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HMGB1 induces secretion of matrix vesicles which participate in microcalcification of atherosclerotic plaques

中国病理生理杂志 2016年第8期32卷 1492-1536页

作者： CHEN Qiang BEI Jun-jie LIU Chuan FENG Shi-bin ZHAO Wei-bo ZHOU Zhou YU Zheng-ping DU Xiao-jun HU Hou-yuan department of cardiology Southwest HospitalThird Military Medical University department of Occupational Health Faculty of Preventive MedicineThird Military Medical University experimental cardiology Baker IDI Heart and Diabetes Instituteand Central Clinical SchoolMonash University

AIM: Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1( HMGB1),a cytokine associated with biomineralizing process under physiological and pathological conditions. Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles( MVs) from macrophages. METHODS: HMGB1 was added to the medium of macrophages,the secretion of MVs in the supernatant was tested by flow cytometry analysis. The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining. Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs. Then we subcutaneous injection into mice with MVs to induce regional mineralization. RESULTS: HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis. TNAP activity,considered as a marker of MVs maturation,was higher in HMGB1-induced MVs compared to the control-MVs. HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model. Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization. Mechanistic experiments revealed that HMGB1 activated neutral sphingomyelinase 2( n SMase2) that involved the receptor for advanced glycation end products( RAGE) and p38MAPK( upstream of n SMase2). Inhibition of n SMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and mineral deposition. CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part,via the RAGE / p38 MAPK /n SMase2 signaling pathway. Our findings thus reveal a novel mechanism by which HMGB1 may participated in the early calcification of atherosclerotic plaques.

关键词： HMGB1 动脉粥样硬化细胞分泌 p38丝裂原活化蛋白激酶诱导钙化斑块小泡

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The relation between serum phosphorus levels and long-term mortality in Chinese patients with ST-segment elevation myocardial infarction

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Journal of Geriatric cardiology 2019年第10期16卷 775-781页

作者： Guo-Hua ZHU Xi-Peng SUN Zhi LIU Zhen-Xing FAN Yan-Ling WANG Jing TAN Jing LI Qi HUA department of cardiology Xuanwu Hospital Capital Medical University

Background Elevated serum phosphorus levels may be associated with adverse outcomes in cardiovascular disease. This study aimed to investigate the relation between serum phosphorus levels and risk of all-cause mortality in Chinese patients with ST-segment elevation myocardial infarction (STEMI) who had preserved renal function at baseline. Methods We enrolled patients with STEMI who had preserved renal function at baseline in Xuanwu Hospital from January 2011 to December 2016. Those patients were divided into four groups based on serum phosphorus levels. All-cause mortality rates were compared between groups. Mean duration of follow up was 54.6 months. We used Cox proportional-hazards models to examine the relation between serum phosphorus levels and all-cause mortality after adjustment for potential confounders. Results 1989 patients were involved and 211 patients (10.6%) died during follow-up. Based on serum phosphorus levels, patients were categorized into the following groups: 4.50 mg/dL (n = 162), respectively. The lowest mortality occurred in patients with serum phosphorus levels between 2.51–3.50 mg/dL, with a multivariable-adjusted hazard ratio of 1.19 (95% CI: 0.64–1.54), 1.37 (95% CI: 1.22–1.74), and 1.46 (95% CI: 1.35–1.83) in patients with serum phosphorus levels of 4.50 mg/dL, respectively. Conclusions Elevated serum phosphorus levels were associated with all-cause mortality in Chinese patients with STEMI who had preserved renal function at baseline.

关键词： Mortality Serum phosphorus levels ST-segment elevation myocardial infarction

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Incidence of pocket hematoma after electrophysiological device placement：dual antiplatelet therapy versus low-molecular-weight heparin regimen

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Journal of Geriatric cardiology 2014年第3期11卷 200-205页

作者： Yan CHEN Yun-Tao LI Ming-Dong GAO Ze-Chun ZENG Jin-Rong ZHANG Hong-Liang CONG Yin LIU Ru ZHAO Le-Feng WANG Xin-Cun YANG Kang MENG department of cardiology Tianjin Chest Hospital Tianjin 300200 China department of cardiology Beijing Anzhen Hospital Capital Medical University Beijing 100029 China department of cardiology Beijing Chaoyang Hospital Capital Medical University Beijing 100020 China

Background Given the increasing number of patients who require dual antiplatelet （DAP） therapy and electrophysiological device （EPD） placement, perioperative antiplatelet management is a current challenge. In this study, we investigated the incidence of pocket hema-toma formation after EPD placement in patients undergoing DAP therapy or an alternative low-molecular-weight heparin （LMWH） regimen. Methods This clinical observational study was performed from July 2010 to July 2012. In total, 171 patients were enrolled in the analysis after meeting the inclusion criteria. These patients were divided into two groups： 86 patients were treated with DAP therapy at the time of device implantation, and the DAP therapy was discontinued for 5 to 7 days and replaced with enoxaparin before device implantation in the other 85 patients. Adenosine phosphate （ADP）-mediated platelet aggregation and arachidonic acid-induced platelet aggregation were tested preoperatively. We compared the incidence of pocket hematoma between the two groups and the association of pocket hematoma develop-ment with ADP-mediated platelet aggregation and arachidonic acid-induced platelet *** The incidence of pocket hema-toma in the patients who continued DAP was lower than that in the patients who replaced the dual antiplatelet regimen with LMWH （3.49%vs. 16.47%, respectively;X2 = 6.66,P 〈 0.01）. Among the patients who continued DAP therapies, the rate of ADP-mediated platelet aggre-gation inhibition in patients with pocket hematomas was higher than that in patients without pocket hematomas. None of the patients under-going DAP or enoxaparin therapy developed pocket infection, thromboembolic events, or other serious complications. Multiple logistic re-gression analysis revealed that LMWH therapy was an independent risk factor for the development of pocket hematoma （RR = 0.054, 95%CI = 0.012-0.251）. Furthermore, patients undergoing LMWH therapy were 5.1-fold more likely to develop pocket hemat

关键词： Antiplatelet drug Hematoma Low-molecular-weight heparin Electrophysiological device

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Managing the treatment of the patients with stable angina like a chess player： making moves considering the next move of atherosclerosis

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Journal of Geriatric cardiology 2016年第11期13卷 938-939页

作者： Omer Yiginer Mehmet Tezcan Alptug Tokatli Gokhan Degirmencioglu department of cardiology GMMA Haydarpasa Training Hospital Istanbul Turkey department of cardiology Crumussuyu Military Hospital Istanbul Turkey department of cardiology Golcuk Military Hospital Kocaeli Turkey

We read the article entitled Coronary revascularization in the elderly with stable angina with interest. In the guidelines related to stable coronary artery disease, it does not exist any age-related net proposals for... 详细信息

关键词： Atherosclerosis Coronary artery bypass grafting Coronary artery disease Stable angina

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The predictive value of triglyceride-glucose index for in-hospital and one-year mortality in elderly non-diabetic patients with ST-segment elevation myocardial infarction

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Journal of Geriatric cardiology 2022年第8期19卷 610-617页

作者： FaysalŞaylık TufanÇınar Murat Selçuk İbrahim Halil Tanboğa department of cardiology Van Training and Research HospitalVanTurkey department of cardiology Sultan II.Abdülhamid Han Training and Research HospitalIstanbulTurkey department of cardiology and Biostatistics Nisantasi University Medical SchoolIstanbulTurkey

BACKGROUND Triglyceride-glucose(TyG)index,a reliable marker of insulin resistance,was associated with cardiovascular morbidity and *** study aimed to evaluate the predictive value of TyG index for mortality in elderly non-diabetic pa-tients with ST-segment elevation myocardial infarction(STEMI).METHODS In total,430 non-diabetic patients aged over 65 years with STEMI were consecutively *** TyG index was calculated by using the following formula:TyG index=ln(fasting triglyceride×fasting glucose/2).The 5-item modified frailty index score was utilized to determine *** were divided into three groups based on TyG index *** Patients included into high TyG index tertile were male and had higher body mass index,glucose,triglyceride,low-density lipoprotein cholesterol,5-item modified frailty index and GRACE risk score;and had low systolic blood pressure,estim-ated glomerular filtration rate and left ventricular ejection fraction.A one-unit increase in TyG index was associated with 3.03 ex-tra cases per 1000 person-day for in-hospital mortality and 0.29 extra cases per 1000 person-day for long-term *** was a non-linear relationship between TyG index and the risk of mortality with an increased risk above 8.5 for TyG ***-Meier survival curves revealed that patients in high TyG index tertile had higher in-hospital and long-term mortality rates than those in low TyG index *** This was the first study to demonstrate that the TyG index could predict in-hospital and long-term mortality in elderly non-diabetic STEMI patients.

关键词： patients mortality diabetic

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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael S.Wolfe Computational Medicine Program and department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

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The incidence of sporadic viral hepatitis in North India:a preliminary study

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Hepatobiliary & Pancreatic Diseases International 2007年第6期6卷 596-599页

作者： Subrat Kumar Radha Kanta Ratho Yogesh Kumar Chawla Anuradha Chakraborti department of Virology department of Hepatology department of experimental Medicine and Biotechnology

BACKGROUND: Viral hepatitis is one of the major causes of mortality and morbidity in developing countries. Hepatitis E virus (HEV) among the major etiological agents is responsible for both sporadic and epidemic outbreaks. The epidemic outbreak is water-borne whereas the sporadic outbreak is possibly through contact. Various diagnostic tools at times fail to pinpoint the cause of viral hepatitis. This study was carried out to evaluate the utility of ELISA and nRT-PCR (nested reverse transcriptase polymerase chain reaction) for the diagnosis of sporadic and acute viral hepatitis (AVH) caused by HEV in an endemic situation in North India. METHODS: Serum samples were collected from all the affected and suspected persons and subjected to serological detection of HAV IgM, HBsAg, HCV antibody and HEV IgM. The samples that were positive for HEV IgM were further processed for the detection of HEV RNA by nRT-PCR. RESULTS: A total of 843 samples were collected from 685 patients with AVH, 70 patients with fulminant hepatic failure (FHF), 53 patients with chronic liver disease (CLD), 11 patients with antituberculosis therapy (ATT)-induced jaundice, and 24 pregnant women. The percentage of positivity for anti-HEV IgM was 58.3% in the pregnant women, 41.4% in the paients with FHF, 38.6% in the patients with AVH, 9.4% in the patients with CLD and 18.2% in the patients with ATT induced jaundice. 9.4% of HBsAg carriers were positive for anti-HEV IgM. Males outnumbered females (62.8% vs. 37.1%). Furthermore, the rates of fulminant and acute outbreaks of hepatitis with HEV RNA positivity were 41.4% and 9.4%, respectively. CONCLUSION: Serological and molecular analysis should be combined for the diagnosis of viral infections, especially in endemic areas.

关键词： viral hepatitis fulminant liver failure pregnancy

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Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions:an intravascular ultrasound study

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Journal of Geriatric cardiology 2024年第5期21卷 506-522页

作者： Yi XU Tian XU Jia-Cong NONG Xiao-Han KONG Meng-Yao ZHAO Zhi-Jing GAO Yi-Fei WANG Wei YOU Pei-Na MENG Yu-He ZHOU Xiang-Qi WU Zhi-Ming WU Mei-En ZHAN Yan-Qing WANG De-Feng PAN Fei YE department of cardiology Nanjing First HospitalNanjing Hospital Affiliated to Nanjing Medical UniversityNanjing Medical UniversityNanjingChina department of cardiology Clinical Medicine School of Nanjing UniversityNanjingChina department of cardiology Tianchang People’s HospitalTianchangChina department of cardiology the Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina

OBJECTIVES To investigate whether negative remodeling(NR) detected by intravascular ultrasound(IVUS) of the side branch ostium(SBO) would affect in-stent neointimal hyperplasia(NIH) at the one-year follow-up and the clinical outcome of target lesion failure(TLF) at the long-term follow-up for patients with left main bifurcation(LMb) lesions treated with a two-stent *** A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention(PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre-and post-PCI and at the 1-year follow-up were enrolled in phase Ⅰ analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index(RI) for predicting NIH ≥ 50% was analyzed next. The phase Ⅱ analysis focused on the incidence of TLF as the primary endpoint at the 1-to 5-year follow-up for all 328 patients by grouping based on the cutoff value of *** In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic(ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893(0.778, 1.000), P = 0.002. In phase Ⅱ: the TLR rate(35.8% vs. 5.3%, P < 0.0001)was significantly higher in the several NR(s NR, defined as RI ≤ 0.85) group than in the non-s NR *** The NR of LCx O is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy,and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

关键词： lesions remodeling intravascular

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Turning to myelin turnover

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Neural Regeneration Research 2019年第12期14卷 2063-2066页

作者： Tobias J.Buscham Maria A.Eichel Sophie B.Siems Hauke B.Werner department of Neurogenetics Max Planck Institute of Experimental Medicine

Neural plasticity in the adult central nervous system involves the adaptation of myelination, including the formation of novel myelin sheaths by adult-born oligodendrocytes. Yet, mature oligodendrocytes slowly but constantly turn over their pre-existing myelin sheaths, thereby establishing an equilibrium of replenishment and degradation that may also be subject to adaptation with consequences for nerve conduction velocity. In this short review we highlight selected approaches to the normal turnover of adult myelin in vivo, from injecting radioactive precursors of myelin constituents in the 1960s to current strategies involving isotope labeling and tamoxifen-induced gene targeting.

关键词： oligodendrocyte myelin plasticity and turnover degradation tamoxifen metabolic labeling isotope labeling neural plasticity myelinoid bodies central nervous system

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Clinical characteristics, treatment and prognosis of patients with idiopathic dilated cardiomyopathy: a tertiary center experience

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Journal of Geriatric cardiology 2019年第4期16卷 320-328页

作者： Abdullah Hagar Xiao-Bo PU Shi-Jian CHEN Jageshwar-Prasad Shah Mao CHEN department of cardiology West China HospitalSichuan UniversitySichuanChina department of cardiology Affiliated Minda Hospital of Hubei Institute for NationalitiesHubeiChina

Background Contemporary heart failure medications have led to considerable improvement in the survival of patients with heart failure. However,limited evidence is available regarding the effect of those medications in patients with idiopathic dilated cardiomyopathy (IDCM),particularly in China. We sought to analyze the trends in clinical characteristics and the prescription rate of recommended therapies and its prognostic impact in patients with IDCM. Methods From 2009 to 2016,1441 consecutive patients (age: 55±14 years,68% men,LVEF: 33%± 12%) fulfilling World Health Organization criteria for IDCM were enrolled in the current retrospective cohort study. Temporal trends of baseline clinical characteristics,treatment and prognosis were analyzed,and potential influential factors were explored. Results Rates of patients receiving angiotensin-converting enzyme inhibitors/angiotensin II receptors blockers,β-blockers,aldosterone receptor antagonists and diuretics increased from 55%,45%,58%,51% in 2009 to 67%,69%,71%,64% in 2016,respectively (P cardiology ward with the years. Conclusions An improvement in prescription rates of guideline-recommended medications in IDCM patients was observed. However,it remains suboptimal,and there is still some room for improvement. The prognosis of patients with optimal GDMT was better than those without. Moreover,the following patient

关键词： Dilated cardiomyopathy Heart failure Medications Prognosis

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