Stroke increases the expression of ACE2, the SARS-CoV-2 binding receptor, in murine lungs

BackgroundThe newly emerged severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused a worldwide pandemic of human respiratory disease. Angiotensin-converting enzyme (ACE) 2 is the key receptor on lung epithelial cells to facilitate initial binding and infection of SARS-CoV-2. The binding to ACE2 is mediated via the spike glycoprotein present on the virus surface. Recent clinical data have demonstrated that patients suffering from stroke are particularly susceptible to severe courses of SARS-CoV-2 infection, thus forming a defined risk group. However, a mechanistic explanation for this finding is lacking. Sterile tissue injuries including stroke induce lymphocytopenia and systemic inflammation that might modulate the expression levels of surface proteins in distant organs. Whether systemic inflammation following stroke can specifically modulate ACE2 expression in the lung has not been investigated. MethodsMice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min and sacrificed after 24 h and 72 h for analysis of brain and lung tissues. Gene expression and protein levels of ACE2, ACE, IL-6 and IL1{beta} were measured by quantitative PCR and Western blot, respectively. Immune cell populations in lymphoid organs were analyzed by flow cytometry. ResultsStrikingly, 24 h after stroke, we observed a substantial increase in the expression of ACE2 both on the transcriptional and protein levels in the lungs of MCAO mice compared to sham-operated mice. This increased expression persisted until day 3 after stroke. In addition, MCAO increased the expression of inflammatory cytokines IL-6 and IL-1{beta} in the lungs. Higher gene expression of cytokines IL-6 and IL-1{beta} was found in ischemic brain hemispheres and a reduced number of T-lymphocytes were present in the blood and spleen as an indicator of sterile tissue injury-induced immunosuppression. ConclusionsWe demonstrate significantly augmented ACE2 levels and inflammation in murine lungs after experimental stroke. These pre-clinical findings might explain the clinical observation that patients with pre-existing stroke represent a high-risk group for the development of severe SARS-CoV-2 infections. Our studies call for further investigations into the underlying signaling mechanisms and possible therapeutic interventions. HighlightsBrain tissue injury increases ACE2 levels in the lungs Brain injury induces pro-inflammatory cytokine expression in the lungs Brain injury causes parenchymal inflammation and systemic lymphopenia

Status of treatment for atrial fibrillation in a community health service center in Shanghai Pudong New Area / 中华全科医师杂志

Objective To analyze the status of the treatment for atrial fibrillation (AF) in a community health service center in Shanghai Pudong New Area. Methods Clinical data of all patients with AF attended in Hudong Community Health Service Center of Shanghai Pudong from August 2016 to August 2017 were retrospectively reviewed. The gender,age,smoking history,drinking history,concomitant diseases, antithrombotic therapy, rhythm control, ventricular rate control drugs, health education, needs for setting up AF clinics in the community were analyzed. Result The study included 220 patients,with average age of (59.7±10.4) years; 34.1％(75/220)patients had hypertension and the blood pressure was controlled in 41.3％(31/75); 20.5％(45/220)patients had diabetes mellitus and glycosylated hemoglobin(HbA1c)was controlled well in 26.7％(12/45). Three cases of mitral stenosis were treated with warfarin anticoagulation. Among 217 patients without valvular atrial fibrillation,157 had thromboembolic risk score≥2,20.4％ (32/157) of whom used warfarin anticoagulation,10.8％ (17/157) used new oral anticoagulant (NOAG) and 58.1％ (91/157) had never used warfarin or NOAG anticoagulation. The reasons were as follows:doctors did not prescribe (41.9％, 39/91),patients did not accept (35.2％,32/91), and so on. There were 21.8％ (48/220) of patients undergoing drug cardioversion,and 5.9％ (13/220) undergoing electrical cardioversion. For control of ventricular rate, 55.9％ (123/220) patients used beta blockers,13.6％ (30/220) used non?dihydropyridine calcium antagonists, and 23.6％ (52 / 220) used digitalise. Less than 55％ of patients were given health education of physical exercise,weight management and medicine use. For AF clinic in community hospital,56.8％ (125/220) of patients needed,and 17.3％ (38/220) very need; 50.0％ (110/220) patients trusted and 12.3％ (27/220) very trusted in anticoagulation management in community hospitals. Conclusion The anticoagulant rate is relatively low, treatment of concomitant diseases is less satisfactory and the health education might be incomplete in the community surveyed in this study.

Survey on knowledge level of atrial fibrillation among general practitioners in Shanghai Pudong New Area / 中华全科医师杂志

Objective To survey the knowledge level of atrial fibrillation (AF) among general practitioners (GPs) in Shanghai Pudong New Area.Methods From July to September 2016,a stratified cluster sampling method was used to collect questionnaires from GPs who met the inclusion criteria in 12 community health service centers in Shanghai Pudong New Area.A self-made questionnaire was applied according to Current knowledge and management recommendations of atrial fibrillation-2015,which included 5 domains:antithrombotic therapy,rhythm control,ventricular rate control and evaluation of the guideline.Results A total of 377 questionnaires were distributed,and 371 were recovered.Among 371 participants there were 151 males and 220 females aged (41.3±8.3) years,including 156 (42.0％) with junior professional titles,158 (42.6％) with intermediate titles,and 57 (15.4％) with senior titles.More than 90％ of participants recognized that age,hypertension,myocardial infarction,and heart valve disease were risk factors of AF.For patient evaluation,54.2％ (201/371) of participants would use electrocardiogram,47.9％ (1 78/371) would use thyroid function,21.0％ (78/371) would use echocardiography,3.2％ (12/371) would use respiratory sleep monitoring,and 95.4％ (354/371) did not heard of cardiovascular implantable electronic devices.82.2％ (305/ 371) of participants thought rheumatic mitral stenosis,46.4％ (172/371) thought CHA2DS2-VASc score over and 2 and 12.7％ (47/371) thought hypertrophic cardiomyopathy as indications for anticoagulant;and 38.5％ (143/371) of participants rarely used CHA2DS2-VASc.The rhythm conversion would applied for the onset of atrial fibrillation in 42.9％ participants (159/371),for symptoms after the control of ventricular rate in 39.9％ (148/371) participants and for symptomatic patients in 12.7％ participants (47/371).59.8％ (222/371) of participants did not know the anticoagulation therapy for AF cardioversion,44.5％ (165/371) participants had not heard radiofrequency ablation for AF.38.5％ (143/371) of participants knew the Chinese guidelines for AF,of which 45.5％ (65/143) of the GPs used the guidelines;80.4％ (115/143) of the GPs thought the guide was very instructive.GPs with senior professional titles had better mastery of clinical evaluation,antithrombotic therapy,catheter ablation,and awareness of guideline than junior and middle-level general practitioners.Conclusion The survey shows that there is relative lack of knowledge on the risk factors,clinical assessment methods,anticoagulation indications and cardioversion anticoagulation therapy of AF,as well as lack of awareness and application of the AF guideline for GPs in Shanghai Pudong New Area.

Follow up of patients after percutaneous coronary intervention in community / 中华全科医师杂志

Objective Objective To follow up patients after percutaneous coronary intervention ( PCI) in the community.Methods One hundred and eleven patients in Hudong community of Shanghai Pudong New Area , who underwent PCI from august 2014 to august 2016 were followed up.During the follow-up the gender, age, smoking history, drinking history, body mass index ( BMI ), main concomitant disease , drug treatment and health education were surveyed by face to face interview .Results There were 63 males and 48 females with an average age of 67.1 ±10.7 years;51.4%( 57/111 ) patients were overweighted , 9.0%( 10/111 ) were obese; 29.7%( 33/111 ) had family history of early-onset ischemic cardiovascular disease; 60.3%( 67/111 ) patients used aspirin , 36.4%( 16/44 ) patients with aspirin intolerance used clopidogre or tigriello replaced .Drug-coated stents were implanted in 104 patients , 33.7%(35/104) withdrew dual antiplatelet drugs in less than one year; 71.1% (79/111) patients used statins and 60.1% ( 48/79 ) of them LDL-C reached the standard .Sixty seven patients had myocardial infarction or coronary heart disease with heart failure , 49.3% ( 33/67 ) of whom treated with angiotensin converting enzyme inhibitors (ACEI) /angiotensin receptor blockers (ARB).Ninety five patients had acute coronary syndromes or coronary heart disease with heart failure , 43.2% ( 41/95 ) of whom used beta-blockers.Fifty five patients(45.9%)had hypertension, and the blood pressure was controlled successfully in 54.9%(28/51)of them.Fifty five patients(49.5%)had diabetes mellitus and the glycosylated hemoglobin (HbA1c)was <7%in 27.3%(15/55)of them.Seventeen patients (15.3%) received weight management guidance, 50.5%(56/111)) patients received guidance on proper diet , 50.5% (56/111) received guidance on medication and precautions , 80.1%( 90/111 ) patients received guidance on when to call emergency calls.Conclusions The follow-up analysis shows that the compliance rate of anticoagulation and lowering LDL-C drug use is low , and the treatment of concomitant diseases and health education are not satisfactory for patients after PCI in the community .

Knowledge of chronic stable coronary artery disease management among general practitioners in Shanghai Pudong New Area / 中华全科医师杂志

Objective To survey the knowledge of chronic stable coronary artery disease management among general practitioners (GPs) in Shanghai Pudong New Area.Methods The survey was conducted among 363 GPs with at least 2-year work experiences from community health service centers in Shanghai Pudong New Area from July to September in 2014.A self-designed questionnaire based on the guidelines/consensus of chronic stable coronary artery disease management were used in the survey.The questionnaire consisted of 4 parts:diagnosis,drug therapy,revascularization and treatment of special types.Results Among 363 participants 362 questionnaires were completed.History taking,physical examination and electrocardiogram were applied for diagnosis in all participants,49.2％ (178/362) also used coronary computed tomography angiography,26.5％ (96/362)used exercise testing for assistant examination.More than 95.0％ of participants recognized that smoking,obesity,hyperlipidemia,hypertension,diabetes were risk factors.75.7％ (274/362) of participants used aspirin,91.4％ (331/362) knew the dose of aspirin as 75-150 mg;for aspirin intolerance 14.6％ (53/362)would use clopidogrel alternatively.50.6％ (183/ 362) of participants sometimes used statins;and 39.2％ (142/362) did not use stain because of not knowing the contraindication.Facing increases of alanine aminotransferase or aspartate aminotransferase levels 95.3％ (345/362) of participants would immediately discontinue stain;80.4％ (291/362) discontinued statins as creatine kinase increased.32.0％ (116/362) of participants gave enough drug-free period avoiding nitrates resistance.79.6％ (288/362) seldom used β-blockers and 42.5％ (154/362) failed to use β-blockers because not knowing the contraindication.78.7％ (285/362) knew percutaneous coronary intervention but did not know its indications;83.1％ (301/362)knew coronary artery bypass but did not know its indications.27.6％ (100/362) knew calcium antagonists were first-line drugs for variant angina and 93.6％ (339/362) never heard of microvascular angina.Conclusion The survey shows that GPs from community health service centers in Shanghai Pudong are not well familiar with examination of coronary heart disease and lack of sufficient knowledge of drugs recommended by the guideline,not well understand the indications for revascularization and the diagnosis and treatment of special types of coronary heart disease.

Analysis of etiology and drug use in the chronic systolic heart failure patients in two community health service centers of Pudong district in Shanghai / 中华全科医师杂志

Objective To investigate the treatment of chronic heart failure in two communities in Pudong and find the deficiency of standardized treatment in community hospital.Methods A retrospective study of all the inpatient,family bed and outpatient with heart failure who visit Hudong and Lujiazui community health Service center was conducted from March 2012 to March 2015 retrospectively.General situation(gender,age,smoking history,drinking history,daily salt intake,concomitant disease),etiology and if have the acute heart failure onset in half a year and what are the incentives,drug treatment and treatment of concomitant hypertension and diabetes mellitus were analyzed by face to face follow up.Results The study included 300 patients,average age was (58 ± 10) years.Daily salt intake of 55.0％ (165/300)patients was more than 9 g.Coronary heart disease (45.7 ％,137/300),hypertension (30.7％,92/300)and cardiomyopathy (9.0％,27/300)were the chief heart failure etiology.59.3％ (178/300) patients had acute heart failure in half a year.Acute blood pressure(20.8％,37/178),transfusion too fast or too much and infection(14.6％,26/178) were the chief incentives leading to acute heart failure.83.3％ (250/300)patients used ACEI/ARB,but only 32.0％ (80/250) of them applied the target dose.53.7％ (161/300)patients used beta blockers and 98.1％ (158/161) of them could not reach the target dose.Tartaric acid metoprolol (51.6％,83/161),peso parlour (18.6％,30/161) and carvedilol (14.9％,24/161) were commonly used drug in clinic.76.6％ (230/300)patients had hypertension and blood pressure was controlled in 82.2％ (189/230) of them successfully.44.0％ (132/300) patients had diabetes mellitus and glycosylated hemoglobin (HbA1c) was controlled from 7 ％ to 8 ％ in 23.5 ％ (31/132) of them.Conclusion In the community treatment of heart failure,the drugs recommended by guidelines were low usage and achieved the target dose rarely.Treatment of concomitant diseases was not good.The knowledge of new progress was not enough.

Status of knowledge and performance of chronic heart failure guideline in general practitioners of Shanghai Pudong communities / 中华全科医师杂志

Objective To investigate the status of knowledge and performance on Chinese Heart Failure Diagnosis and Treatment Guideline (2014 version) in general practitioners of Shanghai Pudong communities.Methods The survey was conducted from April to June in 2014 with a self-designed questionnaire.Total 390 general practitioners (GPs) in Pudong New Area were selected by cluster sampling method.The contents of questionnaire included:diagnosis and differential diagnosis,drug therapy,non drug therapy of chronic heart failure.Result Total 385 questionnaires were retrieved with a response rate of 98.7％ (385/390).The results showed that in aspect of diagnosis and differential diagnosis,373 (96.9％) Gps made the diagnosis based on history and physical examination,171 (44.4％)Gps never used BNP or NTPro-BNP tests,280 (72.7％)GPs did not know how to identify systolic or diastolic heart failure,86 (22.3％)Gps made the differential diagnosis according to the EF value.In aspects of drug therapy,the rate of beta blockers use was 10％-30％ in 284 (73.8％) Gps,149 (38.7％) Gps did not use beta blockers because of not knowing the contraindications,289 (75.1％) Gps used a maximum dose of betaloc for 25-50 mg,no one used 101-200 mg,242 (62.9％)Gps did not know the target dose of betaloc,the rate of ACEI/ARB use was 10％-30％ in 330 (85.7％) Gps,258 (67.0％) Gps would increase the dose but not knowing the target dose.The main reason for not using the target dose of Betaloc and ACEI/ARB was not knowing the dose.In aspect of non-drug therapy:240 (62.3％)Gps never heard of cardiac resynchronization therapy (CRT) and 271 (70.4％)Gps never heard of implantable cardioverter defibrillator (ICD).The senior rank GPs grasped the guideline much better than Gps with primary and intermediate professional ranks.Conclusion General practitioners in community health centers should further study the guideline of heart failure,particularly need to strengthen the knowledge and ability of drug therapy.