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Clinical characteristics and management of coexistent cardiomyopathy in patients with bicuspid aortic valve

Journal of Geriatric cardiology 2023年第3期20卷 205-213页

作者： Di ZHANG Yi-Ting LU Ze-Min ZHOU Yu-Xiao HU Xin-Chang LIU Yi QU Ya-Xin LIU Xian-Liang ZHOU Department of cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Emergency and Critical Care Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

BACKGROUND Bicuspid aortic valve(BAV)is the most common congenital heart ***,the prevalence,clinical characteristics,and current management of BAV associated with inherited cardiomyopathy,including hypertrophic cardiomy-opathy(HCM),dilated cardiomyopathy(DCM),and left ventricular noncompaction(LVNC)have not been well *** Consecutive patients diagnosed with BAV at a large tertiary cardiovascular referral center between 2009 and 2018 were retrospectively assessed for HCM,DCM,and LVNC based on clinical and echocardiographic *** with coexist-ent conditions were investigated *** Of 3533 patients with BAV screened,57(1.6%)had concomitant *** was combined with HCM in 30 of these patients,with DCM in 19,and with LVNC in ***-six patients(80.7%)were male,and the mean age at first dia-gnosis was 47 years for BAV with HCM,49 years for BAV with DCM,and 35 years for BAV with *** failure and aortic valve dysfunction were common in these patients,and the prevalence of coexisting aortopathy was 43.3%,26.3%and 25.0%,re-spectively,for BAV with HCM,DCM and *** the index hospitalization,24 of the 57 patients(42.1%)underwent sur-gery,16(28%)underwent aortic valve and/or aortic surgery,and 16 of the 30 patients with HCM had a Morrow *** were no deaths or other major adverse cardiovascular *** The prevalence of inherited cardiomyopathy was higher in our patients with BAV than in the general *** and heart failure were common,with almost half of patients requiring surgery at diagnosis.

关键词： patients cardiomyopathy aortic

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Prevalence, risk factors, and survival associated with pulmonary hypertension and heart failure among patients with underlying coronary artery disease: a national prospective, multicenter registry study in China

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Chinese Medical Journal 2022年第15期135卷 1837-1845页

作者： Li Huang Lingpin Pang Qing Gu Tao Yang Wen Li Ruilin Quan Weiqing Su Weifeng Wu Fangming Tang Xiulong Zhu Jieyan Shen Jingzhi Sun Guangliang Shan Changming Xiong Shian Huang Jianguo He Department of cardiology Guangdong Cardiovascular InstuteGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong 510080China cardiovascular Medicine Center Afliated Hospital of Guangdong Medical UniversityZhanjangGuangdong 510180China Center of Pulmonary Vascular Disease State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100007China Department of cardiology Lianjang People's HospitalLianjangGuangdong 524499China Department of cardiology the First Afliated Hospital of Guangxi Medical UniversityNaningGuangxi 530021China Department of cardiology Nongken Central Hospital of Guangdong ProvinceZhanjangGuangdong 529632China Department of cardiology People's Hospital of GaozhouGaozhouGuangdong 525232China Department of cardiology Renji HospitalShanghai Jiaotong University School of MedicineShanghai 200025China Department of cardiology ffliated Hospital of Jining Medical UniversityJiningShandong 272007China Department of pidemiology and Biostatistis Insttute of Basic Medical SciencesChinese Academy of Medical SciencesScholf Basic MedicinePeking Union Medial CollegeBeijing 100006China

Background: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with ***: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was ***: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF];left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF];LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with ***: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH *** Registration: ***, NCT02164526.

关键词： Coronary artery disease Heart failure Pulmonary hypertension Registry study

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USH1C新杂合突变影响耳蜗毛细胞机械电转导功能并导致渐进性听力损伤（英文）

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Science Bulletin 2024年第2期 167-172页

作者：贾岩岩贾高干郭荦宋楠王雨萌蒋罗颖舒易来陈岩竺淑佳李华伟李文妍 ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan University Institutes of Biomedical sciences Fudan University NHC Key Laboratory of Hearing Medicine (Fudan University) The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science Fudan University Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology Institute of Neuroscience State Key Laboratory of Neuroscience CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Department of cardiology and Institute for Developmental and Regenerative Cardiovascular Medicine Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Hearing loss is one of the most common sensory disorders worldwide, affecting approximately 466 million people, including34 million children [1]. Genetic mutations accounts for approximately 60% of inherited hearing l...

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Severity of non-alcoholic fatty liver disease is a risk factor for developing hypertension from prehypertension

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Chinese Medical Journal 2023年第13期136卷 1591-1597页

作者： Qirui Song Qianhui Ling Luyun Fan Yue Deng Qiannan Gao Ruixue Yang Shuohua Chen Shouling Wu Jun Cai Hypertension Center Fuwai HospitalState Key Laboratory of Cardiovascular Disease of ChinaNational Center for Cardiovascular Diseases of ChinaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China State Key Laboratory of cardiovascular Disease of China Fuwai HospitalNational Center for Cardiovascular Diseases of ChinaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of cardiology Kailuan General HospitalTangshanHebei 063000China

Background:There is little published evidence about the role of non-alcoholic fatty liver disease(NAFLD)in the progression from prehypertension to *** study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from ***:The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline;those with excessive alcohol consumption and other liver diseases were *** was diagnosed by ultrasonography and stratified as mild,moderate,or *** and multivariable Cox proportional hazard regression was used to calculate the hazard ratios(HRs)and 95%confidence intervals(CIs)of incident hypertension according to the presence and 3 categories of severity of ***:During a median of 12.6 years of follow-up,10,638 participants progressed to hypertension from *** adjusting for multiple risk factors,patients with prehypertension and NAFLD had a 15%higher risk of incident hypertension than those without NAFLD(HR=1.15,95%CI 1.10-1.21).Moreover,the severity of NAFLD was associated with the incidence of hypertension,which was higher in patients with more severe NAFLD(HR=1.15[95%CI 1.10-1.21]in the mild NAFLD group;HR=1.15[95%CI 1.07-1.24]in the moderate NAFLD group;and HR=1.20[95%CI 1.03-1.41]in the severe NAFLD group).Subgroup analysis indicated that age and baseline systolic blood pressure may modify this ***:NAFLD is an independent risk factor for hypertension in patients with *** risk of incident hypertension increases with the severity of NAFLD.

关键词： Hypertension Non-alcoholic fatty liver disease Prehypertension

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The mechanism and therapy of aortic aneurysms

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Signal Transduction and Targeted Therapy 2023年第3期8卷 963-982页

作者： Jianing Gao Huanhuan Cao Gaofei Hu Yufei Wu Yangkai Xu Hongtu Cui Hong S.Lu Lemin Zheng The Institute of cardiovascular sciences and Institute of Systems Biomedicine School of Basic Medical SciencesKey Laboratory of Molecular Cardiovascular Science of Ministry of EducationNHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesBeijing Key Laboratory of Cardiovascular Receptors ResearchHealth Science CenterPeking University100191 BeijingChina Department of cardiology and Institute of Vascular Medicine Peking University Third HospitalNHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing Key Laboratory of Cardiovascular Receptors ResearchResearch Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular DiseasesChinese Academy of Medical Sciences100191 BeijingChina Department of Physiology Saha Cardiovascular Research CenterUniversity of KentuckySouth LimestoneLexingtonKY 40536-0298USA

Aortic aneurysm is a chronic aortic disease affected by many *** it is generally asymptomatic,it poses a significant threat to human life due to a high risk of *** of its strong concealment,it is difficult to diagnose the disease in the early *** present,there are no effective drugs for the treatment of *** intervention and endovascular treatment are the only *** current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm,the specific mechanisms remain *** are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and *** better understand aortic aneurysm,this review elaborates on the discovery history of aortic aneurysm,main classification and clinical manifestations,related molecular mechanisms,clinical cohort studies and animal models,with the ultimate goal of providing insights into the treatment of this devastating *** underlying problem with aneurysm disease is weakening of the aortic wall,leading to progressive *** not treated in time,the aortic aneurysm eventually *** aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic *** disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.

关键词： aortic diagnosis drugs treatment

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Assessment of causal direction between thyroid function and cardiometabolic health:a Mendelian randomization study

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Journal of Geriatric cardiology 2022年第1期19卷 61-70页

作者： Jing-Jia WANG Zhen-Huang ZHUANG Can-Qing YU Wen-Yao WANG Wen-Xiu WANG Kuo ZHANG Xiang-Bin MENG Jun GAO Jian TIAN Ji-Lin ZHENG Jie YANG Tao HUANG Chun-Li SHAO Yi-Da TANG Department of cardiology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Epidemiology&Biostatistics School of Public HealthPeking UniversityBeijingChina Center for Intelligent Public Health Academy for Artificial IntelligencePeking UniversityBeijingChina Department of cardiology and Institute of Vascular Medicine Peking University Third HospitalBeijingChina Key Laboratory of Molecular cardiovascular sciences(Peking University) Ministry of EducationBeijingChina

BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular ***,the causal relationship of thyroid function and cardiometabolic health remains partly *** The Mendelian randomization(MR)was used to test genetic,potentially causal relationships between instrumental variables and cardiometabolic *** variants of free thyroxine(FT4)and thyrotropin(TSH)levels within the reference range were used as instrumental *** for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen,CARDIoGRAM and CARDIoGRAMplusC4D,CHARGE,and *** study was conducted using summary statistic data from large,previously described *** between thyroid function and essential hypertension(EHTN),secondary hypertension(SHTN),hyperlipidemia(HPL),type 2 diabetes mellitus(T2DM),ischemic heart disease(IHD),myocardial infarction(MI),heart failure(HF),pulmonary heart disease(PHD),stroke,and non-rheumatic valve disease(NRVD)were *** Genetically predicted FT4 levels were associated with SHTN(odds ratio=0.48;95%CI=0.04−0.82,P=0.027),HPL(odds ratio=0.67;95%CI=0.18−0.88,P=0.023),T2DM(odds ratio=0.80;95%CI=0.42−0.86,P=0.005),IHD(odds ratio=0.85;95%CI=0.49−0.98,P=0.039),NRVD(odds ratio=0.75;95%CI=0.27−0.97,P=0.039).Additionally,genetically predicted TSH levels were associated with HF(odds ratio=0.82;95%CI=0.68−0.99,P=0.042),PHD(odds ratio=0.75;95%CI=0.32−0.82,P=0.006),stroke(odds ratio=0.95;95%CI=0.81−0.97,P=0.007).However,genetically predicted thyroid function traits were not associated with EHTN and *** Our study suggests FT4 and TSH are associated with cardiometabolic diseases,underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.

关键词： cardio function random

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Early identification of STEMI patients with emergency chest pain using lipidomics combined with machine learning

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Journal of Geriatric cardiology 2022年第9期19卷 685-695页

作者： Zhi SHANG Yang LIU Yu-Yao YUAN Xin-Yu WANG Hai-Yi YU Wei GAO Department of cardiology Peking University Third HospitalNHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijingChina Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesPeking-Tsinghua Center for Life SciencesPeking University Health Science CenterBeijingChina

OBJECTIVES To analyze the differential expression of lipid spectrum between ST-segment elevated myocardial infarction(STEMI)and patients with emergency chest pain and excluded coronary artery disease(CAD),and establish the predictive model which could predict STEMI in the early *** We conducted a single-center,nested case-control study using the emergency chest pain cohort of Peking Univer-sity Third *** lipidomics were conducted while LASSO regression as well as XGBoost combined with greedy algorithm were used to select lipid *** Fifty-two STEMI patients along with 52 controls were enrolled.A total of 1925 lipid molecules were *** were 93 lipid molecules in the positive ion mode which were differentially expressed between the STEMI and the control group,while in the negative ion mode,there were 73 differentially expressed lipid *** the positive ion mode,the differentially expressed lipid subclasses were mainly diacylglycerol(DG),lysophophatidylcholine(LPC),acylcarnitine(CAR),lysophospha-tidyl ethanolamine(LPE),and phosphatidylcholine(PC),while in the negative ion mode,significantly expressed lipid subclasses were mainly free fatty acid(FA),LPE,PC,phosphatidylethanolamine(PE),and phosphatidylinositol(PI).LASSO regression se-lected 22 lipids while XGBoost combined with greedy algorithm selected 10 ***(15:0/18:2),PI(19:4),and LPI(20:3)were the overlapping lipid molecules selected by the two feature screening *** model established using the three lipids had excellent performance in discrimination and calibration both in the derivation set(AUC:0.972)and an internal validation set(AUC:0.967).In 19 STEMI patients with normal cardiac troponin,18 patients were correctly diagnosed using lipid *** The differentially expressed lipids were mainly DG,CAR,LPC,LPE,PC,PI,PE,and *** lipid molecules selected by XGBoost combined with greedy algorithm and LASSO regression to establish mode

关键词： STEMI patients pain

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Target versus sub-target dose of renin–angiotensin system inhibitors on survival in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis

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Journal of Geriatric cardiology 2023年第6期20卷 469-478页

作者： Long-Kun SUN Jing KONG Xiao-Wei YANG Jing WANG Peng-Fei ZHANG The Key Laboratory of cardiovascular Remodeling and Function Research Chinese Ministry of EducationChinese National Health Commission and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineDepartment of CardiologyQilu HospitalCheeloo College of MedicineShandong UniversityJinanChina

BACKGROUND The efficiency of the target versus sub-target dose of renin–angiotensin system inhibitors(RASIs)in elderly patients with heart failure(HF)with reduced ejection fraction(HErEF)remains *** PubMed,Embase,and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials(RCTs)and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients(≥60 years)with *** primary outcome was all-cause *** secondary outcomes were cardiac mortality,HF hospitalization,and the composite endpoint of mortality or HF hospitalization.A meta-analysis was conducted to generate combined hazard ratio(HR)and 95%*** Seven studies(two RCTs and five observational studies)enrolling 16,634 patients were included.A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality(HR=0.92,95%CI:0.87–0.98,I2=21%)and cardiac mortality(HR=0.93,95%CI:0.85–1.00,I2=15%)but not reduced rates of HF hospitalization(HR=0.94,95%CI:0.88–1.01,I2=0)and the composite endpoint(HR=1.03,95%CI:0.91–1.15,I2=51%).However,the target dose of RASIs was associated with a similar primary outcome(HR=0.85,95%CI:0.64–1.14,I2=0)in a subgroup of very elderly patients>75 years of *** Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of ***,the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients>75 years of *** high-quality and adequately powered RCTs are warranted.

关键词： patients analysis fraction

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Exercise training attenuates angiotensinⅡ-induced cardiac fibrosis by reducing POU2F1 expression

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Journal of Sport and Health Science 2023年第4期12卷 464-476页

作者： Na Feng Haiyi Yu Yueshen Wang Youyi Zhang Han Xiao Wei Gao Department of cardiology and Institute of Vascular Medicine Peking University Third HospitalNational Health Commission Key Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing 100191China Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic cardiovascular Diseases Chinese Academy of Medical SciencesBeijing 100191China

Background:Exercise training protects against heart ***,the mechanism underlying the protective effect of exercise training on angiotensinⅡ(AngⅡ)-induced cardiac fibrosis remains ***:An exercise model involving C57BL/6N mice and 6 weeks of treadmill training was ***Ⅱ(1.44 mg/kg/day)was administered to induce cardiac *** sequencing and bioinformatic analysis were used to identify the key factors mediating the effects of exercise training on cardiac *** adult mouse cardiac fibroblasts(CFs)were used in ***-associated virus serotype 9 was used to overexpress POU domain,class 2,transcription factor 1(POU2F1)in ***:Exercise training attenuated AngⅡ-induced cardiac fibrosis and reversed 39 gene expression *** transcription factor regulating the largest number of these genes was *** to controls,POU2F1 was shown to be signififcantly upregulated by AngⅡ,which is itself reduced by exercise *** vivo,POU2F1 overexpression nullified the benefits of exercise training on cardiac *** CFs,POU2F1 promoted cardiac *** enhancer-binding proteinβ(C/EBPβ)was predicted to be the transcription factor of POU2F1and verified using a dual-luciferase reporter *** vivo,exercise training activated AMP-activated protein kinase(AMPK)and alleviated the increase in C/EBPβinduced by AngⅡ.In CFs,AMPK agonist inhibited the increase in C/EBPβand POU2F1 induced by Ang II,whereas AMPK inhibitor reversed this ***:Exercise training attenuates AngⅡ-induced cardiac fibrosis by reducing *** training inhibits POU2F1 by activating AMPK,which is followed by the downregulation of C/EBPβ,the transcription factor of POU2F1.

关键词： AMPK C/EBPβ Cardiac fibrosis Exercise POU2F1

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Chinese Society of cardiology guidelines on the diagnosis and treatment of adult fulminant myocarditis

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Science China(Life sciences) 2024年第5期67卷 913-939页

作者： Chinese Society of cardiology,Chinese Medical Association,Writing Group Jiangang Jiang Hongyang Shu Dao Wen Wang Rutai Hui Chenze Li Xiao Ran Hong Wang Jing Zhang Shaoping Nie Guanglin Cui Dingcheng Xiang Qun Shao Shengyong Xu Discussion experts:Ning Zhou Yuming Li Wei Gao Yuguo Chen Yuan Bian Guoping Wang Liming Xia Yan Wang Chunxia Zhao Zhiren Zhang Yuhua Zhao Jianan Wang Shaoliang Chen Hong Jiang Jing Chen Xianjin Du Mao Chen Yinxian Sun Sheng Li Hu Ding Xueping Ma Hesong Zeng Li Lin Shenghua Zhou Likun Ma Ling Tao Juan Chen Yiwu Zhou Xiaomei Guo 不详 Tongji Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Fuwai Hospital National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Zhongnan Hospital of Wuhan University Wuhan 430062China Fuwai Huazhong cardiovascular Hospital Zhengzhou 450003China Beijing Anzhen Hospital Capital Medical UniversityBeijing 100029China Guangzhou General Hospital of Guangzhou Military Command Guangzhou 510010China Harbin Medical University Cancer Hospital Harbin 150081China Union Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Taida Hospital Tianjin 300457China Peking University Third Hospital Beijing 100191China Qilu Hospital of Shandong University Jinan 250012China Kanghua Hospital DongguanGuangzhou 523080China Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003China Nanjing First Hospital Nanjing Medical UniversityNanjing 210006China Renmin Hospital of Wuhan University Wuhan 430060Wuhan West China Hospital Sichuan UniversityChengdu 610044China First Hospital of China Medical University Shenyang 110002China General Hospital of Ningxia Medical University Yinchuan 750003China The Second Xiangya Hospital Central South UniversityChangsha 410012China The First Affiliated Hospital of USTC University of Science and Technology of ChinaHefei 230002China The First Affiliated Hospital of Air Force Medical University Xi’an 710032China Central Hospital of Wuhan City Wuhan 430014China Tongji Medical College Huazhong University of Science and TechnologyWuhan 430030China

Fulminant myocarditis is an acute diffuse inflammatory disease of *** is characterized by acute onset,rapid progress and high risk of *** pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory *** to China’s practical experience,the adoption of the“life support-based comprehensive treatment regimen”(with mechanical circulation support and immunomodulation therapy as the core)can significantly improve the survival rate and long-term *** emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.

关键词： fulminant myocarditis guidelines life support-based comprehensive treatment regimen diagnosis treatment cytokine storm overactivation of immunity

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