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Integrin β5 subunit regulates hyperglycemia-induced vascular endothelial cell apoptosis through FoxO1-mediated macroautophagy

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Chinese Medical Journal 2024年第5期137卷 565-576页

作者： Xuze Lin Sizhuang Huang Side Gao Jinxing Liu Jiong Tang Mengyue Yu department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100037China department of Cardiology Fuwai Yunnan Cardiovascular HospitalKunmingYunnan 650000China

Background:Hyperglycemia frequently induces apoptosis in endothelial cells and ultimately contributes to microvascular dysfunction in patients with diabetes mellitus(DM).Previous research reported that the expression of integrins as well as their ligands was elevated in the diseased vessels of DM ***,the association between integrins and hyperglycemia-induced cell death is still *** research was designed to investigate the role played by integrin subunit β5(ITGB5)in hyperglycemia-induced endothelial cell ***:We used leptin receptor knockout(Lepr-KO)(db/db)mice as spontaneous diabetes animal *** deletion of ITGB5 in endothelial cell was achieved by injecting vascular targeted adeno-associated virus via tail ***,we also applied small interfering RNA in vitro to study the mechanism of ITGB5 in regulating high glucose-induced cell ***:ITGB5 and its ligand,fibronectin,were both upregulated after exposure to high glucose in vivo and in ***5 knockdown alleviated hyperglycemia-induced vascular endothelial cell apoptosis and microvascular rarefaction in *** vitro analysis revealed that knockdown of either ITGB5 or fibronectin ameliorated high glucose-induced apoptosis in human umbilical vascular endothelial cells(HUVECs).In addition,knockdown of ITGB5 inhibited fibronectin-induced HUVEC apoptosis,which indicated that the fibronectin-ITGB5 interaction participated in high glucose-induced endothelial cell *** using RNA-sequencing technology and bioinformatic analysis,we identified Forkhead Box Protein O1(FoxO1)as an important downstream target regulated by ***,we demonstrated that the excessive macroautophagy induced by high glucose can contribute to HUVEC apoptosis,which was regulated by the ITGB5-FoxO1 ***:The study revealed that high glucose-induced endothelial cell apoptosis was positively regulated by ITGB5,which suggested that ITGB5 could potentially be used

关键词： Endothelial cell apoptosis Integrin Autophagy Diabetes

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ccdc141 is required for left-right axis development by regulating cilia formation in the Kupffer's vesicle of zebrafish

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Journal of Genetics and Genomics 2024年第9期51卷 934-946页

作者： Pengcheng Wang Wenxiang Shi Sijie Liu Yunjing Shi Xuechao Jiang Fen Li Sun Chen Kun Sun Rang Xu department of Pediatric Cardiology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China department of cardiovascular Medicine Heart Failure CenterRuijin HospitalRuijin Hospital Lu Wan BranchShanghai Jiao Tong University School of MedicineShanghai 200025China Scientific Research center Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China department of Pediatric Cardiology Shanghai Children's Medical CenterShanghai Jiao Tong University School of MedicineShanghai 200127China

Laterality is a crucial physiological process intricately linked to the cilium-centrosome complex during embryo *** in the process can result in severe organ ***-coil domain containing 141(CCDC141)has been previously known as a centrosome-related gene,but its role in left-right(LR)asymmetry has not been *** this study,we utilize the zebrafish model and human exome analysis to elucidate the function of ccdc141 in laterality *** knockdown of ccdc141 in zebrafish disrupts early LR signaling pathways,cilia function,and Kupffer's vesicle *** ccdc141-knockdown embryos exhibiting aberrant LR patterns,ccdc141-null mutants show no apparent abnormality,suggesting a genetic compensation response *** parallel,we observe a marked reduction inα-tubulin acetylation levels in the ccdc141 *** treatment with histone deacetylase(HDAC)inhibitors,particularly the HDAC6 inhibitor,rescues the ccdc141 crispant ***,exome analysis of 70 patients with laterality defects reveals an increased burden of CCDC141 mutations,with in-vivo studies verifying the pathogenicity of the patient mutation *** findings highlight the critical role of ccdc141 in ciliogenesis and demonstrate that CCDC141 mutations lead to abnormal LR patterns,identifying it as a candidate gene for laterality defects.

关键词： Left-right axis Cilia WES Laterality defects Zebrafish CCDC141

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When Glanzmann thrombasthenia encounters antithrombin defi ciency: how do we balance the risk and benefi t of antithrombotic therapy?

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World Journal of Emergency Medicine 2024年第1期15卷 67-69页

作者： Yu Wang Zhihao Liu Haoyu Weng Jianping Li department of Endocrinology Peking University First HospitalBeijing 100034China department of Cardiology Peking University First HospitalBeijing 100034China Key Laboratory of Molecular cardiovascular Sciences of Ministry of Education Health Science CenterPeking UniversityBeijing 100034China

Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and *** this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic *** is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous ***,we describe a rare case of GT and antithrombin deficiency coexisting in a single *** was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).

关键词： thrombin throm bleeding

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Association of stage 1 hypertension defined by the 2017 ACC/AHA guideline with cardiovascular events and mortality in Chinese adults

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Chinese Medical Journal 2024年第1期137卷 63-72页

作者： Qiannan Gao Liuxin Li Jingjing Bai Luyun Fan Jiangshan Tan Shouling Wu Jun Cai Hypertension center Fuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100037China department of Cardiology Kailuan General HospitalNorth China University of Science and TechnologyTangshanHebei 063000China Emergency center Fuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100037China

Background:The 2017 American College of Cardiology/American Heart Association(ACC/AHA)blood pressure(BP)guideline lowered the threshold defining hypertension to 130/80 ***,how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains *** study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese ***:Participants with stage 1 hypertension(n=69,509)or normal BP(n=34,142)were followed in this study from 2006/2007 to *** 1 hypertension was defined as a systolic blood pressure of 130-139 mmHg or a diastolic blood pressure of 80-89 *** were taking antihypertensive medication or had a history of myocardial infarction(MI),stroke,or cancer at *** primary outcome was a composite of MI,stroke,and all-cause *** secondary outcomes were individual components of the primary *** proportional hazards models were used for the ***:During a median follow-up of 11.09 years,we observed 10,479 events(MI,n=995;stroke,n=3408;all-cause mortality,n=7094).After multivariable adjustment,the hazard ratios for stage 1 hypertension *** BP were 1.20(95%confidence interval[CI],1.13-1.25)for primary outcome,1.24(95%CI,1.05-1.46)for MI,1.45(95%CI,1.33-1.59)for stroke,and 1.11(95%CI,1.04-1.17)for all-cause *** hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90(95%CI,0.85-0.96).Conclusions:Using the new definition,Chinese adults with untreated stage 1 hypertension are at higher risk for MI,stroke,and all-cause *** finding may help to validate the new BP classification system in China.

关键词： Hypertension cardiovascular disease All-cause mortality Cox regression analysis

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Transient induction of actin cytoskeletal remodeling associated with dedifferentiation,proliferation,and redifferentiation stimulates cardiac regeneration

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2537-2553页

作者： Wenbin Fu Qiao Liao Yu Shi Wujian Liu Hongmei Ren Chunmei Xu Chunyu Zeng department of Cardiology Daping Hospitalthe Third Military Medical University(Army Medical University)Chongqing 400042China Key Laboratory of Geriatric cardiovascular and Cerebrovascular Disease Research Ministry of Education of ChinaChongqing 400042China Chongqing Key Laboratory for Hypertension Research Chongqing Cardiovascular Clinical Research CenterChongqing Institute of CardiologyChongqing 400042China State Key Laboratory of Trauma Burns and Combined InjuryDaping Hospitalthe Third Military Medical UniversityChongqing 400042China cardiovascular Research center Chongqing CollegeUniversity of Chinese Academy of SciencesChongqing 400042China State Key Laboratory of Trauma and Chemical Poisoning Chongqing 400042China

The formation of new and functional cardiomyocytes requires a 3-step process:dedifferentiation,proliferation,and redifferentiation,but the critical genes required for efficient dedifferentiation,proliferation,and redifferentiation remain *** our study,a circular trajectory using single-nucleus RNA sequencing of the pericentriolar material 1 positive(PCM1^(+))cardiomyocyte nuclei from hearts 1 and 3 days after surgery-induced myocardial infarction(MI)on postnatal Day 1 was reconstructed and demonstrated that actin remodeling contributed to the dedifferentiation,proliferation,and redifferentiation of cardiomyocytes after *** identified four top actin-remodeling regulators,namely Tmsb4x,Tmsb10,Dmd,and Ctnna3,which we collectively referred to as *** expressed changes of 2D2P,using a polycistronic non-integrating lentivirus driven by Tnnt2(cardiac-specific troponin T)promoters(Tnnt2-2D2P-NIL),efficiently induced transiently proliferative activation and actin remodeling in postnatal Day 7 cardiomyocytes and adult ***,the intramyocardial delivery of Tnnt2-2D2P-NIL resulted in a sustained improvement in cardiac function without ventricular dilatation,thickened septum,or fatal arrhythmia for at least 4 *** conclusion,this study highlights the importance of actin remodeling in cardiac regeneration and provides a foundation for new gene-cocktail-therapy approaches to improve cardiac repair and treat heart failure using a novel transient and cardiomyocyte-specific viral construct.

关键词： Single cell analysis Actin remodeling Tmsb4x Tmsb10 Dmd Ctnna3 Myocardial infarction Cardiomyocytes proliferation Cardiac regeneration Genetic therapy

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Unveiling the next generation of MRI contrast agents:current insights and perspectives on ferumoxytol-enhanced MRI

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National Science Review 2024年第5期11卷 385-404页

作者： Guangxiang Si Yue Du Peng Tang Gao Ma Zhaochen Jia Xiaoyue Zhou Dan Mu Yan Shen Yi Lu Yu Mao Chuan Chen Yan Li Ning Gu Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Science and Medical EngineeringSoutheast University Key Laboratory for Bio-Electromagnetic Environment and Advanced Medical Theranostics School of Biomedical Engineering and InformaticsNanjing Medical University department of radiology the First Affiliated Hospital of Nanjing Medical University MR Collaboration Siemens Healthineers Ltd. department of radiology Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School School of Mathematical Sciences Capital Normal University Nanjing Key Laboratory for cardiovascular Information and Health Engineering Medicine Institute of Clinical Medicine Nanjing Drum Tower HospitalMedical SchoolNanjing University

Contrast-enhanced magnetic resonance imaging(CE-MRI) is a pivotal tool for global disease diagnosis and management. Since its clinical availability in 2009, the off-label use of ferumoxytol for ferumoxytol-enhanced MRI(FE-MRI) has significantly reshaped CE-MRI practices. Unlike MRI that is enhanced by gadolinium-based contrast agents, FE-MRI offers advantages such as reduced contrast agent dosage, extended imaging windows, no nephrotoxicity, higher MRI time efficiency and the capability for molecular imaging. As a leading superparamagnetic iron oxide contrast agent, ferumoxytol is heralded as the next generation of contrast agents. This review delineates the pivotal clinical applications and inherent technical superiority of FE-MRI, providing an avant-garde medical-engineering interdisciplinary lens, thus bridging the gap between clinical demands and engineering innovations. Concurrently, we spotlight the emerging imaging themes and new technical breakthroughs. Lastly, we share our own insights on the potential trajectory of FE-MRI, shedding light on its future within the medical imaging realm.

关键词： ferumoxytol contrast agent contrast-enhanced MRI ferumoxytol-enhanced MRI

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Next‑Generation Sequencing‑Based Copy Number Variation Analysis in Chinese Patients with Primary Ciliary Dyskinesia Revealed Novel DNAH5 Copy Number Variations

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Phenomics 2024年第1期4卷 24-33页

作者： Weicheng Chen Zhuoyao Guo Mengru Li Wei Sheng Guoying Huang cardiovascular center Children’s Hospital of Fudan University399 Wanyuan RoadShanghai 201102China Respirology department Children’s Hospital of Fudan UniversityShanghai 201102China

Primary ciliary dyskinesia(PCD)is a rare disorder characterized by extensive genetic ***,in the genetic pathogenesis of PCD,copy number variation(CNV)has not received sufcient attention and has rarely been reported,especially in ***-generation sequencing(NGS)followed by targeted CNV analysis was used in patients highly suspected to have PCD with negative results in routine whole-exome sequencing(WES)*** real-time polymerase chain reaction(qPCR)and Sanger sequencing were used to confrm these *** further characterize the ciliary phenotypes,high-speed video microscopy analysis(HSVA),transmission electron microscopy(TEM),and immunofuorescence(IF)analysis were *** 1(F1:II-1),a 0.6-year-old girl,came from a nonconsanguineous *** presented with situs inversus totalis,neonatal respiratory distress,and *** nasal nitric oxide level was markedly *** respiratory cilia beat with reduced *** revealed shortened outer dynein arms(ODA)of ***5:13717907-13722661del spanning exons 71–72 was identifed by NGS-based CNV *** 2(F2:IV-4),a 37-year-old man,and his eldest brother Patient 3(F2:IV-2)came from a consanguineous *** had sinusitis,bronchiectasis and situs inversus *** respiratory cilia of Patient 2 and Patient 3 were found to be uniformly immotile,with ODA *** novel homozygous deletions chr5:13720087_13733030delinsGTTTTC and chr5:13649539_13707643del,spanning exons 69–71 and exons 77–79 were identifed by NGS-based CNV *** in DNA copy number were confrmed by qPCR *** showed that the respiratory cilia of Patient 1 and Patient 2 were defcient in dynein axonemal heavy chain 5(DNAH5)protein *** report identifed three novel DNAH5 disease-associated variants by WES-based CNV *** study expands the genetic spectrum of PCD with DNAH5 in the Chinese population.

关键词： Primary ciliary dyskinesia DNAH5 gene Copy number variation Phenotypic heterogeneity

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A rechargeable Ca/Cl_(2) battery

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Science China Chemistry 2024年第9期67卷 2794-2795页

作者： Shixun Wang Chunyi Zhi department of Materials Science and Engineering City University of Hong KongHong Kong S.A.R.999077China Hong Kong center for Cerebro-cardiovascular Health Engineering(COCHE) ShatinNTHong Kong S.A.R.999077China

Multivalent metal-ion batteries have attracted wide attention with the expectation of tackling the needs of large-scale electrochemical energy storage[1].Among them,rechargeable calcium(Ca)-ion batteries are known as a promising alternative to conventional lithium(Li)-ion batteries due to the high abundance of calcium(the fifth most abundant element in the earth’s crust)and its large theoretical capacity(2,073 m Ah cm^(-3))and potential(-2.87 V *** hydrogen electrode,SHE)comparable to that of Li(-3.04 V ***).Furthermore,unlike monovalent cations,the divalent calcium cations favor a two-electron transfer to increase the specific energies[2].

关键词： valent lithium expectation

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Brain Functional Network Changes in Patients with Poststroke Cognitive Impairment Following Acupuncture Therapy

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Health 2024年第9期16卷 856-871页

作者： Ran Wang Nian Liu Hao Xu Peng Zhang Xiaohua Huang Lin Yang Xiaoming Zhang Science and Technology Innovation center Interventional Medical Center Department of Radiology Affiliated Hospital of North Sichuan Medical College Nanchong China department of radiology Sichuan Province Orthopedic Hospital Chengdu China

Background: The mechanisms by which acupuncture affects poststroke cognitive impairment (PSCI) remain unclear. Objective: To investigate brain functional network (BFN) changes in patients with PSCI after acupuncture therapy. Methods: Twenty-two PSCI patients who underwent acupuncture therapy in our hospital were enrolled as research subjects. Another 14 people matched for age, sex, and education level were included in the normal control (HC) group. All the subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans;the PSCI patients underwent one scan before acupuncture therapy and another after. The network metric difference between PSCI patients and HCs was analyzed via the independent-sample t test, whereas the paired-sample t test was employed to analyze the network metric changes in PSCI patients before vs. after treatment. Results: Small-world network attributes were observed in both groups for sparsities between 0.1 and 0.28. Compared with the HC group, the PSCI group presented significantly lower values for the global topological properties (γ, Cp, and Eloc) of the brain;significantly greater values for the nodal attributes of betweenness centrality in the CUN. L and the HES. R, degree centrality in the SFGdor. L, PCG. L, IPL. L, and HES. R, and nodal local efficiency in the ORBsup. R, ORBsupmed. R, DCG. L, SMG. R, and TPOsup. L;and decreased degree centrality in the MFG. R, IFGoperc. R, and SOG. R. After treatment, PSCI patients presented increased degree centrality in the LING.L, LING.R, and IOG. L and nodal local efficiency in PHG. L, IOG. R, FFG. L, and the HES. L, and decreased betweenness centrality in the PCG. L and CUN. L, degree centrality in the ORBsupmed. R, and nodal local efficiency in ANG. R. Conclusion: Cognitive decline in PSCI patients may be related to BFN disorders;acupuncture therapy may modulate the topological properties of the BFNs of PSCI patients.

关键词： Cognitive Decline Poststroke Cognitive Impairment Functional Magnetic Resonance imaging Brain Functional Network Graph Theoretical Analysis

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Continuous age-and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease

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World Journal of Pediatrics 2024年第9期20卷 949-956页

作者： Zhao-Yuan Wu Si-Wei Chi Liu-Jian Ouyang Xiao-Qin Xu Jing-Nan Chen Bing-Han Jin Rahim Ullah Xue-Lian Zhou Ke Huang Guan-Ping Dong Zhe-Ming Li Ying Shen Jie Shao Yan Ni Jun-Fen Fu Qiang Shu Wei Wu department of Endocrinology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child Health3333 Binsheng RoadHangzhou310051China department of Data and Information Children’s HospitalZhejiang University School of MedicineHangzhouChina department of Child Health Care Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouChina department of Thoracic&cardiovascular Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthNational Children’s Regional Medical Center3333 Binsheng RoadHangzhou310051China

Background Alanine aminotransferase(ALT)is widely used to screen patients with hepatic ***,the current reference ranges(<50 U/L)were developed by laboratories and have not been validated in populations with a large nu... 详细信息

Background Alanine aminotransferase(ALT)is widely used to screen patients with hepatic ***,the current reference ranges(department of Pediatric *** applied the least mean square algorithm to establish age-and sex-related reference percentiles of serum levels of *** validation,we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the *** receiver operating characteristic curves,we determined age-and sex-specific upper limit percentiles of liver enzymes for fatty liver *** This study revealed a significant correlation between serum transaminase levels and age and sex(P<0.01).These transaminase levels exhibited age-and sex-specific *** individuals in the non-alcoholic fatty liver disease(NAFLD)cohort,elevated ALT levels displayed a positive association with clinical markers of disease severity,including homeostatic model assessment of insulin resistance,waist-hip ratio,and serum uric acid levels(P<0.01).According to the receiver operating characteristic curves,ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and *** This study provides age-and sex-specific reference ranges for ALT,aspartate aminotransferase,andγ-glutamyltransferase in Chinese children and adolescents,making it the largest population study to ***,the study establishes a precise upper limit for ALT levels,facilitating their use in NAFLD screening.

关键词： Alanine aminotransferase Childhood Fatty liver diseases

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