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Impact of Social Determinants of Health on Self-Perceived Resilience: An Exploratory Study of Two Cohorts of Adults with Congenital Heart Disease

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Congenital Heart Disease 2024年第1期19卷 33-48页

作者： Albert Osom Krysta S.Barton Katie Sexton Lyndia Brumback Joyce P.Yi-Frazier Abby R.Rosenberg Ruth Engelberg Jill M.Steiner Department of Biostatistics University of WashingtonSeattleWA98195USA Biostatistics Epidemiology and Analytics for Research(BEAR)Core Seattle Children’s Research InstituteSeattleWA98101USA College of medicine University of WashingtonSeattleWA98195USA center for Clinical and Translational Research Seattle Children’s Research InstituteSeattleWA98101USA Department of Psychosocial Oncology and Palliative care Dana-Farber Cancer InstituteDepartment of MedicineBoston Children’s HospitalBostonMA02215USA Department of Pediatrics Harvard Medical SchoolBostonMA02215USA division of pulmonary Critical Care and Sleep MedicineDepartment of Medicine&Cambia Palliative Care Center of ExcellenceUniversity of WashingtonHarborview Medical CenterSeattleWA98104USA division of Cardiology Department of Medicine&Cambia Palliative Care Center of ExcellenceUniversity of WashingtonSeattleWA98195USA

Social determinants of health(SDOH)affect quality of *** investigated SDOH impacts on self-perceived resilience among people with adult congenital heart disease(ACHD).Secondary analysis of data from two com-plementary studies:a survey study conducted May 2021–June 2022 and a qualitative study conducted June 2020–August *** was assessed through CD-RISC10 score(range 0–40,higher scores reﬂect greater self-perceived resilience)and interview *** and SDOH(education,employment,living situa-tion,monetary stability,ﬁnancial dependency,area deprivation index)data were collected by healthcare record review and *** used linear regression with robust standard errors to analyze survey data and performed a thematic analysis of interview *** participants(N=127)mean age was 42±14 years;51%were female,87%*** was moderate(75%)or complex(25%);41%functional class C or ***(mean 30±7)varied by monetary stability:compared to people with difﬁculty paying bills,resilience was 15.0 points higher(95%CI:6.9–23.1,pcare access and *** stability may be important for supporting self-perceived resi-lience in *** knowledge can inform the development of resilience interventions for this population.

关键词： Social determinants of health adult congenital heart disease resilience ﬁnancial stability

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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA division of pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

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Outcomes of combined mitochondria and mesenchymal stem cellsderived exosome therapy in rat acute respiratory distress syndrome and sepsis

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World Journal of Stem Cells 2024年第6期16卷 690-707页

作者： Kun-Chen Lin Wen-Feng Fang Jui-Ning Yeh John Y Chiang Hsin-Ju Chiang Pei-Lin Shao Pei-Hsun Sung Hon-Kan Yip Department of Anesthesiology Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301TaiwanChina division of pulmonary and critical care medicine Department of Internal MedicineKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiung 83301TaiwanChina Department of Cardiology The First Affiliated Hospital of Jinan UniversityGuangzhou 510630Guangdong ProvinceChina Department of Computer Science and Engineering National Sun Yat-sen UniversityKaohsiung 804201TaiwanChina Department of Healthcare Administration and medical Informatics Kaohsiung Medical UniversityKaohsiung 80708TaiwanChina School of medicine Chung Shan Medical UniversityTaichung 40201TaiwanChina Department of Nursing Asia UniversityTaichung 41354TaiwanChina division of Cardiology Department of Internal MedicineKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung 83301TaiwanChina Institute for Translational Research in Biomedicine Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301TaiwanChina center for Shockwave medicine and Tissue Engineering Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301TaiwanChina Department of medical Research China Medical University HospitalChina Medical UniversityTaichung 40402TaiwanChina School of medicine College of MedicineChang Gung UniversityTaoyuan 33302TaiwanChina

BACKGROUND The treatment of acute respiratory distress syndrome(ARDS)complicated by sepsis syndrome(SS)remains *** To investigate whether combined adipose-derived mesenchymal-stem-cells(ADMSCs)-derived exosome(EXAD)and exogenous mitochondria(mitoEx)protect the lung from ARDS complicated by *** In vitro study,including L2 cells treated with lipopolysaccharide(LPS)and in vivo study including male-adult-SD rats categorized into groups 1(sham-operated-control),2(ARDS-SS),3(ARDS-SS+EXAD),4(ARDS-SS+mitoEx),and 5(ARDS-SS+EXAD+mitoEx),were included in the present *** In vitro study showed an abundance of mitoEx found in recipient-L2 cells,resulting in significantly higher mitochondrial-cytochrome-C,adenosine triphosphate and relative mitochondrial DNA levels(P<0.001).The protein levels of inflammation[interleukin(IL)-1β/tumor necrosis factor(TNF)-α/nuclear factor-κB/toll-like receptor(TLR)-4/matrix-metalloproteinase(MMP)-9/oxidative-stress(NOX-1/NOX-2)/apoptosis(cleaved-caspase3/cleaved-poly(ADP-ribose)polymerase)]were significantly attenuated in lipopolysaccharide(LPS)-treated L2 cells with EXAD treatment than without EXAD treatment,whereas the protein expressions of cellular junctions[occluding/β-catenin/zonula occludens(ZO)-1/E-cadherin]exhibited an opposite pattern of inflam-mation(all P<0.001).Animals were euthanized by 72 h post-48 h-ARDS induction,and lung tissues were *** 72 h,flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflam-matory cells(Ly6G+/CD14+/CD68+/CD11b/c+/myeloperoxidase+)and albumin were lowest in group 1,highest in group 2,and significantly higher in groups 3 and 4 than in group 5(all P<0.0001),whereas arterial oxygen-saturation(SaO2%)displayed an opposite pattern of albumin among the *** findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers(CD68+/γ-H2AX)displayed an identical pattern of SaO2%among the groups(all P<0.0001).The pro

关键词： Acute respiratory distress syndrome Sepsis syndrome Exosomes Mitochondria Adipose tissue-derived mesenchymal stem cells Inflammation

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Assessment of respiratory support decision and the outcome of invasive mechanical ventilation in severe COVID-19 with ARDS

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Journal of Intensive medicine 2022年第2期2卷 92-102页

作者： Shuhan Cai Fangfang Zhu Hongtao Hu Hui Xiang Dawei Wang Jing Wang Lu Li Xiao Yang Aihua Qin Xin Rao Yun Luo Jianguo Li Kianoush B.Kashani Bo Hu Zhiyong Peng Department of critical care medicine Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Clinical Research center of Hubei critical care medicine WuhanHubei 430071China division of Nephrology and Hypertension Division of Pulmonary and Critical Care MedicineDepartment of MedicineMayo ClinicRochesterMN 55905USA division of pulmonary and critical care medicine Department of MedicineMayo ClinicRochesterMN 55905USA

Background:The coronavirus disease 2019(COVID-19)is an ongoing *** mechanical ventilation(IMV)is essential for the management of COVID-19 with acute respiratory distress syndrome(ARDS).We aimed to assess the impact of compliance with a respiratory decision support system on the outcomes of patients with COVID-19-associated ARDS who required ***:In this retrospective,single-center,case series study,patients with COVID-19-associated ARDS who required IMV at Zhongnan Hospital of Wuhan University,China,from January 8th,2020,to March 24th,2020,with the final follow-up date of April 20th,2020,were ***,clinical,laboratory,imaging,and management information were collected and *** with the respiratory support decision system was documented,and its relationship with 28-day mortality was ***:The study included 46 COVID-19-associated ARDS patients who required *** median age of the 46 patients was 68.5 years,and 31 were *** partial pressure of arterial oxygen(PaO_(2))/fraction of inspired oxygen(FiO_(2))ratio at intensive care unit(ICU)admission was 104 *** median total length of IMV was 12.0(interquartile range[IQR]:6.0–27.3)days,and the median respiratory support decision score was 11.0(IQR:7.8–16.0).To 28 days after ICU admission,18(39.1%)patients *** had a significantly higher respiratory support decision score than non-survivors(15.0[10.3–17.0]vs.8.5(6.0–10.3),P=0.001).Using receiver operating characteristic(ROC)curve to assess the discrimination of respiratory support decision score to 28-day mortality,the area under the curve(AUC)was 0.796(95%confidence interval[CI]:0.657–0.934,P=0.001)and the cut-offwas 11.5(sensitivity=0.679,specificity=0.889).Patients with a higher score(>11.5)were more likely to survive at 28 days after ICU admission(log-rank test,P<0.001).Conclusions:For severe COVID-19-associated ARDS with IMV,following the respiratory support decision and assessing complet

关键词： COVID-19 Acute respiratory distress syndrome(ARDS) Respiratory support decision Invasive mechanical ventilation Severe acute respiratory coronavirus 2 (SARS-CoV-2)

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Characteristics of staphylococcal cassette chromosome mec and lugdunin operon genes in the complete genome of Staphylococcus lugdunensis

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Chinese medical Journal 2023年第11期136卷 1367-1369页

作者： Shining Fu Yusheng Chen Ke Hu Tian Qin Yukun He Lili Zhao Xinqian Ma Li Chen Wenyi Yu Yan Yu Yu Xie Yifan Wang Donghong Yang Yu Xu Zhancheng Gao Department of Respiratory and critical care medicine Peking University People’s HospitalBeijing 100044China Department of pulmonary and critical care medicine Fujian Provincial HospitalFuzhouFujian 350000China Second division of Respiratory and critical care medicine Renmin Hospital of Wuhan UniversityWuhanHubei 430060China National Institute for Communicable Disease Control and Prevention State Key Laboratory for Infectious Disease Prevention and ControlChinese Center for Disease Control and PreventionBeijing 102206China Department of Respiratory medicine Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of pulmonary and critical care medicine Beijing Jishuitan HospitalBeijing 100035China

Staphylococcus lugdunensis(***)is a coagulase-negative Staphylococcus comprising the normal skin microbiota,primarily colonizing the lower abdomen and extremities.[1]*** has attracted substantial attention in recent years since the discovery of lugdunin by Zipperer et al[2]in *** is a secondary metabolite synthesized by non-ribosomal peptide synthetase(NRPS)that inhibits the growth of various grampositive bacteria,including methicillin-resistant ***(MRSA),[2]suggesting its potential as an antibiotic.

关键词： mec primarily abdomen

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Risk stratification of patients who present with chest pain and have normal troponins using a machine learning model

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World Journal of Cardiology 2022年第11期14卷 565-575页

作者： Muhammad Shafiq Diego Robles Mazzotti Cheryl Gibson division of General and Geriatric medicine Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160United States division of medical Informatics&division of pulmonary critical care and Sleep medicine Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160United States

BACKGROUND Risk stratification tools exist for patients presenting with chest pain to the emergency room and have achieved the recommended negative predictive value(NPV)of 99%.However,due to low positive predictive value(PPV),current stratification tools result in unwarranted investigations such as serial laboratory tests and cardiac stress tests(CSTs).AIM To create a machine learning model(MLM)for risk stratification of chest pain with a better *** This retrospective cohort study used de-identified hospital data from January 2016 until November *** criteria were patients aged>21 years who presented to the ER,had at least two serum troponins measured,were subsequently admitted to the hospital,and had a CST within 4 d of *** criteria were elevated troponin value(>0.05 ng/mL)and missing values for body mass *** primary outcome was abnormal ***,coronary artery disease(CAD)history,hypertension,hyperlipidemia,diabetes mellitus,chronic kidney disease,obesity,and smoking were evaluated as potential risk factors for abnormal *** were also categorized into a high-risk group(CAD history or more than two risk factors)and a low-risk group(all other patients)for *** analysis was performed using a χ^(2) test or Fisher’s exact *** was compared by t *** regression(BR),random forest,and XGBoost MLMs were used for *** was used for the internal validation of prediction *** was also used for *** criterion was set at 0.05 for all statistical tests.R software was used for statistical *** The final cohort of the study included 2328 patients,of which 245(10.52%)patients had abnormal *** adjusted for covariates in the BR model,male sex[risk ratio(RR)=1.52,95%confidence interval(CI):1.2-1.94,P<0.001],CAD history(RR=4.46,95%CI:3.08-6.72,P<0.001),and hyperlipidemia(RR=3.87,95%CI:2.12-8.12,P<0.001)remained statistically ***

关键词： Machine learning Chest pain Risk stratification Risk factors Cardiac stress test Cardiac catheterization

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Factors Predicting Progression to Severe COVID-19: A Competing Risk Survival Analysis of 1753 Patients in Community Isolation in Wuhan, China

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Engineering 2022年第6期8卷 99-106页

作者： Simiao Chen Hui Sun Mei Heng Xunliang Tong Pascal Geldsetzer Zhuoran Wang Peixin Wu Juntao Yang Yu Hu Chen Wang Till Bärnighausen Chinese Academy of medical Sciences&Peking Union medical College Beijing 100730China Heidelberg Institute of Global Health(HIGH) Faculty of Medicine and University HospitalHeidelberg UniversityHeidelberg 69120Germany Institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of pulmonary and critical care medicine Beijing HospitalBeijing 100730China National center of Gerontology Institute of Geriatric MedicineBeijing 100730China division of Primary care and Population Health Department of MedicineStanford UniversityStanfordCA 94305USA Peking Union medical College Hospital Beijing 100730China State Key Laboratory of medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China National Clinical Research center for Respiratory Diseases Beijing 100029China Department of pulmonary and critical care medicine Center of Respiratory MedicineChina–Japan Friendship HospitalBeijing 100029China

Most studies of coronavirus disease 2019(COVID-19)progression have focused on the transfer of patients within secondary or tertiary care hospitals from regular wards to intensive care *** is known about the risk factors predicting the progression to severe COVID-19 among patients in community iso-lation,who are either asymptomatic or suffer from only mild to moderate *** a multivari-able competing risk survival analysis,we identify several important predictors of progression to severe COVID-19—rather than to recovery—among patients in the largest community isolation center in Wuhan,China from 6 February 2020(when the center opened)to 9 March 2020(when it closed).All patients in community isolation in Wuhan were either asymptomatic or suffered from mild to moderate COVID-19 *** performed competing risk survival analysis on time-to-event data from a cohort study of all COVID-19 patients(n=1753)in the isolation *** potential predictors we inves-tigated were the routine patient data collected upon admission to the isolation center:age,sex,respira-tory symptoms,gastrointestinal symptoms,general symptoms,and computed tomography(CT)scan *** main outcomes were time to severe COVID-19 or *** factors predicting progression to severe COVID-19 were:male sex(hazard ratio(HR)=1.29,95%confidence interval(CI)1.04–1.58,p=0.018),young and old age,dyspnea(HR=1.58,95%CI 1.24–2.01,p<0.001),and CT signs of ground-glass opacity(HR=1.39,95%CI 1.04–1.86,p=0.024)and infiltrating shadows(HR=1.84,95%CI 1.22–2.78,p=0.004).The risk of progression was found to be lower among patients with nausea or vomiting(HR=0.53,95%CI 0.30–0.96,p=0.036)and headaches(HR=0.54,95%CI 0.29–0.99,p=0.046).Our results suggest that several factors that can be easily measured even in resource-poor set-tings(dyspnea,sex,and age)can be used to identify mild COVID-19 patients who are at increased risk of disease *** for CT signs of ground-glass opacity and i

关键词： COVID-19 Asymptomatic and mild Community isolation Fangcang shelter hospital Competing risk survival analysis

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Pre-Lung transplant reflux testing demonstrates high prevalence of gastroesophageal reflux in cystic fibrosis and reduces chronic rejection risk

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World Journal of Transplantation 2023年第4期13卷 138-146页

作者： Wai-Kit Lo Ryan Flanagan Nirmal Sharma Hilary J Goldberg Walter W Chan division of Gastroenterology Hepatology and EndoscopyBrigham and Women's HospitalHarvard Medical SchoolBostonMA division of pulmonary and critical care medicine Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02115United States

BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic *** is common in cystic fibrosis(CF),but factors influencing the likelihood of pre-transplant pH testing,and the impact of testing on clinical management and transplant outcomes in patients with CF are *** To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with *** This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung *** with pretransplant anti-reflux surgery were *** characteristics(age at transplantation,gender,race,body mass index),self-reported GER symptoms prior to transplantation,and pre-transplant cardiopulmonary testing results,were *** testing consisted of either 24-h pH-or combined multichannel intraluminal impedance and pH ***-transplant care included a standard immunosuppressive regimen,and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic *** primary outcome of chronic lung allograft dysfunction(CLAD)was defined clinically and histologically per International Society of Heart and Lung Transplantation *** analysis was performed with Fisher’s exact test to assess differences between cohorts,and time-to-event Cox proportional hazards *** After applying inclusion and exclusion criteria,a total of 60 patients were included in the *** all CF patients,41(68.3%)completed reflux monitoring as part of pre-lung transplant *** evidence of pathologic reflux,defined as acid exposure time>4%,was found in 24 subjects,representing 58%of the tested *** patients with pre-transplant reflux testing were older(35.8 vs 30.1 years,P=0.01)and more commonly reported typical

关键词： Cystic fibrosis Gastroesophageal reflux Lung transplantation pH monitoring

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Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression

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Military medical Research 2023年第3期10卷 281-298页

作者： Fei Pei Ren‑Qi Yao Chao Ren Soheyl Bahrami Timothy RBilliar Irshad HChaudry De‑Chang Chen Xu‑Lin Chen Na Cui Xiang‑Ming Fang Yan Kang Wei‑Qin Li Wen‑Xiong Li Hua‑Ping Liang Hong‑Yuan Lin Ke‑Xuan Liu Ben Lu Zhong‑Qiu Lu Marc Maegele Tian‑Qing Peng You Shang Lei Su Bing‑Wei Sun Chang‑Song Wang Jian Wang Jiang‑Huai Wang Ping Wang Jian‑Feng Xie Li‑Xin Xie Li‑Na Zhang Basilia Zingarelli Xiang‑Dong Guan Jian‑Feng Wu Yong‑Ming Yao Department of critical care medicine the First Affiliated Hospital of Sun Yat-Sen University58 Zhongshan Er RoadYuexiu DistrictGuangzhou 510080GuangdongChina Translational medicine Research center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital28 Fuxing RoadHaidian DistrictBeijing 100853China Department of Burn Surgery the First Affiliated Hospital of Naval Medical UniversityShanghai 200433China Ludwig-Boltzmann Institute for Experimental and Clinical Traumatology 1200 ViennaAustria Department of Surgery University of Pittsburgh Medical CenterPittsburghPA 15213USA center for Surgical Research and Department of Surgery University of Alabama at BirminghamBirminghamAL 35294USA Department of critical care medicine Ruijin HospitalShanghai Jiaotong UniversityShanghai 200025China Department of Burns the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Department of critical care medicine Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Department of Anesthesiology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 31003China Department of critical care medicine West China Hospital of Sichuan UniversityChengdu 610041China Department of critical care medicine General Hospital of Eastern Theater Command of Chinese PLANanjing 210002China Department of Surgical Intensive critical Unit Beijing Chao‑Yang HospitalCapital Medical UniversityBeijing 100020China State Key Laboratory of Trauma Burns and Combined InjuryResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China Department of critical care medicine Fourth Medical Center of the Chinese PLA General HospitalBeijing 100048China Department of Anesthesiology Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of critical care medicine and Hematology the Third Xiangya HospitalCentral South UniversityChangs

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of *** provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was *** related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online ***,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus *** consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good *** summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were ***,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this *** summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

关键词： Sepsis Immune function monitoring Immunomodulatory therapy Immunosuppression

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SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3780-3793页

作者： Kai Yang Shiyun Liu Han Yan Wenju Lu Xiaoqian Shan Haixia Chen Changlei Bao Huazhuo Feng Jing Liao Shuxin Liang Lei Xu Haiyang Tang Jason X-J.Yuan Nanshan Zhong Jian Wang State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangdong Key Laboratory of Vascular DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Guangzhou National Laboratory Guangzhou International Bio IslandGuangzhouGuangdongChina Department of pulmonary and critical care medicine The Affiliated Hospital of Inner Mongolia Medical UniversityHohhotInner Mongolia Autonomous RegionChina Department of Pathology The Affiliated Cancer Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina School of medicine Southern University of Science and TechnologyShenzhenGuangdongChina Section of Physiology Division of PulmonaryCritical Care and Sleep MedicineDepartment of MedicineUniversity of California San DiegoLa JollaCAUSA

Exposure to the spike protein or receptor-binding domain(S-RBD)of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular *** this study,angiotensin-converting enzyme 2 humanized inbred(hACE2 Tg)mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular *** show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration([Ca^(2+)]i)via acute activation of TRPV4,and prolonged upregulation of mechanosensitive channel Piezo1 and store-operated calcium channel(SOCC)key component Orai1 in cultured human pulmonary arterial endothelial cells(PAECs).In mechanism,S-RBD interacts with ACE2 to induce formation of clusters involving Orai1,Piezo1 and TRPC1,facilitate the channel activation of Piezo1 and SOCC,and lead to elevated *** effects are blocked by Kobophenol A,which inhibits the binding between S-RBD and ACE2,or intracellular calcium chelator,*** of Piezo1 and SOCC by GsMTx4 effectively protects the S-RBDinduced pulmonary microvascular endothelial damage in hACE2 Tg mice via normalizing the elevated[Ca^(2+)]*** to prototypic strain,Omicron variants(BA.5.2 and XBB)of S-RBD induces significantly less severe cell *** analysis indicates that prototypic S-RBD confers more severe acute impacts than Delta or Lambda *** summary,this study provides compelling evidence that S-RBD could induce persistent pulmonary vascular endothelial damage by binding to ACE2 and triggering[Ca^(2+)]i through upregulation of Piezo1 and *** inhibition of ACE2-Piezo1/SOCC-[Ca^(2+)]i axis proves a powerful strategy to treat S-RBD-induced pulmonary vascular diseases.

关键词： ACE2 elevated homeostasis

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