The curtain call of "medicine king"! Trillion drug-free track opens a new competition

The year 2023 is of great significance to the drugs for autoimmune diseases and even to the global innovative drug market. With the expiration of patents in key markets, Hummel (adalimumab) will officially hand over the title of global sales champion for 11 years, and the first generation of "drug king" will officially end.

Due to the complex pathogenesis, the number of patients with autoimmune diseases is large and it is difficult to cure. The long-term or even lifelong demand for drugs has spawned a huge market for autoimmune drugs, which has become a hotbed for the growth of heavy drugs.

Under the demonstration effect of "drug king", major pharmaceutical companies around the world have been scrambling for layout in recent years. At present, breakthroughs have been made in the development of new drugs for potential targets such as JAK and interleukin, and the free drug track is expected to usher in a new round of competition. Local innovative drug companies try to gain a place in the domestic free drug market through differentiated distribution of indications and continuous optimization of safety.

The market for self-exempted drugs continues to grow steadily.

Autoimmune system diseases refer to diseases caused by immune response to autoantigens and self-tissue damage. Genetic defects and environmental factors are all important links in inducing autoimmune diseases. The complex disease mechanism leads to a wide variety of autoimmune diseases and a large patient base. At present, there are more than 100 known main disease types, including psoriasis, atopic dermatitis, compulsory spondylitis, rheumatoid arthritis and systemic lupus erythematosus.

As a chronic disease, autoimmune diseases usually do not directly kill people, but it is also difficult to cure them. Such as compulsory spondylitis, systemic lupus erythematosus, etc., once suffering from it, it will be difficult to reverse, which is called "undead cancer". Patients need long-term or even lifelong medication, thus giving birth to the long-term and stable growth of market demand for self-immune drugs.

Based on the financial report data of major pharmaceutical companies, in 2022, there were 22 self-disease-free drugs in the list of TOP100 drugs with global sales scale, of which 10 drugs exceeded $3 billion and the total sales exceeded $70 billion.

According to the statistics of AARDA, patients with autoimmune diseases account for 7.6%-9.4% of the global population in recent years. Jost Sullivan’s statistics show that there are nearly 500 million patients with various kinds of self-immune diseases in the world, and the global self-immune drug market will reach about 132.3 billion US dollars in 2022, which has become the second largest disease market after cancer.

Jost Sullivan predicted that by 2030, the global self-exempted drug market is expected to reach US$ 176 billion, with a compound annual growth rate of 3.6% from 2022 to 2030. Among them, the self-exempted drug market in China is expected to reach nearly US$ 25 billion in 2030, a tenfold increase compared with 2020, which is an important incremental source of global self-exempted drugs.

The "King of Medicine" made a curtain call, and new drugs rose one after another.

Treatment strategies for autoimmune diseases include inflammation alleviation and immunosuppression. Although non-steroidal anti-inflammatory drugs, corticosteroids and anti-rheumatic drugs have good anti-inflammatory effects, they are difficult to fundamentally stop the development of the disease, and they are easy to relapse after stopping taking drugs. However, traditional non-selective immunosuppressants such as cyclosporine and methotrexate are not only slow to take effect, but also lead to a higher risk of cancer. As new immunosuppressants, bio-targeted drugs can selectively suppress the immune system, ensuring the safety while improving the curative effect, which is the most promising.

Hummel is a fully humanized monoclonal antibody against TNF-α developed by AbbVie Company, which was approved by FDA in 2002 for the treatment of rheumatoid arthritis. Because of its remarkable efficacy and safety in the treatment of self-immune diseases, Hummel’s indications have been expanding since its listing, and it has gradually become the highest-selling self-immune drug, and ranked first in global drug sales in 2012. Since then, through a series of marketing and patent strategies, AbbVie has made great efforts to extend the life cycle of Hummel, and promoted the drug to become the "drug king" in the world for ten consecutive years, with accumulated sales exceeding 200 billion US dollars since its listing.

With the official expiration of the patent in the United States in 2023, the market share of self-exempted drugs controlled by Hummel was quickly robbed by many similar biological drugs. According to AbbVie’s third quarterly report in 2023, nearly 10 biologically similar drugs have entered the market. As a result, the cumulative sales of Humele in the first three quarters of 2023 was only $11.1 billion, a sharp drop of 29.1% year-on-year. Nature Reviews Drug Discovery, a well-known medical journal, predicts that the annual sales of Hummel in 2023 will be about $13.6 billion, less than 60% of Keytruda of Top1, and the first generation of drug kings will soon "abdicate".

Corresponding to the curtain call of "King of Medicine", many innovative drugs with potential targets have risen rapidly, and a new generation of heavy drugs is coming out.

According to the global sales forecast of innovative drugs in 2023 recently released by Nature Review of Drug Discovery, the sales of self-immune biological agents Dupixent and Stelara, which target IL-4/IL-13 and IL-12/IL-23 respectively, have increased rapidly, and it is estimated that they will rank among the Top10 with sales of more than 10.6 billion US dollars.

Abbey, the owner of Hummel, is also actively looking for the next generation of self-free drugs. The sales amount of oral JAK1 inhibitor Rinvoq (upatinib) and IL-23 monoclonal antibody Skyrizi (risazhuzumab) under the company has increased rapidly in recent years. In 2022, the total sales revenue has exceeded 7 billion US dollars, and the growth rate is higher than 50%. Abbway predicts that by 2027, the combined sales revenue of these two drugs is expected to exceed the sales peak of Hummel’s $20 billion.

Domestic pharmaceutical companies compete for the next potential target.

Compared with the highly competitive innovative cancer drugs, the number of participants and innovative drugs in the self-exempt drug market is still relatively limited, and the overall market competition pattern is good. However, the huge unmet clinical needs and the continuous improvement of the diagnosis rate in China have also attracted more and more domestic innovative pharmaceutical companies to enter the drug-free track, and tried to gain a competitive advantage by virtue of differentiated layout potential targets and occupy a place in the domestic market.

So far, the targets of self-immune targeted drugs mainly focus on TNF-α, JAK, interleukin and BlyS, and the main indications are common rheumatoid arthritis, psoriasis, systemic lupus erythematosus and so on. Among them, targeted TNF-α drugs are the most classic targeted drugs for autoimmune diseases because of their early market time, mature targets and the widest range of indications. However, this track has basically been controlled by foreign-funded enterprises, and the development space of local manufacturers that follow is relatively limited. Domestic innovative drug companies have turned their research direction to JAK, interleukin and other targets.

Interleukin and its receptors are important target families in human immune regulation, and play an important role in various immune and inflammatory reactions. Psoriasis is the main indication of interleukin targeted drugs at present, and some targeted drugs have been proved to be safer than TNF-α antagonists in certain circumstances.

At present, the effective interleukin-targeting drugs listed in the world include tosilizumab targeting IL-6, ulinuzumab targeting IL-12/23, skukiyuzumab targeting IL-17A and gusechizumab targeting IL-23. Among domestic enterprises, Hengrui Pharma (600276.SH), Zhixiang Jintai (688443.SH) and Kangfang Bio (09926.HK) all have approved the listing of interleukin-targeted biological agents, and Quanxin Bio (01883.HK), Livzon Group (000513.SZ), Junshi Bio (688180.SH) and Cinda Bio.

JAK signaling pathway plays a very important role in autoimmune, tumor, hematological and other diseases, and it is one of the promising potential targets. Because the first generation of JAK inhibitors showed great toxic and side effects in the treatment process, the main research and development direction of major pharmaceutical companies is the second generation of JAK inhibitors targeting JAK1, JAK3, TYK2 and other targets with high specificity.

In clinical trials, the second generation JAK inhibitors have shown good data in terms of safety and efficacy. Among them, Upatinib, a JAK1 inhibitor listed by AbbVie, showed a better key remission index under the same safety in the head-to-head experiment of treating rheumatoid arthritis and adalimumab. In the first three quarters of 2023, the sales amount of Upatinib has reached US$ 2.71 billion, exceeding the annual performance in 2022. AbbVie expects that the drug is expected to achieve sales of more than $7.5 billion in 2025.

In view of the good performance of this target, the research on JAK-specific subunits has become one of the important directions of global innovative drug companies. Among domestic enterprises, Hengrui Pharma, Dizhe Medicine (688192.SH) and Nuocheng Jianhua (688428.SH) are in the top of the research and development progress. Among them, Nuocheng Jianhua recently disclosed that its TYK2 inhibitor ICP-488 under research has completed the first clinical administration for psoriasis patients in Phase II. ICP-332, another self-immune drug with the same target, disclosed the second phase clinical data of moderate and severe atopic dermatitis indications in December 2023. Orient securities believes that domestic JAK-targeted self-immune drugs are expected to achieve rapid volume increase after marketing through differentiated distribution of indications and optimized breakthrough in safety.

BlyS is one of the key factors in the differentiation and maturation of B lymphocytes, which is the most important effector cell of autoimmune diseases. By inhibiting BlyS, many autoimmune diseases can be treated. At present, there are two BlyS inhibitors on the market, namely, GlaxoSmithKline’s Beliyuzumab and Rongchang Bio (688331.SH)’ s Tatasip. The main indications are systemic lupus erythematosus, and the market structure is good.

Tetasip is an innovative drug of BLyS/APRIL dual-target fusion protein independently developed by Rongchang Bio. Clinical data show that the drug has the same level of efficacy and safety as Belizumab. In 2021, National Medical Products Administration conditionally approved Tatasip for the treatment of adult patients with systemic lupus erythematosus, and included it in the 2022 edition of the National Medical Insurance Catalogue; In November, 2023, the treatment of Tatasip in this indication was fully approved.

Rongchang Bio is also continuing to promote the clinical research on other indications of Tatasip, and the research on many indications such as rheumatoid arthritis, Sjogren’s syndrome and multiple sclerosis has entered the final clinical stage. In August, 2023, Tatasip was used to treat patients with rheumatoid arthritis in Phase III, and submitted an application for domestic marketing. On December 20th, the global multicenter Phase III clinical IND of Tatasip in the treatment of active primary Sjogren’s syndrome in adults was approved by the FDA of the United States, and clinical research will be carried out in many countries and regions around the world. The continuous enrichment of the clinical pipeline of Tetasip is expected to consolidate the innovative product matrix of the company and promote the continuous growth of the company’s income.

Take more than 200 million yuan to award the prize, and the result is "a Gree mobile phone"? Gree Electric: Free mobile phones have nothing to do with year-end awards.

Gree Electric vision china data map

Gree Electric’s extra year-end award of 200 million yuan is actually "a Gree G3 mobile phone for employees"?

On January 31, Gree Electric issued an official statement to clarify that the company was concerned about the false news circulating on the Internet, such as "On January 28, Chairman Dong Mingzhu said at the Gree 2024 Global Dream Festival that an extra year-end bonus of 200 million yuan was actually sent to Gree mobile phones".

Gree Electric mentioned two points in the statement: First, in order to better adapt to the company’s work software, facilitate mobile office work and improve work efficiency, the company decided to provide each employee with free work mobile phones (including free communication packages), which will be distributed in batches around the Spring Festival.

Second, the year-end bonus of 200 million yuan increased by the company has nothing to do with the free work mobile phone. The scope of the increased year-end bonus does not include middle and senior cadres, and the increased part is inclined to the front-line employees.

Gree Electric said that the company reserves the right to investigate the legal responsibility of media and individuals who spread rumors and rumors according to law.

Previously, a related person in Gree Electric said, "Fake, nonsense."

On January 28th, Dong Mingzhu, Chairman and President of Gree Electric, said at the Gree 2024 Global Dream Festival that her performance reached a new high last year, creating a profit of 29 billion yuan. At the same time, she also announced that she would "give employees an extra 200 million yuan for the year-end bonus".

However, while Gree Electric’s heroic 200 million year-end bonus has aroused widespread concern, there are also questions about this year-end bonus on the Internet.

On January 30th, there were rumors on the Internet that the 200 million year-end bonus was actually "one Gree G3 mobile phone for each person" and "giving employees more G3 mobile phones with a value of 200 million". Moreover, these G3 mobile phones "can’t be sold at the price of idle fish only around 300 yuan, but the company has issued 80,000 sets at a price of 3,599 yuan".

For these rumors, Gree Electric insiders told the media: "The fake, extra 200 million bonus is not deducted by G3 mobile phone, but a real year-end bonus."

Regarding the rumor that "Gree’s year-end award is deducted with points", Gree also said that "the year-end award is not issued in the form of points".

On the short video platform, some Gree Electric employees have already got their own year-end awards, which are divided into two parts: cash+points for products. The employee of Gree Electric’s subsidiary got a year-end bonus of 4,500 yuan in cash, and also exchanged the points for products such as rice cookers, health pots and electric fans, with a value of about 4,000 yuan.

At the Gree 2024 Global Dream Festival, Dong Mingzhu said that 2023 was the best year for Gree Electric since its founding 33 years ago, and the corporate tax revenue reached a record high. This achievement can not be separated from the hard work of every employee and the teamwork spirit.

Dong Mingzhu said that in order to let employees fully enjoy the fruits of the company’s development, he decided to give employees an extra 200 million yuan for the year-end bonus. At the same time, Dong Mingzhu also expressed the hope that the tax revenue for the country will exceed 20 billion in 2024.

Dong Mingzhu also said that Gree Electric doesn’t care about the stock price, because it doesn’t depend on the stock price to survive.

Previously, the performance forecast released by Gree Electric showed that the total operating income in 2023 is expected to be between 205 billion yuan and 210 billion yuan, up by 7.8% to 10.4% year-on-year; It is estimated that the net profit attributable to shareholders of the parent company will be between 27 billion yuan and 29.3 billion yuan, up 10.2% to 19.6% year-on-year; It is estimated that the net profit attributable to shareholders of the parent company after deducting non-recurring gains and losses will be between 26.1 billion yuan and 27.8 billion yuan, up 8.8% to 15.9% year-on-year.

As of January 31st, Gree Electric rose 0.28% to close at 35.25 yuan.

State Post Bureau: On the day of "double 11", the country handled 535 million express mail.

Data map: Taiyuan, Shanxi, postal workers are sorting express delivery. China News Service reporter Zhang Yunshe

  BEIJING, Nov. 12 (Xinhua) According to the official WeChat news of the State Post Bureau, on November 11, according to the monitoring data of the State Post Bureau, postal and express delivery companies handled 535 million express mail all day, which was three times the daily processing volume since the second quarter, with a year-on-year increase of 28.6%, a record high.

  It is estimated that the peak season of "double 11" this year will last from November 11th to 18th. During the peak period, the whole industry will handle 2.8 billion pieces of express mail. The whole industry still regards "peak-shifting delivery and balanced promotion" as the core mechanism, and strictly controls the peak delivery volume according to the delivery carrying capacity of each enterprise and the planned push volume. Through big data platforms such as postal industry safety supervision information system and e-commerce collaborative platform, the State Post Bureau will pay close attention to the whole network operation in real time, guide enterprises to control the dispatching rhythm, and moderately extend the delivery time limit of double 11.

  In order to achieve the goals of "two noes" (no paralysis of the whole network and no explosion of important nodes) and "three guarantees" (smooth flow, safety and stability), on the basis of the existing service capacity, the whole industry temporarily hired nearly 400,000 people and 120,000 vehicles, and added more than 3.6 million square meters of processing sites and more than 3,000 sets of automatic and semi-automatic sorting equipment. Technically, unmanned warehouses, drones and unmanned vehicles have gradually achieved mass production and large-scale application. More than 200 intelligent distribution centers have been built nationwide, and many unmanned warehouses have been set up by enterprises such as SF, JD.COM, Cainiao and Suning. A large number of heavy-duty storage robots and distribution robots have been promoted and applied in different occasions, and the "illegal operation AI intelligent identification system" that automatically identifies violent sorting behavior has been put into operation in some enterprises. In urban areas, 82,000 terminal public service stations have been built nationwide, and more than 380,000 sets of intelligent express boxes have been deployed, effectively supplementing the terminal service capacity of express delivery. The establishment of 59,000 rural express public pick-up and delivery points will better meet the delivery service needs of rural residents. In terms of international business, the outlets of express delivery enterprises in more than 60 countries, overseas warehouses covering more than 50 countries and regions and new international routes will play a very positive role. In terms of after-sales, AI intelligent customer service robots that can achieve 24-hour service have been put into use in many enterprises, which will effectively improve customer service capacity during peak hours.

  In response to the consumer’s concern about the "last mile" in rural areas in the peak season, the relevant person in charge of the State Post Bureau pointed out that up to now, express outlets have covered more than 30,000 towns and villages, and the coverage rate of express outlets in towns and villages nationwide has reached 96%, effectively improving the distribution capacity in rural areas. At the same time, the State Post Bureau specially issued the "Implementation Plan for Accelerating Express Delivery to the Countryside" this year, intensified efforts to build a terminal delivery service system consisting of home delivery, box delivery and platform delivery, and constantly promoted the integrated development of transportation and postal express delivery, and promoted the coordinated development of express delivery and rural e-commerce. In addition, since April this year, two rounds of cleaning up and rectifying illegal charges for express terminal services have been deployed nationwide, effectively safeguarding the legitimate rights and interests of farmers. On the issue of express packaging, with the help of "double 11", the industry has vigorously promoted the "9571" project of green development, continuously reduced the secondary packaging of e-commerce express mail, and deployed 27,000 standardized express packaging recycling devices at terminal service stations. At the same time, enterprises have done a lot of work in reducing the use of packaging materials, promoting electronic face sheets, circulating transfer bags and packaging recycling boxes.

Sichuan is still beautiful. The Dragon Boat Festival holiday is warm everywhere.

Special topic: Wenchuan earthquake in Sichuan

  Yesterday was the first small holiday after the Wenchuan Earthquake. The sky is raining, and the earthquake relief continues, but strings of zongzi, sachets, calamus and mugwort leaves convey a warm festive atmosphere in this cool weather. On the first day of the Dragon Boat Festival holiday, while many citizens were reunited with their families, many people chose to go out and enjoy the holiday. They relaxed their pent-up feelings during their travels and experienced the still beautiful Sichuan for themselves.



Yesterday morning, hundreds of married couples took photos in Hejiang Pavilion as a souvenir.


  Yesterday was the first small holiday after the Wenchuan Earthquake. The sky is raining, and the earthquake relief continues, but strings of zongzi, sachets, calamus and mugwort leaves convey a warm festive atmosphere in this cool weather. On the first day of the Dragon Boat Festival holiday, while many citizens were reunited with their families, many people chose to go out and enjoy the holiday. They relaxed their pent-up feelings during their travels and experienced the still beautiful Sichuan for themselves.


  Emei Mountain: The number of tourists increased year on year.


  Yesterday, Emei Mountain Scenic Area received more than 5000 tourists. "Obviously better than our previous expectations." The relevant person in charge of Emei Mountain Scenic Area introduced. Among the tourists who came to Emei Mountain yesterday, self-driving tourists became the main force. According to the statistics of Emei Mountain digital monitoring system, the number of self-driving vehicles that came to Emei Mountain yesterday reached 1768.


  Among them, self-driving cars from Chengdu accounted for half. "Many of them are to relax." It is understood that in addition, there are more self-driving cars from Chongqing and Zhejiang, as well as from surrounding areas such as Meishan. Wang Xiaoqing, a tourist from Chongqing, came to Mount Emei for the first time. After coming down the mountain, he said that Mount Emei was more beautiful than he expected.


  Team tourism is also recovering. Yesterday, there were six teams coming to Emei Mountain, and three in Chengdu and Chongqing respectively. "Since we held the Chengdu-Yule Line Boutique Conference two days ago, the travel agencies in Chengdu have sent delegations every day." Emei Mountain Scenic Area said that they are very confident in the tourism market after the earthquake.


  According to statistics, Mount Emei received a total of 5,000 tourists yesterday, a slight increase compared with the same period last year. The hotel occupancy rate is over 60% on average. It is expected that the number of tourists will reach its peak at the Dragon Boat Festival today.


  Chengdu: Tourists enjoy the Dragon Boat Festival.


  The first Dragon Boat Festival holiday forecast issued by Chengdu Holiday Office shows that the tourist attractions and attractions in Chengdu that are unaffected and fully open have attracted a large number of tourists. Huaxiang Rural Residence in Hongsha Village in Jinjiang District received 15,000 tourists, Huanglongxi in Shuangliu County received 12,000 tourists, and Wenjiang Northern Ecological Zone received 8,000 tourists. Although the number of tourists is less than the previous small holiday, the rapid start of the market has made these scenic spots even "unexpected".


  It is reported that there are 65 scenic spots (spots) that have been opened and received tourists in Chengdu except Dujiangyan, Pengzhou and chongzhou city. The "Dragon Boat Festival" held in Shuangliu, Wenjiang, Qionglai and other districts (cities) and counties, such as blessing, setting off river lanterns and eating zongzi, as well as rural tours in the suburbs of the city, also attracted many tourists.


  At the same time, the Law Enforcement Brigade of the Municipal Tourism Bureau went to the major travel agencies and scenic spots in the city to inspect the safety precautions and market order, and focused on setting safety warning signs and unblocked safety passages to ensure the tourism safety during the Dragon Boat Festival holiday.


  Travel Agency: More people will visit Sichuan!


  After the earthquake, many travel agencies in Sichuan closed down or were semi-closed. However, with the arrival of the Dragon Boat Festival, many travel agencies in Chengdu received their first business after the earthquake. "Although the amount is small, we see hope in it." A staff member of the Provincial Youth Travel Service introduced. Before the Dragon Boat Festival, guests kept calling for advice, which surprised them. It is understood that during the Dragon Boat Festival, many citizens in Chengdu also traveled to other provinces by participating in tour groups. These routes are mainly Yunnan, Guilin, Guizhou and East China. Although the number is small, the citizens’ willingness to travel has gradually increased, which has enhanced the confidence of travel agencies.


  According to the analysis of a senior person in the tourism industry, the overall travel situation of the Dragon Boat Festival is definitely worse than that of previous years. There are three main reasons. First, yesterday happened to be the college entrance examination, and many parents had to accompany their children to take the exam; Second, the general rainfall yesterday affected people’s mood for traveling; Third, after the earthquake, many people want to go home to reunite with their loved ones and spend the holidays at home. He believes that with people’s lives on the right track, more people will be willing to travel. "With the joint efforts of everyone, more people will come to visit the still beautiful Sichuan!" (Reporter Tao Ying Intern Huang Lian)

Ru Zhengang, the maker of "anti-fate wheat": what you want all your life is a bumper harvest.

Image source: China Radio Network

Image source: China Radio Network

CCTV News:"Family, less idle month, people twice as busy in June. At night, the south wind rises and the wheat is covered with yellow. " It’s the wheat harvest season in a year. Under the blue sky in the distance, golden wheat waves are surging. The newly harvested wheat is ground into fragrant flour and enters the kitchens of various households. ……

One out of every eight steamed buns eaten by more than 1.3 billion people in China comes from the wheat variety "Bainong Aikang 58", which is known as "the first wheat in Huanghuai". It is "Mai Da" Ru Zhengang who successfully cultivated this new wheat variety. He is the vice president of the School of Life Science and Technology of Henan University of Science and Technology, the director of the Henan Hybrid Wheat Engineering Technology Research Center, and the chief expert of wheat disease and pest resistance breeding in Henan Province.

Ru Zhengang often said: "As an agricultural science and technology worker, you can’t help farmers increase production and income. You are nothing!" His lifelong aspiration is to fill the granary of China with the power of science and technology.

Change the world with a "go against the sky wheat seed"

Food is scarce and farming is difficult. These childhood memories make Ru Zhengang have an indescribable feeling for wheat. He has always had a "wheat dream", "We must have enough food in Chinese, and the granary is full of our own wheat".

In 1981, Ru Zhengang, who graduated from agronomy, was selected by Professor Huang Guangzheng, a national expert who was famous in the breeding field at that time and won the second prize of national invention, and "pulled into" the breeding industry. Since then, it has been persistent for 36 years.

In order to find the root of the problem of wheat growth, Ru Zhengang ate and lived in the wheat field for several days. In order to ensure the accuracy of the data, he took the research team to manually thresh one by one; In order to understand the growth of wheat in various places, he traveled almost every wheat producing area in China.

In the process of breeding new wheat varieties such as "Aikang 58", Ru Zhengang explored and created a set of nearly complete scientific methods, theoretical systems and scientific research equipment and breeding platform established from it. In his breeding base, from the molecular biology laboratory to the artificial climate room, to the intelligent greenhouse, and then to the outdoor experimental field, it takes only a few minutes to be fully prepared. It is these few minutes’ path that shortens the time of wheat breeding by six years.

Ruzhengang successively cultivated and popularized many varieties such as "Bainong 62", "Bainong 64", "Bainong 160" and "Bainong Aikang 58", and the wheat varieties with stable and high yield filled the granaries of China, which also made the people happy. Ruzhengang has become an out-and-out "God of Grain".

The inspiration for scientific research propositions comes from ordinary people.

"All my scientific research topics and the inspiration and source of technological innovation come from ordinary people." Ru Zhengang traveled all over the country in most wheat fields, and no matter where he went, he never forgot to ask the villagers to "find fault" with their own seeds.

Can wheat be high-yielding and lodging-resistant? Can wheat be planted whenever it wants? The ears of wheat are big, can you make more grains? There are too many ears, can you make the straw shorter? The wheat straw is short, can it tolerate barren and drought? … … Seemingly harsh problems are thrown at him from time to time, and if Ru Zhengang gets the treasure, it will eventually turn into his most breakthrough and creative scientific research topic.

Many experts believe that the wheat yield in Huanghuai area of China has reached the "ceiling", and it is "even more difficult" to further increase the yield. Ru Zhengang’s thoughts and vision jumped to the northeast and Guangdong, Fujian and other places, hoping to find a record-breaking "artifact" in these places.

He constantly challenges himself and his limits. "Even though the frost of time has stained my temples and the knife of years has carved my forehead, why don’t I change my mind and be as heroic as yesterday?" Ru Zhengang expressed his ambition to charge for hybrid wheat breeding in poetic language.

Loving wheat is like your own daughter.

Ru Zhengang said that after 36 years of research, Wheat is actually like his daughter. It can understand his words, and he knows how it can be good, what it likes, what it doesn’t like, and how to make it happy.

"When you chat with wheat with your heart, you can feel the power of its life. Although the breeding work has to face failure 90% of the time, every improvement is an exploration of life and a spiritual enjoyment." Ru Zhengang said.

In Ru Zhengang’s view, wheat that can give people full returns, like wheat, is not wheat, but wheat of a work of art.. He wants to cultivate better wheat varieties, serve the strategic needs of modern agricultural production and national food security, and make new contributions to China’s food security and agricultural harvest. (Source: Ministry of Science and Technology)

Rational planning, avoiding over-consumption and over-consumption, are you willing to spend money by stages?

  The report of the 19th National Congress proposed that we should implement the new development concept and build a modern economic system.

  In this regard, it is an important content to improve the system and mechanism of promoting consumption and enhance the basic role of consumption in economic development. In recent years, consumption has replaced investment as the first driving force of economic growth. Behind this, the innovation of payment methods brought by technical means has contributed greatly, and installment consumption is one of them. "Spend tomorrow’s money and enjoy today’s resources", whether it is life consumption such as digital electronics, home appliances and furniture, or service consumption such as training, tourism and entertainment, the tentacles of phased consumption have extended to all aspects of life.

  Can installment consumption really make people enjoy life ahead of schedule easily? In the face of the network staging platform with spurt growth, how should consumers rationally stage and make good use of staging?

  How hot is the market?

  "It is no exaggeration to say that more than 90% of college students around me have used installment consumption, and food, clothing, housing and transportation, leisure and entertainment can all be solved by installment consumption."

  "With children at home, the requirements for environmental sanitation are relatively high. My British Dyson vacuum cleaner was made of JD.COM white stripes. I often shop in JD.COM, and I can avoid paying interest by installments with coupons. It is much more economical to installment this year than to use a bank credit card. " Hao Yihang, an employee of a large state-owned enterprise in Beijing, is a fan of JD.COM IOUs. In his words, the slogan of "Consumption by stages, so that youth does not leave blank" attracts young people. The service of "Shopping first, paying later" and "30 days interest-free and staging at will" makes life consumption zero obstacles. "Consumption by stages is so cool!"

  It reduces the pressure of one-time payment, and the relaxed shopping experience of "installment consumption" makes people happy. Hao Yihang said that Apple’s upcoming iPhone X, which he also intends to buy in stages, will not cause economic pressure and keep up with the trend. Staging consumption can make the monthly salary diversified and meet more new consumption needs.

  The application method is flexible, the application procedure is convenient, there is no need for mortgage guarantee, and the approval speed is fast. With these characteristics, installment consumption quickly wins the favor of young people. The group represented by "post-90 s" grew up in the era of rapid development of the Internet, and accepted new technologies, new things and new products with a high degree. Pursuing efficiency and enjoying the present are their main consumption concepts, and this group is the main force of phased consumption.

  "It is no exaggeration to say that more than 90% of college students around me have used installment consumption, and food, clothing, housing and transportation, leisure and entertainment can all be solved through installment consumption." Wang Peng is a junior in a university in Beijing. As early as when he first entered school, he began to use installment consumption, which was very convenient.

  "This year, the money I signed up for the TOEFL training class was solved by stages. A TOEFL class costs more than 30 thousand yuan, and I ask my parents directly. I’m a little embarrassed. After using the staging platform, I will take out some money from the living expenses to repay the loan on schedule every month. Although there is some interest, I think it is worthwhile. " Wang Peng said that installment consumption is very common among college students, ranging from buying computers and mobile phones, education and training, to recharging phone bills and purchasing tickets for movies. They all like to choose installment.

  In the past two years, the installment consumption platform has developed rapidly, especially the "internet plus installment consumption" platform has made up for the shortcomings of the traditional financial industry and served the groups that it failed to cover. Recently, the industry has welcomed the "regular army", banks have returned to the field of campus installment consumer credit, and the market is gradually standardizing. According to the forecast of relevant institutions, in the past five years, the average annual growth rate of installment consumption loans exceeded 20%.

  How tempting is it?

  Some merchants deliberately weaken the intermediary fees and induce consumers with the gimmick of "low threshold, zero interest and zero down payment", while the handling fee and service fee behind the products are actually higher than the interest.

  "I obviously bought a 5799 yuan mobile phone, but the final repayment was more than 1700 yuan, which means that I spent nearly 8000 yuan on this mobile phone. Although the mobile phone was used more than one year in advance, it also paid a price. " Speaking of installment consumption, Zhao Xiaoxian, a chef in a restaurant in Hefei, Anhui Province, felt quite helpless. "It is very difficult for migrant workers like me who have no stable income to apply for bank credit cards. Online merchants lied to me that installment consumption threshold is low, procedures are convenient and interest is low. However, in the final calculation, the handling fees are higher than the interest. "

  Dong Ximiao, a senior researcher at Chongyang Financial Research Institute of Renmin University of China, believes that the staged consumer market is developing rapidly, but the good and the bad are mixed, and many services are falsely advertised. The main purpose of staging business on the consumer platform is to expand users’ staging consumption, but the way to expand customers mainly comes from offline, and salesmen are easy to cheat and induce consumers for the sake of performance. Some merchants deliberately weaken the intermediary fees, and basically induce consumers with the gimmick of "low threshold, zero interest and zero down payment", while the handling fee and service fee behind the products are actually higher than the interest, which makes consumers feel miserable.

  "The development of bank credit card business is relatively mature, and both the bank’s own risk control system and regulatory regulations are relatively perfect. However, the staged market has outstanding problems such as false propaganda and induced sales promotion in a fierce competitive environment. " Dong Ximiao said.

  The installment consumption business of traditional commercial banks is standardized, mainly for consumers with stable income. Consumers have lower risk in using it and can effectively protect their rights and interests. The market gap that traditional commercial banks can’t cover has inspired the rise of Internet staging platforms, which have low thresholds and are aimed at social groups such as students and migrant workers. Coupled with the lag of regulatory policies, some disadvantages of installment consumption are constantly emerging.

  For example, it is inevitable that unqualified consumers will default in time on the staging platform. Salespeople usually "salute before soldiers", but the effect of "collection" will be linked to performance. Because there is no standardized and legalized collection supervision policy at present, there are different kinds of violent collection behaviors in the staged market in reality.

  The risk of disclosure of personal information makes installment consumption a safety hazard. Many people have encountered the problem of "receiving a collection message without a loan" and "being registered under an assumed name without registration". Most people will choose to ignore it, but doing so may affect consumers’ credit information and bring inconvenience to life and work.

  In addition, from the consumer’s own point of view, staged consumption increases irrational consumption behavior. The amount of payment is reduced when the installment is consumed, which makes people have the illusion of spending less. The risk monitoring measures of many platforms are not in place, which may easily lead to credit problems such as overdue default by unqualified consumers.

  How hard is it to choose?

  By means of digital management and information sharing, we will strengthen the construction of credit system and prevent multi-head lending. Consumers should abandon vanity, comparison and blind obedience.

  Behind the popularity of installment consumption, how can we rationally use and manage installment consumption?

  Dong Ximiao believes that from the perspective of regulators, we should continue to carry out the special rectification of Internet finance and increase the cleaning and rectification of various stages of consumption platforms. For the platform with disorderly operation and chaotic management, if it fails to pass the filing in accordance with the regulations, measures should be taken to resolutely close it.

  "At present, China’s credit information market still needs to be further improved, and the problem of long-term lending in the industry has not been completely solved. I believe that after the sharing of credit information data at the national level in the future, the whole industry will develop more healthily and orderly." Dong Ximiao said.

  Credit data is an important link in risk control of phased consumption platform. Companies such as Taobao, JD.COM, Ctrip, etc., which have mastered the consumption scenes of hundreds of millions of users, have a large user base and many data resources, and can keenly capture the credit rating of users, and the cost of risk control is low. It is difficult for other financial platforms to accurately judge consumers’ credit information "Facebook".

  "Now, for installment consumption, we have to put a lot of energy into risk prevention and control. It can be said that if the risk control is done well, the operating cost will be reduced, and the platform installment consumption interest rate will be reduced accordingly, thus attracting more quality customers." Gao Sheng, the public relations director of Staged Music Mall, said, "For example, we are now using artificial intelligence technology to develop ‘ Hawkeye ’ The intelligent risk control engine has more than 6,000 risk control model data variables, which can greatly improve the efficiency of risk control audit. "

  Dong Ximiao suggested strengthening the construction of credit infrastructure, consolidating and enriching the credit information system by means of digital management and information sharing, improving the risk identification ability and risk prevention efficiency of installment consumption business, and enabling institutions and customers to enjoy more convenience in inclusive finance.

  Banks and internet platforms should further improve or establish their own risk assessment and monitoring systems, objectively evaluate users’ consumption levels, and reasonably set credit lines; Staging consumption business institutions and platforms should correctly carry out marketing propaganda, put an end to false propaganda and induced propaganda, and set up necessary punishment mechanisms.

  For consumers, we should carefully choose between bank credit card and installment payment platform, and try to choose a bank credit card with a more formal and perfect management system. If you choose the internet installment consumption platform, you should carefully check how to calculate the installment consumption interest, handling fee and service fee to prevent being charged with high interest and service fee.

  "Installment consumption is a form of prepayment. If the repayment is overdue, it will not only increase the overdue interest, but also affect their credit rating, and even some financial institutions will terminate the installment business." Dong Ximiao said that consumers should abandon the bad mentality of vanity, comparison and blind obedience, carefully weigh whether the purchase of goods is reasonable, and formulate reasonable consumption and repayment plans to avoid over-consumption and over-consumption.

  The insiders believe that for platforms with relatively standardized operations, the principle of "same business, same supervision" should be adopted to implement penetrating supervision, safeguard the legitimate rights and interests of financial consumers and protect the security of personal information. At the same time, we will strengthen the monitoring of the installment business it provides in terms of loan purposes and capital flow. Consumers should also enhance their risk awareness, strengthen the study of financial consumption and network security knowledge, and not disclose personal information at will to improve their ability to identify and prevent bad businesses.

  What are the installment consumption platforms? (link)

  In the past two years, staged consumption platforms have mushroomed, with different application scenarios and different characteristics.

  JD.COM White Strip: the first Internet consumer financial product in the industry. You can enjoy a deferred payment period of up to 30 days or a payment by installments of up to 24 days if you use white bars for payment on JD.COM website. In recent years, JD.COM White Bar has been integrated into more consumption scenes, gradually covering the fields of renting, tourism, decoration, education, wedding and so on, extending from credit purchase service to providing credit consumption loans to provide credit consumption services for more consumers.

  Ant Flower Garden: Born in the e-commerce department, it mainly supports multi-scene shopping. Its main application scenarios are Taobao and Tmall. Recently, it has also settled in most e-commerce shopping platforms, such as Amazon, Suning and local life service websites, such as word of mouth, Meituan, public comment, etc., and also involved some overseas shopping websites.

  Staging music: Staging music in the staged shopping mall under Lexin Group is a new consumption platform of "e-commerce+finance". The shopping mall consumption scene involves 3C digital, outdoor sports, beauty care, eating, drinking and having fun, etc. It is the official authorized distributor of Apple mobile phones. The platform provides phased consumption services for mainstream consumer groups such as young people and white-collar workers.

  Consumer finance company: it is a non-bank financial institution that provides unsecured and unsecured consumer loans. According to the "2017 Internet Consumer Finance Development Report and Outlook" by Suning Financial Research Institute, there are currently 22 licensed consumer finance companies in China, of which banks account for more than 90%. Consumer finance companies have offline channels, and offline outlets basically involve the whole country. Many licensed financial consumer companies have launched in-store consumption business to expand the financial consumer market. With the development of internet finance in recent years, many consumer finance companies have begun to cooperate with e-commerce platforms to develop online consumer credit business.

  (Song Chao)

Notice on printing and distributing the vaccination work plan to deal with the recent infection situation in Covid-19

Notice on printing and distributing the vaccination work plan to deal with the recent infection situation in Covid-19
Guo Wei Ming Dian [2023] No.46

All provinces, autonomous regions, municipalities directly under the Central Government and Xinjiang Production and Construction Corps should respond to the joint prevention and control mechanism (leading group and headquarters) of novel coronavirus infection, and the State Council should respond to the members of the vaccination coordination group of the joint prevention and control mechanism of novel coronavirus infection:

The "Work Plan for Vaccination in Response to Recent Infections in Covid-19" is hereby printed and distributed to you, please conscientiously implement it according to the actual situation.

The State Council responds to novel coronavirus infection.Comprehensive group of epidemic prevention and control mechanism
April 6, 2023

(Information disclosure form: voluntary disclosure)

Respond to the recent Covid-19 infection epidemic.Vaccination work plan

In order to thoroughly implement the decision-making arrangements of the CPC Central Committee and the State Council, effectively respond to the recent epidemic situation in Covid-19, and ensure and safeguard people’s health, this work plan is formulated in combination with the epidemic situation, vaccine research and development, immune effect evaluation, population immunity level and other factors.

First, the target population

At this stage, the focus of vaccination is to fill the gap in immune level for different target groups and further reduce the risk of severe illness and death. The target population is as follows:

(a) people who are not infected and have not completed the established immunization program. Including uninfected people aged 3-17 who have not completed basic immunization, uninfected people aged over 18 who have not completed the first dose of booster immunization, and uninfected people aged over 18 who have not completed the second dose of booster immunization (high-risk people with infection, elderly people over 60 years old, people with serious basic diseases and people with low immunity).

(two) people who have been infected and have not completed basic immunization.

Second, the time interval and vaccine selection

(1) Time interval.

The uninfected target population completes the follow-up vaccination according to the established immunization program and its time interval requirements. Among them, for people over 18 who have completed basic immunization, the interval of the first dose of booster immunization is adjusted to more than 3 months.

People who have been infected and have not completed basic immunization can be vaccinated with one dose after 3 months of infection.

(2) vaccine selection.

Shenzhou cell recombinant Covid-19 tetravalent S trimer protein vaccine and Unacon Covid-19 mRNA vaccine have been included in emergency use, which can be used for intensive immunization of people over 18 years old.

The vaccines used for basic immunization of uninfected target population shall be implemented with reference to the relevant requirements in the previous period. In order to strengthen immunization, it is recommended to use Shenzhou cell recombinant Covid-19 tetravalent S trimer protein vaccine and Unacon Covid-19 mRNA vaccine. Other recombinant protein vaccines or virus vector vaccines that have been approved for conditional marketing or emergency use can also be selected for sequential enhanced immunization.

People over the age of 18 who have been infected and have not completed basic immunization are recommended to use Shenzhou cell recombinant Covid-19 tetravalent S trimer protein vaccine and Unacon Covid-19 mRNA vaccine, or choose other recombinant protein vaccines or virus vector vaccines that have been approved for conditional marketing or emergency use. For people aged 3-17 who have been infected and have not completed basic immunization, the vaccines used for vaccination shall be implemented according to the relevant requirements of the previous period.

Follow-up will be based on the progress of vaccine research and development, approval, combined with the epidemic situation, virus variation and other conditions, timely research and adjustment of vaccination strategies.

Third, ensure vaccination safety

All localities should continue to give priority to vaccination safety, and organize vaccination implementation in strict accordance with the requirements of the Code for Vaccination Work. Local health departments should implement the "four haves" requirement that vaccination units should have emergency personnel stationed in general hospitals at or above the second level, emergency equipment and medicines, 120 ambulances on duty, and green channels for treatment in general hospitals at or above the second level to ensure vaccination safety. Inoculation units should do a good job in vaccination information registration and vaccine flow management, and update the vaccination records in the immunization planning information system and vaccination vouchers in a timely and accurate manner.

Fourth, strengthen organization and implementation

(1) Strengthening the responsibility of territorial subjects. All localities should implement the responsibility of territorial management, attach great importance to and co-ordinate the vaccination work in Covid-19. It is necessary to strengthen the guidance of vaccination work within the jurisdiction and fully grasp the progress of the work. Relevant local departments should strengthen docking and do a good job of coordination.

(two) to play the role of the competent department of industry. The competent departments of relevant industries should guide the units where the personnel in this industry work to actively cooperate with local unified arrangements and jointly do a good job in organizing and mobilizing.

(3) Strengthen supervision and guidance. It is necessary to closely track and monitor the progress of vaccination in various places, and find and study and solve related problems in time. Improve the traceability system of vaccine flow, improve the safety supervision mechanism of vaccine chain, continuously strengthen the whole process management and safety precautions, and effectively ensure the efficient and smooth transportation of vaccines.

(4) Do a good job in publicity and guidance. All localities and relevant departments should, according to the needs of work, formulate targeted publicity measures for vaccination work, focus on the purpose and significance of vaccination, respond to social concerns, sum up and popularize typical experiences and practices, actively guide the target population to take the initiative to vaccinate, and especially guide and improve the vaccination rate of the elderly population.

Note: People aged 3-17 can only use Covid-19 inactivated vaccine of Sinopharm Zhongsheng Beijing Company, Beijing Kexing Company, Sinopharm Zhongsheng Wuhan Company and Zhifeilong Kema recombinant Covid-19 vaccine (CHO cells).

Ministry of Industry and Information Technology: In the first quarter, the development of industry and information technology achieved a smooth start, showing a stable and good trend.

  Cctv newsAt 15: 00 on April 20th, the State Council Press Office held a press conference to introduce the development of industry and informatization in the first quarter of 2023 and answer questions from reporters.

  Zhao Zhiguo, chief engineer and spokesperson of the Ministry of Industry and Information Technology, said that overall, the development of industry and information technology achieved a smooth start in the first quarter, showing a trend of stabilization and improvement.

  First, the industrial economy has maintained a stable operation. It mainly presents three characteristics. First, industrial production has steadily picked up. In the first quarter, the added value of industrial enterprises above designated size increased by 3% year-on-year, which was 0.3 percentage points higher than that in the fourth quarter of last year, reversing the continuous downward trend since October last year. According to the data of China Association of Automobile Manufacturers, the production and sales of automobiles in March increased by 15.3% and 9.7% respectively, and the production and sales of new energy vehicles increased by 44.8% and 34.8% respectively. Second, investment in manufacturing industry continued to grow steadily. In the first quarter, manufacturing investment increased by 7% year-on-year, which was 1.9 percentage points higher than the national fixed assets investment, and maintained a rapid growth rate on the basis of a high base for two consecutive years. Third, the role of industrial provinces is obvious. The industrial growth rate of Hebei, Shandong, Jiangsu and other major industrial provinces is significantly higher than the national level. Since March, the industrial economy of Guangdong, Zhejiang and other provinces has picked up.

  Second, the advanced manufacturing industry is developing well. Vigorously develop advanced manufacturing industry and promote the high-end, intelligent and green development of manufacturing industry. Solidly promote the industrial base reconstruction project and major technical equipment research projects, and make significant progress in some areas. ARJ21 has safely transported more than 6.55 million passengers and has recently been put into overseas commercial operation. Delivered the world’s largest 24188 TEU super-large container ship, and the first domestic extracorporeal membrane oxygenation machine (ECMO) was successfully developed and certified for listing. Deeply implement intelligent manufacturing engineering and promote the digital transformation of the industry. The three functional systems of industrial internet network, platform and security were completed, and the scale of core industries exceeded 1.2 trillion yuan. Accelerate the transformation and development of green and low-carbon industries. Accelerate the development of new energy vehicles, photovoltaics and other emerging industries. In the first quarter, the investment in fixed assets of high-tech manufacturing industry increased by 15.2% year-on-year, and the output of new energy vehicles, solar cells and other emerging products increased by 22.5% and 53.2% respectively.

  Third, the empowerment effect of the information and communication industry is constantly emerging. We will fully consolidate new infrastructure and strongly support high-quality economic and social development. In the first quarter, telecom business revenue increased by 7.7% year-on-year. Steadily promote the construction of "double Gigabit" network, with the cumulative number of 5G base stations exceeding 2.64 million, and the number of Gigabit access users exceeding 100 million. Continue to deepen the application of convergence, and 5G is fully integrated into 52 national economic categories. Improve the ability of application services, further enhance the supply of mobile Internet application services, and accelerate the demonstration and promotion of excellent cases of aging and barrier-free transformation of Internet applications. Coordinate development and security, introduce policies to promote the development of data security industry, strengthen the security protection of key information infrastructure in the industry, and ensure the safe and stable operation of basic telecommunications networks.

  Fourth, the industrial development environment has been further optimized. Adhere to the better combination of effective market and promising government, and strive to create a good ecology conducive to industrial development. In-depth implementation of the "14 th Five-Year Plan" in the field of industry and information technology, and organization and formulation of work plans for steady growth of key industries such as automobiles and electronics. Focusing on the "urgent difficulties and worries" of small and medium-sized enterprises, together with relevant departments, we have issued a series of policy measures to help stabilize growth and adjust structural strength, and started the cultivation of the fifth batch of "little giants" that specialize in specialty and innovation. Convene the 2023 Working Meeting of the Inter-Ministerial Joint Conference on Reducing the Burden of Enterprises in the State Council. Deepen the precise docking of industry and finance, and the national industry-finance integration platform has helped enterprises to raise more than 500 billion yuan.

  Of course, we must also see that there are still some difficulties and challenges in the current industrial economic development, but the fundamentals of China’s industrial economic development have not changed for a long time, and we are full of confidence in this. In the next step, we will adhere to the guidance of Socialism with Chinese characteristics Thought of the Supreme Leader in the New Era, thoroughly implement the decision-making arrangements of the CPC Central Committee and the State Council, strengthen our confidence, be determined to innovate, stabilize the development of key industries, support leading enterprises and specialized new enterprises, work hard to draw long boards, forge new boards and fill short boards, promote the sustained stabilization and improvement of the industrial economy in the second quarter, and accelerate the development of the information and communication industry, thus laying a solid foundation for achieving the objectives and tasks for the whole year.

Members of the North Korean leader’s family set foot in South Korea for the first time. Kim Jong-un’s sister’s resume is extraordinary

  CCTV News:South Korean Presidential Palace Cheongwadae announced on the 8th that Moon Jae in will meet with a visiting high-level delegation from the DPRK on the 10th. Members of the delegation include Jin Yongnan, Chairman of the Standing Committee of the Supreme People’s Assembly of the DPRK, Jin Yuzheng, First Deputy Minister of the Central Committee of the Workers’ Party of Korea, Cui Hui, Chairman of the State Sports Steering Committee, and Li Shanquan, Chairman of the Peaceful Reunification Committee of the Motherland. According to Xinhua News Agency, the DPRK delegation arrived at Incheon Airport in South Korea by special plane at noon on the 9th.

  Who’s Jin Yuzheng? What is the future trend of the situation on the peninsula? Will the representatives of North Korea, South Korea and the United States interact outside of sports events? The PyeongChang Winter Olympics in 2018 was full of topics before it started.

  Rare! Kim Jong-un once only took his twin sister to inspect the troops.

  Jin Yuzheng is the daughter of the late North Korean leader Kim Jong Il and the younger sister of Kim Jong Un.

  On March 9, 2014, Jin Yuzheng made her first "official appearance" in a report on North Korean national television. At that time, Kim Jong-un was elected as the representative of Baitoushan Constituency No.111 with 100% support rate. Jin Yuzheng, known as "Comrade", appeared for the first time in the report, and a "close-up" of her voting was shown.

  On November 27th, 2014, Kim Jong-un inspected the 426 Animation Studio. Korean Central News Agency mentioned Jin Yuzheng, Vice Minister of the Central Committee of the Labor Party, when introducing the accompanying personnel. This was the first time that the North Korean media publicized Jin Yuzheng’s position, which attracted the attention of foreign media.

  After that, Jin Yuzheng can always be seen in Kim Jong-un’s activities reported by North Korea’s official media. From watching performances, to inspecting factories and museums, to inspecting military training activities, Jin Yuzheng’s name can always be found in the list of accompanying persons.

  From March 9, 2014 to March 12, 2015, Jin Yuzheng accompanied Kim Jong-un on 25 inspections. Since November, 2014, Jin Yuzheng has been accompanying Kim Jong-un to inspect more and more frequently, accounting for more than half of the total times. Generally speaking, Jin Yuzheng’s people’s livelihood and cultural performances are twice as many as her military and political visits. However, since November 2014, her visits to the army have been basically the same as other activities. In January 2015, Jin Yuzheng’s public activities were particularly active, and he accompanied Kim Jong-un on seven inspections.

  On March 12, 2015, Kim Jong-un, the top leader of North Korea, visited a defense squadron in the front post on the east coast of North Korea. In Korean Central News Agency’s report, only the name of Kim Jong-un’s sister Jin Yuzheng was mentioned, but the names of other accompanying persons were not mentioned. Judging from the pictures released by the Workers’ Party of Korea, Jin Yuzheng not only accompanied Kim Jong-un to inspect the whole process, but also participated in the final photo. This kind of situation is rare. Usually, the entourage of Kim Jong-un does not take part in the group photo during the inspection activities, and it is the first time that only Kim Jong-un’s brother and sister inspect the troops in the official media of North Korea.

  At present, it is a critical moment for the DPRK and the ROK to release goodwill and improve bilateral relations. Kim Jong-un sent Jin Yuzheng to represent North Korea in the opening ceremony of the PyeongChang Winter Olympics, and the position of the younger sister in North Korea’s political arena is self-evident.

  The South Korean side also attaches great importance to the first entry of North Korean Kim family members into Korea. A spokesman for South Korea’s Cheongwadae said that all preparations would be made to ensure the smooth visit of the DPRK high-level delegation to South Korea to participate in the Olympic Games, and called Jin Yuzheng’s visit "of great significance". As Jin Yuzheng is an important figure in the Labor Party, the ROK expects that she will have considerable discretion in this trip, which is more important than Jin Yongnan’s coming to hankyung alone, and the ROK and the DPRK may take this opportunity to have a more meaningful dialogue.

  The close interaction between the DPRK and the ROK, the United States and Japan secretly "make bad"

  The 23rd Winter Olympics in Pyeongchang, South Korea in 2018 is destined to be an "unusual" Winter Olympics. Before that, the Vice President of the United States invited "special guests" to pour cold water on the relations between the DPRK and the ROK, and then members of the North Korean "Baitoushan family" (Kim family) entered Korea for the first time. During this period, it was reported that Trump’s daughter would attend the closing ceremony of the Winter Olympics and the South Korean Unification Ministry made intensive statements four times in three days … … The "feature film" of the 2018 Winter Olympics has not yet started, and the "trailer" alone is as wonderful as any Hollywood movie.

  At the beginning of the new year in 2018, the DPRK and the ROK changed the normal state of "arrogance" and "angry words", shelved the dispute between nuclear weapons and Sadr, and launched active "ice-breaking" talks around the Winter Olympics in a "double pause" posture, which achieved many results. For example, the DPRK and the ROK will jointly hold the flag of the Korean Peninsula at the opening ceremony of the Winter Olympics, the Korean art troupe will perform the opening ceremony in South Korea, and the DPRK and the ROK have expressed their positive will to improve the bilateral relations in the future … …

  At the same time of close interaction between the DPRK and the ROK, the United States began to "pour cold water" on the slowly warming DPRK-ROK relations.

  US President Donald Trump confirmed last month that he would send Vice President Burns as the head of the US delegation to attend the PyeongChang Winter Olympics. However, it is not known what attitude Burns will take to intervene in the situation on the Korean Peninsula. A White House official said that Burns believed that the DPRK wanted to use the Winter Olympics to "engage in propaganda activities" and he intended to "show up" at the Winter Olympics to "offset" the DPRK’s influence and self-promotion efforts.

  According to Washington post, Burns will invite a "special guest", namely Fred, the father of the late American college student Otto Warmbier, to visit Korea. Otto Warmbier was charged and convicted of conspiring to subvert the state in North Korea, and was detained for more than a year. He was released to China in June last year, but he was in a coma and died a few days later. This incident once prompted the State Council to issue a travel ban to the DPRK.

  It is also reported that US President Trump’s daughter ivanka will lead a presidential delegation to attend the closing ceremony of the 2018 PyeongChang Winter Olympics. Some South Korean media analysts said that if ivanka really attended the closing ceremony of PyeongChang Winter Olympics as reported by CNN, and Kim Jong-un’s younger sister Jin Yuzheng also went south for a pre-meeting, it might be possible for them to meet in the closing ceremony of Winter Olympics.

  The DPRK, the United States and South Korea are playing hot, and Japan is also joining in the fun. According to the news released by the Japanese government on the 3rd, Prime Minister Shinzo Abe will meet with Burns before attending the opening ceremony of the Winter Olympics, suggesting that the US-South Korea joint military exercise should not be scaled down after the Winter Olympics.

  … …

  The Korean Peninsula crisis has lasted for more than 20 years, and the biggest obstacle is the "return to Asia-Pacific strategy" of the United States. However, this "door-to-door talk" between the DPRK and the ROK is a sincere attempt by the DPRK. It is hoped that with the efforts of all parties, the stability of the DPRK and the ROK will be further developed, and the rare "warm drama" between the DPRK and the ROK will not become a "farce" with no end in some countries. (Text/Cheng Xiang)

It’s urgent, the reason of false negative in COVID-19 nucleic acid test and its countermeasures!

Author: Hongge comes from Medical Wechat WeChat official account.

        Recent epidemic situation in ChinaIn the process of getting up, there are some situations that deserve our attention.the most importantIsFalse negatives in nucleic acid detection. Intercepting relevant news, it was found that 8 confirmed patients in Shijiazhuang on the 22nd were repeatedly negative for nucleic acid detection, and 5 confirmed patients in Shijiazhuang on the 24th were repeatedly negative for nucleic acid detection.


   On the 22nd, there were 11 new confirmed cases in Shijiazhuang, including:

Case 1: Male, 52 years old, from Huangjiazhuang Village. On the evening of 21st.Ninth nucleic acid positive;

Case 2: Male, 13 years old, Niujiazhuang Village. On the evening of the 21st.Nine times nucleic acid positive;

Case 3: Female, 11 years old, Zhongyao Village. On the evening of the 21st.Nine times nucleic acid positive;

Case 4: Male, 49 years old, Nanqiaozhai Village. On the evening of 21st.Ninth nucleic acid positive;

Case 5: Male, 47 years old, Niujiazhuang Village. On the evening of 21st.Ninth nucleic acid positive;

Case 6: Female, 65 years old, Niujiazhuang Village. On the evening of 21st.Ninth nucleic acid positive;

Case 7: Male, 11 years old, grandson of Case 6. On the evening of 21st.Ninth nucleic acid positive;

Case 11: Male, 67 years old, Xiaoguozhuang Village, husband of Case 2 on January 7th. On January 3, it was transferred to centralized isolation medical observation; On the evening of 21st.11th nucleic acid detectionFinally positive;

On the 24th, there were 7 new confirmed cases in Shijiazhuang:

Case 1: Female, 65 years old, Nanqiaozhai Village. Centralized isolation on the 11 th.Nucleic acid after 9 times, 22 positive.

Case 2: Female, 4 years old, Nanqiaozhai Village. Centralized isolation on the 11 th.Nucleic acid after 9 times, 22 positive.

Case 3: Female, 4 years old, Mi Jie, Chang ‘an District. Centralized isolation on the 13 th.Nucleic acid after 8 times, 23 positive.

Case 4: Female, 64 years old, Xiaoguozhuang Village. Centralized isolation on the 10 th.After 11 nucleic acids, 24 positive.

Case 5: Male, 34 years old, Xiaoguozhuang Village. Centralized isolation on the 8 th.After 11 nucleic acids, 24 positive.

Case 6: 34-year-old female, Liujiazuo Village, was positive for nucleic acid on the 5th, was diagnosed as asymptomatic infection on the 6th, and was clinically confirmed on the 24th.

Case 7: A 28-year-old male, living in Yuhua District, went to work by car at Zhengding Airport on weekdays. He was diagnosed as asymptomatic infected with nucleic acid on the 5th, and was clinically confirmed on the 24th.


Since the outbreak of COVID-19 last year, the topic of high false negative rate of nucleic acid detection has been the focus of attention. It has been reported that the positive rate of Covid-19 detection by fluorescence quantitative RT-PCR is only 30%-50% at present, which leads to extremely high false negative rate.

For Hongge, who doesn’t know much about the test, this paper analyzes the relatively high false negative test by searching articles and documents, and summarizes some reasons to discuss with you.

First, the incidence of COVID-19 suggests that it is highly possible to collect positive samples in a proper time.

Academician Yuan Guoyong’s team conducted this cohort study in Hong Kong Princess Margaret Hospital and Queen Mary Hospital. From January 22 to February 12, 2020, 23 hospitalized patients who were diagnosed as COVID-19 by laboratory examination of nasopharyngeal or sputum specimens were screened in the two hospitals.

A total of 173 respiratory specimens were collected from 23 patients. The researchers used RT-QCPR to determine the viral load in the samples. The results showed that the median viral load of respiratory tract samples was 5.2 log10 copies /mL (interquartile range was 4.1-7.0), and only 3 patients (13%) did not detect Covid-19 RNA in saliva samples.

The researchers observed that,The viral load in saliva was the highest in the first week after the patient developed symptoms, and then gradually decreased.Eight days after the patient developed symptoms, airway extracts were collected, and there was no obvious downward trend in viral load. Of the 21 patients who did not die,Seven people (33%) could still detect viral RNA after 20 days of symptoms, but this was not related to the severity of the disease.

▲ Changes of viral load in saliva (blue line) and airway extract (red line) of all 23 patients. Abscissa D- days after symptoms appear; S/E- number of saliva/airway samples.

AprilAccording to a study published in Nature Medicine, COVID-19 patients are most infectious before symptoms appear, and they begin to shed SARS-CoV-2 2 2-3 days before the first symptoms appear.

https://doi.org/10.1038/s41591-020-0869-5

The study, led by Eric Lau of the University of Hong Kong, involved 94 patients with COVID-19 admitted to the Eighth People’s Hospital of Guangzhou, China, 50% of whom were male, with a median age of 47 years. Among them, 61 of 93 patients were mild. Specifically, the researchers collected the throat swabs of 94 COVID-19 patients who were treated in the Eighth People’s Hospital of Guangzhou, China from January 21st to February 14th. From the onset of symptoms to 23 days after onset, 414 throat swabs were collected.

The results show that the researchers areThe high viral load was detected shortly after the patient developed symptoms, and then gradually decreased to the detection limit around the 21st day.There is no significant difference in viral load among different sexes, age groups and disease severity.

In addition, the researchers also analyzed 77 samples of "transmission pairs" from public data to assess how much time passed between the onset of symptoms in each patient. It assumes that the median incubation period (the time from infection to symptoms) is 5.2 days.The research team concluded that infectivity began 2.3 days before symptoms appeared, and peaked 0.7 days before symptoms appeared.

In the sensitivity analysis, the same estimation procedure is used, but assuming that the infectious attack is unchanged 1-7 days before the symptom occurs, thenIt was found that the infectivity reached its peak 0-2 days before the onset of symptoms, and the transmission ratio before the onset of symptoms was 46% to 55%.

The study also found that,The virus may start shedding 2-3 days before the first symptoms appear.After the symptoms appear, the viral load in the patient’s body decreases faster. This is consistent with the results of two recent studies. On April 1st, teams from Munich, Germany, Berlin and Cambridge, England published the article "Viro logical assessment of hospital patients with Covid-2019" on Nature. It was found that the shedding peak of Covid-19 occurred in the early upper respiratory tract infection.This shows that virus carriers may be the most infectious when they have mild symptoms or almost no obvious symptoms.

Brother Hong:From the above two documents, we can draw a conclusion that the virus shed and spread 2-3 days before the symptoms appear after infection, and after the symptoms appear, with the passage of time,The viral load of throat swab decreases gradually, and the viral load detected within 7 days after symptoms. If symptoms have existed for more than 20 days, the reliability of negative conclusion of throat swab is poor.

Solution:We need to publicize the law of the new crown to the people and medical workers, and improve our vigilance against COVID-19. It is best for patients to see a doctor in time, and doctors can also suspect this possibility. Only at the right time can we collect high-content samples and diagnose and control them in time.

Second, accurate sampling strategy is the best means to reduce false negative results.

In February, a study published by Medrxir, a pre-printed website, collected respiratory tract samples such as nasal swab, throat swab, sputum and bronchoalveolar lavage fluid (BALF) from patients diagnosed with COVID-19, and included 213 Covid-19-infected patients admitted to the Third People’s Hospital of Shenzhen from January 11th to February 3rd, 2020, who were diagnosed by Guangdong CDC. A total of 866 respiratory tract samples, including 490 nasal swabs, 205 throat swabs, 142 sputum samples and 29 BALF samples, were collected at the time of admission and after each time point. According to the collection date, the samples were divided into 0~7 days, 8~14 days and ≥15 days after onset. According to the guidelines on prevention and treatment of Covid-19 infection issued by National Health Commission, patients were divided into severe and mild cases.

Three groups were divided according to the sample collection time after onset, and the viral nucleic acid was quantitatively determined.The positive rate of viral nucleic acid in sputum samples was the highest in the group of 0~7 days after onset.The positive rates of severe and mild cases were 88.9% and 82.2% respectively.Followed by a nasal swab.(73.3% and 72.1% respectively),The throat swab again.(60.0% and 61.3% respectively). In mild cases, the positive rate of nasal swab and sputum samples is similar.

The positive rate of BLAF samples collected from 8 to 14 days after the onset of severe cases was 100%.However, the BALF samples of 3 mild cases were negative. In all cases, the positive rate of sputum samples was the highest in the 8~14 days after onset, which was much higher than that of nasal swab and throat swab. It is worth noting that the positive rate of throat swab in severe patients is only 50%, and that in mild patients is only 29.6%.

In the group ≥15 days after onset,The positive rates of BALF, sputum and nasal swab from severe cases were similar. In mild cases, the positive rate of sputum and nasal swab is similar, which is much higher than that of throat swab.

For the diagnosis of viral nucleic acid in COVID-19’s patients,Sputum samples are the most accurate, followed by nasal swabs. It is not recommended to collect throat swabs for diagnosis.

The difference between oropharyngeal swab and nasopharyngeal swab

anusswab

Brother Hong:

1. Oropharyngeal swab is the least painful and most acceptable, but it has to bear the consequences of high false negative results. My suggestion is to use it according to the epidemic risk in the first epidemic area.

2. The positive rate of nasopharyngeal swab is higher than that of oropharyngeal swab, which is why nasopharyngeal swab is introduced into laboratory examination in the fifth edition of Diagnosis and Treatment Plan for Pneumonia Infected by Covid-19 (the fourth edition is still pharyngeal swab). If we want to pursue accuracy, it is suggested to use it, or to use it when screening people in close contact or sub-close contact. At present, the examination of returnees in domestic reports seems to be nasopharyngeal swab method.

3. Alveolar lavage fluid can’t be used for screening in the general population, so it is suggested that hospitals with ICU should use it for screening severe pneumonia patients living in ICU for COVID-19 patients.

4. Deep expectoration seems to be the best sample, but many patients in COVID-19 have a dry cough, which may not be possible.

5、anusSwabs were used in Daxing epidemic in Beijing, which is the first time to use this method in the screening process. In some literatures,anusAlthough the positive rate of swabs is not high, as I remember, it seems to be more than 10%, but it does not seem to coincide with the patients with oropharyngeal swabs, suggesting that the virus may attack the gastrointestinal tract, and also suggesting that there may be the possibility of gastrointestinal transmission in Covid-19. Although the initial symptoms of some patients are gastrointestinal symptoms such as abdominal pain and diarrhea, there are also ACE2 receptors in the digestive tract, which is theoretically possible, but it has not been confirmed at present. So,anusMy suggestion is that swabs can only be used as a supplement to nasopharyngeal swabs, and it is better to select patients whose first symptoms are digestive tract symptoms more accurately, which is unlikely to be used as a means of large-scale screening.

Solution:It is best for National Health Commission to issue a guiding document for large-scale screening, and make detailed regulations on what population and what sampling methods to adopt under what circumstances.,When local governments encounter an outbreak in COVID-19, it’s best to ask professionals to act as consultants and make choices according to the actual situation.

Third, the consistency of sampling ability of sampling personnel affects the sampling results.

Garbage in, garbage out (garbage samples produce garbage results), which is a sentence that inspectors often say.

The sampling team is huge, and the ability of sampling personnel must be uneven. In addition, people may have such fears about sampling, which often leads to unqualified samples.

Generally, there is an internal standard in the molecular diagnostic reagent to monitor the detection process, for example, RNaseP is used as the internal standard. If both the sample response curve and the internal standard response curve displayed by the fluorescence PCR platform do not jump, it means that the quality of the collected samples may have problems or false negatives may occur due to improper experimental operation, which needs to attract the attention of medical workers. The RNaseP internal standard can monitor the sample collection and ensure the accuracy of the test results.

Note: RNaseP is ribonuclease P, which is one of the most important ribozymes in human body. It is ubiquitous in all organs, tissues and cells of human body, and can detect RNA nucleic acid fragments from human body samples, and can also be used as an internal standard.

And I privately asked the relevant person in charge of our city’s temporary inspection center. He told me that every day in our hospital, some samples were told that they needed to be re-sampled because the internal standard did not jump. Imagine that you didn’t wipe down a few cells in your throat swab collection, so will the negative of this nucleic acid be accurate?

Solution:Consistency training for nucleic acid sampling personnel will greatly reduce the human influence, and it is easier to standardize the sampling process by taking such sampling methods as nasopharyngeal swab. Our city seems to have trained the nucleic acid emergency sampling team very early. What about your city?

In addition, if in the environment of large-scale nucleic acid sampling, when testing under the standard of 5-mixed 1 and 10-mixed 1, according to the above principle of internal standard, it seems that there is no single-tube ability in the quality control of internal standard. Therefore, especially those in the emergency sampling team, we must pay attention to the standard sampling methods and remember to collect qualified samples as much as possible.

Fourth, choose the right oneSampling device

The virus preservation tube mainly consists of a sampling swab and a virus nucleic acid preservation tube (containing virus nucleic acid preservation solution). There are many kinds of virus preservation tubes on the market at present.It is very important for epidemic prevention and disease diagnosis to choose the appropriate virus preservation tube, reduce the infection risk of medical inspectors as much as possible, and keep the virus RNA stable without degradation..

The preservation solution UTM used in traditional virus collection tubes is based on Hank’s solution, with gentamicin, fungal antibiotics, BSA (V), cryoprotectant, biological buffer and amino acids added. Its main purpose is to maintain the virus activity within a certain temperature range, so that it is convenient for health and epidemic prevention departments to further isolate, culture and trace the virus and determine the pathogen. This kind of non-inactivated tube, which I call it, is good for further work, but the sameLive virus increases the infection risk of medical staff in the whole process of sample collection, transportation and testing!Personally, I think this kind of sampling tube for inactivated virus should be a better choice for disease control sampling.

And clinicalIn order to achieve the purpose of rapid detection, it is not necessary to cultivate the virus, but only to crack the virus, so as long as the integrity and stability of the virus nucleic acid can be guaranteed.nowCommonly known as inactivation tube.Many inactivation tubes in China are used.The inactivation component is guanidine salt, which is in this inactivation tube in our hospital.Guanidine salt can crack the virus, but it can’t protect the integrity of nucleic acid for a long time.The virus nucleic acid may have been degraded during the delivery of the sample to the laboratory, which will also cause a "false negative" in the detection. Many studies show that both temperature and time can affect the test results, so the COVID-19 Laboratory Testing Guide has clear requirements for samples to be tested within 24 hours after collection and transported at 4 degrees Celsius. If it is necessary to exceed 24 hours, it should be stored at -70 degrees Celsius.

And some manufacturers put forward another inactivation tube, a kind of.containNon-guanidine saltThe virus preservation tube containing protein denaturant can inactivate the virus and ensure the preservation of virus nucleic acid at room temperature.And the virus nucleic acid is stably stored for 7 days.Does not degrade.

Solution:

1, from sampling to testing, it is necessary to mark the time, so that quality control can be carried out on the preservation time, which is basically no problem in a better hospital.

2. For the front-line staff to do the corresponding training, they should know the advantages and disadvantages of various types of preservation tubes and adopt the best sampling tubes suitable for local conditions.

3. It is best for the country to recommend the selection of sampling tubes with the support of relevant experimental data.

5. Failure of reagents caused by virus mutation?

After the virus mutation in South Africa, Britain, Brazil and other places, there have been cases that turned positive after ten tests in various parts of the world, including China.The FDA recently warned that virus mutation has caused some reagents to fail, and listed several kits that may be affected by mutation. This means that virus mutation may have led to the failure of some nucleic acid detection or persistent false negative.

The FDA listed several kits that may be affected by mutation:

Accula SARS-Cov-2 detection (Mesa Biotech): If the virus mutates at the 28881st base (GGG to AAC), the detection of this kit will be affected;

TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific): This kit detects three genes at the same time, and the variant B.1.1.7 appearing in Britain will affect one of the detection results;

Linea COVID-19 detection (Applied DNA Sciences): This kit detects two genes at the same time, and the variant B.1.1.7 appearing in Britain will affect one of the detection results;

Helix, an American company doing nucleic acid detection, also noticed the influence of virus mutation on detection. The company’s nucleic acid detection simultaneously detected three Covid-19 genes: ORF1ab, N, and S. Because the B.1.1.7 strain that appeared in Britain had deletion mutation in S gene, ORF1ab and N could be detected in the detection, but S gene could not be detected (4). This phenomenon is called "S gene withdrawal".

In addition, the sensitivity of reagents from different manufacturers to COVID-19 is different, and the country also organized a national evaluation of reagents last year. butIn an evaluation study on the consistency and detection ability of seven domestic novel coronavirus nucleic acid detection kits published by Chinese Journal of Laboratory Medicine in July, 2020, it was proposed that "some kits have poor detection ability for weakly positive samples,It is suggested that weak positive samples should be rechecked by kits from at least two manufacturers to ensure the accuracy of the results."

Several targets of nucleic acid detection in Covid-19 are ORF1ab gene, N gene and S gene.

In the Technical Guide for Laboratory Detection of Pneumonia Infected in novel coronavirus issued by China CDC (hereinafter referred to as the Technical Guide), the two targets of nucleic acid detection in Covid-19 are ORF1ab gene and N gene respectively.

On January 6th, the Weekly Report of China Center for Disease Control and Prevention published the results of gene sequencing analysis of two cases of Covid-19 infection in Shijiazhuang and Xingtai. According to the published results, the strain prevalent in Gaocheng, Hebei Province, is different from the strain found in other places in China recently, and is homologous to the strain reported in Russia last July, belonging to strain B.1.1.123

Coincidentally, the mutation happened at the 28881 ~ 28883 bases of the virus gene of this strain, and this is exactly the position of the forward primer of the N gene!

This also explains why there were many negative results at that time.

I guess this is one of the reasons why the criteria for judging nucleic acid positivity have also changed.The judgment position that the single target is still positive after retest is positive.

Figure/Current Criteria for Judging Positive Cases in Technical Guide

Solution:

1. Require manufacturers of nucleic acid reagents to conduct confirmatory experiments on the current mutant strains and propose technical solutions.

2, all localities should introduce at least two kinds of better quality detection reagents, for control use.

3. Information about the failure of test reagents that may be caused by mutated viruses should be effectively and widely reported in domestic laboratories.

Six, the standard implementation in the process of laboratory testing

the pastAccording to the guidelines issued by relevant institutions, the collected samples need to be inactivated at 56℃ before nucleic acid detection, which is very likely to degrade the Covid-19 nucleic acid, which will lead to the failure of normal detection and ultimately improve the false negative rate.In the early daysInactivation treatment is carried out for the sake of biological safety, to protect the staff engaged in testing from virus infection.

But later, there were many voices of doubt in the academic circles, becauseViral RNA is easily degraded by ribonuclease, because this enzyme has the highest activity at 60℃. Ribonuclease comes from two aspects, one is the sample cells, and the other is the foreign pollutants in the process of collection, preservation and transportation.

Last February, there was a similar research article.The high-temperature inactivation process before virus nucleic acid extraction significantly reduces the amount of detectable virus nucleic acid templates, which has been pre-published on the platform of scientific papers of China Academy of Sciences.

And last May,The Journal of Clinical Chemistry published the research of Chinese scholars on Covid-19’s false negative test.The study confirmed that,Thermal inactivation can cause the increase of Ct value reflected by PCR and cause false negative results.Specifically, 46.7%(7/15) of the weakly positive samples were false negative after inactivation (a surprising proportion). Another inactivation method is to inactivate the virus by dissolving the virus protein with guanidine hydrochloride. This study confirmed that guanidine hydrochloride had little effect on PCR reaction, and the false negative rate was low, although there was also a false negative rate of 13.3%(2/15).

Related address: https://academic.oup.com/clinchem/article/66/6/794/5815979

I also inquired whether there was a 56-degree inactivation step in the detection process of CDC in the United States. Although my English ability was poor, I didn’t see this step by machine translation.

Including some other documents retrieved, it is also very clear that 56-degree inactivation does have a great influence on weakly positive specimens.

No matter the Manual of Nucleic Acid Detection in Medical Institutions in novel coronavirus (Trial) on July 13th, 2020 or the Manual of Nucleic Acid Detection in Medical Institutions in novel coronavirus (Trial 2nd Edition) on December 30th, 2020, there are corresponding descriptions.For the laboratory that has been inactivated with the sampling tube containing guanidine salt, there is no need to inactivate at 56 degrees for 30 minutes.This is only true if non-inactivated sampling tubes are used.


However, I learned from the familiar laboratory leaders that this is not the case. Many laboratories still require samples to be pretreated at 56 degrees for 30 minutes regardless of whether the tubes are inactivated or not. I can understand that they are worried about hospital infection and laboratory exposure. But generally speaking, reducing the false negative rate, increasing the detection amount and taking corresponding measures to control the epidemic situation as soon as possible, I think the corresponding suggestions in the corresponding guidelines are also the best choice from the overall situation and supported by data.

Our laboratory should not control the occurrence of hospital sensation and laboratory exposure at the expense of reducing the detection rate, but should focus on stricter control of experimental steps, more cautious PPE wear and higher laboratory environment.

Solution:

1. It is suggested that the state give special instructions to laboratories at all levels on this matter.

2. It is suggested that the country should further study the preservation solution of sampling tubes, and if there is any preservation solution that can not reduce the detection rate at 56 degrees for 30 minutes, it can also be recommended.

The above zero zero always said a lot of points, mainly about how to reduce false negative conclusions, hoping to give you a reference.

It’s been many days since I wrote this afternoon, mainly considering Spring Festival travel rush. Although the scale of Spring Festival travel rush is reported to have dropped by more than 75% this year compared with previous years, the population flow is still very strong. We may face the rising trend of an epidemic after Spring Festival travel rush, and how to make the work better may be a more urgent need before us.