Clinical Effect of Yinhuang Qingfei Capsules in Treatment of Asymptomatic and Mild/Common Severe Acute Respiratory Syndrome Coronavirus 2 Infection:An Analysis of 242 Cases

[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 may cause liver injury via Na^(+)/H^(+) exchanger

The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.

Huu S. TIEU’s Predicting Outcome of Severe Acute Respiratory Syndrome (SARS) and Preparing the Treatment for COVID-19 (Coronavirus) and Other Viral Pandemics

This project paper is to give a prediction for the future of other viral pandemics and to provide recommendations for preparing therapies that could help in the success of effective treatments and benefits for patients in life-threatening situations. The theory of prediction was proposed by Huu S. TIEU on March 25, 2019, and he hypothesized that any malfunctioning cell in the body could have a damaging effect. This paper discusses the prediction that Localized Oxygen Deprivation could be a contributing factor for a future epidemic or other viral pandemics that could affect body function. This paper is based on opinion and does not have sufficient evidence to support the claims made. Therefore, further in-depth study is needed to prove the findings. The author cites Hypoxia to support his idea, but he is not claiming that Hypoxia-Inducible Factor (HIF) has worked on his predictions. The author also tested a theory using cow blood curd for body function, but this test was not a structured test and the findings were not supported by other evidence. To further prove the idea or theory, further study into the subject should be conducted.

Outpatient insulin use in type 2 diabetes mellitus and acute respiratory distress syndrome outcomes:A retrospective cohort study

BACKGROUND The impact of type 2 diabetes mellitus(T2DM)on acute respiratory distress syndrome(ARDS)is debatable.T2DM was suspected to reduce the risk and complications of ARDS.However,during coronavirus disease 2019(COVID-19),T2DM predisposed patients to ARDS,especially those who were on insulin at home.AIMTo evaluate the impact of outpatient insulin use in T2DM patients on non-COVID-19 ARDS outcomes.METHODS We conducted a retrospective cohort analysis using the Nationwide Inpatient Sample database.Adult patients diagnosed with ARDS were stratified into insulin-dependent diabetes mellitus(DM)(IDDM)and non-insulindependent DM(NIDDM)groups.After applying exclusion criteria and matching over 20 variables,we compared cohorts for mortality,duration of mechanical ventilation,incidence of acute kidney injury(AKI),length of stay(LOS),hospitalization costs,and other clinical outcomes.RESULTS Following 1:1 propensity score matching,the analysis included 274 patients in each group.Notably,no statistically significant differences emerged between the IDDM and NIDDM groups in terms of mortality rates(32.8%vs 31.0%,P=0.520),median hospital LOS(10 d,P=0.537),requirement for mechanical ventilation,incidence rates of sepsis,pneumonia or AKI,median total hospitalization costs,or patient disposition upon discharge.CONCLUSION Compared to alternative anti-diabetic medications,outpatient insulin treatment does not appear to exert an independent influence on in-hospital morbidity or mortality in diabetic patients with non-COVID-19 ARDS.

Biology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the humoral immunoresponse:a systematic review of evidence to support global policy-level actions and research

Background Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,there remains a paucity of systemized data on this subject.Objective In this review,we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies.We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity,transmission potential,and prognosis.Data Sources and Methods Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications.Search terms included:“Novel Coronavirus”OR“COVID-19”OR“SARS-CoV-2”OR“2019-nCoV”AND“Immunity”OR“Immune Response”OR“Antibody Response”OR“Immunologic Response”.Studies published from December 31,2019 to December 31,2020 were included.To ensure validity,papers in pre-print were excluded.Results Of 2889 identified papers,36 were included.Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2.Antibody titers appear to markedly increase two weeks after infection,followed by a plateau.A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations.This trend persists with regard to the length of antibody maintenance.However,overall immunity appears to wane within two to three months post-infection.Conclusion Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection.Immunity generated through natural infection appears to be short,suggesting a need for long-term efforts to control the pandemic.Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention.Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.

Fear can be more harmful than the severe acute respiratory syndrome coronavirus 2 in controlling the corona virus disease 2019 epidemic

The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to strengthen global health security,China has made great efforts to control the epidemic.Many in the global community have joined China to limit the epidemic.However,discrimination and prejudice driven by fear or misinformation have been flowing globally,superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts.We analyze this phenomenon and its underlying causes and suggest practical solutions.

A Case of Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 in Pregnancy: A Multidisciplinary Approach

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is a truly novel, multifaceted disease that has negatively impacted the lives of many including the pregnant women. We present a 34-year-old pregnant patient at 35 weeks with SARS-COV-2 requiring emergent cesarean section under general endotracheal anesthesia and a prolonged postoperative course in the ICU with multiple end organ function derangement of this disease. After nearly 1 month, she was discharged home. Her baby did not have any manifestations of SARS-COV-2 and was able to go home after 5 days.

The role of immunoinformatics in analysis of immune response against severe acute respiratory syndrome (SARS) coronavirus

In order to analyze the immune response to severe acute respiratory syndrome （SARS） coronavirus （SARS-CoV）, immunoinformatics and computational analyses were performed to study the immunological characters of SARS-CoV. According to the results of immunoinformatics analysis, the obvious variation of HLA-A2 associated T cell epitopes between SARS vires and HCoV-229E was found as follows： （1） Disappearance of HIA-A2 binding site; （2） variation sequence on the HLA-A2 associated epitope; （3） emergence of a new HLA-A2 associated epitope. The immunoinfomatics results were evidenced by T2 cell binding assay, ELISPOT and DimerX staining. In conclusion, immunoinformatics is a useful method to analyze the immunological character of a new finding infectious pathogen, like SARS-CoV. These findings of immunoinformatics are confirmed by lab and clinical experiments. In this case, immunoinformatics seems a very useful tool in the study of immune response and the evaluation of vaccine in infectious diseases, such as SARS.

Epidemiological Characteristics of An Outbreak of Severe Acute Respiratory Syndrome in Dongcheng District of Beijing From March to May 2003

Objective To describe epidemiologic features of an outbreak of severe acute respiratory syndrome (SARS) in Dongcheng District, Beijing occurred in a period between March and May 2003. Methods Data of SARS cases notified from Dongcheng District Center for Disease Control and Prevention (CDC )and supplemented by other channels were collected. Clinicians and officials of local hospitals were interviewed in groups and medical records of fatal cases of SARS were reviewed to verify the diagnosis. Stored serum specimens of the patients were detected for IgG antibody against SARS Co-V by enzyme-linked immunosorbent assay (ELISA). All the data were input into dataset files by Microsoft Excel-2000 software and analyzed with SPSS version 10.0 software. Results Outbreak of SARS in Dongcheng District started on March 14, 2003 with a peak in mid- and late April, and dropped in early May. A total of 572 reported cases were collected during this period in Dongcheng District, Beijing, and 99 of them were excluded from SARS, because of diagnosis of common cold, regular pneumonia, measles and rubella, etc. Actually, 473 SARS cases, which included 390 (82.5%) probable cases and 83 (17.5%) suspect cases, were analyzed. About 90% of the probable cases were positive for IgG antibody. Attack rate of SARS in permanent residents of Dongcheng District was 28.3 per 100 000. Forty-one of them died, with a case-fatality rate of 8.7%. Persons were all susceptible to infection of SARS Co-V, with the highest proportion at ages of 20-50 years, which accounted for 68.7% of the total cases. Average age of the patients at their onset was 40.7 years. No gender difference in SARS cases was found. Number of SARS cases in health-care workers (HCWs) accounted for 18.0% and that in retired workers accounted for 15.4% of the total cases. Cases occurred in all 10 sub-districts of Dongcheng, with the highest in Beixinqiao and Andingmen Sub-districts. Totally, 230 of the 572 notified cases (40.2%) were hospitalized at local hospitals under the jurisdiction of Dongcheng District. Eighteen of 85 cases of SARS occurred in HCWs of local hospitals, accounting for 4.5% of the total number of HCWs working at wards caring for SARS patients or fever clinics. There were 34.7% of SARS cases without any histories of contact before the onset of the disease. Familial aggregation phenomena were observed in 41.8% of the cases and 18.1% of households. And 7.4% (attack rate ) of those exposed to SARS cases suffered from the illness during the periods of quarantine. Conclusions SARS appeared to be infectious in origin and caused outbreak in Dongcheng District, Beijing introduced by an imported case traveling from Hong Kong in a period between March and May 2003. People are all susceptible to infection of SARS Co-V, which mainly threatens the young adults and the middle-aged, as well as HCWs and the retired workers. The main mode of transmission is direct exposure to SARS patients in a near distance at hospitals or families via droplets spread. Prevention and control of SARS should be focused on early isolation of patients and quarantine for close contacts. Current available measures to prevent and control SARS are proved to be effective.

Expression of Prothrombinase/fibroleukin Gene fg12 in Lung Impairment in a Murine Severe Acute Respiratory Syndrome Model

To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.

Extracorporeal membrane oxygenation for coronavirus disease 2019-associated acute respiratory distress syndrome:Report of two cases and review of the literature

BACKGROUND Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus-2,is a worldwide pandemic.Some COVID-19 patients develop severe acute respiratory distress syndrome and progress to respiratory failure.In such cases,extracorporeal membrane oxygenation(ECMO)treatment is a necessary life-saving procedure.CASE SUMMARY Two special COVID-19 cases—one full-term pregnant woman and one elderly(72-year-old)man—were treated by veno-venous(VV)-ECMO in the Second People’s Hospital of Zhongshan,Zhongshan City,Guangdong Province,China.Both patients had developed refractory hypoxemia shortly after hospital admission,despite conventional support,and were therefore managed by VV-ECMO.Although both experienced multiple ECMO-related complications on top of the COVID-19 disease,their conditions improved gradually.Both patients were weaned successfully from the ECMO therapy.At the time of writing of this report,the woman has recovered completely and been discharged from hospital to home;the man remains on mechanical ventilation,due to respiratory muscle weakness and suspected lung fibrosis.As ECMO itself is associated with various complications,it is very important to understand and treat these complications to achieve optimal outcome.CONCLUSION VV-ECMO can provide sufficient gas exchange for COVID-19 patients with acute respiratory distress syndrome.However,it is crucial to understand and treat ECMO-related complications.

Elevated Plasma Tissue-type Plasminogen Activator (t-PA) and Soluble Throm-bomodulin in Patients Suffering From Severe Acute Respiratory Syndrome (SARS) as a Possible Index for Prognosis and Treatment Strategy

To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Case patients were from Xuanwu Hospital （Capital University of Medical Sciences, Beijing, China）, and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA： 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L （P〈0.0001）, and sTM： 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L （P〈0.05）]. The only patient who died had extremely high levels of these endothelial injury markers （t-PA： 2.77 nmol/L and sTM： 1.01 nmol/L）. The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 （P〈0.05）. Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.

Clinical and Spatial Characteristics of Severe Acute Respiratory Syndrome by COVID-19 in Indigenous of Brazil

The new coronavirus (SARS-CoV-2) broke out in Wuhan in China in December 2019, causing severe pneumonia and deaths, soon in March 2020, it reached pandemic level, affecting several countries including Brazil. The disease was named COVID-19, with characteristics of most infected having mild and moderate symptoms and a part severe symptom. The disease has already reached 158 ethnic groups, which have high vulnerability and limited access to health services. The objective is to investigate the clinical and spatial characteristics of Severe Acute Respiratory Syndrome of COVID-19 in the indigenous peoples of Brazil. It is an epidemiological, cross-sectional, analytical ecological study, based on data from the OpenDataSUS platform from 01/01/2020 to 31/08/2020. Profile variables, signs and symptoms and risk factors/comorbidities. The data were analyzed by Bioestat 5.3. There were 1,207 cases and 470 deaths. Profile: male gender (59.48%) means age 53 years. Signs and symptoms: fever (74.23%), cough (77.71%), sore throat (35.62%), dyspnea (69.34%), respiratory discomfort (62.80%), O2 saturation < 95% (56.42%);and associated with mortality: dyspnea (80.0%) and O2 saturation < 95% (69.36%). Risk factors and comorbidities (45.89%) were associated with deaths (54.04%). About comorbidities, chronic cardiovascular diseases represented (18.97%) and Diabetes Mellitus (18.97%), and associated with deaths: Chronic Cardiovascular Disease (24.46%). Being admitted to the ICU has a risk of death in (OR-3.96- < 0.0001-CI-2913/5383) followed by not being vaccinated against influenza (OR-1.85- < 0.0001-CI-1358/2528). The public and health policies of Brazil should be directed to control the dissemination of COVID-19 in this population, that COVID-19 evolves in the same intensity, however, the indigenous have vulnerabilities that can increase the impact of the pandemic in this population.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection as A Risk Factor for Thromboembolic and Acute Ischemic Stroke:A Case Report

Increasing evidence reports a greater incidence of stroke in patients with coronavirus disease 2019(COVID-19)than in the non-COVID-19 population and suggests that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection represents a risk factor for thromboembolic and acute ischemic stroke.Elderly people have higher risk factors for acute ischemic stroke or embolic vascular events,and advanced age is strongly associated with severe COVID-19 and death.We reported,instead,a case of an ischemic stroke in a young woman during her hospitalization for COVID-19-related pneumonia.A 29-year-old woman presented to the emergency department of the First Affiliated Hospital,Zhejiang University School of Medicine with progressive respiratory distress associated with a 2-day history of fever,nausea,and vomiting.The patient was transferred to the intensive care unit(ICU),where she underwent tracheostomy for mechanical ventilation due to her severe clinical condition and very low arterial partial pressure of oxygen.The nasopharyngeal swab test confirmed SARS-CoV-2 infection.Laboratory tests revealed neutrophilic leukocytosis,prolonged prothrombin time,and elevated D-dimer and fibrinogen levels.Left hemiplegia was reported 18 days later during her stay in the ICU after discontinuation of the sedative medications.Central facial palsy on the left side,dysarthria,and facial droop were present,with complete paralysis of the ipsilateral upper and lower limbs.Computed tomography(CT)of the head and magnetic resonance imaging of the brain confirmed the presence of lesions in the right hemisphere affecting the territories of the anterior and middle cerebral arteries,consistent with ischemic stroke.Pulmonary and splenic infarcts were also found after CT of the chest.The age of the patient and the absence of serious concomitant cardiovascular diseases place the emphasis on the capacity of SARS-CoV-2 infection to be an independent cerebrovascular risk factor.Increased levels of D-dimer and positivity forβ2-glycoprotein antibody could confirm the theory of endothelial activation and hypercoagulability,but other mechanisms-still under discussion-should not be excluded.

Comparison of acute pneumonia caused by SARS-CoV-2 and other respiratory viruses in children:a retrospective multi-center cohort study during COVID-19 outbreak

Background:Until January 18,2021,coronavirus disease-2019(COVID-19)has infected more than 93 million individuals and has caused a certain degree of panic.Viral pneumonia caused by common viruses such as respiratory syncytial virus,rhinovirus,human metapneumovirus,human bocavirus,and parainfluenza viruses have been more common in children.However,the incidence of COVID-19 in children was significantly lower than that in adults.The purpose of this study was to describe the clinical manifestations,treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak.Methods:Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study.A total of 64 children with COVID-19 were defined as the COVID-19 cohort,of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort.Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort.The epidemiologic,clinical,and laboratory findings were compared by Kolmogorov-Smirnov test,t-test,Mann-Whitney U test and Contingency table method.Drug usage,immunotherapy,blood transfusion,and need for oxygen support were collected as the treatment indexes.Mortality,intensive care needs and symptomatic duration were collected as the outcome indicators.Results:Compared with the viral pneumonia cohort,children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19(53/64 vs.23/284),were of older median age(6.3 years vs.3.2 years),and had a higher proportion of ground-glass opacity(GGO)on computed tomography(18/40 vs.0/38,P<0.001).Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases(1/40 vs.38/284,P=0.048),and lower cases with high fever(3/40 vs.167/284,P<0.001),requiring intensive care(1/40 vs.32/284,P<0.047)and with shorter symptomatic duration(median 5d vs.8d,P<0.001).The proportion of cases with evaluated inflammatory indicators,biochemical indicators related to organ or tissue damage,D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort(P<0.05).No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs(lopinavir-ritonavir,ribavirin,and arbidol)as compared with duration in 39 children without antiviral therapy(median 10d vs.9d,P=0.885).Conclusions:The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia.Lopinavir-ritonavir,ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19.During the COVID-19 outbreak,attention also must be given to children with infection by other pathogens infection.

Mesenchymal stem cells as living anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome

Coronavirus disease 2019(COVID-19),a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2),is growing at an exponential rate worldwide.Manifestations of this disease are heterogeneous;however,advanced cases often exhibit various acute respiratory distress syndrome-like symptoms,systemic inflammatory reactions,coagulopathy,and organ involvements.A common theme in advanced COVID-19 is unrestrained immune activation,classically referred to as a“cytokine storm”,as well as deficiencies in immune regulatory mechanisms such as T regulatory cells.While mesenchymal stem cells(MSCs)themselves are objects of cytokine regulation,they can secrete cytokines to modulate immune cells by inducing antiinflammatory regulatory Treg cells,macrophages and neutrophils;and by reducing the activation of T and B cells,dendritic and nature killer cells.Consequently,they have therapeutic potential for treating severe cases of COVID-19.Here we discuss the unique ability of MSCs,to act as a“living antiinflammatory”,which can“rebalance”the cytokine/immune responses to restore equilibrium.We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.

SARS-CoV-2靶向CypA/CD147受体途径诱导心肌细胞凋亡

目的探究SARS-CoV-2靶向亲环素A(CypA)/细胞外金属蛋白酶诱导剂(CD147)受体途径诱导心肌细胞凋亡的可能机制。方法构建pEncmv-SARS-CoV-2 S-3xflag重组载体质粒转染H9c2细胞,TUNEL实验、流式细胞术和DNA ladder分析细胞凋亡,免疫共沉淀(CoIP)验证CD147与SARS-CoV-2 S蛋白之间相互作用,Western blotting法检测细胞凋亡信号通路相关蛋白表达。结果与对照组比较,TUNEL实验和流式细胞术结果显示转染组细胞凋亡显著增加(P<0.05),DNA ladder分析发现DNA降解明显。Western blotting法检测显示Caspase12、DR3表达显著升高(P<0.001),FAS表达升高(P<0.01),TRF1、DR4表达降低(P<0.01)。结论SARS-CoV-2 S蛋白靶向CypA/CD147受体入侵宿主细胞,激活内质网通路(Caspase12)和死亡受体通路(DR3、FAS),以内源性和外源性凋亡途径诱导心肌细胞凋亡。

SARS-COV-2 M^(pro)抑制剂2-(2-氯苯基)-7-(异喹啉-4-基)-5,7-二氮杂螺[3.4]辛-6,8-二酮的合成

目的研究SARS-COV-2 M^(pro)抑制剂2-(2-氯苯基)-7-(异喹啉-4-基)-5,7-二氮杂螺[3.4]辛-6,8-二酮(1)的合成方法,为其深入研究和其衍生物的合成提供借鉴方法。方法以(2-氯苯基)乙酸甲酯为起始原料,经亲电取代、还原、磺酰化、环化、选择性水解得到3-(2-氯苯基)-1-乙氧羰基环丁烷-1-甲酸(6),在三乙胺存在下,化合物6与叠氮磷酸二苯酯反应,生成的酰基叠氮化合物经Curtius重排生成相应的异氰酸酯;再与4-氨基异喹啉反应,并在碳酸钠的作用下进一步环合生成目标化合物。结果中间体及目标化合物的化学结构经^(1)H-NMR、^(13)C-NMR、ESI-MS确证。结论对化合物6的合成路线进行了优化;通过化合物6获得了一条更精简的化合物1的合成路线,该路线既避免了有毒的三光气的使用,也避免了副反应的发生;通过制备型HPLC得到化合物1的两个顺反异构体,并使用NOESY确定了化合物的构型。

CypA/CD147在SARS-CoV-2感染性心血管疾病诊疗中的作用研究进展

新型冠状病毒感染(COVID-19)疫情当前已得到有效控制,然而其相关并发症仍不容忽视,尤其是心血管循环系统更是新型冠状病毒(SARS-CoV-2)活跃的场所。血管紧张素转换酶2(ACE2)是一种高表达于心脏、肾脏和睾丸的Ⅰ型跨膜糖蛋白,新型冠状病毒刺突蛋白通过结合细胞表面受体ACE2入侵宿主细胞,但以此为靶点研发的疫苗、药物在临床应用中仍存在诸多不足。亲环素A(CypA)作为分子伴侣可促进蛋白质折叠及T细胞活化,CD147是研究最为广泛的CypA受体之一,CypA/CD147相互作用在新型冠状病毒进入宿主细胞时发挥重要作用,但新型冠状病毒通过CypA/CD147信号通路入侵心血管系统的研究鲜有报道。基于此,本文在总结前期研究证据并结合课题组研究的基础上,通过对CypA/CD147结构功能、CypA/CD147在心血管疾病中的作用及新型冠状病毒靶向CypA/CD147信号通路引发的心血管疾病进行综述,以期为COVID-19感染并发心血管系统疾病的诊疗提供参考。

SARS-CoV-2刺突糖蛋白对神经细胞的损伤效应及机制

目的探讨严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突糖蛋白(S蛋白)对人神经母细胞瘤细胞(SH-SY5Y)的损伤效应及其机制。方法用S蛋白0(细胞对照组),25,50,75和100 mg·L^(-1)处理SH-SY5Y 24 h,CCK-8法检测细胞活力;比色法检测乳酸脱氢酶(LDH)释放率;EdU试剂盒检测细胞增殖;荧光素酶发光法检测细胞内ATP含量;JC-1荧光探针法检测细胞线粒体膜电位(MMP);Seahorse XF检测细胞糖酵解及线粒体氧化磷酸化水平。结果与细胞对照组相比,S蛋白25,50,75和100 mg·L^(-1)组细胞活力显著降低(P<0.01),半数抑制浓度(IC_(50))为65.05 mg·L^(-1);LDH释放率显著增加(P<0.01);EdU阳性细胞比例显著降低(P<0.01);S蛋白75和100 mg·L^(-1)组细胞内ATP含量显著降低(P<0.01);S蛋白50和75 mg·L^(-1)组细胞内MMP显著降低(P<0.05,P<0.01);S蛋白50 mg·L^(-1)组基础糖酵解水平和糖酵解能力的最大值显著升高(P<0.05,P<0.01),S蛋白25和50 mg·L^(-1)组呼吸能力最大值显著升高(P<0.05,P<0.01)。SH-SY5Y细胞活力与细胞内ATP含量和MMP均呈正相关(r^(2)=0.9209,P=0.001;r^(2)=0.6170,P=0.0025);与反映细胞糖酵解水平的细胞基础糖酵解水平和糖酵解能力最大值呈负相关(r^(2)=0.5194,P=0.0285;r^(2)=0.6664,P=0.0073),与反映线粒体氧化磷酸化水平的ATP生成能力呈负相关(r^(2)=0.8204,P=0.0008)。结论S蛋白使SH-SY5Y细胞活力下降,抑制细胞增殖,其机制可能与干扰神经细胞内能量代谢密切相关。