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Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

Zoological Research 2024年第4期45卷 747-766页

作者： Hong-Yi Zheng Tian-Zhang Song Yong-Tang Zheng State Key Laboratory of Genetic Evolution&Animal Models KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China National Resource Center for Non-Human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole ***,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 *** among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of *** effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and *** animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

关键词： SARS-CoV-2 COVID-19 Animal models Infection immunology Immunotherapy

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Real-world utility of serological tests in patients with suspected scrub typhus in the Republic of Korea:A single-center,retrospective,observational study

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Asian Pacific Journal of Tropical Medicine 2024年第6期17卷 273-280,I0004,I0005页

作者： Seulki Kim A Reum Kim Seungjin Lim Su Jin Lee Moonsuk Bae Division of Infectious diseases Department of Internal MedicinePusan National University Yangsan HospitalYangsanRepublic of Korea Research institute for Convergence of Biomedical Science and Technology Pusan National University Yangsan HospitalYangsanRepublic of Korea Department of Internal Medicine Pusan National University School of MedicineBusanRepublic of Korea

Objective:Serological tests are widely used for scrub typhus diagnosis;however,their limitations are *** study aims to assess their practical value in clinical ***:We analyzed the data of adult patients with suspected scrub typhus who visited a tertiary care hospital in the Republic of Korea from September to December from 2019 to *** included patients had an acute fever and at least one of the following ten secondary findings:myalgia,skin rash,eschar,headache,thrombocytopenia,increased liver enzyme levels,lymphadenopathy,hepatomegaly,splenomegaly,and pleural *** diagnoses were grouped as scrub typhus or other diseases by two infectious disease ***:Among 136 patients who met the eligibility criteria,109 had scrub typhus and 27 had different *** and paired total antibodies using immunofluorescence assay(IFA),and total antibodies using immunochromatography-based rapid diagnostic testing(ICT)were measured in 98%,22%,and 75%of all patients,*** using paired samples for scrub typhus was established at a median of 11[interquartile range(IQR)10-16]days following the first *** the 82 admitted patients,the median admission time was 9(IQR 7-13)*** to IFA,58(55%)patients with scrub typhus had total immunoglobulin titers≥1:320,while 23(85%)patients with other disease had titersdiseases showed negative ICT ***:Serological testing for scrub typhus is currently insufficient for decision-making in clinical practice.

关键词： Scrub typhus Serological test Immunofluorescence assay Immunochromatography Rapid detecting test

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Targeting complement hyperactivation:a novel therapeutic approach for severe pneumonia induced by influenza virus/staphylococcus aureus coinfection

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Signal Transduction and Targeted Therapy 2024年第1期9卷 51-54页

作者： Leili Jia Haihua Luo Lizhong Li Mingyao Wang Jiangfeng Liu Yuan Liang Shan Li Yong Jiang Juntao Yang Hongbin Song institute for Disease Control and Prevention of PLA BeijingChina Guangdong Provincial Key Laboratory of Proteomics State Key Laboratory of Organ Failure ResearchSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Common Mechanism Research for Major diseases Institute of Basic Medical SciencesChinese Academy of Medical Science and Peking Union Medical College100005 BeijingChina

Dear Editor,Infections by the influenza virus are a significant and widespread global health threat,as these infections have an annual death toll ranging from 290,000 to 650,000.1 A significant proportion of these fatalities are attributed to secondary bacterial pneumonia,a severe complication commonly caused by ubiquitous respiratory pathogens such as Staphylococcus aureus(***).2 Of particular concern is the increased morbidity and mortality rates in individuals infected simultaneously with influenza virus and methicillin-resistant ***(MRSA).3 The concurrent presence of bacteria and influenza virus usually causes acute respiratory distress syndrome(ARDS),which is associated with acute lung injury(ALI),severe lung tissue edema,and widespread ***,determining the complex mechanisms underlying the synergistic interplay will require further investigation with a suitable coinfection mouse *** our previous study,we utilized different sequential coinfections at various time points to model influenza A virus and MRSA coinfection.

关键词： influenza pneumonia lung

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Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus

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World Journal of Diabetes 2024年第4期15卷 606-622页

作者： Ashwin Kumar Shukla Komal Awasthi Kauser Usman Monisha Banerjee Molecular and Human Genetics Laboratory Department of ZoologyUniversity of LucknowLucknow 226007Uttar PradeshIndia Department of Medicine King Georges’Medical UniversityLucknow 226003Uttar PradeshIndia institute of Advanced Molecular Genetics and Infectious Diseases(IAMGID)University of LucknowLucknow 226007Uttar PradeshIndia

Coronavirus disease 2019(COVID-19)is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 *** has affected over 768 million people worldwide,resulting in approx-imately 6900000 ***-risk groups,identified by the Centers for Disease Control and Prevention,include individuals with conditions like type 2 diabetes mellitus(T2DM),obesity,chronic lung disease,serious heart conditions,and chronic kidney *** indicates that those with T2DM face a hei-ghtened susceptibility to COVID-19 and increased mortality compared to non-diabetic *** the renin-angiotensin system(RAS),a vital regulator of blood pressure and pulmonary stability,reveals the significance of the angiotensin-converting enzyme(ACE)and ACE2 *** converts angiotensin-I to the vasoconstrictor angiotensin-II,while ACE2 counters this by converting angiotensin-II to angiotensin 1-7,a *** ACE2 exp-ression,common in diabetes,intensifies RAS activity,contributing to conditions like inflammation and *** ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels,concerns arise regarding the potential elevation of ACE2 receptors on cell membranes,potentially facilitating COVID-19 *** review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome cor-onavirus 2 infection and associated complications in *** treatment strategies,including recombinant human ACE2 therapy,broad-spectrum antiviral drugs,and epigenetic signature detection,are discussed as promising avenues in the battle against this pandemic.

关键词： Angiotensin-converting enzyme 2 Angiotensin-converting enzyme inhibitors Angiotensin-II receptor blockers Complex diseases COVID-19 Type 2 diabetes

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Epidemiological Characteristics of Human Parainfluenza Viruses Infections-China,2019-2023

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China CDC weekly 2024年第12期6卷 235-241,I0003,I0004页

作者： Yixuan Gao Yingwei Ma Daxing Feng Feng Zhang Biao Wang Xiaoqing Liu Bing Zhu Hui Xie Linqing Zhao Xiaoru Long Ying Chen Bing Wang Jie Jiang Zhen Zhu Yan Zhang Aili Cui Baicheng Xia Naiying Mao National Key Laboratory of Intelligent Tracking and Forecasting for Infectious diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Precision Medicine Research Center Children’s Hospital of ChangchunChangchun CityJilin ProvinceChina Henan Provincial Center for Disease Control and Prevention Zhengzhou CityHenan ProvinceChina Laboratory of Viral diseases Qingdao Municipal Centre for Disease Control and PreventionQingdao CityShandong ProvinceChina Virus Laboratory Gansu Provincial Center for Disease Control and PreventionLanzhou CityGansu ProvinceChina Jiangxi Provincial Center for Disease Control and Prevention Nanchang CityGansu ProvinceChina Virus Laboratory Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina institute for Immunization and Prevention Beijing Center for Disease Prevention and ControlAcademy for Preventive MedicineInstitute of Tuberculosis Control Research and PreventionBeijingChina Laboratory of Virology Beijing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBeijingChina Department of Infection Children’s Hospital of Chongqing Medical UniversityChongqingChina Inner Mongolia Autonomous Region Comprehensive Center for Disease Control and Prevention Hohhot CityInner Mongolia Autonomous RegionChina Shenyang Prefecture Center for Disease Control and Prevention Shenyang CityLiaoning ProvinceChina

Introduction:A retrospective study based on sentinel surveillance was conducted in 10 provinciallevel administrative divisions(PLADs)in China to enhance the understanding of the epidemiological characteristics of human parainfluenza viruses(HPIVs).Methods:From January 2019 to June 2023,respiratory specimens were collected from individuals with acute respiratory infections(ARIs)and screened for four HPIVs serotypes and other common respiratory viruses using multiplex real-time polymerase chain reaction(PCR).This study analyzed the association of HPIVs infections with seasonal patterns,geographical distribution,demographic profiles,clinical features,and co-infection ***:During the study period,a total of 12,866 ARIs were *** overall detection rate of HPIVs was 6.15%,varying from 5.04%in 2022 to 9.70%in *** median age of HPIVs-infected patients was 3 ***2 was more prevalent among individuals aged 5–17 years(42.57%),while HPIV4 was more common in those over 65 years(12.24%).HPIV3(54.16%)and HPIV1(27.18%)were the predominant serotypes,and their prevalence exhibited significant seasonal fluctuations postcoronavirus disease 2019(COVID-19)*** peak of HPIV3 shifted three months later in 2020 compared to 2019 and returned to a summer peak *** peaks of HPIV1 were observed in 2021 following the peak of ***,coinfections were frequent in HPIVs cases(overall rate:22.12%),with human rhinovirus being the most common co-infecting ***:The prevalence of HPIVs in China was predominantly due to HPIV3 and HPIV1,and their seasonal patterns were altered by pandemic ***,continuous surveillance of HPIVs is essential.

关键词： prevalence seasonal Human

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A cross-sectional analysis of the effectiveness of a nutritional support programme for people with tuberculosis in Southern Madagascar using secondary data from a non-governmental organisation

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Infectious diseases of Poverty 2024年第1期13卷 101-102页

作者： Mara Anna Franke Julius Valentin Emmrich Fierenantsoa Ranjaharinony Onja GbrilleRavololohanitra Harizaka Emmanuel Andriamasy Samuel Knauss Nadine Muller Global Digital Health Lab at Charité Center for Global Health Charité – Universitätsmedizin Berlin Berlin Germany London School of Hygiene and Tropical Medicine London UK Ärzte Für Madagaskar E.V. Leipzig Germany Heidelberg institute of Global Health Heidelberg University Heidelberg Germany Berlin institute of Health at Charité - Universitätsmedizin Berlin Berlin Germany Doctors for Madagascar Antananarivo Madagascar Speciality Network: Infectious diseases and Respiratory Medicine Charité - Universitätsmedizin Berlin Berlin Germany

Background There is a strong,bi-directional link between tuberculosis(TB)and undernutrition:TB often causes undernutrition,and undernourished people are more likely to contract TB and experience worse ***,several TB nutritional support programmes exist;however,evidence on their effectiveness is limited and *** study evaluates the effect of a nutritional support programme implemented for people with TB in the Atsimo-Andrefana region,Madagascar in *** this programme,undernourished people with TB[with a body mass index(BMI)ofacute malnutrition at treatment *** the average BMl of adults with TB receiving food support increased over time,from 17.1 kg/m^(2)(interquartile range:15.8-18.3,range:10.3-22.5)to 17.9 kg/m^(2)(interquartile range:16.6-19.1,range:11.9-24.1),most adults remained undernourished even after completing TB *** The current TB nutritional support programme falls short of sufficiently increasing the BM

关键词： Tuberculosis Sub-Saharan Africa Undernutrition Nutritional support

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Two antibodies show broad,synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

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Protein & Cell 2024年第2期15卷 121-134页

作者： Hui Sun Tingting Deng Yali Zhang Yanling Lin Yanan Jiang Yichao Jiang Yang Huang Shuo Song Lingyan Cui Tingting Li Hualong Xiong Miaolin Lan Liqin Liu Yu Li Qianjiao Fang Kunyu Yu Wenling Jiang Lizhi Zhou Yuqiong Que Tianying Zhang Quan Yuan Tong Cheng Zheng Zhang Hai Yu Jun Zhang Wenxin Luo Shaowei Li Qingbing Zheng Ying Gu Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China National institute of Diagnostics and Vaccine Development in Infectious diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China State Key Laboratory of Vaccines for Infectious diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China Xiang An Biomedicine Laboratory Xiamen 361102China institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalSchool of MedicineSouthem University of Science and TechnologyShenzhen 518112China The Second Affliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China

Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or *** rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus ***,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron ***-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric *** antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant ***,these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

关键词： SARS-CoV-2 broad neutralizing antibody rearrangement synergistic neutralization

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The protective effects of fermented vinegar on acute alcohol-induced hepatic and neuro-toxicity by regulating ethanol metabolism and gut microbiota

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Food Science and Human Wellness 2024年

作者： Yuan Meng Yunfan Liu Ting Xia Beibei Geng Yinglei Tian Hailong Cao Jin Yan Xiaoqi Pang Kai Liang Yufeng Yan Min Wang State Key Laboratory of Food Nutrition and Safety Key Laboratory of Industrial Fermentation Microbiology College of Biotechnology Tianjin University of Science and Technology Department of Gastroenterology and Hepatology General Hospital Tianjin Medical University National Key Clinical Specialty Tianjin institute of Digestive diseases Tianjin Key Laboratory of Digestive diseases Shanxi Provincial Key Laboratory for Vinegar Fermentation Science and Engineering Shanxi Zilin Vinegar Industry Co. Ltd.

Alcohol abuse constitutes a significant health hazard， leading to various organ damage， notably the liver and brain. Shanxi aged vinegar (SAV) is one of the famous fermented and functional foods containing a variety of bioactive ingredients with beneficial effects on the human body. This study aimed to explore the potential protective effect of SAV in alleviating acute alcohol intoxication (AAI) in mice. It was found that SAV at 2.5 mg/kg BW effectively ameliorated the decline in behavioral abilities following alcohol consumption， characterized by a shortened sobering period. SAV reduces alcohol-induced liver damage by inhibiting hepatic function enzymes and oxidative stress levels. Additionally， SAV mitigated the overactivation of microglia and the downregulation of neurotransmitter levels (AchE， 5-HT， and DA)， thereby reducing ethanol-induced brain damage. Meanwhile， SAV significantly decreased concentrations of alcohol and acetaldehyde in the blood and increased ADH and ALDH activities in the liver， indicating enhancement of ethanol metabolism. Moreover， we found that some gut microbiota including Verrucomicrobiota， Akkermansia， and Enterococcus were downregulated after SAV treatment in mice with AAI. These bacteria showed a negative correlation with anti-oxidative markers (GSH and CAT) and enzymes related to ethanol metabolism pathways (ADH and ALDH)， and a positive correlation with hepatic function markers (ALT， AST， and MDA)， alcohol metabolites (alcohol and acetaldehyde) and neurotransmitters (AchE， 5-HT， and DA). However， Bacteroidota， norank＿f＿Muribaculaceae， and Alistipes exhibited the opposite direction. These findings suggest that SAV possesses protective effects against hepatic and neuro-toxicity， and could be a potential functional food for AAI prevention.

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Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2669-2678页

作者： Biqi Zhou Jia Chen Tianhui Liu Yishan Ye Yanming Zhang Yiyang Ding Hong Liu MingQing Zhu Xiao Ma Xiaoli Li Longfei Zhao Zhihong Lin He Huang Yang Xu Depei Wu National Clinical Research Center for Hematologic diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina institute of Blood and Marrow Transplantation Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Department of Hematology The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina Soochow Hopes Hematology Hospital SuzhouChina Department of Hematology Hygeia Suzhou Yongding HospitalSuzhouChina

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient *** multicenter,randomized,phase 3 trial(*** NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this *** median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT *** 3-4 adverse events(AEs)within two years posttransplantation in the two groups were ***-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period ***-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

关键词： hematopoietic acute phase

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Virtual reality-based cognitive-behavioural therapy for the treatment of anxiety in patients with acute myocardial infarction:a randomised clinical trial

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General Psychiatry 2024年第2期37卷 189-196页

作者： Yuanyuan Li Juan Peng Pingyuan Yang Jiajun Weng Yan'e Lu Jiajia Liu Shikun Xu Lihua Guan Dong Huang Qibing Wang Juying Qian Zexin Zhao Yabin Wei Junbo Ge Xiao Huang Department of Psychological Medicine Zhongshan Hospital Fudan UniversityShanghaiChina Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesNational Clinical Research Center for Interventional MedicineShanghaiChina Department of Psychological Medicine Shanghai Geriatric Medical CenterShanghaiChina School of Nursing Peking UniversityBeijingChina Beijing Key Laboratory of Drug Dependence Research National Institute on Drug DependencePeking UniversityBeijingChina

Background The presence of mental health conditions is pervasive in patients who experienced acute myocardial infarction(AMI),significantly disrupting their *** timely and easily accessible psychological interventions using virtual reality-based cognitive-behavioural therapy(VR-CBT)could potentially improve both acute and long-term symptoms affecting their mental *** We aim to examine the effectiveness of VR-CBT on anxiety symptoms in patients with AMI who were admitted to the intensive care unit(ICU)during the acute stage of their *** In this single-blind randomised clinical trial,participants with anxiety symptoms who were admitted to the ICU due to AMI were continuously recruited from December 2022 to February *** who were Han Chinese aged 18-75 years were randomly assigned(1:1)via block randomisation to either the VR-CBT group to receive VR-CBT in addition to standard mental health support,or the control group to receive standard mental health support ***-CBT consisted of four modules and was delivered at the bedside over a 1-week *** were done at baseline,immediately after treatment and at 3-month *** intention-to-treat analysis began in June *** primary outcome measure was the changes in anxiety symptoms as assessed by the Hamilton Anxiety Rating Scale(HAM-A).Results Among 148 randomised participants,70 were assigned to the VR-CBT group and 78 to the control *** 1-week VR-CBT intervention plus standard mental health support significantly reduced the anxiety symptoms compared with standard mental health support alone in terms of HAM-A scores at both post intervention(Cohen’s d=−1.27(95%confidence interval(CI):−1.64 to−0.90,p<0.001)and 3-month follow-up(Cohen’s d=−0.37(95%CI:−0.72 to−0.01,p=0.024).Of the 70 participants who received VR-CBT,62(88.6%)completed the entire *** was the main reported adverse event(n=5).Conclusions Our results indicate that VR-CB

关键词： admitted behaviour treatment

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