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Comparing the efficacy and safety of low,medium,and high dosages of selexipag for treating pulmonary hypertension:A systematic review and meta-analysis

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Animal Models and Experimental Medicine 2024年第1期7卷 56-70页

作者： Shang Wang Yi Yan Jian Zhang Ping Yuan Ci-Jun Luo Hong-Ling Qiu Hui-Ting Li Jian Xu Lan Wang Tian-Lan Li Rong Jiang Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina heart center and shanghai institute of pediatric congenital heart disease Shanghai Children's Medical CenterNational Children's Medical CenterShanghai Jiaotong University School of MedicineShanghaiChina Department of Respiratory and Critical Care Medicine The 416 Hospital of Nuclear IndustryThe Second Affiliated Hospital of Chengdu Medical CollegeChengduChina Department of Hematology The Affiliated Hospital of Qingdao UniversityQingdaoChina

Background:The maintenance dosage of selexipag is categorized as low,medium or *** order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension(PAH),we performed a sys-tematic review and ***:Studies assessing PAH risk stratification indices,such as the World Health Organization functional class(WHO-FC),six-minute walk distance(6MWD),N-terminal pro-B-type natriuretic peptide(NT-proBNP)level,right atrial pressure(RAP),cardiac index(CI)and mixed venous oxygen saturation(SvO2),were ***:Thirteen studies were *** led to improvements in the 6MWD(MD:24.20 m,95%CI:10.74-37.67),NT-proBNP(SMD:-0.41,95%CI:-0.79-0.04),CI(MD:0.47 L/min/m^(2),95%CI:0.17-0.77)and WHO-FC(OR:0.564,95%CI:0.457-0.697).Subgroup analysis demonstrated that all three dosages improved the 6MWD.A moderate dosage led to improvements in the CI(MD:0.30 L/min/m^(2),95%CI:0.15-0.46)and WHO-FC(OR:0.589,95%CI:0.376-0.922).Within 6 months of treatment,only the WHO-FC and CI were significantly improved(OR:0.614,95%CI:0.380-0.993;MD:0.30 L/min/m^(2),95%CI:0.16-0.45,respectively).More than 6 months of treatment significantly improved the 6MWD,WHO-FC and NT-proBNP(MD:40.87 m,95%CI:10.97-70.77;OR:0.557,95%CI:0.440-0.705;SMD:-0.61,95%CI:-1.17-0.05,respectively).Conclusions:Low,medium,and high dosages of selexipag all exhibited good *** treatment lasted for more than 6 months,selexipag exerted obvious effects,even in the low-dosage *** finding is important for guiding individualized treatments.

关键词： individualized treatments meta-analysis prostacyclin receptor agonist risk stratification systematic review

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A 63-Year-Old Male with D-Transposition of the Great Arteries Who Had an Early Form of the Arterial Switch Operation

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congenital heart disease 2024年第1期19卷 65-68页

作者： Michael A.Rebolledo Jane S.Yao Jason N.Johnson Umar S.Boston Benjamin R.Waller III Division of pediatric Cardiology Department of PediatricsThe University of Tennessee Health Science CenterThe Heart InstituteLe Bonheur Children’s HospitalMemphisUSA College of Medicine The University of Tennessee Health ScienceMemphisUSA Division of pediatric Cardiothoracic Surgery Department of SurgeryThe University of Tennessee Health Science CenterHeart InstituteLe Bonheur Children’s HospitalMemphisUSA

We describe a 63-year-old male who appears to have undergone an early form of the arterial switch operation for D-transposition of the great arteries performed in the *** review the clinical and imaging data that support our *** had a diagnostic cardiac catheterization which demonstrated severe pulmonary hypertension responsive to epoprostenol and *** case may represent one example of the experimental surgical work done prior to *** Jatene’s description of theﬁrst successful arterial switch performed in 1975.

关键词： Adult congenital heart disease arterial switch operation great vessel anomaly imaging(all modalities)

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Prognosis and outcome of intrauterine treatment of fetuses with critical congenital heart disease

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Chinese Medical Journal 2024年第12期137卷 1431-1436页

作者： Liqing Zhao Lei Wang Hongping Xia Yurong Wu Xianting Jiao Hong Zhu Sun Chen Kun Sun Department of pediatric Cardiology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Diagnosis and Treatment center for in utero pediatric disease Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Neonatology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China

Background:Intrauterine valvuloplasty is an innovative therapy,which promotes ventricular growth and function in some congenital heart diseases(CHDs).The technique remains challenging and can only be performed in a few *** study aimed to assess the feasibility and mid-term outcomes of fetal cardiac intervention(FCI)in fetuses with critical CHD in an experienced tertiary ***:Five fetal aortic valvuloplasty(FAV)or fetal pulmonary valvuloplasty(FPV)procedures were performed in our fetal heart center between August 2018 and May *** success was defined as crossing the aortic or pulmonary valve and balloon inflation,followed by evidence of increased blood flow across the valve and/or new ***-up clinical records and echocardiography were obtained during the prenatal and postnatal ***:Five fetuses received FAV or FPV,including critical aortic stenosis(n=2)and pulmonary atresia with intact ventricular septum(n=3).The mean maternal age was 33.0±2.6 *** median gestational age(GA)at diagnosis was 24 weeks(range,22-26 weeks).The median GA at intervention was 29 weeks(range,28-32 weeks).All five cases underwent successful or partially successful *** patient had pulmonary valve perforation without balloon *** procedure-related deaths or significant complications ***,one neonatal death occurred due to heart and renal *** median follow-up period was 29.5 months(range,8.0-48.0 months).The four surviving patients had achieved biventricular circulation,exhibited improved valve,and ventricular development at the last follow-up ***:Intrauterine FCI could be performed safely with good prognosis in critical CHD.

关键词： Fetal cardiac intervention Valvuloplasty Pulmonary atresia Critical aortic stenosis congenital heart disease

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Intelligent diagnosis of atrial septal defect in children using echocardiography with deep learning

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虚拟现实与智能硬件（中英文） 2024年第3期6卷 217-225页

作者： Yiman LIU Size HOU Xiaoxiang HAN Tongtong LIANG Menghan HU Xin WANG Wei GU Yuqi ZHANG Qingli LI Jiangang CHEN shanghai Key Laboratory of Multidimensional Information Processing School of Communication&Electronic EngineeringEast China Normal UniversityShanghaiChina Department of pediatric Cardiology Shanghai Children's Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Applied Mathematics Xi'an Jiaotong-Liverpool UniversitySchool of ScienceSuzhouChina School of Health Sciences and Engineering University of Shanghai for Science and TechnologyShanghaiChina Minhang District centers for disease Control and Prevention ShanghaiChina Faculty of Traditional Chinese Medicine Naval Medical UniversityShanghaiChina Engineering Research center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghai 201203China

Background Atrial septal defect(ASD)is one of the most common congenital heart *** diagnosis of ASD via transthoracic echocardiography is subjective and *** The objective of this study was to evaluate the feasibility and accuracy of automatic detection of ASD in children based on color Doppler echocardiographic static images using end-to-end convolutional neural *** proposed depthwise separable convolution model identifies ASDs with static color Doppler images in a standard *** the standard views,we selected two echocardiographic views,i.e.,the subcostal sagittal view of the atrium septum and the low parasternal four-chamber *** developed ASD detection system was validated using a training set consisting of 396 echocardiographic images corresponding to 198 ***,an independent test dataset of 112 images corresponding to 56 cases was used,including 101 cases with ASDs and 153 cases with normal *** The average area under the receiver operating characteristic curve,recall,precision,specificity,F1-score,and accuracy of the proposed ASD detection model were 91.99,80.00,82.22,87.50,79.57,and 83.04,*** The proposed model can accurately and automatically identify ASD,providing a strong foundation for the intelligent diagnosis of congenital heart diseases.

关键词： Deep learning Atrial septal defect Echocardiography

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DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for congenital heart diseases

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congenital heart disease 2024年第2期19卷 247-256页

作者： Shuliang Xia Huikang Tao Shixin Su Xinxin Chen Li Ma Jianru Li Bei Gao Xumei Liu Lei Pi Jinqing Feng Fengxiang Li Jia Li Zhiwei Zhang Guangdong Provincial People’s Hospital Southern Medical UniversityGuangzhou510100China Department of Cardiovascular Surgery Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhou510623China Department of pediatric Cardiology Guangdong Cardiovascular InstituteGuangdong Provincial Key Laboratory of South China Structural Heart DiseaseGuangzhou510100China Clinical Physiology Laboratory Institute of PediatricsGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangzhou510623China Department of Echocardiogram Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhou510623China Department of pediatrics Washington University School of MedicineSt.LouisMO63130USA Clinical Biological Resource Bank of Guangzhou Women and Children’s Medical center Guangzhou Medical UniversityGuangzhou510623China

Aims:Multiple genes and environmental factors are known to be involved in congenital heart disease(CHD),but epigenetic variation has received little ***(MZ)twins with CHD provide a unique model for exploring this *** order to investigate the potential role of Deoxyribonucleic Acid(DNA)methyla-tion in CHD pathogenesis,the present study examined DNA methylation variation in MZ twins discordant for CHD,especially ventricular septal defect(VSD).Methods and Results:Using genome-wide DNA methylation profiles,we identified 4004 differentially methylated regions(DMRs)in 18 MZ twin pairs discordant for CHD,and 2826 genes were *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed a list of CHD-associated *** further investigate the role of DNA methylation in VSD,data from 7 pairs of MZ twins with VSD were *** identified 1614 DMRs corresponding to 1443 genes associated with arrhythmogenic right ventricular cardiomyopathy,cyclic guanosine monopho-sphate-protein kinase G(cGMP-PKG)signaling pathway by KEGG analysis,and cell-cell adhesion,calcium ion transmembrane transport by GO analysis.A proportion of DMR-associated genes were involved in calcium signaling *** methylation changes of calcium signaling genes might be related to VSD ***:CHD is associated with differential DNA methylation in MZ *** may be etiologically linked to DNA methylation,and methylation of calcium signaling genes may be involved in the development of VSD.

关键词： congenital heart disease monozygotic twins methylation modification epigenetics

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Biallelic variants in RBM42 cause a multisystem disorder with neurological,facial,cardiac,and musculoskeletal involvement

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Protein & Cell 2024年第1期15卷 52-68页

作者： Yiyao Chen Bingxin Yang Xiaoyu Merlin Zhang Songchang Chen Minhui Wang Liya Hu Nina Pan Shuyuan Li Weihui Shi Zhenhua Yang Li Wang Yajing Tan Jian Wang Yanlin Wang Qinghe Xing Zhonghua Ma Jinsong Li He-Feng Huang Jinglan Zhang Chenming Xu institutes of Biomedical Sciences Fudan UniversityShanghai 200032China bstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200011China Intermational Peace Matermity and Child Health Hospital School of MedicineShanghai Jiao Tong UniversityShanghai 200030China shanghai Key Laboratory of Embryo Original diseases Shanghai 200030China State Key Laboratory of Cell Biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China State Key Laboratory of Rice Biology the Key Laboratory of Molecular Biology of Crop Pathogens and InsectsInstitute of BiotechnologyZhejiang UniversityHangzhou 310058China Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of MedicineHoustonTX 77030USA Children's hospital of Fudan University Shanghai 201102China School of Life Science and Technology Shanghai Tech UniversityShanghai 201210China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024ZhejiangChina Research Units of Embryo Original diseases Chinese Academy of Medical Sciences(No.2019RU056)Shanghai 200011China

Here,we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 *** patient is a 2-year-old female with severe central nervous system(CNs)abnormalities,hypotonia,hearing loss,congenital heart defects,and dysmorphic facial *** whole-exome sequencing(WEs)reveals that the patient has two compound heterozygous variants,c.304C>T(p.R102*)and c.1312G>A(p.A438T),in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein *** p.A438T variant is in the RRM domain which impairs RBM42 pro-tein stability in ***,p.A438T disrupts the interaction of RBM42 with hnRNP K,which is the causa-tive gene for Au-Kline syndrome with overlapping disease characteristics seen in the index *** human R102*or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout△FgRbp1 in Fusarium while it was rescued by the wild-type(WT)human RBM42.A mouse model carying Rbm42 compound heterozygous variants,c.280C>T(p.Q94*)and c.1306_1308delinsACA(p.A436T),demonstrated gross fetal develop-mental defects and most of the double mutant animals died by ***-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing(As).Overall,we present clinical,genetic,and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

关键词： RBM42 gene RNA-binding protein neurodevelopmental disorder Au-Kline syndrome alternative splicing

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Changing profiles of cardiovascular disease and risk factors in China:a secondary analysis for the Global Burden of disease Study 2019

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Chinese Medical Journal 2023年第20期136卷 2431-2441页

作者： Huan Wang Hao Zhang Zhiyong Zou institute of Child and Adolescent Health School of Public HealthPeking UniversityNational Health Commission Key Laboratory of Reproductive HealthBeijing 100191China heart center and shanghai institute of pediatric congenital heart disease Shanghai Children’s Medical CenterNational Children’s Medical CenterShanghai Jiaotong University School of MedicineShanghai 200127China

Background:Understanding the changing profiles of cardiovascular disease(CVD)and modifiable risk factors is essential for CVD prevention and *** aimed to report the comprehensive trends in CVD and risk factors in China from 1990 to ***:Data on the incidence,death,and disability-adjusted life years(DALYs)of total CVD and its 11 subtypes for China were obtained from the Global Burden of disease Study *** CVD burden attributable to 12 risk factors was also retrieved.A secondary analysis was conducted to summarize the leading causes of CVD burden and attributable risk ***:From 1990 to 2019,the number of CVD incidence,death,and DALYs considerably increased by 132.8%,89.1%,and 52.6%,***,ischemic heart disease,and hypertensive heart disease accounted for over 95.0%of CVD deaths in 2019 and remained the top three causes during the past 30 *** 1990 and 2019,the age-standardized rate of stroke decreased significantly(percentage of decreased incidence:-9.3%;death:-39.8%;DALYs:-41.6%),while the rate of ischemic heart disease increased(percentage of increased incidence:11.5%;death:17.6%;DALYs:2.2%).High systolic blood pressure,unhealthy diet,tobacco,and air pollution continued to be the major contributors to CVD deaths and DALYs(attributing to over 70%of the CVD burden),and the high body mass index(BMI)-associated CVD burden had the largest increase between 1990 and ***:The significant increases in the number of CVD incident cases,deaths,and DALYs suggest that the CVD burden is still a *** strategies and policies are needed to maintain promising progress in stroke and to reduce the escalating burden of ischemic heart *** CVD burden attributable to risk factors has not yet made adequate achievements;even worse,high BMI has contributed to the increasing CVD burden.

关键词： Cardiovascular disease Stroke Ischemic heart disease Risk factors Global Burden of disease Hypertensive heart disease

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Minor Pressure Differences within the Fontan-Anastomosis in Patients with Total Cavopulmonary Connection by 4D-Flow Magnetic Resonance Imaging

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congenital heart disease 2023年第4期18卷 461-474页

作者： Nerejda Shehu Christian Meierhofer Anja Hennemuth Markus Hüllebrand Pavlo Yevtushenko Peter Ewert Stefan Martinoff Heiko Stern Department of congenital heart disease and pediatric Cardiology German Heart Center MunichTechnical University of MunichMunichGermany Fraunhofer institute for Digital Medicine—MEVIS BerlinGermany institute for Cardiovascular Computer-Assisted Medicine CharitéUniversitätsmedizinBerlinGermany Department of Radiology German Heart Center MunichTechnical University of MunichMunichGermany

Background: Pressure measurement in total cavopulmonary connection (TCPC) patients is a domain of cardiaccatheterization. 4D velocity encoded cardiovascular magnetic resonance (4D–flow MRI) offers an alternative forassessment of even minor pressure differences. The scope of this study was to measure even minor pressure differencesin the anastomosis of TCPC patients, who are clinically uncompromised. Methods: Twenty-four patients(median 15 years [8;34]) with TCPC were studied prospectively by 4D-flow MRI. Pressure differences betweensuperior vena cava (SVC) and extracardiac conduit (C) to both right pulmonary artery (RPA) and left pulmonaryartery (LPA) were assessed. Small fluid obstructions as vortices within the anastomosis were detected by flowpathlines from 4D-flow MRI. In two patients pressure differences were calculated also by computational flowdynamics (CFD) as a plausibility check for the order of magnitude. Results: Median values of pressure differencesin the anastomosis between SVC and RPA were 0.63 (0.21–2.1) mmHg, between C and RPA 0.67 (0.3–2.2)mmHg, between SVC and LPA 0.8 (0.3–2.4) mmHg and between C and LPA 0.7 (0.2–1.9) mmHg. Patients withpotential flow obstruction (stents, occluder, vortices) had significantly higher gradients at the anastomosis (p <0.05) than patients without potential obstructions, although the absolute values were small. CFD- and measurement-based pressure difference showed good agreement. Conclusion: 4D-flow MRI is able to detect minor pressuredifferences within the Fontan circuit even in patients with apparently satisfactory TCPC. Slightly higherpressure differences are due to the presence of small flow obstruction.

关键词： 4D-flow MRI pressure differences TCPC Fontan

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Analysis and prediction of research hotspots and trends in pediatric medicine from 2,580,642 studies published between 1940 and 2021

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世界儿科杂志:英文版 2023年第8期19卷 793-797页

作者： Ze‑Ye Liu Yuan Huang Jing Xu Li Xiang Zhan‑Hao Su Yi‑Wei Liu Hao Zhang Department of Structural heart disease National Center for Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China State Key Laboratory of Cardiovascular disease Fuwai HospitalNational Center for Cardiovascular DiseasesPediatric Cardiac Surgery CenterFuwai HospitalChinese Academy of Medical Sciencesand Peking Union Medical CollegeBeijingChina State Key Laboratory of Cardiovascular disease Fuwai HospitalNational Center for Cardiovascular DiseasesFuwai HospitalChinese Academy of Medical Sciencesand Peking Union Medical CollegeBeijingChina heart center and shanghai institute of pediatric congenital heart disease Shanghai Children’s Medical CenterNational Children’s Medical CenterShanghai Jiaotong University School of MedicineNo.1678 Dongfang RoadShanghai 200127China Department of Cardiovascular Surgery Guangdong Cardiovascular InstituteGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510060China shanghai Clinical Research center for Rare pediatric diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

From 1990 to 2019,there has been a substantial increase in the global population from 5.3 billion to 7.7 billion(about 44.6%)[1,2].Simultaneously,the global death population among people under 20 years of age has increased from 6.22 million to 13.93 million,accounting for an increase of 124%[1,2,3].This means that the mortality rate of children/adolescents is almost three times higher than the growth rate of the global population.

关键词： mortality population. pediatric

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The effect of rehabilitation exercise on the expression of glutaminase and cardiopulmonary remodeling in pulmonary hypertension

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Medicine in Novel Technology and Devices 2022年第3期15卷 134-143页

作者： Shang Wang Ping Yuan Yuan-Yuan Sun Yi Yan Yu-Xia Huang Xiao-Yi Hu Lan Wang Kuan Cheng Rong Jiang Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai200433China heart center and shanghai institute of pediatric congenital heart disease Shanghai Children's Medical CenterNational Children's Medical CenterShanghai Jiaotong University School of MedicineShanghaiChina institute for Cardiovascular Prevention(IPEK) Ludwig Maximilian University MunichMunichGermany Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghai200032China

Pulmonary hypertension(PH)is featured by pulmonary vascular and cardiac *** exercise can improve patients’quality of *** previously pinpointed a potential glutamine metabolism dysfunction in ***,we aim to investigate whether rehabilitation exercise could mitigate right ventricular and pulmonary vascular remodeling and its effect on glutaminase(GLS).We collected clinical indicators of PH patients and analyzed their correlation with *** exercise(moderate intensity swimming exercise)was performed in monocrotaline-induced PH(MCT-PH)*** found that plasma GLS1 level in patients was lower than healthy subjects,and it was negatively correlated with end-systolic stage eccentricity index,right atrial transverse dimension and right atrial longitudinal ***-PH rats displayed pulmonary vascular remodeling and right ventricular *** to control rats,higher levels of GLS1 and GLS2 mRNA in lung and lower levels of these two isoforms of GLS in right ventricle(RV)were displayed in MCT-PH *** swimming exercise,GLS mRNA levels in the lung and RV were significantly upregulated,and the cross-sectional area of right ventricular cardiomyocytes was significantly decreased although the percentage of pulmonary arteriolar medial wall thickness was not significantly ***,we hold the opinion that plasma GLS1 level was decreased in *** transcriptional levels of GLS1 and GLS2 were increased in the lung tissues in PH,but were decreased in the RV ***,the changes of GLS levels indicated the pulmonary vascular and right ventricular *** moderate intensity swimming exercise might improve the right ventricular remodeling by regulating the levels of GLS.

关键词： Pulmonary hypertension Pulmonary vascular remodeling Cardiac remodeling Glutaminase

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