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Reconstructions of model equations of time-delay system from short experimental time series

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International Journal of Modeling, Simulation, and Scientific Computing 2020年第2期11卷 91-99页

作者： Anatoly S.Karavaev Yurii M.Ishbulatov Ekaterina I.Borovkova Danil D.Kulminskiy Vladimir S.Khorev Anton R.Kiselev Vladimir I.Ponomarenko Vladimir I.Gridnev Mikhail D.Prokhorov Boris P.Bezruchko Department of Dynamic Modeling and Biomedical Engineering Saratov State University 83 Astrakhanskaya Street Saratov410012Russia Laboratory of Nonlinear Dynamics Modeling Saratov Branch of the Institute of Radio Engineering and Electronics of Russian Academy of sciences 38 Zelyonaya Street Saratov410019Russia Department of New cardiological Informational Technologies Institute of cardiological Research Saratov State Medical University 112 Bolshaya Kazachaya StreetSaratov410012Russia

This study aims to investigate the scope of methods for the reconstruction of time-delay *** consider an approach to the reconstruction of time-delay systems based on the synchronous response of the driven system with the structure similar to the structure of the studied *** approach is used for the recovery of the parameters of timedelay systems from short and noisy time *** show the operational performance and capabilities of this approach,the parameters were reconstructed for a radiophysical chaotic generator with quadratic nonlinearity and for the model of a system for the baroreflectory regulation of the mean arterial pressure.

关键词： Time-delay systems reconstruction chaos radiophysical experiment

Endothelial dysfunction in COVID-19 calls for immediate attention:the emerging roles of the endothelium in inflammation caused by SARS-CoV-2

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Frontiers of Medicine 2021年第4期15卷 638-643页

作者： Weijian Hang Chen Chen Xin AZhang Dao Wen Wang Division of Cardiology Department of Internal Medicineand Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological DisordersTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Physiology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104

The COVID-19 pandemic has caused numerous deaths around the world.A growing body of evidence points to the important role of overwhelming inflammatory responses in the pathogenesis of COVID-19 and the effectiveness of anti-inflammation therapy against COVID-19 is *** addition to affecting the lungs,COVID-19 can be a severe systemic inflammatory disease that is related to endothelial *** are calling for closer attention to endothelial dysfunction in COVID-19 not only for fully revealing the pathogenic mechanism of COVID-19 but also for properly adjusting the strategy of clinical intervention.

关键词： COVID-19 endothelial dysfunction inflammation reaction cytokine storm

Fulminant myocarditis:a comprehensive review from etiology to treatments and outcomes

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Signal Transduction and Targeted Therapy 2021年第1期6卷 26-40页

作者： Weijian Hang Chen Chen John MSeubert Dao Wen Wang Division of Cardiology Department of Internal Medicineand Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological DisordersTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Faculty of Pharmacy and Pharmaceutical sciences University of Alberta EdmontonAlberta T6G 2E1Canada

Fulminant myocarditis(FM)is characterized by a rapid progressive decline in cardiac function and a high mortality *** the first report of FM patients in the 1980s,several clinical trials and research studies have been published increasing our knowledge regarding ***,the diagnosis of FM depends on various techniques including electrocardiography,echocardiography,endomyocardial biopsy,and cardiac magnetic *** development of mechanical circulation support(MCS)devices and progress in our understanding of the pathophysiological mechanisms underlying FM,treatment regimens have evolved from simple symptomatic treatment to a life support-based comprehensive treatment *** core mechanism underlying the development of FM is the occurrence of an inflammatory cytokine *** review provides a comprehensive account of the current understanding of FM pathophysiology and knowledge regarding its etiology,pathophysiology,treatments,and outcomes.

关键词： etiology myocarditis treatment

Immunopathogenesis and immunomodulatory therapy for myocarditis

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中国科学:生命科学英文版 2023年第9期66卷 2112-2137页

作者： Wu He Ling Zhou Ke Xu Huihui Li James Jiqi Wang Chen Chen DaoWen Wang Division of Cardiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyHubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological DisordersWuhan 430030China

Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The aetiology of myocarditis continues to broaden as new pathogens and drugs emerge. The relationship between immune checkpoint inhibitors, severe acute respiratory syndrome coronavirus 2, vaccines against coronavirus disease-2019, and myocarditis has attracted increased attention. Immunopathological processes play an important role in the different phases of myocarditis, affecting disease occurrence, development, and prognosis. Excessive immune activation can induce severe myocardial injury and lead to fulminant myocarditis,whereas chronic inflammation can lead to cardiac remodelling and inflammatory dilated cardiomyopathy. The use of immunosuppressive treatments, particularly cytotoxic agents, for myocarditis, remains controversial. While reasonable and effective immunomodulatory therapy is the general trend. This review focuses on the current understanding of the aetiology and immunopathogenesis of myocarditis and offers new perspectives on immunomodulatory therapies.

关键词： myocarditis etiology pathogen immunopathogenesis immunomodulatory

A life support-based comprehensive treatment regimen dramatically lowers the in-hospital mortality of patients with fulminant myocarditis: a multiple center study

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Science China(Life sciences) 2019年第3期62卷 369-380页

作者： Sheng Li Shengyong Xu Chenze Li Xiao Ran Guanglin Cui Mengying He Kun Miao Chunxia Zhao Jiangtao Yan Rutai Hui Ning Zhou Yan Wang Jiangang Jiang Jing Zhang Daowen Wang Division of Cardiology Department of Internal Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Hubei Key Laboratory of Genetics and Molecular Mechanisms of cardiological Disorders Emergency Department of Union Hospital Peking Union Medical College Chinese Academy of Medical Sciences Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences Peking Union Medical College Fuwai Huazhong Cardiovascular Hospital

Fulminant myocarditis(FM) has unacceptable high mortality. This study aimed to evaluate the therapeutic efficacy of a life support-based comprehensive treatment regimen(LSBCTR), a completely novel treatment regimen, for FM. A total of 169 FM patients recruited from January 2008 to December 2018 were divided into two groups: patients receiving LSBCTR(81 cases),which includes(i) mechanical life support(positive pressure respiration, intra-aortic balloon pump with or without extracorporeal membrane oxygenation),(ii) immunomodulation therapy using sufficient doses of glucocorticoids and immunoglobulins, and(iii) application of neuraminidase inhibitors, and those receiving conventional treatment(88 cases). The endpoints were in-hospital death and heart-transplantation. Of all the population, 44 patients(26.0%) died in hospitals. Inhospital mortality was 3.7%(3/81) for LSBCTR group and 46.6%(41/88) for traditional treatment(P<0.001). Early application of LSBCTR, mechanical life support, neuraminidase inhibitors, and immunomodulation therapy significantly contributed to reduction in in-hospital mortality. This study describes a novel treatment regimen for FM patients that dramatically reduces inhospital mortality. Its generalization and clinical application will efficiently save lives although further optimization is *** study offers an insight that virus infection induced inflammatory waterfall results in cardiac injury and cardiogenic shock and is the therapeutic target.

关键词： fulminant myocarditis in-hospital mortality life support-based comprehensive treatment regimen

Nuclear miR-665 aggravates heart failure via suppressing phosphatase and tensin homolog transcription

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Science China(Life sciences) 2020年第5期63卷 724-736页

作者： Jiahui Fan Xudong Zhang Xiang Nie Huaping Li Shuai Yuan Beibei Dai Jiabing Zhan Zheng Wen Jiangang Jiang Chen Chen Daowen Wang Division of Cardiology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Hubei Key Laboratory of Genetics and Molecular Mechanisms of cardiological Disorders Wuhan 430030China

Although numerous miRNAs have been discovered,their functions in the different subcellular organelles have remained *** this study,we found that miR-665 was enriched in the nucleus of cardiomyocytes,and then investigated the underlying role of nuclear miR-665 in heart *** fluorescence in situ hybridization assays in human heart tissue sections and primary cardiomyocytes showed that miR-665 was localized in the nucleus of *** expression of nuclear miR-665 was observed not only in the cardiomyocytes isolated from the heart of mice treated in vivo by transverse aortic constriction(TAC),but also in phenylephrine(PE)-treated cultured cardiomyocytes in *** further explore the role of miR-665 in heart failure,a type 9 recombinant adeno-associated virus(rAAV)system was employed to manipulate the expression of miR-665 in *** of miR-665 aggravated TAC-induced cardiac dysfunction,while down-expression of miR-665 showed opposite *** prediction and biological validation confirmed that the PTEN(phosphatase and tensin homolog)gene was one of the targets of miR-665 in the ***,restoring PTEN expression significantly eliminated the destructive effects of miR-665 over-expression in TAC-induced cardiac *** data showed that nuclear miR-665 aggravates heart failure via inhibiting PTEN expression,which provided a therapeutic approach for heart failure.

关键词： nucleus miR-665 heart failure phosphatase and tensin homolog

MYH7B variants cause hypertrophic cardiomyopathy by activating the Ca MK-signaling pathway

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Science China(Life sciences) 2020年第9期63卷 1347-1362页

作者： Peng Chen Zongzhe Li Jiali Nie Hong Wang Bo Yu Zheng Wen Yang Sun Xiaolu Shi Li Jin Dao-Wen Wang Division of Cardiology Departments of Internal Medicine and Genetic Diagnosis CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Hubei Key Laboratory of Genetics and Molecular Mechanism of cardiological Disorders Wuhan 430030China Collaborative Innovation Center for Genetics and Development School of Life SciencesFudan UniversityShanghai 200438China Experimental Research Center China Academy of Chinese Medical SciencesBeijing 100700China

Hypertrophic cardiomyopathy(HCM) is a common genetic disease, predominantly caused by mutations in cardiac sarcomere genes;however, whether MYH7 B causes HCM is not known. In this study, 549 unrelated patients with HCM and 500 healthycontrols were screened using targeted sequencing and whole exome sequencing together. We observed seven variants in MYH7 B causing HCM in 8/549 patients, which accounted for 1.46% of HCM cases. Of these seven variants, three likely pathogenic variants in MYH7 B co-segregating with 5 HCM patients were identified in three HCM pedigrees without other HCM-associated variants. Myh7 b knockout rats were generated and cardiac functions were detected by Millar pressure-volume catheterization and echocardiography. Spontaneous HCM phenotypes, cellular disarray and cardiac fibrosis were observed in both Myh7 b^+/–/Myh7 b^–/–rats. Transcriptome sequencing showed that calcium is the key mediator of cardiac hypertrophy in Myh7 b knockout. Subsequent analysis confirmed over-activation of Ca MK-signaling pathway in cardiomyocytes of Myh7 b^–/–***, MYH7 B expression in human and rat hearts was identified and micro RNA-208 a and micro RNA-499 levels are unchanged in HCM patients and Myh7 b^+/–/Myh7 b^–/–rats. This study is the first to identify MYH7 B variants as cause of HCM,which account for 1.46% of pathogenesisin HCM patients. Activation of Ca MK-signaling pathway may be involved in its pathophysiology.

关键词： MYH7B hypertrophic cardiomyopathy whole exome sequencing transcriptome sequencing Ca MK-signaling pathway

Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases

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Science China(Life sciences) 2020年第11期63卷 1678-1687页

作者： Wei Huang Chenze Li Zhiquan Wang Hong Wang Ning Zhou Jiangang Jiang Li Ni Xin A.Zhang Dao-Wen Wang Division of Cardiology Department of Internal Medicineand Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological DisordersTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430010China Department of Cardiology Chinese PLA Central War Command General HospitalWuhan 430010China Stephenson Cancer Center and Department of Physiology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA

Coronavirus disease 2019(COVID-19) is a global pandemic which has caused numerous deaths worldwide. The present study investigated the roles of hypoproteinemia in the clinical outcome and liver dysfunction of COVID-19 patients. In this retrospective study, we extracted data from 2,623 clinically confirmed adult COVID-19 patients(≥18 years old) between January 29,2020 and March 6, 2020 in Tongji Hospital, Wuhan, China. The patients were divided into three groups—non-critically ill,critically ill, and death groups—in accordance with the Chinese Clinical Guideline for COVID-19. Serum albumin, low-density lipoproteins cholesterol(LDL-C), and high-density lipoproteins cholesterol(HDL-C) concentrations and inflammatory cytokines levels were measured and compared among these three groups. The median age of these 2,623 patients was 64 years old(interquartile range(IQR), 52–71). Among the patients enrolled in the study, 2,008(76.6%) were diagnosed as non-critically ill and 615(23.4%) were critically ill patients, including 383(14.6%) critically ill survivors and 232(8.8%) critically ill deaths in the hospital. Marked hypoalbuminemia occurred in 38.2%, 71.2%, and 82.4% patients in non-critically ill, critically ill, and death groups, respectively, on admission and 45.9%, 77.7%, and 95.6% of these three groups, respectively, during hospitalization. We also discovered that serum low-density lipoprotein(LDL) and HDL levels were significantly lower in critically ill and death groups compared to non-critically ill group. Meanwhile, the patients displayed dramatically elevated levels of serum inflammatory factors, while a markedly prolonged activated partial thromboplastin time(APTT) in critically ill patients reflected coagulopathy. This study suggests that COVID-19-induced cytokine storm causes hepatotoxicity and subsequently critical hypoalbuminemia, which are associated with exacerbation of disease-associated inflammatory responses and progression of the disease and ultimately

关键词： albumin hepatic injury COVID-19

Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19

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Science China(Life sciences) 2020年第10期63卷 1515-1521页

作者： Bo Yu Chenze Li Peng Chen Ning Zhou Luyun Wang Jia Li Hualiang Jiang Dao-Wen Wang Division of Cardiology Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological DisordersTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology Shanghai Tech UniversityShanghai 201210China

Coronavirus disease 2019(COVID-19)is a pandemic with no specific drugs and high *** most urgent need is to find effective *** sought to determine whether hydroxychloroquine(HCQ)application may reduce the death risk of critically ill COVID-19 *** this retrospective study,we included 550 critically ill COVID-19 patients who need mechanical ventilation in Tongji Hospital,Wuhan,from February 1,2020 to April 4,*** 550 patients received comparable basic treatments including antiviral drugs and antibiotics,and 48 of them were treated with oral HCQ treatment(200 mg twice a day for 7–10 days)in addition to the basic *** endpoint is fatality of patients,and inflammatory cytokine levels were compared between HCQ and non-hydroxychloroquine(NHCQ)*** found that fatalities are 18.8%(9/48)in HCQ group,which is significantly lower than 47.4%(238/502)in the NHCQ group(P<0.001).The time of hospital stay before patient death is 15(10–21)days and 8(4–14)days for the HCQ and NHCQ groups,respectively(P<0.05).The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2(8.3–118.9)pg mL–1 at the beginning of the treatment to 5.2(3.0–23.4)pg mL–1(P<0.05)at the end of the treatment in the HCQ group but there is no change in the NHCQ *** data demonstrate that addition of HCQ on top of the basic treatments is highly effective in reducing the fatality of critically ill patients of COVID-19 through attenuation of inflammatory cytokine ***,HCQ should be prescribed as a part of treatment for critically ill COVID-19 patients,with possible outcome of saving lives.

关键词： patients drugs critically

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