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Original porridge medical digestive liver disease channel included in the topic #2020 CGC18.

I’ve heard of many kinds of vaccines. Is there an Hp vaccine?

Speaking of Helicobacter pylori (Hp), I think everyone is familiar with it. Hp is a gram-negative spiral bacteria, which mainly spreads from person to person through oral route [1]. The infection rate of Hp in Chinese is very high, exceeding 50%, and the current research proves that Hp has an ambiguous relationship with gastric cancer, and the World Health Organization (WHO) has identified it as a grade I carcinogen of gastric cancer.

Traditional treatment has always relied mainly on acid inhibitors combined with antibiotics to eliminate Hp to treat related diseases caused by it, but the abuse of antibiotics has led to the rising drug resistance rate of Hp. So, can we eradicate Hp? I’ve heard of many kinds of vaccines. Is there an Hp vaccine?

At the just-concluded 20th National Academic Conference on Digestive Diseases of Chinese Medical Association, Professor Zou Quanming from the Biopharmaceutical Teaching and Research Section of the Department of Pharmacy of Army Military Medical University gave a wonderful report on the theme "How far is Hp vaccine from us?".

Do we need Hp vaccine?

First of all, Professor Zou Quanming raised a question: Do we need Hp vaccine?

▎Hp is closely related to gastric cancer and has serious harm.

At present, there are three different views on Hp in the medical field:

1. The pathogenicity of Hp is serious, and vaccine is needed for radical cure;

2. Hp is still helpful to the human body, even probiotics;

3. Hp and human beings have coexisted for a long time, and their existence is reasonable.

These different viewpoints have seriously affected the research and appearance of Hp vaccine.

According to the data released by the National Cancer Center in 2017, there are about 680,000 new cases of gastric cancer in China each year, accounting for nearly one-third of all cancers in China, accounting for about 50% of the total incidence in the world, and the mortality rate also accounts for about 50% of the world total. Hp infection can almost always cause active inflammation of gastric mucosa. On the basis of chronic inflammation, some patients can also develop a series of diseases such as peptic ulcer and gastric cancer (1%).

Hp infection has brought great disease burden and economic loss to people, but at present, people pay insufficient attention to Hp. Professor Zou Quanming emphasized that Hp is very harmful and we need Hp vaccine.

▎ At present, antibiotics are used to treat Hp, but the symptoms are not cured.

Traditional treatment has always relied mainly on acid inhibitors combined with antibiotics to eliminate Hp to treat related diseases, but antibiotics can only eliminate the existence of individual Hp or suppress its proliferation, and can not achieve the goal of eradicating Hp for the whole society. And the drug resistance caused by frequent use of antibiotics, such as clarithromycin and metronidazole, has become a serious problem in some countries. In addition, the use of antibacterial therapy to eradicate Hp is not sustainable. In some countries, the annual recurrence rate of Hp is as high as 15%-30%.

Professor Zou Quanming said that China, Japan, South Korea and other countries in the Far East, including many countries in Eastern Europe, have a high incidence of gastric cancer. Under the condition of extensive vaccination, even if the hidden Hp infection of patients is not detected, the incidence of gastric cancer can be reduced. In developed countries, it is calculated that a 10-year vaccination program can greatly reduce the prevalence of ulcer and gastric cancer caused by Hp, and also reduce the incidence of related diseases and economic losses.

Basic questions to be answered in Hp vaccine research

However, the research of Hp vaccine is not smooth sailing. Professor Zou Quanming pointed out that it is very difficult to study Hp vaccine and the following problems need to be solved:

1. Why is the immune response caused by natural infection of the host not protective?

2. What are the mechanisms and differences between immune protective response and pathological injury?

3. Screening and transformation of vaccine effective antigen?

In addition, the immune mechanism of Hp infection is very complicated.

Figure 1: Infection immune mechanism of 1：Hp

Research progress of preventive Hp vaccine

Next, Professor Zou Quanming introduced the research progress of Hp vaccine at home and abroad:

Figure 2: Research progress of Hp vaccine at home and abroad.

Professor Zou Quanming and his research team established the strategy of "intramolecular adjuvant mucosal vaccine of Hp", which has been verified by practice. This technique can produce sIgA antibody in gastrointestinal mucus (which is completely different from serum IgG antibody), thus blocking Hp infection.

Fig. 3: Mechanism of action of intramolecular adjuvant mucosal vaccine of 3：Hp.

Animal experiments show that the protective rate of the oral recombinant Hp vaccine in mice, rats and rhesus monkeys is more than 80%.

In addition, Professor Zou Quanming and his research team established an efficient system for screening components of Hp vaccine for the first time, and successfully constructed an engineering strain of Hp vaccine that can be used for production. More than 300 strains of Hp and more than 1,500 candidate protein components were collected from patients in 20 provinces and cities in China, and finally the Hp vaccine components were selected, and an efficient and stable vaccine purification process was established. The purity of the produced vaccine protein was over 80%, and the output was 400,000 mg/time (reaching the production scale).

In 2015, the clinical research results of "Oral Helicobacter pylori vaccine phase III" conducted by Professor Zou Quanming and his research team were published online in the top medical journal The Lancet.

Figure 4: The research results are published online in The Lancet.

In this study, more than 30 technical specifications, standards and experimental detection technologies necessary for human clinical trials of Hp vaccine I, II and III were established. And through the invention and creation of the above key technologies, more than 4,000 volunteers aged 6-15 have been developed and completed in phase I, II and III human clinical trials.

Figure 5: Distribution and shedding of subjects

Figure 6: Analysis results of infection prevention effect

The results showed that there were 64 cases of Hp infection during the follow-up period, that is, 14 cases were infected in the vaccine group (2025 people) and 51 cases were infected in the control group (2058 people). The total protection rate of oral recombinant Hp vaccine against infection was 71.8%.

In terms of safety, 157 (7%) people in the experimental group and 161 (7%) people in the control group had one or more adverse reactions during the study. Among them, 5 (< 1%) people in the experimental group and 7 (< 1%) people in the control group had serious adverse reactions, but they all thought it had nothing to do with vaccination [2].

This shows that oral recombinant Hp vaccine is "effective, safe and immunogenic" among children who are not infected with Hp, which can significantly reduce the incidence of Hp infection.

Professor Zou Quanming said that he also took the Hp vaccine at that time. Up to now, he has been tested for Hp once a year, and the results have been negative.

This study is the first phase III trial of Hp vaccine in the world. Professor Philip Sutton of Melbourne University in Australia made a special comment on this study: "The successful development of this vaccine has taken an important step towards preventing gastric cancer caused by Hp. This will rekindle human passion for this important topic, further encourage more investment, and promote continuous progress in this field through in-depth clinical trials. "

The Hp vaccine is still in the approval stage and has not been approved for marketing. At the scene, Professor Zou Quanming also expressed his expectation and called on academic organizations and Hp study groups to jointly promote the listing of Hp vaccine.

Reference source:

[1] Chinese Medical Association, et al. Guidelines for primary diagnosis and treatment of Helicobacter pylori infection (2019). Chinese Journal of General Practitioners .2020,5 (19) 5.

[2]Ming Zeng,Prof Xu-Hu Mao,et,al.Efficacy, Safety, and Immunogenicity of an Oral Recombinant Helicobacter pylori Vaccine in Children in China: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial.The Lancet.2015,6(30).

Review of this article

Professor Cao xiaocang

Chief physician, professor, master tutor of Tianjin Medical University General Hospital of Gastroenterology.

Member of Digestive Endoscopy Committee of Inflammatory Bowel Disease Group of Digestive Branch of Chinese Medical Association.

Vice Chairman of the Youth Committee of Behavioral Medicine Branch of Chinese Medical Association

Member of Clinical Epidemiology Collaboration Group of Digestive Branch of Chinese Medical Association.

Member of Inflammatory Bowel Disease Group, Committee of Gastroenterology Branch of China Medical Equipment Association.

Member of anorectal difficult disease Committee of inflammatory bowel disease Committee of anorectal physician branch of Chinese Medical Doctor Association

Member of Expert Committee of Inflammatory Bowel Disease, Gastroenterology Professional Committee, China Society of Integrated Traditional Chinese and Western Medicine.

Member of the Expert Committee of Inflammatory Bowel Disease of Beijing Medical Award Foundation.

Standing Committee of Inflammatory Bowel Disease Alliance of Wu Jieping Medical Foundation, Standing Committee of Intestinal Microecology Professional Committee

Standing Committee of the Committee of Stem Cell Engineering Technology Branch of China Biomedical Engineering Society

Vice Chairman of Inflammatory Bowel Disease Group of Gastroenterology Branch of Tianjin Medical Association

This article starts: medical digestive liver disease channel

Author: CGC report group porridge

Original title: Helicobacter pylori vaccine, how far is it from us? 》

Read the original text

Xinhua News Agency, Zhengzhou, October 21st Title: Innovation of Science and Technology Broadens the Road to High-quality Employment

Xinhua News Agency reporter Han Chaoyang

In 2020, there will be 278,000 high-tech enterprises in China, which will provide 38.588 million jobs. During the National Mass Entrepreneurship Innovation Week in 2021, innovation and entrepreneurship in the field of science and technology promoted high-quality employment, which became the consensus of experts attending the main venue in Zhengzhou.

Zhang Mu, a second-level researcher at the Torch Center of the Ministry of Science and Technology, said at the High-quality Development Forum of Science and Technology Innovation in the New Era held recently that since 2014, all kinds of science and technology entrepreneurial service institutions have sprung up all over the country, achieving a leap-forward growth, and it will grow to 14,500 in 2020, serving nearly 680,000 entrepreneurial teams and enterprises, and its support for science and technology innovation is increasing day by day.

At the same time, the integration mechanism of scientific and technological achievements transformation and innovation and entrepreneurship has gradually taken shape. By the end of 2020, more than 2,100 new R&D institutions with R&D, transformation and incubation functions have been established nationwide to accelerate the commercialization of scientific research results and support industrial technological innovation.

At present, high-tech enterprises account for 25.2% of the total number of industrial enterprises in China, achieving 33.4% of operating income and 40.3% of total profits. In 2020, domestic invention patents authorized by high-tech enterprises accounted for 49.2% of the country.

Experts attending the meeting generally believe that after opening up the chain of application research and development, transfer and transformation, business incubation and industrialization, the main position of technological innovation of enterprises has been greatly improved, and the role of technological innovation in driving high-quality employment has become increasingly prominent.

"Technological innovation drives the migration of occupations, industries and even social structures." Mao Daqing, founder and chairman of Youke Workshop, said at the "Science and Technology Innovation China" new era entrepreneur talk activity that the technological revolution promotes the transformation and upgrading of traditional industries, and technological innovation is the core of the industry transformation and upgrading. In this process, some low-creative jobs will be replaced, a large number of new jobs will be created, and at the same time, knowledge and technology upgrading of some jobs will be promoted.

It is reported that high-tech enterprises will provide 38.588 million jobs in 2020, among which 516,000 new college graduates will start businesses.

Participants pointed out that in the process of technological innovation, financing difficulties are still the shortcomings of technological innovation. "Scientific and technological innovation needs ecological environment, innovative talents are seeds, venture capital is sunshine, and market environment is soil." Yuan Hongwei, the founding partner and chairman of Zhuo Yuan Capital, believes that the long-term continuous positive movement of the three elements can create a good innovation ecology, but the low proportion of long-term capital is the shortcoming of the current innovation ecology.

China Science and Technology Innovation Work Development Report 2020 issued by Torch Center of Ministry of Science and Technology also points out that the financing difficulties of start-ups are more serious. After the epidemic, venture capital funds, bank credit and other financing channels pay less attention to start-ups and lack capital support channels.

Yuan Hongwei said that he hopes that more social resources can be allocated to this field and contribute to creating a good innovation and entrepreneurship ecology.

Special feature of 1905 film network Director and screenwriter Anxian Lü never thought that the movie (hereinafter referred to as "Than Sadness") could achieve such high results at the box office. In the eyes of the outside world, while their creation caused a sensation, it would be followed by pressure.

Admittedly, the two did worry in a short time. How to make a difference between the next work and Than Sadness? Will you have greater expectations for yourself?

After calming down, they found that the answer turned out to be no, so it is better to devote themselves more to their creation.

Perhaps from the outside world, Friends of the Week and Than Sadness have many similar keywords: remake, illness, emotion &hellip; &hellip;But in fact, Lin Xiaoqian and Anxian Lü took over Friends of the Week much earlier than the latter.

Although the outside world always thinks that Lin Xiaoqian has made many works with youthful elements, in reality, he has never really made a youth film in school uniform. So, he hit it off with the screenwriter Anxian Lü, so it’s better to say goodbye to their youth with Friends of the Week.

Just like the movie slogan, "Let’s meet! Summer and friendship can’t live up to it. " Then, what kind of work will "Friends of the Week" come slowly after "Than Sadness"?

A different adaptation

The original "A Week’s Friends" is a well-known Japanese girl, who has produced an animated series and a live-action movie, which is quite difficult for the China version.

Whether it is localization or difference, these old-fashioned topics have long appeared in the plans of directors and screenwriters. While the audience was still wondering whether the director would remake the story frame by frame, the screenwriter had already made a subversive adaptation of the story.

Just like the title of the film, time memory is the starting point of the work itself, and emotion is just a branch line that spreads along it.

So does human memory lie? There may be no solution. After all, the Mandela effect tells us that people sometimes have some false memories. Director Lin Xiaoqian grasped this point, "I want to differentiate between memory and truth and falsehood."

Screenwriter Anxian Lü also thinks that many plots in the original work are difficult to happen in China, and even some emotional expressions are not in line with everyone’s cognition, so it is better to make some more daring and exciting adaptations on the basis of following the original story.

As a result, the first half of the story of Friends for a Week retains the logic of the original story, but it is subverted later and expanded more richly.

To this end, the team also translated the script into Japanese and handed it to the original author. "I didn’t expect you to have such an idea." The new idea surprised Ye Yue Matcha very much.

Since youth can’t stay, it’s better to make youth more dreamy. In Anxian Lü’s view, everyone in youth has an unconstrained style.

Lin Xiaoqian, the director, also didn’t want to make the story too realistic, with some fantasy, like the cup of Corbis in the summer afternoon, with refreshing bubbles.

So, he planted a small egg in the movie.

"In the scene where Lin Xiangzhi went to buy a goldfish, she bought a goldfish on an overpass. The street lamp of that overpass caught a glimpse, but what did it look like?" He made a wonderful change to the street lamp. Is it a lamp or something else? Whether Lin Xiangzhi is in reality or divorced from reality, "whether it is true or not, perhaps the answer lies in the hearts of the audience."

Compared with the original infatuation with love, Friends of the Week focuses on the relationship between four good friends.As Lin Xiaoqian said, "Our youth is not so ignorant of love, but more firm and fettered by youth friendship."

The casting of youth

Emotional touch, the audience is looking at resonance and empathy, cp will add points, and the emotional ties between friends are the same.

"Friends of a Week" not only puts pen and ink on the man and woman, but also allows the audience to see the friendship between the four friends, extending from the film to the outside.

When casting, Lin Xiaoqian and Anxian Lü were very sure that the actor’s age should be similar to the role, otherwise it would be distorted.

It was first decided, and then Angel recommended Lin Yi to visit Chengdu, during which he met the director and contributed to this cooperation.In Lin Xiaoqian’s eyes, "Lin Yi is the perfect candidate".

Before the audition, Lin Xiaoqian saw a lot of Lin Yi’s past works, but most of them were cold and handsome images of Xueba, and never had a similar temperament to Xu Youshu. "I was worried at that time." Later, the director designed a method &mdash; &mdash; Find a unique flavor of essential oil for each character.

In a scene where Xu Youshu and Lin Xiangzhi quarreled, the director told Lin Yi, "From today on, this smell will disappear from your life." The words sound just fell and Lin burst into tears for an instant. Even later, when the dubbing was made up, the director took out the taste again. "He told me that the director should not come. Now when he smells this smell, he will think of the scene of quarreling with Jinmai."

So, what do they all smell like? "Today’s wheat is a Bulgarian rose, and Lin Yi is a lavender."

Not only that, but a lot of shooting work has brought the team back to youth. In order to reflect the atmosphere more truly, the director found the college entrance examination paper with the corresponding time background, taught Angel to solve problems with PK on the spot, and taught Lin Yi to draw auxiliary lines.

Filled with youthful breath, Lin Xiaoqian and Anxian Lü recalled that they were all infected.

Because the screenwriter Anxian Lü wrote a lot of underwater scenes, the director Lin Xiaoqian frequently shouted, "The water scene was filmed for 8 days, and I really’ collapsed’." It is even more difficult for the actors with poor water quality. Even so, everyone still worked hard to complete the filming.

"After we finished filming the water show, the actors all threw us into the water." Celebrations among young people are always full of vitality.

Fantasy shooting

As a matter of fact, the arrangement of water play once made the screenwriter in a dilemma.

In the middle of the story, it is necessary to arrange an accident. The original story is a car accident. "But I don’t want it to be a car accident. Everyone has already filmed it. I want to write something special." Anxian Lü knows that no matter how to deal with it, there will be a spit, so it is better to follow his own creation.

Because the film "Friends for a Week" was shot in Chengdu, there are many lakes around. In the pastoral investigation, Anxian Lü found that there were many similar accidents in Chengdu. Not only that, but this design can be more realistic and close to the struggle of the victims’ inner choices and self-suggestion.

In addition to underwater scenes, director Lin Xiaoqian also unlocked many new ways of playing in Friends for a Week.In the movie, four friends turned the abandoned astronomy classroom into a secret base.

Anxian Lü specifically noted in the script whether it can be realized by case-by-case animation. Finally, the director filmed the whole day for the scene that lasted only a few minutes, and then invited an animator to complete the imaginary effect.

Compared with the creation of many real movies, this form of frame-by-frame animation will often appear in music movies (MV), and the implantation of novel forms will naturally face many doubts.

Whether it’s MV shooting or innovation, Lin Xiaoqian is not worried about the audience’s opinion. After all, the film has developed for more than a hundred years, and the most attractive place is to create it with images. Even in the later period of Friends of the Week, the director did a lot of tricks in mixing. "We will mix the bass with the stress and the drums will be very clear."

The partner is not stingy with his praise for the director. "This is already the director’s style, and" Friends of the Week "is not a realistic theme. We hope to have a space for imagination and play."

If so, "Friends of the Week" may be half finished in production.The remaining half, everything is handed over to the audience. For the director and screenwriter, the next project has already started.

It’s just that after two consecutive remakes, people can’t help wondering whether they will return to the original script.

Anxian Lü told us that his next work is an original project. Lin Xiaoqian sold a pass. "I really want to shoot a story about the combination of soft science fiction and love."As for the story, "I don’t want to give myself that burden."

　　Beijing News: Domestic revolvers weighing 0.70 kg and equipped with rubber warheads will be distributed to frontline patrol police in the near future to replace the existing standard pistols. At present, the gun has been distributed to all district and county public security bureaus in Beijing and stored in gun depots, and the police have also started shooting training.

　　It is understood that the revolver magazine can hold six bullets, with small recoil and high shooting accuracy. The effective and accurate killing distance is about 50 meters, and the current standard pistol has an effective killing distance of 150 meters.

　　The main reason for changing guns this time is to avoid unnecessary fatal shots. Judging from the effect, the revolver has a strong deterrent, while the gun is slightly less powerful, so there will be no situation that "the bullet penetrates the suspect and hurts the nearby people". After the suspect was shot, he basically lost his combat effectiveness and would not be killed on the spot. Revolvers can be equipped with steel warheads and rubber warheads, and frontline patrol police will mainly use rubber warheads in their daily patrols. As long as you avoid the weak parts such as the eyes and ears of the target person, the rubber warhead will not be fatal.

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