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.

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.

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.

Mitofusion 2 Overexpression Decreased Proliferation of Human Embryonic Lung Fibroblasts in Acute Respiratory Distress Syndrome through Inhibiting RAS-RAF-1-ERK1/2 Pathway

Acute respiratory distress syndrome(ARDS)is one of the most fatal diseases worldwide.Pulmonary fibrosis occurs early in ARDS,and its severity plays a crucial role in ARDS mortality rate.Some studies suggested that fibroproliferation is an essential mechanism in ARDS.Mitofusion2(Mfn2)overexpression plays a role in inhibiting cell proliferation.However,the role and potential mechanism of Mfn2 on the proliferation of fibroblasts is still unknown.In this study,we aimed at exploring the effect of Mfn2 on the human embryonic lung fibroblasts(HELF)and discussed its related mechanism.The HELF were treated with the Mfn2 overexpressing lentivirus(adv-Mfn2).The cell cycle was detected by flow cytometry.MTT,PCR and Western blotting were used to investigate the effect of Mfn2 on the proliferation of the HELF,collagen expression,the RAS-RAF-1-ERK1/2 pathway and the expression of cycle-related proteins(p21,p27,Rb,Raf-1,p-Raf-1,Erk1/2 and p-Erk1/2).The co-immunoprecipitation assay was used to explore the interaction between Mfn2 and Ras.The results showed that the overexpression of Mfn2 inhibited the proliferation of the HELF and induced the cell cycle arrest at the G0/G1 phase.Meanwhile,Mfn2 also inhibited the expression of collagen I,p-Erk and p-Raf-1.In addition,an interaction between Mfn2 and Ras existed in the HELF.This study suggests that the overexpression of Mfn2 can decrease the proliferation of HELF in ARDS,which was associated with the inhibition of the RAS-RAF-1-ERK1/2 pathway.The results may offer a potential therapeutic intervention for patients with ARDS.

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.

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.

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.

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.

The Concept Study of Recombinant Human Soluble Thrombomodulin in Patients with Acute Respiratory Distress Syndrome

Background: Recombinant human soluble thrombomodulin (rhTM) was approved for the treatment of disseminated intravascular coagulation in Japan, and rhTM has anti-inflammatory effects. Disordered coagulation is a part of the acute respiratory distress syndrome (ARDS) pathophysiology and thus we hypothesize that anticoagulant therapy may help. This preliminary study was to observe the safety of rhTM administration and the improvement on biomarker levels after the therapy for ARDS-patients. Objectives: Case series of ARDS-patients. Methods: Seventeen ARDS-patients that required ventilatory management were treated with rhTM and clinical and laboratory data were collected including platelets, thrombin-antithrombin complex (TAT), fibrinogen degradation products, oxygen saturation/the fraction of inspired oxygen (SpO2/FIO2), and high-mobility group-1 (HMG-1). The administration of rhTM was started during 6 days at a bolus dose of 0.06 mg/kg/day immediately after the diagnosis of ARDS. Results: Eleven of the 17 ARDS-patients were alive at 28 days after the beginning of the administration of rhTM. The serial pattern of the SpO2/FIO2 showed remarkable differences between the survivors and nonsurvivors from day 5 to day 7. The TAT in the survivors significantly decreased after treatment, and there were significantly lower levels in the TAT on day 7 in comparison to that of the nonsurvivors. The serial changes of HMG-1 showed increased levels in the nonsurvivors until day 5 after the administration of rhTM. Conclusions: Additional rhTM administration can safely improve the parameters in survival ARDS-patients, as demonstrated by significant improvements in the SpO2/FIO2, HMG-1 and TAT.

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.

成人接种2剂新冠灭活疫苗12个月后T细胞免疫应答特点

目的评估成年人接种新型冠状病毒(SARS-CoV-2)灭活疫苗12个月后不同抗原特异性T细胞免疫应答的特点。方法解放军总医院第五医学中心2022年4-6月招募15名健康成年人,于接种2剂新冠灭活疫苗12个月后采集其静脉血标本,以基于多色流式细胞术的活化诱导标记法(AIM)检测SARS-CoV-2抗原特异性T淋巴细胞水平,并分析其记忆表型与亚群分化特点。结果成年人接种2剂灭活疫苗12个月后,90%以上个体可检测到Spike及Non-spike特异性CD4^(+)T细胞反应(S:14/15,P=0.0001;NS:15/15,P<0.0001);80%个体检测到Spike及Non-spike特异性CD8^(+)T细胞反应(S:12/15,P=0.0463;NS:12/15,P=0.0806)。抗原特异性CD4^(+)T细胞主要表现为中央记忆细胞(CM)、1型效应记忆细胞(EM1)记忆表型,以及1/17型辅助性T细胞(Th1/17)、2型辅助性T细胞(Th2)辅助表型。结论灭活疫苗接种后能诱导广泛且持久的抗原特异性CD4^(+)T细胞反应,可能是当前国内新型冠状病毒感染重症化比例较低的关键因素。

上海市某方舱医院2897例新型冠状病毒Omicron变异株轻型/无症状感染者住院时间影响因素分析

目的探讨上海市某方舱医院新型冠状病毒奥密克戎(Omicron)变异株轻型/无症状感染者住院时间的影响因素。方法回顾性收集上海宝山泾灿路(罗泾京东)方舱医院收治的2897例Omicron变异株轻型/无症状感染者的病历资料,分析其一般资料、住院时间等基本情况,探究不同特征的新冠病毒Omicron变异株感染者住院时间差异,采用多重线性回归方法分析住院时间的影响因素。根据单因素分析结果,采用二元logistic回归分析住院时间≥14 d可能的影响因素。结果2897例Omicron变异株轻型/无症状感染者的平均住院时间为(9.1±4.6)d,不同年龄段、入舱前核酸阳性时间以及伴有咳嗽、咳痰、咽痛、发热、流涕、鼻塞、口干咽燥、头痛、乏力、肌痛、腹泻、恶寒、恶心呕吐、头晕症状的感染者住院时间不同,差异具有统计学意义(P<0.05)。多重线性回归结果显示,年龄增加、患有糖尿病史以及咽痛、发热、流涕、肌痛症状会增加住院天数,而入舱前核酸阳性时间长则会减少住院天数。住院时间≥14 d者,高龄、糖尿病史以及出现咽痛、发热、口干咽燥、肌痛、恶心呕吐症状的占比更高,入舱前核酸阳性时间相对更短,接种2针及以上疫苗占比更低,差异具有统计学意义(P<0.05)。二元Logistic回归结果显示,高龄、入舱前核酸阳性时间短、糖尿病史以及发热和口干咽燥症状可能是导致住院时间超过14 d的危险因素,接种2针及以上疫苗可能是保护因素。结论Omicron变异株轻型/无症状感染者平均住院时间约为9 d,高龄、疫苗接种2针及以上、患有糖尿病史、入舱前核酸阳性时间短以及咽痛、发热、流涕、口干咽燥、肌痛等正气虚衰、病邪入里、化热伤阴表现对于住院时间可能产生重要影响。通过尽早识别核酸转阴慢、住院时间长的高危患者,以期为缩短核酸转阴时间、指导重点人群精准防控提供指导方向。

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。

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。

沈阳市1209例新型冠状病毒感染者“长新冠”特征及风险因素分析

本研究旨在探究新型冠状病毒(简称新冠)感染者长新冠的临床特点及相关风险因素。选取2023年8月以前至少感染过一次新冠病毒的感染者1209例,随访收集人口学资料、长新冠症状,进行血常规等实验室检查,并通过单因素和多因素logistic回归分析长新冠的相关风险因素。结果显示,1209例感染者中有146例(12.08%)报告长新冠症状,主要以乏力、咳嗽、记忆力减退等症状为主,同时实验室检查结果和非长新冠感染者相比无明显异常。多因素logistic回归分析结果显示,长新冠的风险因素包括女性(aOR=1.69,P=0.007)、合并3种及以上基础疾病(aOR=4.07,P<0.001)以及再感染(aOR=1.94,P=0.002)。本研究发现疫情防控措施优化后,以奥密克戎毒株感染为主的感染者长新冠的发生率较既往毒株低,女性、合并较多基础疾病(≥3)以及再感染是长新冠的风险因素。

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.

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。

严重急性呼吸综合征冠状病毒2感染后突发性耳聋发生机制研究进展

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的新型冠状病毒感染(COVID-19)传播迅速,影响范围广,除了肺部并发症外还包括突发性耳聋。然而,其病理机制尚不清楚。可能的机制包括:病毒直接侵入并损伤耳蜗神经或耳蜗组织;耳蜗微血管血栓形成并导致耳蜗血管阻塞;病毒引起细胞因子风暴,导致耳蜗炎症。研究SARS-CoV-2作为突发性感音神经性听力损失病因的作用,可能为疾病的早期诊断、制定治疗策略以最大限度地提高临床恢复和避免不良反应提供机会。