Raw material medicine enterprises urgently need to be upgraded, and in the process of upgrading, some enterprises closed down because they could not bear the cost of upgrading.

Only a few companies have the qualification for examination and approval and the production capacity. In addition, with the increase of costs, the number of API enterprises has further decreased, and the output has also been affected.

According to the data of the National Bureau of Statistics, since 2018, the output of APIs in China has experienced a cliff-like decline, from 3.478 million tons in 2017 to 2.823 million tons in 2018, and then to 2.621 million tons in 2019. In the case of "scarcity is precious", the price of raw materials has also soared. In 2018, the price of roxithromycin rose from 590 yuan/kg in May to 735 yuan/kg in October. The price of chlorpheniramine, commonly used in cold medicine, rose from 400 yuan /kg to 23,300 yuan /kg in just one month, up 58 times.

In view of the "passive" monopoly of API enterprises, Wu Huifang, the general manager and chief researcher of Health Network, has conducted an analysis before. "There are mainly two aspects: on the one hand, the output is not large, although there are some approval numbers for APIs, there are few manufacturers that can actually produce them normally, and the size of preparation manufacturers is uneven. In this case, the price increase of APIs is also a last resort; On the other hand, the monopoly of many APIs is not caused by the active behavior of API companies, but by the competitive means of preparation distributors, especially for preparation bidding, that is, the underwriting party forces competitors to make concessions in preparation bidding by controlling the supply of APIs. "

In addition to the "passive" factors, there are also many enterprises in the market who choose to "do it intentionally". According to insiders, some of the monopoly phenomena of APIs are due to human manipulation. One mode is to indirectly control several natural persons to acquire the approval documents, so that all the market of the API is assigned to its own "circle", and finally only one of them is allowed to produce, and the rest of the approval documents are idle, resulting in monopoly of the market, and then the price is raised. Another mode is to sign a "National General Underwriting Agreement" between a third-party commercial company and an API enterprise, so that all APIs can be brought together. If you want to buy APIs, you can only buy them through the channels provided by the company, but API enterprises can’t participate in the pricing, resulting in monopoly.

These models make it more difficult for the regulatory authorities to investigate and deal with monopoly events.

In addition, according to Article 47 of the Anti-Monopoly Law, "if an operator violates the provisions of this law and abuses the dominant position in the market, the anti-monopoly law enforcement agency shall order him to stop the illegal act, confiscate the illegal income and impose a fine of more than 1% and less than 10% of the sales in the previous year."

In the monopoly case of Tianyao shares, Tianyao shares were fined 4% of sales in 2019 and confiscated illegal income. The proportion of 4% is not high in recent years because of the monopoly of APIs. Previously, Kanghui Company, Puyunhui Company and Taiyangshen Company were fined 10%, 9% and 7% of the annual sales in 2018 respectively for the monopoly of calcium gluconate for API injection.

However, in terms of the amount, the 4% sales of Tianyao Co., Ltd. in 2019 corresponds to about 35.1247 million yuan, while the 9% sales of Puyunhui Company in 2018 are 48.3 million yuan, and the 7% sales of Helios Company in 2018 are 12.4 million yuan. After receiving the ticket, Tianyao Co., Ltd. lowered its estimated net profit in 2020 from the original "55 million yuan-75 million yuan" to "31 million yuan-37 million yuan", which is equivalent to a fine of nearly half of the net profit for one year.

Compared with the sales of 10% in the previous year, the price difference and huge profits brought by monopoly for several consecutive years will still make some companies choose to take risks, which is one of the reasons why the monopoly of APIs has been repeatedly banned.

How to deal with the downstream pharmaceutical enterprises

The monopoly of APIs is undoubtedly "strangled" for some downstream pharmaceutical companies. The price of raw materials is rising, and the price of centralized drugs is low. The profit margin of pharmaceutical enterprises is constantly being compressed and even the phenomenon of "price upside down" appears. Without profit margin, many pharmaceutical companies can’t give up drug production, which leads to the shortage and interruption of supply of commonly used drugs, which is extremely unfavorable to society and ordinary people.

Faced with the monopoly of APIs, the national regulatory authorities have been "striking hard" and cracking down on monopoly. And how should pharmaceutical companies in the downstream "save themselves"?

Wu Huifang said that in the market competition, the powerful preparation manufacturers left behind have sufficient purchasing power, and they are planned and do not owe debts; In addition, we can follow the procurement mode of pharmaceutical preparations, and pharmaceutical enterprises can jointly bid for the procurement of raw materials.

It is also reported that Dongrui Pharmaceutical, which withdrew from the network due to the interruption of the supply of raw materials, will build its own raw material drug production line in the future and "take its fate in its own hands".

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Announcement of Beijing Local Taxation Bureau and Beijing Environmental Protection Bureau on Issuing the Interim Measures for the Verification and Calculation of Beijing Environmental Protection Tax

No.3 of 2018

  The Interim Measures for the Verification and Calculation of Beijing Environmental Protection Tax are hereby promulgated and shall come into force as of January 1, 2018.

  It is hereby announced.

  Annex: 1. Table of Characteristic Value Coefficient of Sewage Discharge of Some Small Tertiary Industries (omitted)

     2. Water pollution equivalent value of livestock breeding, small enterprises and tertiary industry (omitted)

     3. Adjustment coefficient of dust emission from construction site (omitted)

     4. Construction site dust management grade standard (omitted)

     5. Policy Interpretation on the Announcement of Beijing Municipal Environmental Protection Bureau of Beijing Local Taxation Bureau on Issuing the Interim Measures for the Verification and Calculation of Beijing Environmental Protection Tax (omitted)

  Note: The attachment can be found on the official website of Beijing Local Taxation Bureau (www.tax861.gov.cn).

Beijing Local Taxation Bureau    

Beijing Municipal Environmental Protection Bureau    

March 29, 2018  

Interim Measures of Beijing Municipality on the Verification and Calculation of Environmental Protection Tax

Chapter I General Principles

  the first In order to improve the environmental quality of this Municipality, give full play to the role of taxation in promoting pollution control and emission reduction, and strengthen the collection and management of environmental protection tax, these measures are formulated in accordance with the provisions of People’s Republic of China (PRC) Environmental Protection Tax Law, People’s Republic of China (PRC) Tax Collection and Management Law and its implementation rules and other relevant laws and regulations.

  the second Taxpayers within the scope of this Municipality who cannot calculate the tax payable of air pollutants and water pollutants in accordance with the methods specified in Items 1 to 3 of Article 10 of the People’s Republic of China (PRC) Environmental Protection Tax Law shall verify and calculate the tax payable in accordance with the provisions of these Measures.

  The air pollutants and water pollutants mentioned in the preceding paragraph refer to air and water pollutants discharged by livestock breeding, small enterprises and some tertiary industries, dust (general dust, the same below) generated by construction sites, and sulfur dioxide generated by municipal gas facilities (burning municipal pipeline natural gas).

  Article The local tax authorities at all levels and the competent department of environmental protection shall establish a cooperation mechanism for the verification and calculation of environmental protection tax according to these Measures, and carry out the verification and calculation of environmental protection tax in an orderly manner according to the responsibilities of the departments.

  Article 4 Local tax authorities shall perform the following duties:

  (1) Incorporating taxpayers who meet the approved calculation into tax administration;

  (two) according to the latest pollution characteristic coefficient issued by the competent department of environmental protection, timely maintenance and adjustment of the approved tax-related data;

  (three) to supervise, verify and inspect the basic data of taxpayers’ production and operation, the basic situation of pollutant discharge and the payable amount of environmental protection tax.

  Article 5 The competent department of environmental protection shall perform the following duties:

  (a) the municipal environmental protection department is responsible for formulating and adjusting the sampling measurement methods of this Municipality; To supervise and control the sewage discharge of taxpayers approved for calculation;

  (two) responsible for providing the relevant information obtained in the supervision and management of environmental protection to the district tax authorities;

  (three) to cooperate with the tax authorities to implement the tax inspection of environmental protection tax according to law.

Chapter II Calculation Methods

  Article 6 Taxable amount of pollutants generated by catering industry (without sewage discharge metering equipment), accommodation industry, washing and dyeing service industry (clothing), beauty salon and health care industry, bathing industry (foot washing and bathing), automobile and motorcycle repair and maintenance industry, photography and printing service industry and independent coal-fired boiler that cannot be verified and calculated according to the methods specified in Item 1 to Item 3 of Article 10 of People’s Republic of China (PRC) Environmental Protection Tax Law is:

  Taxable amount = characteristic index value × pollutant discharge characteristic coefficient × specific applicable tax amount

  The characteristic coefficient of emission shall be implemented in accordance with the Table of Characteristic Coefficient of Sewage Discharge of Some Small Tertiary Industries attached to these Measures (see Annex 1). The specific applicable tax amount is the applicable tax amount of taxable pollutants in Beijing.

  Article 7 The taxable amount of water pollutants in livestock breeding, small enterprises, catering and entertainment services (with sewage discharge metering equipment) and hospitals that cannot be calculated according to the methods specified in Items 1 to 3 of Article 10 of People’s Republic of China (PRC) Environmental Protection Tax Law is:

  Taxable amount = pollution equivalent number × specific applicable tax amount

  The pollution equivalent number is calculated by dividing the characteristic value of pollution discharge by the pollution equivalent value, which shall be implemented in accordance with the Water Pollution Equivalent Value of Livestock Breeding, Small Enterprises and Tertiary Industry (see Annex 2) attached to these Measures. The specific applicable tax amount is the applicable tax amount of taxable water pollutants in Beijing.

  Article 8 The taxable amount of dust generated by the construction site of the construction project is:

  Taxable amount = land area of construction site × 0.065 × construction period × adjustment coefficient of dust emission of construction site × specific applicable tax amount.

  The land area of the construction site of the construction project is the land area of the construction unit (including the agent). The construction period shall be calculated on a monthly basis. If the construction period is less than one month, the construction period shall be converted according to the actual construction days in different construction stages divided by the actual days in the current month. The adjustment coefficient of dust emission on the construction site shall be implemented in accordance with the Adjustment Coefficient of Dust Emission on the Construction Site attached to these Measures (see Annex 3). The specific applicable tax amount is the applicable tax amount of taxable air pollutants in Beijing.

  ninthstrip Construction sites include housing construction sites (including industrial plants), decoration sites, municipal infrastructure sites, demolition sites, greening sites, water sites, highway sites, railway sites, etc. within the administrative area of this Municipality.

  Article 10 The construction unit (including the agent) construction land area is determined according to the following methods:

  (a) according to the land, planning, housing and urban-rural construction departments issued by the state-owned land use certificate, the construction project planning conditions from the construction land planning permit (the construction project planning permit from building construction permits), the house ownership certificate or the immovable property certificate, as well as the approval documents of the administrative departments with approval authority or other relevant materials;

  (two) the main technical parameters such as length, width and pipe diameter should be provided when the area of linear projects such as highways, railways, water affairs and pipe networks is approved;

  (three) there is no relevant approval documents to prove the construction area of the project, the construction unit shall calculate the construction area according to the actual land area.

  Article 11 If the construction site of a construction project meets the Class II standard in the Grade Standard for Dust Management of Construction Sites attached to these Measures (see Annex 4) and meets the Class I standard, the tax payable shall be calculated according to the reduction factor of 50%; If it only meets the second-class standard, the tax payable shall be calculated according to the reduction factor of 100%; If the second-class standard is not met, the tax payable shall be calculated according to the reduction factor of 200%.

  If there is grade standard information in the dust management of the relevant government departments in the construction site of the construction project, the tax authorities shall determine the reduction coefficient based on this information.

  Article 12 The taxable amount of sulfur dioxide generated by gas facilities (burning municipal pipeline natural gas) that cannot be actually monitored is:

Taxable amount of sulfur dioxide

Chapter III Approval Methods

  Article 13 Taxpayers who meet the approved calculation conditions should fill in the Basic Information Collection Form of Environmental Protection Tax when registering the tax source of environmental protection tax for the first time, submit it to the competent tax authorities, and be responsible for the authenticity of the application materials.

  Article 14 Taxpayers who implement the approved calculation meet the calculation conditions of taxable pollutants stipulated in Items 1 to 3 of Article 10 of the People’s Republic of China (PRC) Environmental Protection Tax Law by installing, monitoring and measuring the emissions of atmospheric and water pollutants. If these measures are no longer applicable, they should re-fill in the Basic Information Collection Form of Environmental Protection Tax in the next month after the change, and make tax returns according to law.

  Article 15 When taxpayers file tax returns, they shall file and fill in the tax returns according to the following circumstances:

  (1) Taxpayers who are subject to the provisions of Article 12 of these Measures shall fill in the Environmental Protection Tax Declaration Form (Form A) to declare and pay taxes.

  (2) Taxpayers who apply other methods of these Measures shall fill in the Environmental Protection Tax Declaration Form (Form B) to declare and pay taxes.

  Article 16 These Measures shall be interpreted by Beijing Local Taxation Bureau and Beijing Environmental Protection Bureau.

  seventeenthArticle These Measures shall come into force as of January 1, 2018.

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A number of convenient services smooth the flow of Spring Festival travel rush logistics "artery" China is full of vitality

  CCTV News:In 2024, in Spring Festival travel rush, the proportion of cross-regional personnel mobility and self-driving travel will reach a record high, and the business passenger traffic will rebound in an all-round way. On January 16th, the Ministry of Transport said that it would take countermeasures in advance to ensure the organization, service and safety of passenger and freight transportation in Spring Festival travel rush.

  Li Yang, Vice Minister of the Ministry of Transport, said that during his stay in Spring Festival travel rush, he would strengthen the synergy between different modes of transport, promote the optimization of security inspection procedures for railways, civil aviation and urban rail transit, vigorously develop intermodal transport service products such as air-rail combined transport and Komba combined transport, and enhance the comprehensive transport service capacity.

  The transportation department will also strengthen the tracking and monitoring of key scenic spots, strengthen the information sharing of passenger flow and transportation capacity, and increase the transportation capacity in a targeted manner. At the same time, we will increase the care and attention of key groups such as "old and young, sick and pregnant", refine the implementation of humanized service measures such as ticket purchase and waiting, and comprehensively promote services such as online ticket purchase and self-service ticket inspection.

  Ensure the efficient and convenient passage of people’s livelihood materials

  During the period of Spring Festival travel rush, there is a strong demand for transportation of key materials, such as warm energy and people’s livelihood materials. The Ministry of Transport said on January 16 that it will comprehensively implement policies to ensure the smooth and orderly transportation of key materials and people’s livelihood materials.

  The Ministry of Transport has formulated a transportation guarantee plan to strengthen the emergency transportation capacity reserve to ensure the orderly transportation of key materials and people’s livelihood materials in emergencies. Strictly implement the "green channel" policy for the transportation of fresh agricultural products to ensure the efficient and convenient passage of all kinds of vegetables, fruits and other livelihood materials.

  The demand for new year’s goods increased, and there was a small peak in pre-holiday delivery.

  The State Post Bureau said on January 16th that the demand for delivery services fluctuated greatly during Spring Festival travel rush. On the eve of the Spring Festival, with the growth of the demand for new year’s goods delivery, there will be a small peak of business volume higher than the daily level. During the Spring Festival holiday, due to a large number of people returning home for the New Year and traveling abroad, the public’s demand for delivery services will be significantly reduced, and the business volume is also in a low season. After the Spring Festival holiday, the demand for delivery services will recover rapidly, and the business volume will gradually return to the daily level.

  During the Spring Festival, on the one hand, the State Post Bureau urged postal enterprises to continue to provide universal postal services. On the other hand, guide express delivery enterprises to scientifically predict the changes in business demand during the Spring Festival, ensure the maintenance of basic service capabilities during the Spring Festival, rationally arrange production and operation, timely announce service arrangements to the public and strictly fulfill the contents of announcements and commitments.

  The State Post Bureau will also strengthen the dynamic monitoring of post-holiday personnel’s return to work, actively help delivery enterprises to supplement their personnel strength in various ways, and urge terminal outlets and distribution centers to quickly restore their normal service capabilities to ensure the normal operation of the delivery service network as soon as possible.

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Is cell therapy reliable in treating cancer? CAR-T leads the world, and 10 popular and emerging cellular immunotherapy show their magical powers!

The incidence of malignant tumor is increasing year by year, which has become a common problem faced by human beings. Traditional treatment methods such as surgery, traditional chemotherapy and radiotherapy have always played a leading role in cancer treatment, but the effects of these treatments are limited. In particular, it is difficult for advanced patients to benefit from these treatments for a long time, nor can they fundamentally solve or change their quality of life. Therefore, researchers are increasingly focusing on the field of immunotherapy. Immunotherapy has brought new opportunities and hopes for the treatment of tumors, among which Immunocheckpoint inhibitors, therapeutic antibodies, tumor vaccines, immunomodulators, adoptive cell therapy, etc. Significantly improved the prognosis of cancer patients, and some patients with advanced cancer obtained long-term survival. In the past two years, many cellular immunotherapy have emerged and developed rapidly, which undoubtedly set off a wave of cancer treatment. So, is cell therapy reliable in treating cancer? In fact, immunotherapy has a history of more than 100 years, and it has only gradually entered the public’s field of vision in the last two years, and it has been absolutely recognized by the world oncology community.   

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A milestone in the history of cancer immunotherapy In 2013, Science magazine ranked the top ten scientific breakthroughs of the year, and immunotherapy topped the list. In recent years, immunotherapy is one of the hot spots in the research field of tumor treatment at home and abroad, and a large number of clinical studies have shown exciting results. Among them, Cellular immunotherapy uses the self-protection and killing ability of human immune system to achieve anti-tumor effect. Cells with immune function in patients are cultured and proliferated in vitro, and they are given the ability to attack tumor cells by technical means, and then they are imported into patients to realize their own anti-cancer. This therapyAgainst immune cells, not cancer cells.It is not as harmful to the patient’s health as surgery, radiotherapy and chemotherapy. Patients with early cancer can be treated directly, especially with the attack on residual cancer cells after surgery. Judging from the rapid development in scientific research and clinic in recent years, cellular immunotherapy is expected to become the fourth pillar of anticancer therapy in terms of accuracy, effectiveness and safety. Next, the small series of Cancer-free Home gives a general introduction and inventory of a variety of popular and emerging cellular immunotherapy in the biomedical industry, hoping to give cancer friends a general understanding of the general development process of this cancer treatment field. 

0one  CAR-T cell therapy

CAR-T therapy is chimeric antigen receptor T cell immunotherapy, which is a new precise targeted therapy for treating tumors. T cells are activated by genetic engineering technology, and the positioning navigation device CAR (tumor chimeric antigen receptor) is installed to transform the ordinary "warrior" of T cells into "super warrior" CAR-T cells, Specially identify tumor cells in vivo and kill tumor cells efficiently. So as to achieve the purpose of treating malignant tumors. At present, with 2021, Aquilencel injection, Regioscel injection. It was approved for listing in China, in 2022.Cedarchiorense was approved for listing by FDA.CAR-T therapy is expected to enter the blowout period. Indeed, CAR-T technology has shown good curative effect in many hematological tumors, such as leukemia, lymphoma and multiple myeloma, and more than half of hematologic cancer patients who are on the verge of despair and have no cure have achieved good curative effect.  

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CAR-T cell therapy has been listed at home and abroad at present.

Although the clinical effect of CAR-T therapy on solid tumors is not satisfactory, and it has even been sung down by some people, in recent years, CAR-T therapy has made outstanding progress in the fields of gastric cancer, liver cancer and pancreatic cancer. Scholars at home and abroad have made various modifications to CAR-T, and constantly found new targets for the treatment of various solid tumors.    

Clinical study on CAR-T therapy is out of the loop.

0one Gastric cancer and pancreatic cancer As the first CAR-T cell targeting Claudin18.2 in the world, CT041 emerged as early as the ASCO annual meeting in 2019. At that time, the total objective remission rate was 33.3%, which already surprised the world. Now the more remarkable curative effect is undoubtedly the icing on the cake! This clinical data shows a good treatment prospect for digestive system tumors!

Domestic CAR-T therapy CT041 first appeared in ESMO

Developed by Keji Pharmaceutical at the annual meeting of the European Society of Oncology (ESMO) in 2021.Targeting Claudin18.2(CLDN18.2)Autologous CAR-T candidate productsCT041Showing its presenceDigestive system tumorThe outstanding curative effect can be described as brilliant!

The research data is particularly eye-catching!

1. All patients’The objective remission rate was 48.6%, and the disease control rate was 73%.All patients with gastric cancerThe total objective remission rate was 57.1%.

2. Patients with gastric cancer who failed to receive at least 2 lines of treatment in the past:The objective remission rate was 61.1%, and the disease control rate was 83.3%.

3. And the overall tolerance is good!

As of March 3, 2022,CT041 became the first and only CAR-T cell candidate product in the world for the treatment of solid tumors, which entered the confirmatory phase II clinical trial.This is a milestone for CAR-T to conquer the solid tumor field. Congratulations!

In addition, there are many CAR-T cell therapies targeting CLDN18.2.0 2 liver cancer At present, the clinical trial targets of CAR-T in the treatment of liver cancer are mainlyGPC3 (phosphatidylinositol proteoglycan 3). The breakthrough research results completed by Professor Zhai Bo, director of the Department of Tumor Interventions, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, were published in the international authoritative journal Clinical Cancer Research on May 5, 2020. By July 24th, 2019, 13 patients had received CAR-GPC3 T cells with a median value of 19.9×108. All the patients are GPC3 positive, and they have received surgical treatment, local treatment or systemic treatment, and they all carry hepatitis B virus (HBV). Two patients achieved partial remission (PR). The 6-month, 1-year and 3-year survival rates of all patients were 50.3%, 42.0% and 10.5% respectively, and the median survival time (OS) was 278 days (39.7 weeks). At the ASCO annual meeting in 2021, Chinese medical researchers published the latest clinical research data of CAR-T drug targeting GPC3 (Ori-CAR-001) in the treatment of recurrent/refractory hepatocellular carcinoma for the first time. As of March 10, 2021, a total of 11 recurrent subjects who received cell infusion were included.All the subjects had advanced hepatocellular carcinoma, and none of them were effective after chemotherapy, TACE (transcatheter arterial chemoembolization) and targeted therapy.Of the 9 evaluable subjects,4 cases achieved partial remission (PR), 3 cases achieved disease stability (SD) and 2 cases developed disease progression (PD).The objective remission rate was 44%, and the disease control rate reached 78%.. 

02  Treatment of tumor infiltrating lymphocytes (TIL)

TILs therapy, simply speaking, is to separate and purify the lymphocytes in the tumor tissue after surgery, select the lymphocytes that can specifically resist cancer, and then amplify and activate them and reinfusion them. This kind of therapy has a history of more than 30 years, and it was first used for malignant melanoma. In recent years, it has given good data in many solid tumors such as cervical cancer and lung cancer.

This therapy is equivalent to pulling back veterans with combat experience directly from the battlefield. After a round of "political review" and "big competition" in professional ability, the spies and traitors are eliminated as far as possible, leaving the ones with the strongest fighting capacity, providing supplies, and then sending them back to the battlefield to continue fighting. Looking at the whole industry, the voice of "innovative therapy based on Tiles cells LN-144 (Lifelecel) is expected to be approved in 2022" is particularly loud. Tiles therapy, as an "ancient" cell therapy, is expected to usher in the first approved product this year, and its great potential in treating solid tumors can not be underestimated, with strong strength and relatively "out of the circle". TILs domain key node event     In 1982  

Steven A.Rosenberg and others discovered for the first time that TILs can inhibit the metastasis of melanoma cells in patients.

  1988  

The earliest attempt of TILs in clinical treatment: TILs therapy for metastatic melanoma achieved an objective remission rate of 60%.

  In 2011  

Steven A.Rosenberg and others published a phase II clinical research data in Clinical Cancer Research: the objective remission rate (ORR) and complete remission rate (CR) of patients with melanoma treated by TILs were 56% and 24% respectively.

  In 2012  

Melinda Bachini, a patient with advanced intrahepatic cholangiocarcinoma, is called the first patient to achieve complete remission (CR) after TILs therapy.

  2019  

At the ASCO meeting, the clinical results of innovative therapies LN-145 and LN-144(Lifileucel) based on TILS cells in the treatment of cervical cancer and melanoma have attracted wide attention in the medical field.FDA awarded LN-145 breakthrough therapy recognition.

  In 2021  

Phase I clinical results of TILs cell therapy at AACR meeting: among 12 evaluable patients.Non-small cell lung cancer patientsMedium,TIL therapy can achieve a total remission rate of 25%, among whichTwo patients achieved lasting complete remission.

  In 2021  

At the annual meeting of tumor immunotherapy association (SITC), the clinical research results of LN-145 in the treatment of metastatic non-small cell lung cancer (mNSCLC) showed that in 28 cases,In patients with recurrent/refractory mNSCLC,After LN-145 monotherapy,The overall remission rate (ORR) was 21.4%(1 case of CR and 5 cases of PR, including 2 cases of PD-L1 negative tumors), 12 cases were stable, and the disease control rate (DCR) was 64.3%.

03  TCR-T therapy

CAR-T cells and TCR-T cells belong to T cells modified by genetic engineering technology.Compared with CAR-T therapy, TCR-T therapy has unique advantages in the field of solid tumor treatment. TCR-T cell therapy can identify tumor-specific antigens from cell membrane surface or intracellular sources, and has entered clinical application from the initial basic immune research, showing initial efficacy in solid tumors, and has become the most likely T cell immunotherapy to make a breakthrough in the field of solid tumors! 

1、 TCR-T cell therapy in China has been approved for clinical use and has become a potential new therapy for HBV-related hepatocellular carcinoma!

At present, in addition to the global TCR-T in full swing in the research and development and clinical verification stage, China is also constantly breaking through innovation.

On December 22nd, 2021, CDE (Drug Evaluation Center) official website was able to inquire about the clinical application of "SCG101 Autologous T Cell Injection", which is a TCR-T cell therapy for specific hepatitis B virus (HBV) epitopes and a potential new therapy for HBV-related hepatocellular carcinoma (HCC).

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▲ Image source: CDE official website

2、 Advanced liver cancer ushered in a new dawn! TCR-T therapy makes cancer patients completely relieved.

As early as 2020 International Hepatology Conference (ILC), ADP-A2AFP, a new TCR-T therapy for liver cancer based on T cells, caused quite a stir, and also made a new breakthrough in the new therapy for liver cancer.

Among the included patients,One patient showed a complete remission (CR) in cancer progression, and the AFP of the other participants also decreased to varying degrees.This means that the experiment has made progress, and it also shows that this therapy is effective for the treatment of advanced liver cancer.

             

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All the 9 patients involved had undergone surgery and conventional radiotherapy and chemotherapy, but failed or became intolerant. Among the 4 patients who received the highest dose of treatment,One patient achieved complete remission, and CT scan showed that all the lesions in the patient disappeared, and it has lasted for more than half a year without any recurrence!

The best response of other patients (cohort 1, cohort 2) is stable. 1 patient in queue 2After one month of treatment, the volume of the primary lesion did not decrease, but the volume of mediastinal lymph node metastasis decreased obviously!       

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Therefore, TCR-T therapy targeting AFP (alpha-fetoprotein) can kill tumor cells expressing AFP. Based on the positive results of this study, researchers are expected to expand the maximum dose to 5 billion cells, and we look forward to the publication of updated data of this study!

04  CAR-NK therapy

In recent two years, in addition to CAR-T therapy, another new cancer cell therapy- Natural killer (NK) cell therapy It has also gradually attracted attention. The researchers said, NK cell As a cell anticancer therapy, it has more potential, and it may be safer, cheaper and faster. CAR-NK is to add a chimeric antibody to NK cells by genetic engineering that can recognize tumor cells and activate NK cells to kill tumor cells at the same time. 

one   The first "spot" CAR-NK clinical trial in China was approved by the Food and Drug Administration. On November 11, 2021, National Medical Products Administration Drug Evaluation Center passed an independent research and development in China. Mesothelin (MSLN) chimeric antigen receptor NK cells (CAR-NK) injection for the treatment of advanced epithelial ovarian cancer. Application for clinical trial of CAR-NK injection. According to the cancer-free home, This product is the first "spot" CAR-NK product of foreign origin in China. This also marks a new milestone in the research of immune cell drugs in the treatment of solid tumors in China! 

2  The 1-year survival rate doubled, and the curative effect of CAR-NK therapy in solid tumor increased sharply.

Recently, the journal Clinical Oncology Research published a phase II clinical trial for lung cancer. Heat shock protein 70(Hsp70) is highly expressed in about 70% of middle and advanced lung cancer. NK cells are activated by Hsp70 in vitro, which is equivalent to making NK cells meet their future enemies in vitro, "making enemies" first, and then returning them to patients, so that NK cells can formally fight with cancer cells in vivo. This method of stimulating NK cells with antigen peptides in vitro and giving them certain specificity is a hot topic in recent years.

A total of 16 patients with stage III non-small cell lung cancer were enrolled in this clinical trial. One group received traditional chemotherapy combined with radiotherapy and chemotherapy, and the other group received chemotherapy combined with Hsp70 pre-stimulated NK cell reinfusion.

The results show that:The one-year survival rate can be doubled from 33% to 67% by Hsp70 pre-stimulated NK cell reinfusion therapy combined with traditional radiotherapy and chemotherapy, and the preliminary results are encouraging.

Next, Xiaobian shows a typical successful case in combination therapy, as shown in the figure:After 1~2 months of treatment, the lung tumor completely disappeared and the curative effect has been maintained for 18 months.

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In addition to the above-mentioned clinical studies at home and abroad, CAR-NK cells also have a good effect on glioblastoma and neuroblastoma, specifically recognizing and killing breast cancer cells with high efficiency, and have a remarkable effect on multiple myeloma.

05  Dendritic cell vaccine

Cancer vaccine is a form of immunotherapy, which can prevent cancer from developing or kill existing tumors by stimulating or restoring the human immune system. Dendritic cell (DC) vaccine is a new biological therapy for malignant tumor in recent years, which has been paid more and more attention and recognized by oncologists. As an important member of the human immune defense system, Dendritic cells have the strongest antigen presenting function and are known as "sentinels" of the immune system. It is named because its cells extend outward with many dendritic protrusions. It mainly uses modern high-tech biotechnology to collect the peripheral blood of tumor patients, induce and cultivate a large number of dendritic cells in a short time in vitro, and equip them with immune cells that patients do not have, so as to accurately "target" and kill cancer cells. Not only that, It can also induce immune memory in patients, so that patients can obtain long-term anti-cancer effect.

DCVAC/LuCa is a dendritic cell vaccine developed by the United States for patients with non-small cell lung cancer.In a study on the first-line treatment of advanced lung cancer announced at the ASCO conference in 2019, DCVAC/LuCa vaccine combined with chemotherapy groupThe objective remission rate is 45%,The median overall survival time was 15.5 months, and the median progression-free survival time was 6.74 months.Reduce the risk of death by 46%!

In the Phase II clinical study of the latest novel dendritic cell vaccine DCVAC/LuCa (lung cancer dendritic cell vaccine) combined with standard carboplatin/pemetrexed in the treatment of advanced non-squamous cell (nsq) non-small cell lung cancer in 2022,The 1-year survival rate was 72.73% and the 2-year survival rate was 52.57%.By the time the data was published, the median overall survival time had not been reached. The median progression-free survival time was 8.0 months, and the objective remission rate was 31.82%.

  Prostate cancer-Provenge vaccine  

Provenge is the first vaccine approved for treatment in the United States, which initiated a new era of cancer immunotherapy.This is an autologous cell immunotherapy, which was approved by FDA on April 29, 2010 to treat asymptomatic or mild mCRPC. This approval marks the success of 20 years of unremitting efforts.In the United States, Provenge is the only FDA-approved immunotherapy for prostate cancer made from patients’ own immune cells.

  Ovarian cancer-dcvac/ovca vaccine  

At the 50th annual meeting of the Society of Gynecological Oncology (SGO) in 2019, the final result of SOV02, a phase II clinical trial, was announced: DCVAC/OvCa, an immunotherapy based on dendritic cells, was added to standard carboplatin and gemcitabine schemes for patients with recurrent, platinum-sensitive and epithelial ovarian cancer.It can prolong the overall survival (OS) of patients with advanced recurrent ovarian cancer by more than one year.andDCVAC/OvCa reduced the death risk of second-line treatment of ovarian cancer by 62%. The overall survival (OS) increased significantly by 13.4 months. The median progression-free survival rate (mPFS) increased by 1.8 months. The global phase III study will be launched soon.

Melanoma-TLPLDC vaccine

The subgroup analysis results of the phase IIb clinical trial of TLPLDC vaccine in the treatment of melanoma were published at the ASCO-SITC Clinical Immunooncology Conference in 2020.

In that population analysis follow the clinical research protocol (PT), compared with the comfort unit,The 24-month disease-free survival rate in TLPLDC treatment group was significantly improved (62.9% vs 34.8%), indicating that the relative risk of disease recurrence was reduced by nearly 50%.

In the population analysis of Intentional Treatment (ITT),There was no significant improvement in 24-month disease-free survival between TLPLDC treatment group and placebo group (38.5%) vs 27%),But in this analysis,The improvement trend of 24-month overall survival rate (OS) was stronger (86.4% vs 75.1%)..

  Kidney Cancer-Ilixadencel Vaccine  

Ilixadencel is an allogeneic dendritic cell (DC) vaccine. Research shows that,Ilixadencel combined with targeted anticancer drug sunitinib(Sotan, common name: sunitinib)First-line treatment of newly diagnosed advanced metastatic renal cell carcinoma(mRCC)Compared with patients treated with sunitinib alone, the total remission rate is doubled, the complete remission rate is higher and the remission is more lasting!

  Glioblastoma-AV-GBM-1 vaccine   On June 8, 2021, well-known foreign biomedical companies announced the release of phase II clinical trial data of their personalized cancer vaccine AV-GBM-1. The research shows that this new vaccine has great potential for prolonging the overall survival of newly diagnosed glioblastoma patients in the medium term. The median progression-free survival time of patients was 10.4 months, which was about 50% higher than the median progression-free survival time of 6.9 months in the landmark STUPP study, and established a nursing standard for newly diagnosed glioblastoma patients.     Non-small cell lung cancer-tedopi vaccine  

On April 1st, 2020, a new anti-cancer vaccine, TEDPI, achieved positive results in the phase III clinical trial of non-small cell lung cancer. After the immune checkpoint inhibitor (PD-1) was resistant or failed, all patients in the group used TEDPI vaccine in the second or third line, and the overall survival rate for one year reached 46%, far exceeding the preset 25%!

A 54-year-old patient with advanced lung cancer has rapidly shrunk (from 39mm to 23mm) after five injections of the new lung cancer vaccine. At the time of reporting, his survival time has exceeded 20.6 months, and he is still being followed up.

06  CIK cell therapy

  CIK cells, that is, Cytokine-Induced Killer (CIK), are a new type of immunocompetent cells, which have strong proliferative ability and cytotoxicity, and have certain immune characteristics. Because this cell expresses both CD3 and CD56 membrane protein molecules, it is also called NK cell (natural killer cell)-like T lymphocyte, which has both the strong anti-tumor activity of T lymphocyte and the non-MHC-limited anti-tumor advantage of NK cell. If NK cells are the "first line of defense" to protect human health, then CIK cells are undoubtedly the "precision missiles" to kill tumor cells. Especially for patients after surgery or radiotherapy and chemotherapy, it can eliminate residual tiny metastatic lesions, prevent cancer cells from spreading and recurring, and improve immunity. Therefore, CIK cells are considered as the first choice for a new generation of adoptive cellular immunotherapy for tumors. Research progress of representative CIK cell therapy     

nasal pharyngeal cancer  

Among 137 patients with nasopharyngeal carcinoma treated by CIK, 50% of them improved their survival time by 6-9 months, and among 137 patients treated by CIK, 50% of them delayed their tumor progression by 6-7 months.

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  liver cancer  

Among the 819 patients with liver cancer treated by CIK, 50% of them improved their survival time by 13~25 months, and among the 819 patients treated by CIK, 50% of them delayed their tumor progression by 4~7 months.

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  ovarian cancer  

Among 72 patients with ovarian cancer treated by CIK, 50% of them have improved their survival time by 24 months. Among 72 cases of ovarian cancer treated by CIK, 50% of ovarian cancer patients delayed their tumor progression by 14.5 months.

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carcinoma of colon

Among 126 patients with colon cancer treated by CIK, 50% of them have a longer survival time of 30 months. Among 126 patients with colon cancer treated by CIK, 50% of them delayed their tumor progression by 14.5 months.

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  breast cancer  

The probability that the survival time of 150 breast cancer patients treated with CIK can reach 5 years is increased to 85.7%; The probability of keeping breast cancer from recurring in 150 breast cancer patients treated with CIK within 5 years increased to 72.3%.88231650935357798

  Solid tumor  

Of the 31 patients treated with PD-1 antibody combined with DC-CIK, 2 patients’ tumors completely subsided and 5 patients’ tumors partially subsided. Of the above 7 patients, 6 patients’ effects can be maintained for 5 months. The tumors of the other 13 patients remained stable.

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  renal carcinoma  

Among 43 patients with advanced renal cell carcinoma treated by CIK, 50% of them can delay the tumor progression to 14.7 months.

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07  CAR-M therapy 

In recent years, the study of macrophages has also been paid attention to by the industry. How to activate the anti-tumor activity of these macrophages is the direction that immunologists have been working hard. CD47, an immune checkpoint on macrophages, has become a very promising hot target in the field of tumor immunotherapy.

In a recent study published in Nature Biotechnology, researchers from perelman Medical College of the University of Pennsylvania and other research institutions may have an alternative to T cell therapy to overcome these challenges. Their research shows that genetic modification of macrophages (an immune cell that devours intruders in vivo) may be the key to developing effective cell therapy for solid tumors. They were able to confirm these genetically modified expressions. The macrophages of CAR (CAR-M) can kill tumors in human samples and mouse models in the laboratory and prolong their life.   

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CAR-M therapy is centered on macrophages, which devour invading cells instead of destroying them like T cells. T cells are more like Space Invaders games, while macrophages are more like Pac-Man games. Another major difference between macrophages and T cells is that they are the first responders of the body to virus infection. Historically, this poses a challenge in trying to genetically modify them to attack cancer, because macrophages are not easily transfected by standard viral vectors used in gene therapy and cell therapy.

In this experiment, the research team used genetic engineering technology to transform macrophages. They not only expressed CAR targeting HER2 antigen, but also were activated and differentiated into M1 macrophage types that promoted inflammation. In this way,These CAR-M cells can not only target tumor cells, but also change the microenvironment near tumors by secreting pro-inflammatory cytokines. They can also present tumor antigens to T cells and activate T cells’ immune response to tumors, which can be described as "killing three birds with one stone".

On March 18th, 2021, Carisma Company of the United States announced the completion of the first drug delivery to the subjects of CAR-M therapy (CT-0508) targeting Her2, marking a new era of CAR-M transformation therapy for solid tumors. In a word, taking macrophages as effector cells transformed by CAR is expected to reverse the tumor inhibitory microenvironment, so as to break through the obstacles of immune cell therapy in solid tumors. 

08  CTL (cytotoxic T lymphocyte) therapy

What cell therapy can be used as an adjuvant therapy for the majority of patients with inoperable advanced cancer? In recent years, researchers have been developing new immunotherapy schemes for these patients, including CTL(cytotoxic T lymphocytes) technology. This technology mainly uses protein, which is unique to cancer cells and has no or low content in normal cells, as bait to select the truly anticancer lymphocytes in peripheral blood, and then further improve and amplify them in vitro, and then return them to patients. MTCA-CTL immunotherapy is a new generation of biological immunotherapy model introduced in China. While ensuring the expansion of non-MHC-restricted killer NK-T cells, directional expansion of HC-restricted CD8++specific CTL cells can make its proportion in cell products reach 60% ~ 70%. The combined effect of this killer cell makes the efficiency of killing tumor cells higher.  

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At present, the multi-target compound antigen peptide biological immunotherapy technology, which is undergoing the second phase of clinical trials in the Cancer Hospital of China Academy of Medical Sciences, is the fifth and brand-new generation of cellular immunotherapy technology, which can optimize the activation method of DC (dendritic cells) to enhance the killing effect of immune cells on tumor cells. At present, it has achieved good clinical results and I believe it will really benefit cancer patients.

Mainly suitable for solid tumors.Head and neck tumor, esophageal cancer, lung cancer, gastric cancer, breast cancer, liver cancer, membranous adenocarcinoma, colorectal cancer, ovarian cancer, uterine cancer, coma cancer, prostate cancer, malignant melanoma, sarcoma and partial malignant lymphoma.

If economic conditions permit and you want to consult MTCA-CTL therapy, you can contact.Cancer-free Home Medical Department (400-626-9916), a detailed assessment of the condition.

09  CAR-NKT therapy

  Natural killer T cells (NKT) are a group of special T cell subsets that express both T cell receptors (TCR) and NK cell receptors on the cell surface, and can produce a large number of cytokines. Such as IL-4 and INFγ. These cells can not only directly dissolve and kill tumor cells, but also play an anti-tumor role through indirect ways (secreted cytokines, activated immune cells, etc.). Recently, a phase I clinical trial jointly conducted by Baylor Medical College in Houston and Texas Children’s Hospital is evaluating a new treatment for children with recurrent neuroblastoma –CAR-NKT cell therapy is expected to break through this bottleneck. Phase I trial, code-named GINAKIT2, used CAR-NKT cells for the first time to treat recurrent neuroblastoma. Eleven children (1~21 years old, with an average age of 7 years old) were all recurrent/refractory high-risk neuroblastoma, with extensive metastasis and no better treatment plan in clinic. The results are very encouraging: Of the 11 advanced patients, The condition of 4 patients was stable, 2 patients achieved partial remission (tumor was obviously reduced), and one of them had complete remission (CR) after receiving the second CAR-NKT cell infusion. In safety, CAR-NKT is safer than CAR-T therapy. No dose-limiting toxicity was observed in the first 28 days after infusion. 

10  Compound immune cell therapy

This technology will alsoSix kinds of cells, such as γδT cells, NK cells, NKT cells, killer T cells, dendritic cells and helper T cells.Activate, multiply 10 million to 20 million cells to 2 billion to 5 billion cells, and then inject them into patients. Cultivating such important immune cells at the same time greatly improves the therapeutic effect compared with single treatment.

Except for some leukemia and malignant lymphoma,It can be used for the treatment of most cancers, and has a good effect in refractory cancer types and advanced cancers. Besides,Compound immune cells also play a great role in improving immunity and strengthening the body.

Xiaobian has something to say

In recent years, due to the development of medical level, new cancer treatment methods have appeared one after another, among which cellular immunotherapy is in full swing, which brings new hope to cancer patients. According to the latest statistics, compared with patients with advanced lung cancer, gastric cancer and liver cancer who only receive surgery, radiotherapy and chemotherapy, adjuvant cellular immunotherapy can prolong the survival time of patients and significantly improve the data effect. In fact, tumor treatment is actually a complex "project", and it is difficult to achieve good results by relying solely on a certain treatment method. Tumor treatment needs the cooperation of various treatment methods to achieve the final victory in the fight against cancer. 

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Beijing issued a yellow warning for thunder and lightning, with short-term strong winds and small hail of magnitude 7 and 8 in the local area.

According to the Beijing Meteorological Bureau, it is estimated that there will be thunderstorms in most parts of the city from 17: 00 on the 4th to 02: 00 on the 5th, with strong local short-term rain, accompanied by short-term gale and small hail of magnitude 7 and 8. Please take precautions.

Defense guide

(1) the local people’s governments at all levels, relevant departments and units shall do a good job in lightning protection according to their duties, and organize the inspection of lightning strike hidden danger units or departments;

(2) Parks, playgrounds and other open-air places should stop outdoor facilities and guide visitors to safe places;

(3) Outdoor activities (sports) such as mountaineering, sports, farming, swimming and fishing should be stopped, and buildings with lightning protection devices should be avoided in time;

(4) Don’t take shelter from the rain under big trees, stay away from tall buildings such as towers, chimneys, telephone poles, billboards, etc., don’t stay at the top of the mountain, ridges, roofs, watersides or open areas, and don’t use mobile phones;

(5) Don’t carry an umbrella in the open field, and don’t carry farm tools, badminton rackets, golf clubs, especially objects with metal on your shoulders. You should squat down in low places to reduce your body height.

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Shikeng Village in Minhou: "Hollow Village" Diechanged to online celebrity Village.

Look for business opportunities

 

Take the road of summer vacation and health care


The "Benefit Project" dangerous building reconstruction project has successfully gathered the hearts of the whole village, and the road to revitalizing the countryside has become wider and wider since then.



In Shikeng Village, there is the second parents’ canteen in Tingping Township. The elderly in the village can enjoy three meals a day only by paying 200 yuan’s food expenses every month, and the insufficient part is helped by the voluntary donations and materials from the rural sages.



The old man dined in the second parents’ canteen in Tingping Township. Photo by Pan Huijing (data map)

 

"In addition to the elderly in the village, elderly people who come to travel for the summer can also eat here." Lai Qiwu, secretary of the Party branch of Shikeng Village, said that this elderly canteen is an important part of the village to build a migratory bird-style summer resort.

  

In recent years, the migratory bird-style summer vacation and health care model has become an important selling point for Tingping Township to build a brand of old-age care. The so-called migratory bird-style summer resort is to migrate to a place suitable for one’s life like a migratory bird according to the changes of seasons before the arrival of cool summer and severe winter. Shikeng village is one of the hot villages in this model.

  

In Shikeng Village, there is the highest mountain in the county-Niumu Mountain. The ancient trees in the mountains are intertwined with cangteng, and the strange peaks are on a par with the dangerous rocks. There are landscapes such as the first sight, camel peak, Yuzhu peak, Jiangjun rock and Kongmingyan. There is no heat in summer and no ice in winter here, and it is known as "Xishuangbanna" in Bamin. Every summer, more than 5,000 tourists come to visit, and more than half of them are middle-aged and elderly people. Seeing the business opportunities, the two committees of Shikeng Village decided to rely on good natural ecological resources to focus on developing recreational tourism.

 

LaishiTourists visiting Keng Village.

 

In order to wake up the "sleeping" land resources, the party branch of Shikeng Village threw an "olive branch" to the rural sages. In 2019, Lai Qiming, a rural sage, returned to his hometown to take the lead in setting up Fengjing Eco-agriculture Company to build a vegetable planting base in Shikeng, and adopted the development model of "cooperative+farmers" to transfer more than 400 mu of land for planting cauliflower, corn, eggplant, loofah, etc., and develop the high-quality vegetable planting industry in the mountains, with an annual output value of about 2.4 million yuan. This effectively solves the problem of farmland abandonment, realizes agricultural efficiency and income increase, and also provides a good place for tourists who come to Kangyang to experience the four seasons farming.

 

Luffa in Shikeng vegetable planting base.

 

In order to improve the living experience of tourists, the two committees of Shikeng Village actively mobilized the township leaders to contract the idle houses in the village and transform them into characteristic homestays on the basis of building five homestay cabins. Many villagers have changed the old idea that they would rather let their old houses go to waste than rent them to others. Like fellow villagers, they have transformed their old houses into characteristic homestays, adding icing on the cake to the development of their hometown.                 

                                 

Characteristic homestay. Source: Meeting Minhou

  

With the increasing passenger flow, more villagers are willing to participate in creating a strong welcoming atmosphere, and public welfare performances organized by Tingping Township Party Committee and government from time to time often come to the village. Since then, it is common for villagers and tourists to make dumplings, cut rice, sing red songs and learn calligraphy together. The migratory bird-style summer vacation and health care model has increased the annual income of each villager by at least 3,000 yuan.  

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January net text book list | mainly cool

 [Editor’s note]Through the superficial phenomenon of "little white" in online literature, many works with equal emphasis on entertainment and ideology have been born. This book list will introduce a more diverse online world, from the unpopular to the popular, from the small crowd to the public, and those outstanding works of various types.

Simple Martial Arts Yang Pan

A novel and far-reaching collection of martial arts short stories

My friend asked me to recommend a Jin Yong fan, on the condition that I was "most impressed". There are so many derivatives of Jin Yong’s works that I have seen, and the interpretation is as wonderful as Six Gods Lei Lei, and the fan works are like "Boys Here" in Jiangnan, but the first thing that comes to my mind is a short story of Little Soldiers, which is simple and wonderful.

Perhaps this collection of short stories was particularly popular at that time. Simple Martial Arts is a collection of short stories of martial arts, and The Tale of Little Soldiers is one of them. The whole writing style is unpretentious, the writing style is simple and concise, and it has a strong humanistic spirit, paying attention to the fate of the little people, but its conception is novel and far-reaching. "Every article is an answer to’ What else can martial arts write?’ Structurally, these short stories are full of air and impeccable; Ideologically speaking, it seems to be Lu Xun’s essays, like daggers and spears, which plunge into your heart and make you heartache, and then urge you to think in heartache. "

In addition, by the way, old book lovers should know that Yang Pan’s most famous work is The Beijing War. Wen Ruian once commented on the book, "His works are moving and shocking, and his writing is surprisingly simple and beautiful. He strictly abides by the’ three unifications’ of western dramas, describes them, and writes them to the best of China’s traditional novels."

Recommendation index, five stars, recommended to book lovers who like martial arts works.

"I became a koi fish" Daniel Qin

Recently surprising innovative Chinese entertainment articles

The author’s new book, The Bad Star, after the precipitation of two previous works, has become more proficient in skills and obvious in brushwork, which surprises people from creativity to plot.

The protagonist started from a very high starting point and took the acting route. He appeared as a sophomore in Chinese opera, became an actor in the National Theatre, made his debut as a young master in the drama Thunderstorm, and then participated in The Birth of an Actor as an acting instructor and entered the entertainment circle. koi fish, the golden finger, is a system to realize other people’s wishes, which can passively fulfill their wishes and increase their acting skills.

Generally speaking, the story of the novel is smooth, the rhythm is compact, the cool points are dense, the golden finger is interesting, and the starting point is novel. The story of Tik Tok makes people feel cordial, and the description of acting and characters is lively and interesting, which is very professional.

The recommendation index is four stars, and it is recommended to middle-aged and old white book lovers who like Chinese entertainment. This book is regarded as a very good work among middle-aged and old white readers recently, and it is worth a try.

My Time and Space Hostel Golden Jasmine Flower

The relaxed daily flow of the city at the gate of time and space is similar to the anti-wear of The First Chaos in History.

At the beginning, the protagonist’s parents died in a car accident, leaving a sister and a small hotel, which, in the words of book lovers, means "parents are dead, younger sister has a house", and then accidentally found a time-space door leading to multiple time and space in the small hotel, so visitors from different circles came to visit, and the creativity was somewhat similar to "The First Chaos in History", but the selling point was different. "Chaos" was mainly light and funny, and the book was mainly warm and daily.

By running a hostel, the protagonist receives all kinds of people from different circles, from the wise magical sage to the stupid and cute woman, the fake mother mage, and the cute pet from other circles … Learning all kinds of knowledge, knowledge and methods, the shaping of each character is very distinctive, which can be considered as the biggest highlight of this book.

Generally speaking, the author’s writing style is mature, the novel style is warm, the plot is slightly dull and the pace is a bit slow. There is also a lot of controversy about the shaping of Jiaojiao’s younger sister, so it is best to pay attention to the children’s shoes you want to see. Personally, I think this book is still worth reading, but it is best to keep a casual attitude. If you are bored, you can abandon the book for a while without affecting it.

The recommendation index is four stars, which is recommended to book lovers who like the daily warmth of the city.

"[Comprehensive Martial Arts] Holy Monk" is soft on the tripod.

Comprehensive martial arts system with slow work and fine work

In a sense, this book is also a closet work, similar to seventy-two changes of the Dungeon, strategic angel, live broadcast of the western regions of Datang, the devil’s wheel and the eight barren records of mountains and seas, which have been recommended before, and are not new books in the general sense! Although the book has been updated for a year and a half, the number of words is still only 400 thousand words. The so-called lifetime series. Apart from the slow update, the only thing these books have in common is that they are slow to work and fine in work, and the quality is excellent.

This is a comprehensive martial arts article written by a female author about a male master. The protagonist is a former demon leader with a holy monk system, a proper male god and a true holy monk, so there is no cp. Well, simply explained, it is the kind that others like the male master, but the male master doesn’t like others. The author’s writing is excellent, the details are brilliant, the feelings are delicate, the characters are distinct, and the plot is smooth. He doesn’t sell sheepskin to hang dog meat. The novel begins with practicing in the Shaolin Temple, which is a copy of Eternal Heaven. It is worth mentioning that the imitation of the soft Jin Yong style on the tripod is particularly good, and Zhao Min is really super cute!

Recommended index, 4.5 stars, except for the slow update, this book basically has no big shortcomings. Finally, I will give you a reassurance. This book has no hidden bl tendency, so please rest assured for normal readers to watch it.

The sword of dawn: the far pupil

A relaxed and humorous industrial farming text of the magic guide wind in the other world

The new work of the Great God of the Far Pupil, through the bright performance of Hilling Empire and Unusual Creatures, believes that the strength and character of the big eyeball are beyond doubt! Adhere to your own style of second-dimensional hard science fiction, not blindly follow the trend, the brain hole is king, humorous, and self-contained.

After crossing, the protagonist drifted for more than 100,000 years, found a body to climb out of the coffin, and watched the territory fall. He could only play the role of ancestors and later generations to guide the industrial revolution from scratch in the Middle Ages, use magic technology to produce and build territory, and at the same time explore the secrets buried by history around the territory, farm and solve puzzles all the way, and uncover the mysteries of the world little by little, which is very enjoyable to read.

Generally speaking, it continues the author’s humorous writing style, with unconventional stories, interesting brain holes and cheerful spit. A large number of original jokes make people shine at the moment, and all kinds of suspense are fascinating, especially in building the world. There are a lot of magic principles in the writing, but too many theoretical descriptions, on the one hand, give hardcore readers a deeper sense of substitution, on the other hand, will also lead to a sense of separation in the plot.

Recommended index, four stars, recommended to readers who like brain holes, like farming, like light and humorous writing, and can adapt to the unique style of writing in Yuantong. Yuan Tong’s books are neither the ups and downs that make people want to stop, nor the plain daily life. They can always get a sense of satisfaction in the words they talk about. If you can accept his style, you will like it very much, otherwise it will be very uncomfortable, and the polarization is serious. I suggest you try it. Personally, I like it very much.

"Glory to France" regardless of whether it is filled in or not.

Western historical hegemony with both entertainment and popular science

The old author who wrote "In the Name of Revolution" and "The King of Guns" returned to foreign history this year, saying that he would die in France, so he went to the palm reading platform and opened a new book "Glory to France".

The novel was started with the revolution in 1789, and the protagonist was born as a lawyer. He started from politics and used his power to gain money. Then he climbed the scientific tree to collect his younger brother for farming and training. The plot, characters and the restoration of the times have reached a certain level, and the characterization is true and credible, which is in line with the background of the French Revolution.

"From the price fluctuation of bread to the spread and control of grape diseases, the application and promotion of steam engines in France, the products and riots in the West Indies, salons and political parties, everything is all-encompassing", the overall westernized style of writing, the plot is reasonable, the historical development context is clarified, and the true face of the Great Revolution period is restored, which is both entertaining and popular. It’s my favorite kind of writing, good and cool. I don’t think it’s a problem to say that this book is the biggest surprise in foreign history in the past two years.

The recommendation index, 4.5 stars, is recommended for children’s shoes who want to know about the French Revolution through novels.

The Unspeakable Diary: The Farewell of the Sad Man

Decryption of Game Novels by Running Group in Cthulhu Background

The setting is somewhat similar to "Thriller Paradise". The story is made up of a series of games whose copies are decrypted, but these copies of this book will be mapped to reality. Once the tour group fails, it is possible to make the scenes and evil spirits realistic, that is to say, the game will invade reality. The novel is slippery because the author says that I am crazy and even dare to push evil spirits …

The style of writing is generally big, Cthulhu is the main theme, and the story of the running group is more interesting. There is a smell of joy, all kinds of game stalks, and the lines are full of jokes. It may be based on the real running group to write the story, so it is more dramatic than the deliberately designed story, and it is easy to tear up the card and send it … It is also full of fun to watch the investigators and KP fight with each other.

It should be noted that the author started with the story of running a group, but did not explain the rules of running a group game in the book. It was just that all kinds of roll points were judged, which was very unfriendly to book lovers who didn’t know the group. Friends who read books at the starting point can open this chapter and say that there are some knowledge of running a group, otherwise there will be more reading obstacles. If there is no relevant background at all, then the various minority nouns and stalks in the text are extremely probable events.

The recommendation index, 3.5 stars, is recommended to book lovers who like curiosity, group running and Cthulhu works.

"Walking into Cultivating Immortals" My Taoist priest is not alone.

A scientific explanation of the other kind of scholar-tyrant Xianxia’s prose

Since the date of serialization, the novel has been controversial. From the initial graffiti to the gradual improvement in the middle period, it fell into an embarrassing situation of improper quotation, and persisted after regaining confidence. As an alternative academic essay that uses scientific analysis to cultivate immortality, it can be regarded as creating a new genre of scientific cultivation of immortality.

The novel tells the story of a science student’s cultivation of immortals and teaches you how to cultivate immortals scientifically. The language is relaxed, the style of writing is light, and the creativity is similar to the previous "Olympiad", which turns many famous jokes in the scientific community into novel bridges … For example, Darwin, the god of natural selection, and Newton, a man of great power …

Generally speaking, the creativity is good, and the brain hole is very big. It quotes a lot of scientific research terms and theories that make people feel unclear, and ridicules some existing Xianxia articles from the routine and spirit. If the brain waves are right, they will like it very much, otherwise it will make people feel self-satisfied … The "modern law" in the novel is constantly improving, so the development world outlook that is better than the "ancient law" makes me feel bright.

Four stars, recommended to book lovers who like this type of scientific analysis and revision.

"Dominate Hollywood" Yujing Cooking Incense

One of the best female entertainment articles in the history of online writing.

Entertainment is one of the most vital branches of urban novels in recent years, with a hundred flowers blooming and powerful people coming forth in large numbers, among which Chinese entertainment and American entertainment have the most excellent works and the greatest influence. Among the American entertainment articles, the only one that can have a high reputation among both men and women, and is well-received and well-received, is this book "Dominating Hollywood", which has an excellent reputation for killing both men and women. I am afraid that the only one that can compete with the Chinese entertainment articles is "Literary Age".

This is an atypical Jin Jiangwen about the career direction of the female host. More than ten years ago, a broken white family started from Hollywood and fought back all the way in Hollywood with memory and golden fingers. The author has a sophisticated style of writing, a strong sense of pictures, very detailed information, a large number of classic films and self-made films, and excellent integration into the plot, clear priorities, orderly, story-telling ability, writing skills, amazing. The characterization is excellent, the hostess is diligent, totally honest, the emotional drama is mature and realistic, the dialogue is wonderful, witty and interesting, and the film description and career part can be called fairy grass! The title of the novel is "Dominating Hollywood", "In fact, it is a modern woman’s road to self-discovery and growth". Looking at it all the way, this is by no means an ordinary online cool article.

It may be a little melodramatic, but in the end, I still want to emphasize that although this book is exquisitely written, with many climaxes, brilliant characters, numerous dry goods, reasonable deduction and a natural turning point, the protagonist’s struggle is so positive, but the hostess still lets me substitute, especially when watching emotional dramas, not to mention how awkward it is … But the author really has great skills and wants to give up many times, but he can’t bear it, so he looks at it awkwardly.

Let’s end with the words of Fengyuyue. "Jinjiang Literature City is a magical plane. In addition to mass production of poisonous weeds that are high-energy for straight men, one or two fairy grasses suitable for all-round reading will be intermittently born. This book is one of them."

Recommendation index, five stars, if I only read three beautiful entertainment articles in my life, I think this one is definitely one of them.