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High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p

Science China(Life Sciences) 2024年第2期67卷 286-300页

作者： Bi-Ang Kang Hua-Ming Li Ya-Ting Chen Meng-Jie Deng Yan Li Yue-Ming Peng Jian-Jun Gao Zhi-Wei Mo Jia-Guo Zhou Zhi-Jun Ou Jing-Song Ou division of Cardiac Surgery Cardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases Guangzhou 510080China NHC key Laboratory of Assisted Circulation(Sun Yat-sen University) Guangzhou 510080China Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases Guangzhou 510080China division of Vascular Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Pharmacology Cardiac and Cerebral Vascular Research CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China division of Hypertension and Vascular Diseases Department of CardiologyCardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China

We previously demonstrated that normal high-density lipoprotein(nHDL)can promote angiogenesis,whereas HDL from patients with coronary artery disease(d HDL)is dysfunctional and impairs *** plays a critical role in angiogenesis,and HDL regulates ***,it is unclear whether n HDL and d HDL regulate angiogenesis by affecting *** cells(ECs)were treated with n HDL and d HDL with or without an autophagy ***,endothelial nitric oxide synthase(e NOS)expression,miRNA expression,nitric oxide(NO)production,superoxide anion(O2^(·-))generation,EC migration,and tube formation were evaluated.n HDL suppressed the expression of miR-181a-5p,which promotes autophagy and the expression of e NOS,resulting in NO production and the inhibition of O2^(·-)generation,and ultimately increasing in EC migration and tube formation.d HDL showed opposite effects compared to n HDL and ultimately inhibited EC migration and tube *** found that autophagy-related protein 5(ATG5)was a direct target of ***5 silencing or miR-181a-5p mimic inhibited n HDL-induced autophagy,e NOS expression,NO production,EC migration,tube formation,and enhanced O2^(·-)generation,whereas overexpression of ATG5 or miR-181a-5p inhibitor reversed the above effects of d ***5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null(LDLr^(-/-))mice when compared to C57BL/6 ***5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr^(-/-)*** together,nHDL was able to stimulate autophagy by suppressing miR-181a-5p,subsequently increasing e NOS expression,which generated NO and promoted *** contrast,d HDL inhibited angiogenesis,at least partially,by increasing miR-181a-5p expression,which decreased autophagy and e NOS expression,resulting in a decrease in NO production and an increase in O2^(·-)*** findings reveal a nov

关键词： high-density lipoprotein angiogenesis autophagy ATG5 miRNA endothelial nitric oxide synthase

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The Impact of a Prior Norwood Procedure on Cardiac Transplantation in Failed Fontan Physiology

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Congenital Heart Disease 2024年第3期19卷 257-266页

作者： Ryan G.McQueen Nikki M.Singh Ronald K.Woods Medical College of Wisconsin Herma Heart Institute at Children’s WisconsinMilwaukeeUSA division of Pediatric cardiology Medical College of WisconsinHerma Heart Institute at Children’s WisconsinMilwaukeeUSA division of Pediatric Cardiothoracic Surgery Medical College of WisconsinHerma Heart Institute at Children’s WisconsinMilwaukeeUSA

Objective:The objective of this study was to compare cardiac transplant operative and postoperative courses of patients with failed Fontan physiology who were initially palliated with a Norwood(FFN)to those without a prior Norwood(FF).Methods:A single-institution retrospective review of all patients with Fontan failure who under-went cardiac transplantation from 2003–2021 was completed-22 underwent prior Norwood(FFN)and 11 did not(FF).Descriptive and inferential statistics were calculated for operative course and patient ***:The operative course of the FFN cohort appeared to be more complex(not statistically signiﬁcant,but clinically relevant)-this group exclusively experienced sternal re-entry events(3 of 22 patients)and concomitant neo-aor-tic reconstruction(6 patients),had a longer duration of surgery(median of 682 min vs.575.5 min),more time on circulatory arrest(median of 25.5 min vs.12.5 min),and more frequent use of open sternal management[50%of patients(11/22)vs.27.3%of patients(3/11)].Postoperatively,these patients underwent more mediastinal explora-tions[other than sternal closure;40.9%of patients(9/22)vs.18.2%of patients(2/11)],spent more time on mechanical ventilation(median of 5 days vs.2 days),had a longer length of stay(median of 30 days vs.19 days),and required more catheter-based re-interventions[22.7%of patients(5/22)vs.9.1%of patients(1/11)].Conclu-sion:Although underpowered,our results suggest that the operative course of FFN patients is more challenging,based mostly on neo-aortic arch *** turn,this likely leads to a more complex postoperative *** are currently collaborating with other institutions to increase the cohort size and power of the study.

关键词： Fontan Fontan failure Norwood cardiac transplantation

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中国急性冠状动脉综合征患者治疗和预后的地区差异:来自国家胸痛中心的证据

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Science Bulletin 2024年第9期69卷 1302-1312页

作者：周书铎张岩董雪洁马郡雄李娜史红 Sidney C.Smith Jr 金音子许铭向定成郑志杰霍勇 Department of Global Health Peking University School of Public HealthBeijing 100191China Institute for Global Health and Development Peking UniversityBeijing100871China Department of cardiology Peking University First HospitalBeijing 100034China Chinese Medical Association Beijing 100052China division of Cardiovascular Medicine School of MedicineUniversity of North Carolina at Chapel HillNorth Carolina 27599-3140USA Department of cardiology General Hospital of Southern Theater Command of PLAGuangzhou 510010China

Regional variations in acute coronary syndrome(ACS) management and outcomes have been an enormous public health issue. However, studies have yet to explore how to reduce the variations. The National Chest Pain Center Program(NCPCP) is the first nationwide, hospital-based, comprehensive, continuous quality improvement program for improving the quality of care in patients with ACS in China. We evaluated the association of NCPCP and regional variations in ACS healthcare using generalized linear mixed models and interaction analysis. Patients in the Western region had longer onset-to-first medical contact(FMC) time and time stay in non-percutaneous coronary intervention(PCI) hospitals, lower rates of PCI for ST-elevation myocardial infarction(STEMI) patients, and higher rates of medication *** in Central regions had relatively lower in-hospital mortality and in-hospital heart failure *** in the door-to-balloon time(Dto B) and in-hospital mortality between Western and Eastern regions were less after accreditation(β =-8.82, 95% confidence interval(CI)-14.61 to-3.03;OR = 0.79, 95%CI 0.70 to 0.91). Similar results were found in differences in Dto B time, primary PCI rate for STEMI between Central and Eastern regions. The differences in PCI for higher-risk non-ST-segment elevation acute coronary syndrome(NSTE-ACS) patients among different regions had been ***, the differences in medication use between Eastern and Western regions were higher after accreditation. Regional variations remained high in this large cohort of patients with ACS from hospitals participating in the NCPCP in China. More comprehensive interventions and hospital internal system optimizations are needed to further reduce regional variations in the management and outcomes of patients with ACS.

关键词： Acute coronary syndromes Quality improvement Regional variations Quality metrics

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Fulminant Myocarditis Complicated by Stiff-person Syrndrom A Case Report

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cardiology Discovery 2024年第2期4卷 183-186页

作者： Peng Chen Nana Tang Huilan Zhang Dao Wen Wang division of cardiology Departments of Internal Medicine and Genetic Diagnosis CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiological Disorders WuhanHubei 430030China Department of Respiratory and Critical Care Medicine Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China.

This case report described a 61-year-old woman who presented with dizziness,headache,muscle ache,diplopia,and vomiting who lost *** hospital admission,the levels of high-sensitivity cardiac troponin I and partial pressure of carbon dioxide were increased *** of consciousness occurred twice after removal of invasive ventilator *** angiography demonstrated no stenosis in coronary *** revealed inactivity of respiratory *** disturbance and autonomic-nerve dysfunctions were *** antibody against glutamic acid decarboxylase was *** rare phenotypes of persistent stiffness of muscles in the neck,face,bilateral upper and lower limbs were *** patient was diagnosed with fulminant myocarditis complicated by Stiff-person *** treatment(glucocorticoids and immunoglobulins)elicited satisfactory therapeutic *** this case report,it was found that fulminant myocarditis and Stiff-person syndrome shared a common pathogenesis:"cytokine storm".Such patients may benefit from early treatment with immunomodulatory agents.

关键词： Myocarditis Stiff-person syndrome Cytokine storm Immunomodulating treatment

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Increase of PCSK9 expression in diabetes promotes VEGFR2ubiquitination to inhibit endothelial function and skin wound healing

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Science China Life Sciences 2024年

作者： Jian-Jun Gao Fang-Yuan Wu Yu-Jia Liu Le Li Yi-Jun Lin Yue-Ting Kang Yue-Ming Peng Yi-Fang Liu Chen Wang Zhen-Sheng Ma Yang Cao Hong-Yu Cao Zhi-Wei Mo Yan Li Jing-Song Ou Zhi-Jun Ou division of Cardiac Surgery Cardiovascular Diseases Institute The First Affiliated Hospital Sun Yat-sen University National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases NHC key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University) Key Laboratory of Assisted Circulation and Vascular Diseases Chinese Academy of Medical Sciences Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases division of Hypertension and Vascular Diseases Department of Cardiology Heart Center The First Affiliated Hospital Sun Yat-sen University division of Vascular Surgery The First Affiliated Hospital Sun Yat-sen University Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of Medicine Sun Yat-sen University

Diabetic foot ulcers（DFUs） are a serious vascular disease. Currently, no effective methods are available for treating DFUs. Pro-protein convertase subtilisin/kexin type 9（PCSK9） regulates lipid levels to promote atherosclerosis. However, the role of PCSK9 in DFUs remains unclear. In this study, we found that the expression of PCSK9 in endothelial cells（ECs） increased significantly under high glucose（HG）stimulation and in diabetic plasma and vessels. Specifically, PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2（VEGFR2）, which led to the ubiquitination of VEGFR2, resulting in its degradation and downregulation in ECs. Furthermore, PCSK9 suppresses the expression and activation of AKT, endothelial nitric oxide synthase（eNOS）, and ERK1/2, leading to decreased nitric oxide（NO） production and increased superoxide anion(O2·-) generation, which impairs vascular endothelial function and angiogenesis. Importantly, using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O2·-production, as well as inhibited the phosphorylation and expression of AKT, eNOS, and ERK1/***, evolocumab improved vascular endothelial function and angiogenesis, and promoted wound healing in diabetes. Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.

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Disruption of cyclin D1 degradation leads to the development of mantle cell lymphoma

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2977-2991页

作者： Ke Lu Ming Zhang Hongyu Qin Siyu Shen Haiqing Song Hua Jiang Chunxiang Zhang Guozhi Xiao Liping Tong Qing Jiang Di Chen Research Center for Computer-aided drug Discovery Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Faculty of Pharmaceutical Sciences Shenzhen Institute of Advanced TechnologyShenzhen 518055China Oncology Department Johns Hopkins University School of MedicineBaltimoreMD 21205USA division of Spine Surgery the First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic SurgeryNanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolState Key Laboratory of Pharmaceutical BiotechnologyNanjing UniversityNanjing 210008China fWenzhou Institute University of Chinese Academy of SciencesWenzhou 325000China Department of cardiology Basic Medicine Innovation Center for Cardiometabolic Diseases of Ministry of EducationInstitute of Cardiovascular Researchthe Affiliated HospitalSouthwest Medical UniversityLuzhou 646000China School of Medicine Southern University of Science and TechnologyShenzhen 518055China

Cyclin D1 has been recognized as an oncogene due to its abnormal upregulation in different types of ***,we demonstrated that cyclin D1 is SUMOylated,and we identified Itch as a specific E3 ligase recognizing SUMOylated cyclin D1 and mediating SUMO-induced ubiquitination and proteasome degradation of cyclin *** generated cyclin D1 mutant mice with mutations in the SUMOylation site,phosphorylation site,or both sites of cyclin D1,and found that double mutant mice developed a Mantle cell lymphoma(MCL)-like *** showed that arsenic trioxide(ATO)enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes,leading to MCL cell *** of severe combined immunodeficiency(SCID)mice grafted with MCL cells with ATO resulted in a significant reduction in tumor *** this study,we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.

关键词： Cyclin D1 SUMOylation Mantle cell lymphoma Arsenic trioxide SENP2 Proteasome degradation

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

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

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

Social determinants of health(SDOH)affect quality of *** investigated SDOH impacts on self-perceived resilience among people with adult congenital heart disease(ACHD).Secondary analysis of data from two com-plementary studies:a survey study conducted May 2021–June 2022 and a qualitative study conducted June 2020–August *** was assessed through CD-RISC10 score(range 0–40,higher scores reﬂect greater self-perceived resilience)and interview *** and SDOH(education,employment,living situa-tion,monetary stability,ﬁnancial dependency,area deprivation index)data were collected by healthcare record review and *** used linear regression with robust standard errors to analyze survey data and performed a thematic analysis of interview *** participants(N=127)mean age was 42±14 years;51%were female,87%*** was moderate(75%)or complex(25%);41%functional class C or ***(mean 30±7)varied by monetary stability:compared to people with difﬁculty paying bills,resilience was 15.0 points higher(95%CI:6.9–23.1,p<0.001)for people reporting having enough money and 14.2 points higher(95%CI:5.9–22.4,p=0.001)for those reporting just enough *** participants’(N=25)mean age was 32 years(range 22–44);52%were female,72%*** was moderate(56%)or complex(44%);76%functional class C or *** discussed factors affecting resilience aligned with each of the major SDOH,prominently,economic stability and healthcare access and *** stability may be important for supporting self-perceived resi-lience in *** knowledge can inform the development of resilience interventions for this population.

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

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Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics:The Study of Muscle,Mobility and Aging(SOMMA)

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Journal of Sport and Health Science 2024年第5期13卷 621-630页

作者： Yujia(Susanna)Qiao Terri L.Blackwell Peggy M.Cawthon Paul M.Coen Steven R.Cummings Giovanna Distefano Samaneh Farsijani Daniel E.Forman Bret H.Goodpaster Stephen B.Kritchevsky Theresa Mau Frederico G.S.Toledo Anne B.Newman Nancy W.Glynn Department of Epidemiology School of Public HealthUniversity of PittsburghPittsburghPA 15261USA San Francisco Coordinating Center California Pacific Medical Center Research InstituteSan FranciscoCA 94143USA Department of Epidemiology and Biostatistics University of CaliforniaSan FranciscoCA 94143USA Translational Research Institute AdventHealthOrlandoFL 32804USA Department of Medicine(Geriatrics and cardiology) University of Pittsburghand GeriatricsResearchEducationand Clinical Center(GRECC)VA Pittsburgh Healthcare SystemPittsburghPA 15261USA Department of Internal Medicine Section on Gerontology and Geriatric MedicineWake Forest School of MedicineWinston-SalemNC 27109USA division of Endocrinology and Metabolism Department of MedicineUniversity of PittsburghPittsburghPA 15261USA

Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older ***,many studies reporting these effects were based on self-reported PA or structured exercise ***,we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior(SB)with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle ***:As part of the Study of Muscle,Mobility and Aging,enrolled older adults(n=879),810(age=76.4±5.0 years old,mean±SD;58%women)had maximal muscle oxidative capacity measured ex vivo via high-resolution re spirometry of permeabilized myofibers(maximal oxidative phosphorylation(maxOXPHOS))and in vivo by ^(31)phosphorus magnetic resonance spectroscopy(maximal adenosine triphosphate(ATP_(max))).Accelerometry-measured sedentary behavior,light activity,and moderate-to-vigorous PA(MVPA)were assessed using a wrist-worn ActiGraph GT9X over 7 ***-reported sedentary behavior,MVPA,and all PA were assessed with the Community Healthy Activities Model Program for Seniors(CHAMPS)*** regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics,as well as the attenuation of the age/muscle energetics association by MVP A and sedentary *** a sensitivity analysis,we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle ***:Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s×mg)higher maxOXPHOS and 0.012 mM/s higher ATP_(max)after adjusting for age,site/technician,and sex(p<0.05).Light activity was not associated with maxOXPHOS or ATP_(max).Meanwhile,every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s×mg lower maxOXPHOS and0.

关键词： Aging Exercise Mitochondria

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Treatment of nasopharyngeal carcinoma and prevention of nonalcoholic Wernicke’s disease:A case report and review of literature

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World Journal of Clinical Cases 2024年第24期12卷 5628-5635页

作者： Yu-Yang Ma Xiao-Chan He Yu Gao Tian-Tian Ma Gong Cheng Chang-Wu Yue Yan’an Key Laboratory of Microbial drug Innovation and Transformation School of Basic MedicineYan’an UniversityYan’an 716000Shaanxi ProvinceChina Department of cardiology Second DivisionShaanxi Provincial People’s HospitalXi’an 710000Shaanxi ProvinceChina Xi’an Honghui Hospital Xi’an Jiaotong UniversityXi’an 710000Shaanxi ProvinceChina

BACKGROUND Wernicke encephalopathy is a neurological disorder caused by thiamine deficiency,commonly seen in alcoholic populations but also involving other circumstances that may lead to thiamine *** recognition of Wernicke encephalopathy often depends on clinicians’keen ability to detect its typical triad of features;however,most cases do not present with the full constellation of signs,which complicates the timely identification of Wernicke *** SUMMARY This case report describes a patient with nasopharyngeal carcinoma who developed abnormal ocular function and ataxia following concurrent chemoradiotherapy,without a history of alcohol *** the aid of radiological examinations,he received a timely diagnosis and treatment;however,his symptoms did not fully resolve during *** For patients with malignant tumors exhibiting neurological symptoms,clinicians should consider the possibility of Wernicke encephalopathy and provide prophylactic thiamine therapy.

关键词： Nasopharyngeal carcinoma Non-alcoholic Wernicke’s disease Wernicke’s encephalopathy Neurological Case report

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Comparison of QT Correction Methods in the Pediatric Population of a Community Hospital: A Retrospective Study

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Congenital Heart Disease 2024年第1期19卷 107-121页

作者： Koren Hyogene Kwag Ibrahim Kak Ying Li Walid Khass Alec McKechnie Oksana Nulman Brande Brown Manoj Chhabra Department of Pediatrics New York Presbyterian Brooklyn Methodist HospitalBrooklyn11215USA Department of Population Health Sciences Division of BiostatisticsWeill Cornell MedicineNew York10065USA

Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT *** most effective QT correction(QTc)formula has yet to be determined in the pediatric population,although it has intrinsically greater extremes in heart rate(HR)and is more susceptible to errors in *** authors of this study compare six dif-ferent QTc methods(Bazett,Fridericia,Framingham,Hodges,Rautaharju,and a computer algorithm utilizing the Bazett formula)for consistency against variations in HR and RR ***:Descriptive Retrospective *** included participants from a pediatric cardiology practice of a community hospital who had an ECG performed in *** participants were healthy patients with no past medical history and no regular ***:ECGs from 95 participants from one month to 21 years of age(mean 9.7 years)were included with a mean HR of 91 beats per minute(bpm).The two-sample paired t-test or Wilcoxon signed-rank test assessed for any difference between QTc methods.A statistically signiﬁcant difference was observed between every combination of two QTc *** Spearman’s rank correlation analysis explored the QTc/HR and QTc/RR relationships for each *** method was most independent of HR and RR with the lowest absolute value of correlation coefﬁ*** and Computer had moderate correlations,while Framingham and Rautaharju exhibited strong *** were positive for Bazett and Computer,reﬂecting results from prior studies demonstrating an over-correction of Bazett at higher *** the linear QTc/HR regression analysis,Bazett had the slope closest to zero,although Computer,Hodges,and Fridericia had comparable ***,Fridericia had the linear QTc/RR regression coefﬁcient closest to *** Bland-Altman method assessed for bias and the limits of agreement between correction *** an

关键词： Corrected QT interval QT prolongation long QT syndrome electrocardiogram retrospective study bazett fridericia framingham hodges rautaharju computer algorithm

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