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Therapeutic advances in atrial fibrillation based on animal models

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第2期25卷 135-152页

作者： Qian GONG Xuan LE Pengcheng YU Lenan ZHUANG institute of genetics and Reproduction College of Animal SciencesZhejiang UniversityHangzhou310058China Key Laboratory of cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of CardiologySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou310016China

Atrial fibrillation(AF)is the most prevalent sustained cardiac arrhythmia among humans,with its incidence increasing significantly with *** the high frequency of AF in clinical practice,its etiology and management remain *** develop effective treatment strategies,it is imperative to comprehend the underlying mechanisms of AF;therefore,the establishment of animal models of AF is vital to explore its *** spontaneous AF is rare in most animal species,several large animal models,particularly those of pigs,dogs,and horses,have proven as invaluable in recent years in advancing our knowledge of AF pathogenesis and developing novel therapeutic *** review aims to provide a comprehensive discussion of various animal models of AF,with an emphasis on the unique features of each model and its utility in AF research and *** data summarized in this review provide valuable insights into the mechanisms of AF and can be used to evaluate the efficacy and safety of novel therapeutic interventions.

关键词： Atrial fibrillation Animal model Therapeutic

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

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 Wenzhou 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

Effect of plateletcrit and methylenetetrahydrofolate reductase(MTHFR)C677T genotypes on folic acid efficacy in stroke prevention

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2694-2701页

作者： Yuncong Shi Zhengzhipeng Zhang Binyan Wang Yu Wang Xiangyi Kong Yong Sun Aimin Li Yimin Cui Yan Zhang Jianping Li Yong Huo Hui Huang cardiovascular Department The Eighth Affiliated HospitalJoint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic DiseasesSun Yat-sen UniversityShenzhenChina Shenzhen Evergreen medical institute ShenzhenChina Shenzhen Tailored medical Laboratory ShenzhenChina Department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijingChina Department of Neurosurgery The First Affiliated Hospital of Kangda College of Nanjing Medical UniversityLianyungangChina institute of Clinical Pharmacology Peking University First HospitalBeijingChina Department of Cardiology Peking University First HospitalBeijingChina

Previous studies have shown that low platelet count combined with high plasma total homocysteine(tHcy)increased stroke risk and can be lowered by 73% with folic ***,the combined role of other platelet activation parameters and the methylenetetrahydrofolate reductase(MTHFR)C677T genotypes on stroke risk and folic acid treatment benefit remain to be *** study aimed to investigate if platelet activation parameters and MTHFR genotypes jointly impact folic acid treatment efficacy in first stroke *** were derived from the China Stroke Primary Prevention *** study includes a total of 11,185 adult hypertensive patients with relevant platelet activation parameters and MTHFR genotype *** simultaneously considering both platelet activation parameters(plateletcrit,platelet count,mean platelet volume,platelet distribution width)and MTHFR genotypes,patients with both low plateletcrit(Q1)and the TT genotype had the highest stroke incidence rate(5.6%)in the enalapril *** subgroup significantly benefited from folic acid treatment,with a 66% reduction in first stroke(HR:0.34;95%CI:0.14-0.82;p=0.016).Consistently,the subgroup with low plateletcrit(Q1)and the CC/CT genotype also benefited from folic acid treatment(HR:0.40;95%CI:0.23-0.70;p=0.001).In Chinese hypertensive adults,low plateletcrit can identify those who may greatly benefit from folic acid treatment,in particular,those with the TT genotype,a subpopulation known to have the highest stroke risk.

关键词： prevention treatment MTHFR

Early-onset and later-onset cancer:trends,risk factors,and prevention in Northern China

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Science China(Life Sciences) 2024年第9期67卷 1928-1940页

作者： Tong Liu Chen-An Liu Qing-Song Zhang Qi Zhang Yi-Ming Wang Meng-Meng Song Shi-Qi Lin Li Deng Shou-Ling Wu Han-Ping Shi Department of Gastrointestinal Surgery Department of Clinical NutritionBeijing Shijitan HospitalCapital Medical UniversityBeijing 100038China National Clinical Research Center for Geriatric Diseases Xuanwu HospitalCapital Medical UniversityBeijing 100053China Key Laboratory of Cancer FSMP for State Market Regulation Beijing 100038China Laboratory for Clinical Medicine Capital Medical UniversityBeijing 100038China Department of General Surgery Kailuan General HospitalTangshan 063000China Department of genetics Yale School of MedicineNew Haven 06510USA Department of Hepatobiliary Surgery Kailuan General HospitalTangshan 063000China cardiovascular Research institute University of CaliforniaSan Francisco 94158USA Department of Cardiology Kailuan General HospitalTangshan 063000China

The characteristics of early-onset(onset age<50 years)and later-onset(onset age≥50 years)cancers differ *** novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its *** study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset *** conducted a prospective study by drawing data from the Kailuan *** study included 6,741 participants with cancer(624 with early-onset cancer and 6,117 with later-onset cancer)and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to *** primary outcomes were cancer incidence rates,and associated risk factors for early-and later-onset *** Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early-and later-onset cancer by cancer *** risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the *** for liver cancer,incidence rates for nearly all types of cancer increased during the study ***,alcohol consumption,lipid metabolism disorders,hypertension,diabetes mellitus,fatty liver,and inflammation were associated with a significantly increased risk of cancer at multiple sites,but risk factors for cancer incidence differed by ***,alcohol consumption,inflammation,and hypertension were the major contributors to preventable *** incidence of several different types of cancer,including earlyonset cancer,is increasing in northeastern *** in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

关键词： cancer early-onset later-onset trend risk factor prevention

MAPK4 facilitates angiogenesis by inhibiting the ERK pathway in non-small cell lung cancer

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Cancer Innovation 2024年第3期3卷 33-48页

作者： Jing Chen Jing Yang Yufang Liu Xu Zhao Juanjuan Zhao Lin Tang Mengmeng Guo Ya Zhou Chao Chen Dongmei Li Zhenke Wen Guiyou Liang Lin Xu Special Key Laboratory of Gene Detection&Therapy of Guizhou Province ZunyiGuizhouChina Department of Immunology Zunyi Medical UniversityZunyiGuizhouChina Department of medical Physics Zunyi Medical UniversityZunyiGuizhouChina institute of Biomedical Soochow UniversitySuzhouJiangsuChina Department of cardiovascular Surgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhouChina

Background:Angiogenesis plays an important role in the occurrence and development of non-small cell lung cancer(NSCLC).The atypical mitogen-activated protein kinase 4(MAPK4)has been shown to be involved in the pathogenesis of various ***,the potential role of MAPK4 in the tumor angiogenesis of NSCLC remains ***:adult male C57BL/6 wild-type mice were randomly divided into the control group and p-siMAPK4 intervention group,*** cell proliferation was analyzed with flow cytometry and immunofluorescence *** vascular density in tumor mass was analyzed by immuno-fluorescence *** expressions of MAPK4 and related signaling molecules were detected by western blot analysis and immunofluorescence staining,and so ***:We found that the expression of MAPK4,which was dominantly expressed in local endothelial cells(ECs),was correlated with tumor angiogenesis of ***,MAPK4 silencing inhibited the proliferation and migration abilities of human umbilical vein ECs(HUVECs).QKHZC-2020-4Y156,QKH-JC-2018-1428,QKH-RC-2019-5612;Collaborative Innovation Center of Chinese Ministry of Education,Grant/Award Number:2020-39;program for Science and Technology Joint Fund Project in Zunyi Science and Technology Bureau and Zunyi medical University,Grant/Award Numbers:ZSKH-RPT-2020-6,ZSKH-HZ-2021-193;Graduate Research Fund of Zunyi medical University,Grant/Award Number:2023-ZYK-171 Global gene analysis showed that MAPK4 silencing altered the expression of multiple genes related to cell cycle and angiogenesis pathways,and that MAPK4 silencing increased transduction of the extracellular regulated protein kinases 1/2(ERK1/2)pathway but not Akt and c-Jun n-terminal kinase *** analysis showed that MAPK4 silencing inhibited the proliferation and migration abilities of HUVECs cultured in tumor cell supernatant,which was accompanied with increased transduction of the ERK1/2 *** data analysis suggested that the

关键词： angiogenesis endothelial cell MAPK4 NSCLC p-ERK1/2

Clinical application and management of temporary mechanical circulatory support:A clinical consensus

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Chinese medical Journal 2024年第10期137卷 1135-1139页

作者： Nianguo Dong Liangwan Chen Xin Chen Huishan Wang Yingbin Xiao Xianqiang Wang Jinsong Huang Yang Yan Pramod Bonde Neel Sodha Pavan Atluri Juan Pablo Maureira AndréVincentelli Masanobu Yanase Yixuan Wang Haitao Zhang Xiaotong Hou Yoshijuki Takami Pascal Leprince Thierry Folliguet Frank W Sellke Chinese Society for Thoracic and cardiovascular Surgery Chinese Association of cardiovascular Surgeons Cardiac Critical Care Professional Committee of Chinese medical Association Chinese Society of Extracorporeal Life Support European Society of cardiovascular and Endovascular Surgery French Society of Thoracic and cardiovascular Surgery Japanese Society for cardiovascular Surgery Japanese Society of Artificial Organs Department of cardiovascular Surgery Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of cardiovascular Surgery Fujian Medical University Union HospitalFuzhouFujian 350000China Department of Thoracic and cardiovascular Surgery Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210000China Department of cardiovascular Surgery General Hospital of Northern Theater CommandShenyangLiaoning 110000China Department of cardiovascular Surgery Xinqiao HospitalThird Military Medical UniversityChongqing 400037 China Department of cardiovascular Surgery Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100000 China Department of cardiovascular Surgery Guangdong Provincial Cardiovascular InstituteGuangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong 510000 China Department of cardiovascular Surgery First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710061China Department of Cardiac Surgery Yale School of Medicine330 Cedar St204 BoardmanNew HavenCT 06510USA Department of Cardiothoracic Surgery Alpert Medical SchoolBrown University Rhode Island HospitalProvidenceRI 02912USA Department of cardiovascular Surgery Department of SurgeryUniversity of PennsylvaniaPhiladelphiaPA 19113USA Department of cardiovascular Surgery and Transplantation University Hospital of NancyUniversity of LorraineVandoeuvre-lès-Nancy 54500France Department of cardiovascular Surgery University Hospital of LilleUniversity of LilleLille 59037France Department of Cardiology Fujita Health University School of MedicineToyoakeAichi 470-1192Japan Department of adult Surgical Intensive Care Unit Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100000China Department of Cardiac Intensive Care Beijing Institute of HeartLung and B

Temporary mechanical circulatory support(tMCS)plays a pivotal role in managing severe or refractory cardiogenic shock(CS),furnishing essential hemodynamic support,and sustaining organ perfusion from hours to weeks,or to even *** the past decade,the utilization of tMCS has witnessed a signicant increase in American and European *** in Asia,the newly developed concepts and devices constituting tMCS have also made rapid ***,the absence of a consensus or standardized guidelines,especially for the Asian population considering inherited polymorphism,is *** address this knowledge gap,eight associations/societies and experts in thiseld came up with the present consensus after repeated discussions,more specically for the Asian *** comprehensively elucidates the commonly employed tMCS devices,criteria for patient selection,indications and contraindications,clinical management,and the optimal timing for implantation and *** goal of this statement is to promote the standardized application of tMCS and make reasonable decisions in clinical ***-length version of the consensus can be seen in Supplementary File,http://***/CM9/B883.

关键词： application statement discussions

Deletion of Axin1 in aggrecan-expressing cells leads to growth plate cartilage defects in adult mice

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Genes & Diseases 2024年第4期11卷 149-151页

作者： Dan Yi Hongting Jin William W.Lu Chunxiang Zhang Guozhi Xiao Liping Tonag Di Chen Research Center for Computer-aided Drug Discovery Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China PFaculty of Pharmaceutical Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China The First College of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhouZhejiang 310053China Department of Cardiology Basic Medicine Innovation Centerfor Cardiometabolic Diseases of Ministry of EducationInstitute of Cardiovascular ResearchThe Affiliated HospitalSouthwest Medical UniversityLuzhouSichuan 646000China School of Medicine Southern University of Science and TechnologyShenzhenGuangdong 518055China

In mammals,skeletal bone development begins at hyaline cartilage formation at the early embryonic stage.1Then osteoblasts from the periosteum,which are distributed surrounding the hyaline cartilage,build up compact bone to formdiaphysis and spongy bone known as primary ossification center.1 Next,osteoclasts from the hematopoietic system destroy spongy bone to generate a medullary cavity.

关键词： cartilage skeletal medullary

Development and identification of two novel wheat-rye 6R derivative lines with adult-plant resistance to powdery mildew and high-yielding potential

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The Crop Journal 2024年第1期12卷 308-313页

作者： Guohao Han Jing Wang Hanwen Yan Tiantian Gu Lijun Cao Shiyu Liu Xiuquan Li Yilin Zhou Jieru Fan Zhipeng Shi Hong Liu Lihui Li Diaoguo An Center for Agricultural Resources Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuang 050021HebeiChina The National Key Facility for Crop Gene Resources and Genetic Improvement Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China The State Key Laboratory for Biology of Plant Disease and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China

Powdery mildew,caused by Blumeria graminis ***(Bgt),is a devastating disease that seriously threatens wheat yield and *** control this disease,host resistance is the most effective *** with the resistance genes from common wheat,alien resistance genes can better withstand infection of this highly variable *** of elite alien germplasm resources with powdery mildew resistance and other key breeding traits is an attractive strategy in wheat *** this study,three wheat-rye germplasm lines YT4-1,YT4-2,and YT4-3 were developed through hybridization between octoploid triticale and common wheat,out of which the lines YT4-1 and YT4-2 conferred adult-plant resistance(APR)to powdery mildew while the line YT4-3 was susceptible to powdery mildew during all of its growth *** genomic in situ hybridization,multi-color fluorescence in situ hybridization,multi-color GISH,and molecular marker analysis,YT4-1,YT4-2,and YT4-3 were shown to be cytogenetically stable wheat-rye 6R addition and T1RS.1BL translocation line,6RL ditelosomic addition and T1RS.1BL translocation line,and T1RS.1BL translocation line,*** with previously reported wheat-rye derivative lines carrying chromosome 6R,YT4-1 and YT4-2 showed stable APR without undesirable pleiotropic effects on agronomic ***,these novel wheat-rye 6R derivative lines are expected to be promising bridge resources in wheat disease breeding.

关键词： Powdery mildew Secale cereale Triticum aestivum Wheat-rye 6R derivatives Agronomic performance