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Objective: Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified, the neurotropic properties of the causative virus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), remain unknown. We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system, olfactory system, and respiratory system. Method(s): We collected single-cell RNA data from normal brain and nasal epithelium specimens, along with bronchial, tracheal, and lung specimens in public datasets. The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry. We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2 (ACE2) and the spike protein priming enzyme transmembrane serine protease (TMPRSS)/cathepsin L among the specimens. Result(s): The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue;this coexpression was confirmed by immunohistochemistry. In the nasal epithelium, ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS. Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS. However, coexpression was present in ciliated cells, vascular smooth muscle cells, and fibroblasts in tracheal tissue;ciliated cells and goblet cells in bronchial tissue;and alveolar epithelium type 1 cells, AT2 cells, and ciliated cells in lung tissue. Conclusion(s): Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood-brain barrier via pericytes. Additionally, SARS-CoV-2-induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.Copyright © Wolters Kluwer Health, Inc. All rights reserved.
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Objective:To determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229EhCoV-229Epneumonia with Hanshi Yidu Xifei syndrome in vivo. Method(s): Mice were randomly divided into normal group,infection group,cold-dampness group,model group,chloroquine phosphate group0.18 g.kg-1,interferon-alpha2bIFN-alpha2bgroup1.83x106 U.kg-1, Gegentang granules high-dose and low-dose groups6.6,3.3 g.kg-1with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling,and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reactionReal-time PCR,the pathological changes in lung tissue were evaluated by hematoxylin-eosinHEstaining,the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assayELISA,and the percentage of peripheral blood lymphocytes was detected by flow cytometry. Result(s):Comparing with model group,Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome,including listlessness,weakness of limbs,sticky stool,etc. Comparing with model group,Gegentang granules high-dose group significantly reduced lung index,histopathological score of interstitial lung and bronchus,and the level of serum motilinP< 0.05,P<0.01,two doses of Gegentang granules could significantly increase the level of serum gastrinP< 0.05,P<0.01,the percentage of CD4+ ,CD8+ T lymphocytes in peripheral bloodP<0.05,P<0.01,and the level of tumor necrosis factor-alphaTNF-alphain lung tissue was significantly decreasedP<0.01,and the level of interleukin-6IL-6showed decreasing tendency. Conclusion(s): Gegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization,regulate the level of gastrointestinal hormones,decrease lung index and histopathological score,and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.
ABSTRACT
Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method: BALB/c mice were randomly divided into six groups according to their weight grade:normal group,HCoV-229E infection group,cold and damp group,a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome,and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar (0.128,0.064 g.kg-1 )was administrated by gavage for 3 days from the day of infection. The observation indexes included:general state observation of mice,inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was used to detect the viral load in the lung tissues of mice. Serum levels of motilin(MTL),gastrin(GAS),and cytokines interleukin(IL)-10,IL-6, tumor necrosis factor-alpha(TNF-alpha)and interferon-gamma(IFN-gamma)in lung tissue of mice were determined by enzyme-linked immunosorbent assay(ELISA). The percentages of CD4+ T lymphocytes,CD8+ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group, model group mice lung index increased significantly(P<0.01), nucleic acids significantly increased expression of lung tissue in mice(P<0.01),significantly higher serum MTL content in mice,GAS content significantly decreased(P<0.05,P<0.01),lung tissue cells in the immune factor TNF-alpha,IL-10 and IL-6 were significantly increased(P<0.01),peripheral blood lymphocyte CD4+ T cells in mice,The percentages of CD8+ T cells and B cells were significantly decreased(P<0.01). Compared with model group, in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower(P<0.01),the lung tissue of mice express nucleic acid decreased significantly(P<0.01),MTL content decreased significantly(P< 0.01),the lung tissue of mice in the IL-6,IL-10,the TNF-alpha,IFN-gamma levels were significantly lower(P<0.01), in vitro cultivation bezoar high dose group can significantly increase the CD4+ T cell percentage(P<0.05),in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation,pulmonary interstitial edema,as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice,improving the pathological damage of the lung tissue,adjusting the immune effective and inhibiting the clearing of inflammatory factors,and to provide a laboratory basis for clinical medication.Copyright © 2021, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.
ABSTRACT
A 50-year-old male patient with agitated depression and hyperlipemia received oral amoxicillin and clavulanate potassium 0.5 g once daily and 2 lopinavir and ritonavir tablets twice daily for novel coronavirus infection, based on previous drugs including quetiapine, clonazepam, and atorvastatin calcium. After 3 days, lopinavir and ritonavir was changed to oral arbidol 200 mg, thrice daily due to suspicious drug interaction. After taking arbidol for 3 days, the patient developed red papules on the whole body. Considering that it might be related to amoxicillin and clavulanate potassium, the drug was stopped and loratadine was given. But the rashes were aggravated. Considering that the drug eruption was caused by arbidol, arbidol was discontinued and the rashes subsided in a large area the next day. Then vitamin C injection, calcium gluconate injection, and ribavirin were added. After 5 days, the rashes subsided completely. After 17 days, the patient recovered from pneumonia.Copyright © 2020 by the Chinese Medical Association.
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Since the birth of human beings, the spreading of epidemics such as COVID-19 affects our lives heavily and the related studies have become hot topics. All the countries are trying to develop effective prevention and control measures. As a discipline that can simulate the transmission process, complex networks have been applied to epidemic suppression, in which the common approaches are designed to remove the important edges and nodes for controlling the spread of infection. However, the naive removal of nodes and edges in the complex network of the epidemic would be practically infeasible or incur huge costs. With the focus on the effect of epidemic suppression, the existing methods ignore the network connectivity, leading to two serious problems. On the one hand, when we remove nodes, the edges connected to the nodes are also removed, which makes the node is isolated and the connectivity is quickly reduced. On the other hand, although removing edges is less detrimental to network connectivity than removing nodes, existing methods still cause great damage to the network performance in reality. Here, we propose a method to measure edge importance that can protect network connectivity while suppressing epidemic. In the real-world, our method can not only lower the government's spending on epidemic suppression but also persist the economic growth and protect the livelihood of the people to some extent. The proposed method promises to be an effective tool to maintain the functionality of networks while controlling the spread of diseases, for example, diseases spread through contact networks. Copyright © 2023 Liang, Cui and Zhu.
ABSTRACT
Since the outbreak of the novel coronavirus (SARS-CoV-2) disease COVID-19 (also known as 2019-nCoV) caused by SARS-CoV-2 in the end of 2019, it has spread rapidly in worldwide. Besides developing effective vaccines, it is urgent to develop safe and effective anti-SARS-CoV-2 drugs to fight this disease. Paxlovid, molnupiravir, sotrovimab and bebtelovimab are urgently authorized by FDA have been proved to be effective against Omicron. This manuscript mainly reviews the recent progress of effective inhibitors against the virus in the world, including receptor inhibitors, antibodies, natural product inhibitors, synthetic inhibitors and broad-spectrum antiviral drugs that are effective against other RNA viruses. © 2023, Chinese Pharmaceutical Association. All rights reserved.
ABSTRACT
Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method: BALB/c mice were randomly divided into six groups according to their weight grade:normal group,HCoV-229E infection group,cold and damp group,a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome,and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar (0.128,0.064 g.kg-1 )was administrated by gavage for 3 days from the day of infection. The observation indexes included:general state observation of mice,inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was used to detect the viral load in the lung tissues of mice. Serum levels of motilin(MTL),gastrin(GAS),and cytokines interleukin(IL)-10,IL-6, tumor necrosis factor-alpha(TNF-alpha)and interferon-gamma(IFN-gamma)in lung tissue of mice were determined by enzyme-linked immunosorbent assay(ELISA). The percentages of CD4+ T lymphocytes,CD8+ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group, model group mice lung index increased significantly(P<0.01), nucleic acids significantly increased expression of lung tissue in mice(P<0.01),significantly higher serum MTL content in mice,GAS content significantly decreased(P<0.05,P<0.01),lung tissue cells in the immune factor TNF-alpha,IL-10 and IL-6 were significantly increased(P<0.01),peripheral blood lymphocyte CD4+ T cells in mice,The percentages of CD8+ T cells and B cells were significantly decreased(P<0.01). Compared with model group, in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower(P<0.01),the lung tissue of mice express nucleic acid decreased significantly(P<0.01),MTL content decreased significantly(P< 0.01),the lung tissue of mice in the IL-6,IL-10,the TNF-alpha,IFN-gamma levels were significantly lower(P<0.01), in vitro cultivation bezoar high dose group can significantly increase the CD4+ T cell percentage(P<0.05),in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation,pulmonary interstitial edema,as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice,improving the pathological damage of the lung tissue,adjusting the immune effective and inhibiting the clearing of inflammatory factors,and to provide a laboratory basis for clinical medication.Copyright © 2021, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.
ABSTRACT
COVID-19 is the latest and most severe epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides the respiratory system, the effects of SARS-CoV-2 on central and peripheral nervous systems have been recognized by more and more people. Clinically, patients with COVID-19 have been reported from mild anosmia and hypoesthesia to acute necrotizing hemorrhagic encephalopathy and Guillain-Barre syndrome. In order to facilitate clinicians to recognize the nerve injury of COVID-19 patients and give timely treatment to these patients, this paper reviews the latest research progress on the possible pathways of nerve injury, clinical manifestations and pathogenesis of COVID-19 patients.Copyright © 2020 by the Chinese Medical Association.
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The approved worldwide use of two messenger RNA (mRNA) vaccines (BNT162b2 and mRNA-1273) in late 2020 has proven the remarkable success of mRNA therapeutics together with lipid nanoformulation technology in protecting people against coronaviruses during COVID-19 pandemic. This unprecedented and exciting dual strategy with nanoformulations and mRNA therapeutics in play is believed to be a promising paradigm in targeted cancer immunotherapy in future. Recent advances in nanoformulation technologies play a prominent role in adapting mRNA platform in cancer treatment. In this review, we introduce the biologic principles and advancements of mRNA technology, and chemistry fundamentals of intriguing mRNA delivery nanoformulations. We discuss the latest promising nano-mRNA therapeutics for enhanced cancer immunotherapy by modulation of targeted specific subtypes of immune cells, such as dendritic cells (DCs) at peripheral lymphoid organs for initiating mRNA cancer vaccine-mediated antigen specific immunotherapy, and DCs, natural killer (NK) cells, cytotoxic T cells, or multiple immunosuppressive immune cells at tumor microenvironment (TME) for reversing immune evasion. We highlight the clinical progress of advanced nano-mRNA therapeutics in targeted cancer therapy and provide our perspectives on future directions of this transformative integrated technology toward clinical implementation.
ABSTRACT
Since the outbreak of the novel coronavirus (SARS-CoV-2) disease COVID-19 (also known as 2019-nCoV) caused by SARS-CoV-2 in the end of 2019, it has spread rapidly in worldwide. Besides developing effective vaccines, it is urgent to develop safe and effective anti-SARS-CoV-2 drugs to fight this disease. Paxlovid, molnupiravir, sotrovimab and bebtelovimab are urgently authorized by FDA have been proved to be effective against Omicron. This manuscript mainly reviews the recent progress of effective inhibitors against the virus in the world, including receptor inhibitors, antibodies, natural product inhibitors, synthetic inhibitors and broad-spectrum antiviral drugs that are effective against other RNA viruses.
ABSTRACT
Since the outbreak of the novel coronavirus (SARS-CoV-2) disease COVID-19 (also known as 2019-nCoV) caused by SARS-CoV-2 in the end of 2019, it has spread rapidly in worldwide. Besides developing effective vaccines, it is urgent to develop safe and effective anti-SARS-CoV-2 drugs to fight this disease. Paxlovid, molnupiravir, sotrovimab and bebtelovimab are urgently authorized by FDA have been proved to be effective against Omicron. This manuscript mainly reviews the recent progress of effective inhibitors against the virus in the world, including receptor inhibitors, antibodies, natural product inhibitors, synthetic inhibitors and broad-spectrum antiviral drugs that are effective against other RNA viruses. © 2023, Chinese Pharmaceutical Association. All rights reserved.
ABSTRACT
Since the outbreak of the novel coronavirus (SARS-CoV-2) disease COVID-19 (also known as 2019-nCoV) caused by SARS-CoV-2 in the end of 2019, it has spread rapidly in worldwide. Besides developing effective vaccines, it is urgent to develop safe and effective anti-SARS-CoV-2 drugs to fight this disease. Paxlovid, molnupiravir, sotrovimab and bebtelovimab are urgently authorized by FDA have been proved to be effective against Omicron. This manuscript mainly reviews the recent progress of effective inhibitors against the virus in the world, including receptor inhibitors, antibodies, natural product inhibitors, synthetic inhibitors and broad-spectrum antiviral drugs that are effective against other RNA viruses. © 2023, Chinese Pharmaceutical Association. All rights reserved.
ABSTRACT
We focus on a new problem that is formulated to find a longest k-tuple of common sub-strings (abbr. k-CSSs) of two or more strings. We present a suffix tree based algorithm for this problem, which can find a longest k-CSS of m strings in O(kmn-{k}) time and O(kmn) space where n is the length sum of the m strings. This algorithm can be used to approximate the longest k-CSS problem to a performance ratio frac{1}{epsilon} in O(kmn-{lceilepsilon krceil}) time for epsilonin(0,1]. Since the algorithm has the space complexity in linear order of n, it will show advantage in comparing particularly long strings. This algorithm proves that the problem that asks to find a longest gapped pattern of non-constant number of strings is polynomial time solvable if the gap number is restricted constant, although the problem without any restriction on the gap number was proved NP-Hard. Using a C++ tool that is reliant on the algorithm, we performed experiments of finding longest 2-CSSs, 3-CSSs and 5-CSSs of 2 14 COVID-19 S-proteins. Under the help of longest 2-CSSs and 3-CSSs of COVID-19 S-proteins, we identified the mutation sites in the S-proteins of two COVID-19 variants Delta and Omicron. The algorithm based tool is available for downloading at https://github.com/lytt0/k-CSS. © 2022 IEEE.
ABSTRACT
We focus on a new problem that is formulated to find a longest k-tuple of common sub-strings (abbr. k-CSSs) of two or more strings. We present a suffix tree based algorithm for this problem, which can find a longest k-CSS of m strings in O(kmn-{k}) time and O(kmn) space where n is the length sum of the m strings. This algorithm can be used to approximate the longest k-CSS problem to a performance ratio frac{1}{epsilon} in O(kmn-{lceilepsilon krceil}) time for epsilonin(0,1]. Since the algorithm has the space complexity in linear order of n, it will show advantage in comparing particularly long strings. This algorithm proves that the problem that asks to find a longest gapped pattern of non-constant number of strings is polynomial time solvable if the gap number is restricted constant, although the problem without any restriction on the gap number was proved NP-Hard. Using a C++ tool that is reliant on the algorithm, we performed experiments of finding longest 2-CSSs, 3-CSSs and 5-CSSs of 2 14 COVID-19 S-proteins. Under the help of longest 2-CSSs and 3-CSSs of COVID-19 S-proteins, we identified the mutation sites in the S-proteins of two COVID-19 variants Delta and Omicron. The algorithm based tool is available for downloading at https://github.com/lytt0/k-CSS. © 2022 IEEE.
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[Purpose/Significance] To analyze the factors affecting the quality of 24-hour self-service library service under the background of normal state of COVID-19 epidemic prevention and control, and to perform comprehensive and reasonable evaluation. It is of certain guiding significance for self-service libraries to deal with possible public health emergencies in the future. [Method/Process] Through semi-structured interviews, using root theory, combining the characteristics of 24-hour self-service libraries, and from the aspects of literature resources, physical environment, system function, interaction quality and management level, we selected 21 indicators to build service quality evaluation index system, and used hierarchical analysis to determine the weight of various indicators, form a calculation formula of self-service library comprehensive score under the background of normal state of epidemic prevention and control. Finally, two 24-hour self-service libraries were selected for the empirical study. [Results/Conclusions] Under the background of normal state of COVID-19 epidemic prevention and control, and on the basis of ensuring the quality of their information resources, self-service libraries should pay attention to the environment in the libraries, improve management efficiency, and do a good job in daily maintenance. © 2022 by the Author(s).
ABSTRACT
Objective：To determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229E（hCoV-229E）pneumonia with Hanshi Yidu Xifei syndrome in vivo. Method： Mice were randomly divided into normal group，infection group，cold-dampness group，model group，chloroquine phosphate group（0.18 g·kg-1），interferon-α2b（IFN-α2b）group（1.83×106 U·kg-1）， Gegentang granules high-dose and low-dose groups（6.6，3.3 g·kg-1）with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling，and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reaction（Real-time PCR），the pathological changes in lung tissue were evaluated by hematoxylin-eosin（HE）staining，the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay（ELISA），and the percentage of peripheral blood lymphocytes was detected by flow cytometry. Result：Comparing with model group，Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome，including listlessness，weakness of limbs，sticky stool，etc. Comparing with model group，Gegentang granules high-dose group significantly reduced lung index，histopathological score of interstitial lung and bronchus，and the level of serum motilin（P< 0.05，P<0.01），two doses of Gegentang granules could significantly increase the level of serum gastrin（P< 0.05，P<0.01），the percentage of CD4+ ，CD8+ T lymphocytes in peripheral blood（P<0.05，P<0.01），and the level of tumor necrosis factor-α（TNF-α）in lung tissue was significantly decreased（P<0.01），and the level of interleukin-6（IL-6）showed decreasing tendency. Conclusion： Gegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization，regulate the level of gastrointestinal hormones，decrease lung index and histopathological score，and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes. © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.
ABSTRACT
Since the outbreak of a new round of COVID-19 in Xi'an on December 9, 2021, the response capability of the city's and even the province's health system to major public health emergencies has been severely tested and challenged. Faced with the rapid spread of the Delta strain and its multiple hidden transmission chains, The First Affiliated Hospital of Xi'an Jiaotong University, as the largest comprehensive tertiary hospital in Northwest China, has successfully applied the 4R crisis management theory to prevent the pandemic spread and continue the clinic work as well. Balancing of epidemic prevention and medical service with scientific, orderly and standardized procedures has been achieved. Hence, we have contributed to the "The First Affiliated Hospital of Xi'an Jiaotong University model" for controlling the epidemic and restoring normal production and life as soon as possible under the guidance and command of the National Health Commission and provincial and municipal health administrative institutions at all levels. The First Affiliated Hospital of Xi'an Jiaotong University has improved the present management system and enhanced its management level amid epidemic prevention and control. This paper aims to provide new epidemic prevention experience under the changeable environment by explaining and summarizing our theoretical basis, operation mode and practical effects of our management system.
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Rationale: While oxygen therapy is standard for patients with pneumonia, a potential for increased oxidant damage exists. Understanding how oxygen therapy impacts inflammatory lung injury with SARS-CoV-2 infection (COVID-19) and related viruses will inform patient management. We investigated the effects of fractional inspired oxygen concentrations (FiO2s) of 30 or 60% in a mouse hepatitis virus-1 (MHV-1) model of acute lung injury we developed in A/J mice. Methods: MHV-1, a ß-coronavirus like SARS-CoV-2, can be studied at Biosafety Level-2. Intratracheal installation of MHV-1 in our model produces inflammatory lung injury, progressive arterial desaturation, and lethality over 14d, similar to COVID-19. Using this model, we compared outcomes in animals exposed in sealed chambers to atmospheric FiO2s of 21, 30 or 60% beginning 2h after of MHV-1 challenge and continuing for up to 14d. In each of three experiments, MHV-1 challenged animals were randomized to receive FiO2s of 21, 30 or 60% (10 animals per FiO2 group per experiment, 90 animals total). In another experiment, 30 animals challenged with noninfected viral culture medium were randomized to the same three FiO2s. Animals were observed for up to 14d. Results: Compared to FiO2 21%, chambers with FiO2 30 and 60% had similar humidities and temperatures but slightly lower carbon dioxide levels (CO2, p≤0.05) but all chamber CO2s were in the range of 400-2000 ppm. Compared to animals surviving with FiO2 21% in each of the three experiments [#survivors/#total animals (%)] [1/10 (10%);5/10 (50%);4/10 (40%)], and their survival times (Figure-1), survival was reduced in respective experiments with FiO2 30% [1/10 (10%);2/10 (20%);0/10 (0%)] and FiO2 60% [0/10 (0%);0/10 (0%);0/10 (0%)]. Patterns of survival were similar comparing the three experiments for each FiO2 and when combined, there was a significant dose-related difference in survival across the three FiO2's (p<0.0001) (Figure-1). Compared to FiO2 21%, survival decreased with FiO2 30% (p=0.06) and more so with FiO2 60% (p<0.0001) (log-rank test with Dunnett-Hsu adjustment). All animals challenged with noninfected viral culture medium and exposed similarly to FiO2s 21, 30 or 60% (n=10 per group) survived except one 30% animal that died at 12d despite appearing well. Conclusions: FiO2s of 30 and 60% that are considered therapeutic and relatively safe clinically, markedly worsened survival in mice with MHV-1 pneumonia, a ß-coronavirus like SARS-CoV-2. These findings emphasize the need to better understand how oxygen therapy impacts the pathogenesis of SARS-CoV-2 in patients.
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Objective: Overview the systematic review/Meta analysis of Lianhua Qingwen (连花清瘟) combined with conventional western medicine in the treatment of coronavirus disease 2019 (COVID-19). Methods: Systematic reviews/Meta-analysis of Lianhua Qingwen combined with western conventional in the treatment of COVID-19 from CNKI, Wanfang, CBM, VIP, PubMed, Embase, Cochrane Library, and Web of Sciencewere search, retrieved as of October 1, 2021. Two investigators screened the literature according to the inclusion and exclusion criteria, and determined the final inclusion of the literature. AMSTAR-2 scale, GRADE system, and PRISMA statements were used to evaluate the methodological quality and GRADE the evidence quality. Results: A total of eight systematic reviews/Meta analyses were included, including six in Chinese and four in English. The quality evaluation and evidence quality classification results show that the quality of the literature and the level of evidence were low. Conclusion: The existing evidence shows that Lianhua Qingwen combined with conventional western has a good effectin the treatment of COVID-19. However, due to the low methodological quality and evidence quality level of the systematic review/Meta analysis and the low level of evidence quality, more high-quality researchs are needed to obtain high-quality research results for verification.