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Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

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Science China Life Sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng Huang Zhijun Wu Baitao Liu Hongjie Huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang Yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe laboratory of Cell Ecosystem Institute of cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of cardiovascular Sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key laboratory of Sports Injuries Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University Health Science Centre Peking University Department of immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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Rational design of lipid-activatable NIR-II probes for precisely imaging atherosclerotic plaque

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Science China Chemistry 2025年

作者： Xinyu Xu Yuan Ma Hui Cao Li Xu Haoming Chen Sulai Liu Wei Sun Guosheng Song Xiaobing Zhang State Key laboratory for Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical EngineeringHunan University Department of Hepatobiliary Surgery/Central laboratory Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Department of Cardiology the First Affiliated Hospital of Nanjing Medical University Key laboratory of Targeted Intervention of cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical University Shenzhen Research Institute of Hunan University

Atherosclerosis(AS) is a prevalent condition associated with cardiovascular and cerebrovascular diseases, featuring lipid-laden plaque; however, the insufficient resolution and low sensitivity of traditional medical imaging techniques limit their application in lipid imaging. Currently, the second near-infrared(NIR-II) fluorescence imaging offers promising sensitivity and convenience. However, existing probes have limitations in terms of signal-to-background ratio, penetration depth, and tissue scattering. Herein, we use a molecular regulatory strategy to design a lipid-activatable probe Rh-965 with high specificity and NIR-II emission for improved imaging potential in deep tissues. The potential of Rh-965 for imaging plaque lipids in mice with AS is demonstrated by localizing carotid artery plaques using NIR-II imaging. The development of more stable lipid-activated NIR-II probes can significantly enhance atherosclerosis diagnosis and facilitate in vivo imaging in deeper tissues.

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Dietary carbohydrate intake and risk of type 2 diabetes:a 16-year prospective cohort study

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Science China Life Sciences 2025年

作者： Lu Gan Yi Yang Bin Zhao Kai Yu Kehua Guo Fang Fang Zhiguang Zhou Demetrius Albanes Jiaqi Huang Key laboratory of Diabetes immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University CSU-Sinocare Research Center for Nutrition and Metabolic Health Xiangya School of Public Health Central South UniversityFurong Laboratory Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Department of Health and Human Services School of Computer Science and Engineering Central South University Institute of Environmental Medicine Karolinska Institute National Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University

Despite considerable research underscoring the importance of carbohydrate intake in relation to the risk of type 2 diabetes(T2D), a comprehensive assessment of this relationship is currently lacking. We aimed to examine the associations of various types and food sources of dietary carbohydrate intake with the risk of T2D, to evaluate potential effect modification by other factors, including genetic susceptibility,and to explore the potential mediators for such associations. The present study included 161,872 participants of the UK Biobank who were free of prevalent cancer, cardiovascular disease, or diabetes, and had at least one validated 24-h dietary recall assessment. Multivariableadjusted age-stratified Cox proportional hazard regression models were applied to estimate hazard ratios(HRs) and 95% confidence intervals(CI) for the associations of various types and food sources of dietary carbohydrate intake with risk of T2D. During a median follow-up of13.6 years, 4,176 incident cases of T2D were identified. In the multivariable-adjusted models, a greater intake of fiber, carbohydrates from whole grains, and carbohydrates from non-starchy vegetables was significantly associated with a lower risk of T2D(highest vs. lowest quantile, HR [95% CI]=0.70 [0.62–0.79], 0.74 [0.67–0.82], and 0.83 [0.75–0.92], respectively, all P for trend <0.005). In contrast, a higher intake of starch and carbohydrate from starchy vegetables was associated with an increased risk of T2D(highest vs. lowest quantile, HR [95%CI]=1.31 [1.16–1.48] and 1.19 [1.09–1.31], respectively, both P for trend <0.005). Replacing one serving of refined grains or starchy vegetables with an equal amount of whole grains or non-starchy vegetables was associated with 4% to 10% lower risk of T2D(all P values <0.001).The observed associations were generally similar across population subgroups, including individuals with different genetic susceptibility to T2D. Mediation analyses of the inverse association between T

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Association between clustering of cardiovascular risk factors and resting heart rate in Chinese population:a cross-sectional study

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Journal of Geriatric Cardiology 2022年第6期19卷 418-427页

作者： Fu-Yu JING Xiu-Ling WANG Jia-Li SONG Yan GAO Jian-Lan CUI Wei XU Yang YANG Li-Juan SONG Hai-Bo ZHANG Jia-Peng LU Xi LI Xin ZHENG National Clinical Research Center for cardiovascular Diseases NHC Key Laboratory of Clinical Research for Cardiovascular MedicationsState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Center for Cardiovascular DiseasesBeijingChina National Clinical Research Center for cardiovascular Diseases ShenzhenCoronary Artery Disease CenterFuwai Hospital Chinese Academy of Medical SciencesShenzhenChina

BACKGROUND Epidemiologic studies have explored the association between a single cardiovascular risk factor(CVRF)and resting heart rate(RHR),but the research on the relation of multiple risk factors with RHR remains *** study aimed to explore the associations between CVRFs clustering and the risk of elevated *** In this cross-sectional study,adults aged 35-75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August *** focused on seven risk factors:hypertension,diabetes mellitus,dyslipidemia,obesity,smoking,alcohol use,and low physical *** logistic regression was used to calculate odds ratios(OR)for elevated RHR(>80 beats/min).RESULTS Among 1,045,405 participants,the mean age was 55.67±9.86 years,and 60.4%of participants were *** OR(95%CI)for elevated RHR for the groups with 1,2,3,4 and≥5 risk factor were 1.11(1.08-1.13),1.36(1.33-1.39),1.68(1.64-1.72),2.01(1.96-2.07)and 2.58(2.50-2.67),respectively(Ptrend<0.001).The association between the CVRFs clustering number and elevated RHR was much more pronounced in young males than in other age-sex *** comprising more metabolic risk factors were associated with a higher risk of elevated RHR than those comprising more behavioral risk *** There was a significant positive association between the CVRFs clustering number and the risk of elevated RHR,particularly in young *** clusters comprising more behavioral risk factors,clusters comprising more metabolic risk factors were associated with a higher risk of elevated *** may serve as an indicator of the cumulative effect of multiple risk factors.

关键词： elevated cardiovascular sectional

Association of acute glycemic parameters at admission with cardiovascular mortality in the oldest old with acute myocardial infarction

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Journal of Geriatric Cardiology 2024年第3期21卷 349-358页

作者： Hui-Hui LIU Meng ZHANG Yuan-Lin GUO Cheng-Gang ZHU Na-Qiong WU Ying GAO Rui-Xia XU Jie QIAN Ke-Fei DOU Jian-Jun LI Cardiometabolic Center State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVES Stress-related glycemic indicators,including admission blood glucose(ABG),stress-hyperglycemia ratio(SHR),and glycemic gap(GG),have been associated with worse outcomes after acute myocardial infarction(AMI).However,data regarding their prognostic value in the oldest old with AMI are ***,this study aimed to investigate the association of stress-related glycemic indicators with short-and long-term cardiovascular mortality(CVM)in the oldest old(≥80 years)with *** In this prospective study,a total of 933 consecutive old patients with AMI admitted to FuWai hospital(Beijing,China)were *** admission,ABG,SHR,and GG were assessed and all participants were classified according to their ***-Meier,restricted cubic splines(RCS),and multivariate Cox regression analyses were performed to evaluate the association between these glycemic indicators and CVM within 30 days and long-term *** During an average of 1954 patient-years of follow-up,a total of 250 cardiovascular deaths were ***-Meier analyses showed the lowest CVM in quartile 1 of ABG and in quartile 2 of SHR and *** adjusting for potential covariates,patients in quartile 4 of ABG,SHR,and GG had a respective 1.67-fold(95%CI:1.03-2.69;P=0.036),1.80-fold(95%CI:1.16-2.79;P=0.009),and 1.78-fold(95%CI:1.14-2.79;P=0.011)higher risk of long-term CVM risk compared to those in the reference groups(quartile 1 of ABG and quartile 2 of SHR and GG).Furthermore,RCS suggested a J-shaped relationship of ABG and a Ushaped association of SHR and GG with long-term ***,we observed similar associations of these acute glycemic parameters with 30-day *** Our data first indicated that SHR and GG consistently had a U-shaped association with both 30-day and longterm CVM among the oldest old with AMI,suggesting that they may be useful for risk stratification in this special population.

关键词： admitted infarction shaped

A systematic,updated review of Xuezhikang,a domestically developed lipid-lowering drug,in the application of cardiovascular diseases

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Acta Pharmaceutica Sinica B 2024年第10期14卷 4228-4242页

作者： Cheng Yang Yongjian Wu Jie Qian Jian-Jun Li Cardiometabolic Center Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

cardiovascular diseases(CVDs)are a major threat to public health globally.A large proportion of people with dyslipidaemia have poorly controlled lipid levels,emphasizing the need for alternative lipid-lowering treatments that are both effective and ***,a red yeast rice(RYR)extract,containing 13 kinds of monacolins and other bioactive components,emerges as one such promising *** discovery was built on a long history of RYR use as a functional food supplement and traditional Chinese *** randomized,controlled clinical trials have substantiated its lipid-lowering effects and its potential to protect against *** concerns with statins did not arise during decades of experience with Xuezhikang treatment in clinical *** approval of Xuezhikang in multiple regions of Asia marked a conceptual shift in CVD management,moving from single agents to polypills and from synthetic medicines to natural *** review comprehensively addresses important topics related to this medicinal natural extract,including the ancient utilization of RYR,the development of Xuezhikang,its mechanisms of action,pleiotropic effects,clinical studies,challenges,and future perspectives to enhance our understanding regarding the role of Xuezhikang,a representative,domestic lipid-lowering drug of RYR,in prevention and treatment of CVD.

关键词： Red yeast rice Xuezhikang Natural extract Traditional Chinese medicine cardiovascular disease Dyslipidaemia Lipid-lowering cardiovascular prevention

Potential functions of esophageal cancer-related gene-4 in the cardiovascular system

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Frontiers of Medicine 2019年第6期13卷 639-645页

作者： Rui Zhou Yuanshu Liu Wenjun Huang Xitong Dan The Key laboratory of Medical Electrophysiology Ministry of Education&Medical Electrophysiological Key Laboratory of Sichuan ProvinceCollaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan ProvinceInstitute of Cardiovascular ResearchSouthwest Medical UniversityLuzhou 646000China

Esophageal cancer-related gene-4(Ecrg4)is cloned from the normal epithelium of the *** is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis,and Ecrg4 expression levels are inversely correlated with the malignant phenotype of tumor cells,validating that Ecrg4 is a real tumor suppressor *** other tumor suppressor genes that usually encode membrane or intracellular proteins,Ecrg4 encodes a 148-amino acid pre-pro-peptide that is tethered on the cell surface in epithelial cells,specialized epithelial cells,and human leukocytes,where it can be processed tissue dependently into several small peptides upon cell ***4 is expressed in a wide variety of other cells/tissues,including cardiomyocytes and conduction system of the heart,,the glomus cells of the carotid body,adrenal glands,choroid plexus,and leukocytes among others,where it exerts distinct functions,such as promoting/suppressing inflammation,inducing neuron senescence,stimulating the hypothalamus--pituitary--adrenal axis,maintaining the stemness of stem cells,participating in the rhythm and rate control of the heart,and possibly gauging the responsiveness of the cardiovascular system(CVS)to hypoxia,in addition to tumor ***,we briefly review the latest discoveries on Ecrg4 and its underlying molecular mechanisms as a tumor suppressor and focus on the emerging roles of Ecrg4 in the CVS.

关键词： tumor suppressor gene esophageal cancer-related gene-4 cardiovascular disease hypoxia

Effects of loneliness and isolation on cardiovascular diseases:a two sample Mendelian Randomization Study

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Journal of Geriatric Cardiology 2024年第3期21卷 340-348页

作者： Jia-Yin CAI Xin WANG Cong-Yi ZHENG Xue CAO Zhen HU Run-Qing GU Yi-Xin TIAN Ye TIAN Lan SHAO Lin-Feng ZHANG Zeng-Wu WANG Division of Prevention and Community Health National Center for Cardiovascular DiseaseNational Clinical Research Center of Cardiovascular DiseaseState Key Laboratory of Cardiovascular DiseaseFuwai HospitalPeking Union Medical College&Chinese Academy of Medical SciencesBeijingChina

BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally *** conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple *** Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS *** data for 15 CVDs were also obtained from the IEU GWAS *** used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on ***'s Q test and MR-Egger intercept test were used to evaluate the heterogeneity and *** MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this *** Causal relationship of loneliness and isolation with CVDs were found in this study.

关键词： diseases cardiovascular angina

Telomeres,cardiovascular aging,and potential intervention for cellular senescence

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Science China(Life Sciences) 2014年第8期57卷 858-862页

作者： ZHANG WeiLi HUI RuTai YANG ShuJun State Key laboratory of cardiovascular Diseases Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical College

A consistent association has been observed between leukocyte telomere length(LTL)and atherosclerosis,but the mechanisms underlying these associations are still not well *** biology aging was evident in atherosclerotic plaques,characterized by reduced cell proliferation,irreversible growth arrest and apoptosis,and telomere *** atherosclerosis is a state of chronic low-grade inflammation and increased oxidative stress,shortened LTL in patients with atherosclerosis might stem from the two sources,one is an accelerated rate in hematopoietic stem cells(HSCs)replication to replace leukocytes consumed in the inflammatory process,and another is the increase in the loss of telomere repeats per ***,diminished HSC reserves at birth and age-dependent telomere attrition afterward are mirrored in shortened LTL during the *** addition,the inter-individual variation of LTL in the general population can be partly explained by genetic factors regulating telomere maintenance and the rate of HSCs *** is an aging-related disease,and practically all humans develop atherosclerosis if they live long *** we overview the potential roles of LTL dynamics in the imbalance between injurious oxidative stress/inflammation and endothelial repair during the pathogenesis of age-related atherosclerosis,and discuss the possibility that preventing accelerated cellular senescence is a potential target in prevention of atherosclerosis.

关键词： telomere aging atherosclerosis vascular cell senescence