How to prevent and control asymptomatic infected people? Interpretation of expert appearance

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On the evening of April 16, Hou Jinlin, director of the Liver Disease Center of Southern Hospital of Southern Medical University and director of Guangdong Institute of Liver Diseases, accepted the invitation of the future forum to share the theme of "Talking about asymptomatic infection in novel coronavirus from the clinical characteristics and prognosis of viral infection" online, and professionally explained how to find asymptomatic infected people. And how to prevent and control it to reduce its spread and other epidemic-related issues that everyone cares about. The following is the full text of Professor Hou Jinlin's speech:

Hou Jinlin: Thank you very much for inviting me to participate in the future forum and share some experiences about COVID-19 infection. I am a staff member of the infection department of Southern Hospital. About 80% of my work is mainly engaged in the treatment of liver diseases, and the other 20% is dealing with other infectious diseases. This time, I was temporarily transferred to Jingzhou, Hubei Province, responsible for the prevention and treatment of COVID-19. Tonight, I want to share with you some of my own knowledge, including the indicators of aggravating early warning in COVID-19, the data of asymptomatic infection and so on. These data have not been published so far, please criticize and correct me. The topic I discussed with you is "Talking about asymptomatic infection in COVID-19 from the clinical characteristics and prognosis of viral infection".

First of all, let me give you a report on our situation in Honghu. Recently, asymptomatic infection has attracted everyone's attention as a hot spot. Let's take a look at the characteristics of general virus infection to further understand asymptomatic infection. In fact, COVID-19 can cause various disease spectrums, and there are some early warning indicators in clinic, which can predict whether these patients will worsen and become serious or critical diseases. During his stay in Honghu, Zhu, Party Secretary of Southern Hospital, personally led the team, hoping to establish a Honghu model to manage COVID-19 infection in Honghu. This model not only pays attention to the treatment of hospital patients, but also pays attention to the screening of the community.

June 65438+1October 10 arrived in Jingzhou, Hubei, and returned to Guangzhou on March 20th. During this period, I have been to Honghu in Jingzhou and Hankou in Wuhan, where I helped to discuss and coordinate the work of two medical teams in Hankou and Honghu.

Honghu Lake is a land of plenty. Honghu city has a population of 950,000, which is about 1.5-2 hours' drive from Wuhan. After going to Honghu Lake, we all liked this place very much, and even many colleagues in the medical team of our Southern Hospital expressed their willingness to work hard for Honghu Lake. Government-led unified planning, integration of the entire Honghu medical unit, functional classification, and then comprehensive management. Here, we designed an early warning zone according to the severity of the illness, and the recovered patients continued to stay in the rehabilitation zone for follow-up and management.

When we went, we took four laboratory staff and tested the antibodies of 8000 patients with two antibody kits. In addition, we have established a big data platform in cooperation with China Medical. In the next stage, we will make plans to go to Honghu Lake to eliminate hepatitis.

Just now, it was said that the drive from Honghu to Wu Hanyou was 1.5 hours, with a population of 950,000, including Wuhan 1 10,000. Before the closure of Wuhan, 55,000 people returned to Honghu and 45,000 people were trapped in Wuhan. More than 65,438+000 people were hospitalized due to COVID-19-related diseases, 363 people were diagnosed as nucleic acid positive, and 65,438+05 people died. In addition, there are more than 300 people isolated in towns and communities, including more than 50 asymptomatic infected people. By the time we left, there had been no new confirmed cases in Honghu for 20 consecutive days. When we were in Honghu Lake, we met with honghu city Changshen almost every day to discuss and arrange epidemic prevention and control. He also signed my clothes. I think Honghu locals attach great importance to affection and righteousness.

We signed a long-term cooperation agreement with them, hoping to further carry out the work of eliminating viral hepatitis in Honghu, and hope to carry out the zero transmission project of hepatitis B from mother to child there.

Overview of 0 1 virus infection characteristics

In view of the asymptomatic infection that everyone has paid special attention to recently, different majors have different understandings and even caused controversy. Here, I will explain to you how ordinary people understand the characteristics after infection, the characteristics, mechanism and significance of asymptomatic infection.

In fact, there are many kinds of diseases caused by virus infection. COVID-19 is a respiratory disease. Hepatitis B can be transmitted from mother to child, and AIDS can be transmitted through blood. It is especially mentioned here that the infection in COVID-19 is mainly transmitted through respiratory tract, and there is the possibility of aerosol transmission in a relatively closed environment. Previously, it was reported that COVID-19's nucleic acid was detected in feces, but it is not clear whether this has an impact on the prevention and control of the whole epidemic. Hepatitis B and HIV infection can spread vertically, but there is no evidence of vertical transmission in COVID-19.

The source of infection in COVID-19 is not only symptomatic patients, but also asymptomatic people. Everyone is concerned about the proportion of asymptomatic infection, because different studies or models have different denominators, so the reported proportion of asymptomatic infection varies greatly. Low 1%-2%, high 40%-60%.

It is generally believed that the virus can spread locally in the host after infection. Local transmission refers to the proliferation of viruses in local tissues after they invade the body, such as enterovirus in pharyngeal epithelial cells and local lymphoid tissues, and respiratory virus in upper respiratory mucosa epithelial cells. But most classic viruses spread in the body, infected by blood and lymphatic system, and then formed two viremia. Therefore, after virus infection, there can be local infection, only invading local cells, and also forming systemic infection. After spreading through blood, lymph and nerve tissue, it will cause damage to multiple organs and systems.

The result of virus infection: the interaction between virus and host immune system maintains a dynamic balance. If the immune system is dominant and the virus is eliminated, it may or may not be immune. If the virus is dominant, persistent infection will occur; Their common advantages will lead to chronic infection and recurrence. Obviously, so far, we think that COVID-19 is an acute infection, because the organism immunity is dominant, and then the virus will be eliminated soon, so the organism immunity plays a very important role in controlling and eliminating the virus.

In the field of infectious diseases, the results of viral infection and bacterial infection are different. After some bacteria and viruses are infected, we call it "iceberg phenomenon", because a few patients will cause serious infection and die, and most patients are mild or average. There is a certain proportion of patients with recessive infection or subclinical infection. We don't use the word asymptomatic infection here. There are still some people who are not infected after contact. The classification of patients mainly depends on organism immunity, which is the result of the interaction between virus and organism immunity. If a large number of viruses invade the body and replicate abnormally, it can lead to serious or critical diseases. After the virus invades the body, a large number of copies produce a strong immune response, which can cause common and mild infections. Virus invasion can produce immune response without obvious pathological damage, which is recessive infection or subclinical infection. If the virus invades the body and is quickly removed without immune response, these will not be infected after exposure.

Take epidemic cerebrospinal meningitis as an example. Only 1%-2% people actually have meningitis caused by meningitis, less than 10% people have upper respiratory tract infection, and the remaining 90% are recessive infections. There are many other viral infections, including recessive infection, such as common hepatitis B and recessive infection. Taking our current understanding of COVID-19 as an example, we still don't know the proportion of recessive infection or subclinical infection. After the closure of Wuhan in China, such strict measures were taken, and the proportion of recessive infection required large-scale antibody screening.

There may be acute infection and persistent infection after virus infection.

Persistent infection includes chronic infection, latent infection and lentivirus infection.

Chronic infection means that the virus can persist in the body and be discharged to the outside world frequently or intermittently, showing no symptoms. This long-term virus will eventually lead to important target organ damage, such as the continuous accumulation of hepatitis B virus to form chronic hepatitis and cirrhosis, and eventually lead to liver cancer.

Latent infection means that after the initial infection, the virus hides in the body and indirectly causes an acute attack. Here, the representative is the infection of varicella-zoster virus.

Lentivirus infection means that after dominant or invisible infection, the incubation period is quite long. Once it happens, it develops into subacute, progressive and even death. Some people will classify HIV as a lentiviral infection.

The main factors affecting the persistent infection of virus are virus factor and host factor.

Viral factors: the virus forms chronic infection, immune escape occurs, and the virus lurks and hides. Some viruses can form immune tolerance, such as hepatitis B and HIV.

Host factors: such as low immune function of specific T cells, inability of B cells to induce antibody production, immune tolerance, etc. can all form chronic infection. So far, there is no evidence of chronic infection in COVID-19.

Anti-virus depends on all kinds of immunity, including specific immunity and non-specific immunity. Cytokines such as skin mucosal barrier and interferon belong to nonspecific immunity, and specific immunity includes T cell-mediated immunity and B cell-mediated immunity.

Humoral immunity is very important in immunity against virus infection. Specific antibodies can be produced after virus infection, including IgA, IgM and IgG. So far, there is no reagent for IgA after infection in COVID-19. IgM appears early and lasts for a short time, which is generally a sign of recent infection. IgG appears after IgM, later than IgM, and lasts for a long time, which is a sign of past infection. Different diseases have different characteristics of producing antibodies. For example, after the SARS epidemic in 2003, we tested the staff of the whole hospital and compared some patients, but no patients with recessive infection were found. The proportion of dengue infection with recessive infection. After this antibody is produced, there are some neutralizing antibodies, which have protective effect.

Recently, we have also paid attention to some reports that COVID-19 and SARS have certain differential immunity, and some epitopes of them have the same characteristics, which means that the multi-epitope coronavirus vaccine prepared in the future may prevent different coronavirus infections at the same time.

The production of antibodies, as I said just now, has its laws. Here I take hepatitis B as an example. After virus infection, surface antigen appears first. If it is acute infection, IgM appears one after another, and finally three antibodies, namely core antibody, surface antibody and E antibody, appear one after another. Most immunized patients will only produce surface antibodies if they are vaccinated.

Spectrum of infectious diseases and emergency warning in COVID-19.

We understand the characteristics, prognosis and prognosis of viral infection, and then we go back to understand the clinical manifestations of COVID-19, and some key laboratory indicators have changed. We are concerned about the decrease of lymphocytes, the increase of C-reactive protein and the increase of D-dimer, which is more obvious in severe and critical patients. Clinically, according to the characteristics of patients, they are divided into light, ordinary, heavy and critical types. The guide is very clear, so I won't go into details here.

The proportion of clinical types is different in different regions and different stages of infection. In Wuhan, the proportion of severe cases and deaths is higher than that in non-Wuhan, and now imported patients are mainly found through rapid screening, so the proportion of mild and asymptomatic patients is higher, and the proportion of severe cases and deaths will be very low. According to the database of Guangdong Province, there are very few patients who died.

Age is a very important compound factor. The proportion of severe illness in the elderly is high, and the proportion of different sexes is similar.

The first six editions of the Guide did not say which patients would have indicators of aggravating early warning. The seventh edition lists some indicators, such as the decline of adult lymphocytes, the increase of interleukin -6 and C-reactive protein, the increase of lactic acid and the rapid progress of lung diseases. These indicators indicate that the situation may deteriorate.

We want to develop a serious risk early warning model to analyze which indicators may lead to the aggravation of patients' illness, especially in high-incidence areas. If we find the possibility of patients getting worse as soon as possible and then focus on management and intervention, it is possible to avoid serious consequences.

We made a structural analysis of mild and moderate patients in 33 hospitals in Guangdong Province, with a total of *** 1 138 cases. We took 8 18 patients as the modeling group, and 320 mild patients selected from Hankou Hospital in Wuhan and Honghu Hospital in Hubei Province as the verification group. All patients were judged according to the national standard scheme.

We analyzed the clinical features and data of all patients, including patients with and without deterioration. It is obvious that there is no difference between men and women. After multivariate analysis, several indexes such as age, history of chronic diseases, the ratio of white blood cells to lymphocytes, whether C-reactive protein is greater than 25, D- dimer and so on were screened out. Then the patients were divided into low risk group, medium risk group and high risk group. It can be seen that almost 40% patients in the high-risk group will get worse within 14 days of hospitalization.

Infection Management in COVID-19: Honghu Model in Hubei Province

The same trend can be seen by further using the verification group of Honghu Lake, and it can be seen that the overall aggravating ratio of Honghu Lake is low. We refer to the data analyzed in Wuhan and Guangdong in the early stage of the first phase. After arriving in Honghu, patients are managed at different levels, and all medical institutions in Honghu are integrated into management. Patients were divided into critical area, severe early warning area, mild area and discharge observation area. According to some indicators, mainly manage high-risk patients. The diagnosed mild patients are mainly in temporary board houses, and the suspected mild patients are also here. The discharged patients were placed in private hospitals and Chinese medicine hospitals for follow-up after discharge.

Asymptomatic infection in COVID-19.

With the improvement of the overall situation of epidemic prevention and control in China, asymptomatic infection has become a hot spot. The state has specially issued the management guide for asymptomatic pneumonia patients in COVID-19, especially in the management guide, which reiterates that asymptomatic infection is contagious and has the risk of transmission, and the monitoring and discovery of asymptomatic infection should be strengthened, and asymptomatic infection should be included in the epidemic report data, and asymptomatic infection should be closely observed for 14 days. You can see the recent imported cases in Guangdong, as well as the infection of migrants in Guangzhou, especially in Africa. I can tell you responsibly that many people on the Internet say that the data of 1000 people infected there is false. According to my statistics, on April 9th, there were 1 0,097 asymptomatic infected people in 3/kloc-0 provinces and cities nationwide, including 349 imported cases, and the cumulative number of close contacts of asymptomatic infected people exceeded 7 1 10,000.

Asymptomatic infection or subclinical infection, no clinical symptoms, normal chest film, mainly detected by nucleic acid means. At present, we are discussing whether the combined screening of nucleic acid and antibody can further help us quickly identify the types of asymptomatic infected people. For example, asymptomatic infected people or close contacts have produced IgG antibodies, and there is no nucleic acid. Can isolation be cancelled, so as to reduce the cost of medical observation?

Here is a set of data, which we counted in Hubei. We detected the nucleic acids and antibodies of 747 close contacts with nucleic acid and two antibody kits. We can see that 28 patients are nucleic acid positive, which is more than 3% in general. I also asked the CDC in Guangzhou. They have almost more than 4,000 close contacts to screen nucleic acid, and almost 2% of them are positive for nucleic acid. In this way, we can see the antibody levels of the close contacts of nucleic acid positive and negative, and we can also see that the antibody levels of the close contacts of nucleic acid positive and negative are similar. The proportion of antibodies produced at different ages is similar, and there is no difference between men and women.

Among the close contacts, nucleic acid positive accounted for 3.7%, and antibody positive accounted for 1 1%. Obviously, some people may not find the virus in throat swabs, but only detect antibodies, and these people are more in close contact. At present, China has approved many antibody detection kits, including colloidal gold and chemiluminescence kits. Large-scale antibody screening may be needed to evaluate the prevention and control strategies. And whether the joint inspection of nucleic acid and antibody can be used to evaluate the infection and immunity of patients and further classify them for medical management. These are all issues that need to be discussed later.

Let's go back and see how to describe the whole picture of COVID-19 infection results in a group. We have made clear the proportion of patients' death, and different countries report different proportions. The United States and Italy are relatively high, as high as 10%. Severe diseases account for about 15%, and mild and common diseases account for 80%. We don't know the proportion of recessive infection or subclinical or asymptomatic infection in different populations. I'm just showing you that in a specific Honghu area, 1 1% close contacts produced antibodies. In other fields, we need a lot of data to further understand. Whether it is an "inverted triangle" or a "regular triangle" is still unknown. This time, everyone's concern about the concept of group immunity has caused a lot of controversy. If the mortality rate is low and the number of seriously ill patients is low, then the concept of group immunity through natural infection may be relatively established.

Finally, let me summarize. Today, I would like to share with you some data about why the overall infection in COVID-19 has different outcomes, and which part of patients may change from mild and common to severe or aggravated and asymptomatic infection. Here, I would also like to thank Professor Li Jie for his guidance. He provided a slide about the prognosis of viral infection. I also thank all my colleagues who participated in the work, including Wuhan and Guangdong medical teams. Thank you very much

quality assurance

Audience question and answer in live broadcast room

Niu Qijun: Thank you Professor Hou Jinlin for sharing. I also thank Professor Hou Jinlin and his team for their work for the people of Wuhan and Hubei. Below, according to the questions raised by everyone, I will summarize them first and ask Professor Hou Jinlin to answer them.

Q 1: Does the patient have any other injuries or diseases besides pneumonia after being infected with COVID-19 virus?

Hou Jinlin: At present, COVID-19 infection was first named "COVID-19 pneumonia". In fact, the target organ is not only the lung, but also many organs outside the lung, including the blood system and immune system. Recently, it has been reported that pancreatic injury, liver injury and renal function changes have been found. At that time, we had not seen this kind of literature. When we diagnose patients, we take chest X-ray and CT changes as the standard. It is also possible that we missed the positive chest radiograph of this pathogen, but other organs were damaged. I believe there will be.

Q2: As a source of infection, is it possible for asymptomatic infected people to infect others?

Hou Jinlin: The asymptomatic infected people reported now include those in Germany, Hong Kong and Nanjing, and there is no overall large-scale screening for specific groups. By analyzing our data and the results of Guangzhou CDC, we generally think that asymptomatic infected people have low virus level and short duration. Some of them are virus-positive and may be contagious, but some of them have no virus or produced antibodies. These people are not contagious. Therefore, finding asymptomatic infected people is both good news and bad news. I think it is impossible for asymptomatic infection to spread on a large scale at least under such strict screening in China. Basically, it will be managed after screening, but we should attach great importance to asymptomatic infected people.

Question 3: It is reported that cats, dogs and tigers can find COVID-19. What is the significance of these animals as a source of infection?

Hou Jinlin: The detection of COVID-19 in cats and tigers is definitely a very important discovery, but we need more evidence to prove the source of the virus and whether people and animals are cross-infected. We need to carry out epidemiological investigation, compare families with or without pets, and see the infection rate of families with or without pets. It is too early to draw a conclusion, and more evidence is needed. At least now in Guangdong province, pets are not the source of infection.

Niu Qijun: That means we don't have to worry about keeping pets.

Hou Jinlin: I don't think it's necessary to worry too much. During the SARS period, a dog was found infected with the SARS virus on Baiyun Mountain, and it finally went away.

Question 4: Do you think COVID-19 virus will exist in asymptomatic animals for a long time after infection?

Hou Jinlin: So far, we only know that bats are a very special immune system species, which can carry viruses without getting sick. I haven't seen anything else, at least in people, it's acute infection, and there is no evidence of chronic infection.

Q5: What are the reasons why patients are light and heavy? Apart from individual differences, is it related to the number of viruses entering the body?

Hou Jinlin: We believe that the severity of the disease and the number of virus infections are one factor, which should be said to be the result of the interaction between the virus and the immune system. Recently, it has also been reported in the literature that COVID-19 has undergone variation, which seems to have different subtypes, but overall, the change is not too big. The severity of the disease should be related to the genetic background of different people and the difference of individual immune response.

Q6: Some people say that asymptomatic infected people have two forms, one is that they have no symptoms all the time, and the other is that they will have symptoms later. Can you explain these two asymptomatic infected people from the concept of infectious diseases?

Hou Jinlin: Viral infections and bacterial infections generally have incubation periods. In the law of infectious diseases, the average patient is most contagious at the end of incubation period and the beginning of onset. We don't think it is necessary for COVID-19 patients to stay in hospital for a long time during the recovery period. For example, chicken pox, chicken pox scab can be discharged. In fact, asymptomatic infection cannot be classified as asymptomatic infection in this part of patients who are in the incubation period or before symptoms appear. There were no symptoms, fever and respiratory symptoms during the whole course, and there was no abnormality in chest X-ray. We call it asymptomatic infection. What is the proportion of this group of people? Personally, I think that especially in high-prevalence areas, such as the United States and some European countries, the proportion will exceed that of people with symptoms.

Niu Qijun: Asymptomatic infection and latent infection are actually two concepts. Some latent infections should not be included in latent infection.

Hou Jinlin: Right.

Q7: Can IgG and IgM antibodies detected by antibody detection be used as protective indicators?

Hou Jinlin: I don't think so, because if IgG and IgM are detected by colloidal gold method now, they can only be detected qualitatively, but not quantitatively. We use Wan Tai's reagent. If we want to determine whether it is a protective antibody, we need to determine a neutralizing antibody. Neutralizing antibodies generally can't be done, because we need live viruses or fake viruses to do it. At present, there are also views in the industry that antibodies can mediate the damage to the body, so it cannot be directly said that antibodies are protective antibodies.

Q8: Now there is a saying called "group immunity". What is group immunity? What is the mechanism?

Hou Jinlin: Group immunity is a concept of immunology, and it is known to the general public because British Prime Minister Boris Johnson said the concept of group immunity. The establishment of group immunity depends on infection. If the proportion of mild or asymptomatic patients is high, and the proportion of mortality or severe patients is low, then this measure is considered feasible. If the number of patients with severe illness and death is relatively large, this plan needs to be discussed. Especially in the western model, on the basis of such a high prevalence rate, it is necessary to count the proportion of asymptomatic patients in the asymptomatic population to see how high the antibody is. So far, I think that at least the prevention and control of COVID-19 can't be accomplished by group immunization of natural infection.

Niu Qijun: As far as I know, everyone just discusses group immunity as a concept and strategy. It seems that no country has implemented this strategy.

Hou Jinlin: The German model is to control the infection within the tolerance level of the whole medical resources. If we want to ensure that there are no patients and the economic and living costs are too high, this measure cannot be sustained for a long time.

Niu: In other words, we should also consider social and economic issues when controlling the incidence of this disease.

Hou Jinlin: That's right. Now that imported cases have become the norm, it is impossible for us to stop work and suspend classes for a long time to prevent imported cases.

Q9: Do you think the pathogenicity of the virus will become weaker and weaker?

Hou Jinlin: Obviously, compared with SARS, SARS is more harmful to the lungs. The less pathogenic the virus is, the easier it is to spread, because it is not easy to find differences between different strains. If the virus mutates, its pathogenicity may change.

Q 10: There are very few cases in China. When do you think it is necessary to wear a mask?

Hou Jinlin: Personally, I think we wear too many masks, no matter what occasion or place. Infectious diseases doctors wear masks because the concept of infection prevention and control is deeply rooted in the bone marrow, and they also wear masks at work, especially in fever clinics. Now I don't think it's necessary to wear a mask on most occasions. I can walk in the yard. You don't need to wear a mask in a closed environment, but sometimes you have to wear a mask under the pressure of people around you.

Q 1 1: The patient has lung infection. After the improvement of lung performance, are people with positive nucleic acid sequencing still contagious?

Hou Jinlin: When we were in Honghu, there were about 10 patients whose nucleic acid test was negative continuously, and then they were positive according to the discharge standard. One of the reasons is related to the characteristics of respiratory diseases. Different from hepatitis B and AIDS, the sampling and detection of virus in blood is very stable. Respiratory infectious diseases have many effects on nucleic acid detection results, including detoxification rules, sampling errors, sample transmission and preservation. There is still much room for technical optimization of PCR nucleic acid detection methods, and the proportion of false negative results is very high at present. I think the most contagious diseases in COVID-19 are the late incubation period and the early onset, while most diseases are not contagious in the late onset. So I shook hands with the discharged patients, and the local people felt incredible.

Q 12: Please predict whether the global epidemic will recur like the flu, or will it be controlled at a certain point?

Hou Jinlin: This prediction is a bit like fortune telling. When we arrived in Hubei, we didn't expect the epidemic to spread so quickly in many places in the United States and Europe. Now it seems that China is not the first half, and foreign countries are not the second half. China is just the beginning. I guess the virus will spread from one country to another, because no country can take such strict control measures as China. It seems that there are still three or four countries that have not broken out, and there are almost more than 20 thousand cases in Brazil, which shows that the situation is very serious. I think it is still difficult to change the "European Liver Association" to August. I think stopping imports will be a protracted war.

Q 13: Do you think it is necessary to continue the isolation of asymptomatic infected people after isolation 14 days if the nucleic acid test is still positive?

Hou Jinlin: We analyzed the asymptomatic infected people found in the community. It is true that the nucleic acid test is still positive for more than 14 days. It is necessary to isolate it for insurance reasons, but whether it is contagious needs to be judged in combination with other circumstances. Some people think that this virus positive is only a residual virus fragment of the human body.

Q 14: Where did the virus come from or where did the epidemic spread first?

Hou Jinlin: First of all, unexplained pneumonia and COVID-19 infection were diagnosed in Wuhan, China, but the source of the virus is still a "headless case". I agree with several experts, including Professor Zhang Wenhong, that the news on the Internet is basically unreliable now, and we clinicians can't solve this problem. People who study epidemics and animal viruses should solve this problem.

Niu Qijun: Thank you again for the wonderful report of Professor Hou Jinlin, and thank you again for the efforts made by Professor Hou Jinlin and his team for patients in Wuhan, Guangdong and the whole country. Thank you, we see that many people attending the lecture have made efforts for our patients, and we would like to express our heartfelt thanks! Today's lecture is over, thank you!

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