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A Heterozygous Phospholamban Variant(p.R14del)Leads to Left Ventricular Involvement and Heart Failure Phenotypes in Arrhythmogenic Right Ventricular Cardiomyopathy

Phenomics

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Phenomics 2024年第1期4卷 13-23页

作者： Han Mo Xiumeng Hua Mengni Bao Zhe Sun Xiao Chen Mengda Xu Jiangping Song Shenzhen Key Laboratory of cardiovascular Disease Fuwai Hospital Chinese Academy of Medical SciencesShenzhen 518057China State Key Laboratory of cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical College167A Beilishi RoadXi Cheng DistrictBeijing 100037China Beijing Key Laboratory of Preclinical Research and Evaluation for cardiovascular Implant Materials Animal Experimental CentreFuwai HospitalNational Center for Cardiovascular DiseaseChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

This study aimed to determine the prevalence and clinical features of Arrhythmogenic Right Ventricular Cardiomyopathy(ARVC)caused by pathogenic mutations in the Phospholamban(PLN)gene.The study included 170 patients who had a confrmed diagnosis of ARVC and underwent PLN genetic screening using next-generation sequencing.The fndings of this study provide valuable insights into the association between PLN mutations and ARVC,which can aid in the development of more efective diagnostic and treatment strategies for ARVC patients.Out of the patients evaluated,six had a rare pathogenic mutation in PLN with the same p.R14del variant.Family screening revealed that heterozygous carriers of p.R14del exhibited a defnite ARVC phenotype.In clinical studies,individuals with the p.R14del mutation experienced a similar rate of malignant arrhythmia events as those with classic desmosome mutations.After adjusting for covariates,individuals with PLN mutations had a two point one seven times greater likelihood of experiencing transplant-related risks compared to those who did not possess PLN mutations(95%CI 1.08–6.82,p=0.035).The accumulation of left ventricular fat and fbers is a pathological marker for ARVC patients with p.R14del mutations.In a cohort of 170 Chinese ARVC patients,three point fve percent of probands had the PLN pathogenic variant(p.R14del)and all were female.Our data shows that PLN-related ARVC patients are at high risk for ventricular arrhythmias and heart failure,which requires clinical diferentiation from classic ARVC.Furthermore,carrying the p.R14del mutation can be an independent prognostic risk factor in ARVC patients.

关键词： Arrhythmogenic right ventricular cardiomyopathy Phospholamban Left ventricular involvement Heart failure Risk stratifcation

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cardiovascular Risk Factors in China

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Journal of Geriatric Cardiology 2024年第2期21卷 153-199页

作者： Sheng-Shou HU the Writing Committee of the Report on cardiovascular Health and Diseases in China Fuwai Hospital National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina 不详

The Annual Report on cardiovascular Health and Diseases in China(2022) intricate landscape of cardiovascular health in China. This section dissects cardiovascular risk factors in China which including hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease, metabolic syndrome and air pollution. Hypertension prevalence has steadily increased in China,with efforts to control it facing challenges in achieving optimal rates, especially in rural areas. Interventions like salt substitutes and intensive blood pressure control show promise but need improvement. Abnormal lipid levels, indicative of dyslipidemia,have risen significantly, posing a risk for cardiovascular diseases. Despite efforts, many patients struggle to achieve target lipid levels, necessitating improved treatment strategies. Both type 1 and type 2 diabetes mellitus affect millions of adults in China,with long-term complications adding to the disease burden. Early intervention and effective management are crucial to mitigate its impact. Prevalent among older adults, chronic kidney disease is associated with diabetes mellitus, hypertension, and cardiovascular diseases, necessitating comprehensive management approaches. The prevalence of metabolic syndrome, characterized by a cluster of risk factors, has increased in both adults and adolescents, calling for lifestyle modifications and public health interventions. Ambient and household air pollution remain significant environmental risk factors, despite some improvements in air quality. Continued efforts to reduce emissions are essential for mitigating associated health risks. Addressing these risk factors requires a multifaceted approach, including public health initiatives, policy interventions, and individual-level strategies to promote healthy lifestyles and reduce environmental exposures. Surveillance and research efforts are crucial for monitoring trends and developing effective strategies to lessen the burden of cardiovascular diseases in China.

关键词： landscape adding spite

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Relationship between fibrinogen levels and cardiovascular events in patients receiving percutaneous coronary intervention:a large single-center study

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Chinese Medical Journal 2019年第8期132卷 914-921页

作者： Ping Jiang Zhan Gao Wei Zhao Ying Song Xiao-Fang Tang Jing-Jing Xu Huan-Huan Wang Lin Jiang Jue Chen Shu-Bin Qiao Yue-Jin Yang Run-Lin Gao Bo Xu Jin-Qing Yuan Department of Cardiology State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China Information center State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China

Background:It is currently unclear if fibrinogen is a risk factor for adverse events in patients receiving percutaneous coronary intervention(PCI)or merely serves as a marker of pre-existing comorbidities and other causal factors.We therefore investigated the association between fibrinogen levels and 2-year all-cause mortality,and compared the additional predictive value of adding fibrinogen to a basic model including traditional risk factors in patients receiving contemporary PCI.Methods:A total of 6293 patients undergoing PCI with measured baseline fibrinogen levels were enrolied from January to December 2013 in Fuwai Hospital.Patients were divided into three groups according to tertiles of baseline fibrinogen levels:low fibrinogen,<2.98 g/L;medium fibrinogen,2.98 to 3.58 g/L;and high fibrinogen,≥3.58 g/L.Independent predictors of 2-year clinical outcomes were determined by multivariate Cox proportional hazards regression modeling.The increased discriminative value of fibrinogen for predicting all-cause mortality was assessed using the C-statistic and integrated discrimination improvement(IDI).Results:The 2-year all-cause mortality rate was 1.2%.It was significantly higher in the high fibrinogen compared with the low and medium fibrinogen groups according to Kaplan-Meier analyses(1.7%vs.0.9%and 1.7%vs.1.0%,respectively;log-rank,P=0.022).Fibrinogen was significantly associated with all-cause mortality according to multivariate Cox regression(hazard ratio 1.339,95%confidence interval:1.109-1.763,P=0.005),together with traditional risk factors including age,sex,diabetes mellitus,left ventricular ejection fraction,creatinine clearance,and low-density lipoprotein cholesterol.The area under the curve for all-cause mortality in the basic model including traditional risk factors was 0.776,and this value increased to 0.787 when fibrinogen was added to the model(IDI=0.003,Z=0.140,P=0.889).Conclusions:Fibrinogen is associated with 2-year all-cause mortality in patients receiving PCI,but provides no additional information

关键词： Fibrinogen Percutaneous coronary intervention Risk factor Prognosis

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Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2132-2142页

作者： Xinglong Han Lina Qu Miao Yu Lingqun Ye Liujia Shi Guangfu Ye Jingsi Yang Yaning Wang Hao Fan Yong Wang Yingjun Tan Chunyan Wang Qi Li Wei Lei Jianghai Chen Zhaoxia Liu Zhenya Shen Yinghui Li Shijun Hu Department of cardiovascular Surgery of the First Affiliated Hospital&Institute for cardiovascular Science State Key Laboratory of Radiation Medicine and ProtectionSuzhou Medical CollegeSoochow UniversitySuzhouChina State Key Laboratory of Space Medicine China Astronaut Research and Training CenterBeijingChina Department of Hand Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

During spaceflight,the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling.Therefore,the effects and mechanisms of microgravity on cardiac morphology,physiology,metabolism,and cellular biology need to be further investigated.Since China started constructing the China Space Station(CSS)in 2021,we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes(hPSC-CMs)to the Tianhe core module of the CSS.In this study,hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling.Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight,especially thiamine metabolism.The microgravity condition blocked the thiamine intake in hPSC-CMs.The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle.It decreased ATP production,which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs.More importantly,in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity.This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research.These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

关键词： programming battery modified

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An unexpected cellular fountain of youth:platelets provide factors rejuvenating brain functions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 16-18页

作者： Harald F.Langer Department of Cardiology AngiologyHaemostaseology and Medical Intensive CareUniversity Medical Centre MannheimMedical Faculty MannheimHeidelberg UniversityMannheimGermany German Centre for cardiovascular Research(DZHK) Partner Site Heidelberg/MannheimMannheimGermany European center for Angioscience Medical Faculty MannheimHeidelberg UniversityMannheimGermany cardiovascular systems biology Medical Clinic IUniversity Heart Center LübeckLübeckGermany

In a recent manuscript published in Nature,Schroer et al.discovered that platelets and in particular platelet derived PF-4(CXCL4)are a novel factor,which can rejuvenate the mammalian neuronal system.1 These findings have the potential to trigger an entire new field of research opening new platelet-derived candidate effector molecules for supporting regeneration.

关键词： supporting platelets finding

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Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第1期21卷 64-80页

作者： Xiong-Bin MA Yong-Ming LIU Yan-Lin LV Lin QIAN The First Clinical Medical College of Lanzhou University LanzhouGansuChina Geriatric cardiovascular Department and Gansu Clinical Research center for Geriatric Diseases First Hospital of Lanzhou UniversityGansuChina

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is uncertain.This Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction population.METHODS Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association studies.Individuals without myocardial infarction history,HF,or LV ejection fraction(LVEF)cardiovascular Magnetic Resonance Imaging Study constituted the outcome dataset.The dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the results.RESULTS In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni adjustment.Conversely,no significant relationships were observed between other iron and LV parameters.After Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the analysis.CONCLUSIONS We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

关键词： fraction function parameters

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Maternal Preconception Serum Alanine Aminotransferase Levels and Risk of Preterm Birth among Reproductive-Aged Women—China,2013-2017

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China CDC weekly 2024年第10期6卷 181-188,I0001页

作者： Chuanyu Zhao Jiajing Jia Hanbin Wu Qin Xu Xinyi Lyu Meiya Liu Xuan Hu Jueming Lei Yuzhi Deng Yuan He Yuanyuan Wang Zuoqi Peng Ya Zhang Hongguang Zhang Qiaomei Wang Haiping Shen Yiping Zhang Donghai Yan Ying Yang Xu Ma National Research Institute for Family Planning BeijingChina National Human Genetic Resources center BeijingChina Graduate School of Peking Union Medical College BeijingChina Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Summary What is already known about this topic?The significance of maternal liver health concerning preterm birth(PTB)is well recognized;however,there is a gap in understanding the precise influence of preconception s... 详细信息

关键词： Serum precise concerning

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Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

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Bone Research 2024年第1期12卷 199-214页

作者： Laura J.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan Jiang Tobias Malte Ballhause Anke Baranowsky Simon von Kroge Julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer David J.Beech Frank Timo Beil Michael Amling Johannes Keller Anita Ignatius Timur A.Yorgan Tim Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds Institute of cardiovascular and Metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell types.While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage.Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)development.Mice with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate postnatally.Moreover,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth plates.While skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age.Likewise,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage degeneration.Importantly,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) mice.We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes.Finally,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes.Collectively,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

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Circulating biomarker-and magnetic resonance-based nomogram predicting long-term outcomes in dilated cardiomyopathy

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Chinese Medical Journal 2024年第1期137卷 73-81页

作者： Yupeng Liu Wenyao Wang Jingjing Song Jiancheng Wang Yi Fu Yida Tang Department of Cardiology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Guangdong cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Cardiology Institute of Vascular MedicinePeking University Third HospitalBeijing 100191China Department of Cardiology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100083China Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100083China Key Laboratory of Molecular cardiovascular Science Ministry of EducationBeijing 100191China

Background:Dilated cardiomyopathy(DCM)has a high mortality rate and is the most common indication for heart transplantation.Our study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation(ACM/HTx)risk in DCM patients.Methods:The present study is a retrospective cohort study.The demographic,clinical,blood test,and cardiac magnetic resonance imaging(CMRI)data of DCM patients in the tertiary center(Fuwai Hospital)were collected.The primary endpoint was ACM/HTx.The least absolute shrinkage and selection operator(LASSO)Cox regression model was applied for variable selection.Multivariable Cox regression was used to develop a nomogram.The concordance index(C-index),area under the receiver operating characteristic curve(AUC),calibration curve,and decision curve analysis(DCA)were used to evaluate the performance of the nomogram.Results:A total of 218 patients were included in the present study.They were randomly divided into a training cohort and a validation cohort.The nomogram was established based on eight variables,including mid-wall late gadolinium enhancement,systolic blood pressure,diastolic blood pressure,left ventricular ejection fraction,left ventricular end-diastolic diameter,left ventricular end-diastolic volume index,free triiodothyronine,and N-terminal pro-B type natriuretic peptide.The AUCs regarding 1-year,3-year,and 5-year ACM/HTx events were 0.859,0.831,and 0.840 in the training cohort and 0.770,0.789,and 0.819 in the validation cohort,respectively.The calibration curve and DCA showed good accuracy and clinical utility of the nomogram.Conclusions:We established and validated a circulating biomarker-and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients,which might help risk stratification and decision-making in clinical practice.

关键词： Cardiomyopathy,dilated Heart transplantation Mortality Nomograms Least absolute shrinkage and selection operator Decision curve analysis

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Piezoionics:Mechanical-to-ionic transduction for sensing,biointerface,and energy harvesting

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Aggregate 2024年第1期5卷 85-94页

作者： Kongqi Chen Derek Ho Department of Materials Science and Engineering City University of Hong KongHong KongChina Hong Kong center for Cerebro-cardiovascular Health Engineering Hong KongChina

Piezoionic materials consisting of a polymer matrix and mobile ions can produce an electrical output upon an applied pressure inducing an ion concentration gradient.Distinct from charges generated by the piezoelectric or triboelectric effects,the use of generated mobile ions to carry a signal closely resembles many ionic biological processes.Due to this similarity to biology,the piezoionic effect has great potential to enable seamless integration with biological systems,which accelerates the advancement of medical devices and personalized medicine.In this review,a comprehensive description of the piezoionic mechanism,methods,and applications are presented,with the aim to facilitate a dialogue among relevant scientific communities.First,the piezoionic effect is briefly introduced,then the development of mechanistic understanding over time is surveyed.Next,different types of piezoionic materials are reviewed and methods to enhance the piezoionic output via materials properties,electrode interfaces,and device architectures are detailed.Finally,applications,challenges,and outlooks are provided.With its novel properties,piezoionics is expected to play a key role in the overcoming of grand challenges in the areas of sensing,biointerfaces,and energy harvesting.

关键词： flexible electronics intelligent soft matter ionic hydrogel iontronics mechanical energy harvesting

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