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A mitochondria-targeted H_(2)S-activatable fluorogenic probe for tracking hepatic ischemia-reperfusion injury

Chinese Chemical Letters 2024年第6期35卷 370-375页

作者： Bin Fang Jiaqi Yang Limin Wang Haoqin Li Jiaying Guo Jiaxin Zhang Qingyuan Guo Bo Peng Kedi Liu miaomiao xi Hua Bai Li Fu Lin Li School of Materials Science and Engineering Northwestern Polytechnical UniversityXi’an 710072China Frontiers Science Center for Flexible Electronics Xi’an Institute of Flexible Electronics(IFE)and Xi’an Institute of Biomedical Materials&EngineeringNorthwestern Polytechnical UniversityXi’an 710072China Key laboratory of Flexible Electronics of Zhejiang Province Ningbo Institute of Northwestern Polytechnical UniversityNingbo 315103China The Institute of Flexible Electronics(IFE Future Technologies)Xiamen UniversityXiamen 361005China Wuhan National Laboratory for Optoelectronics-Advanced Biomedical Imaging Facility Huazhong University of Science and TechnologyWuhan 430074China TANK Medicinal Biology Institute of xi’an Xi’an 710032China

Hepatic ischemia-reperfusion injury(HIRI)is the cause of postoperative hepatic dysfunction and failure,and even death.As an important biological effector molecule,hydrogen sulfide(H_(2)S)of mitochondria as a gasotransmitter that is usually used to protect against acute HIRI injury.However,the exact relationship between HIRI and mitochondrial H_(2)S remains tangled due to the lack of an effective analytical method.Herein,we have fabricated a mitochondria-targeted H_(2)S-activatable fluorogenic probe(Mito-GW)to explore the stability of mitochondrial H_(2)S and track the changes of mitochondrial H_(2)S during the HIRI.By virtue of pyridinium electropositivity and its amphiphilicity,Mito-GW could accumulate in mitochondria.It goes through an analyte-prompted immolation when reacts with H_(2)S,resulting in the releasing of the fluorophore(GW).Therefore,the extent of Mito-GW conversion to GW can be used to evaluate the changes of mitochondrial H_(2)S level in living cells and tissues.As proof-of-principle,we have used MitoGW to demonstrate the mitochondria H_(2)S-levels increase and then decrease during HIRI in vitro and in vivo.Our research highlights the tremendous potential of Mito-GW as a mitochondrial H_(2)S fluorogenic probe in elucidating the pathogenesis of HIRI,providing a powerful tool for promoting future research on hepatology.

关键词： Mitochondria-targeted Bioimaging H2S-activatable Fluorogenic probe Hepatic ischemia-reperfusion injury(HIRI)

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Antioxidant properties of magnesium lithospermate B contribute to the cardioprotection against myocardial ischemia/reperfusion injury in vivo and in vitro

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Journal of Traditional Chinese Medicine 2013年第1期33卷 85-91页

作者： Wei Quan Ying Yin miaomiao xi Dan Zhou Yanrong Zhu Yue Guan Chao Guo Yanhua Wang Jialin Duan Aidong Wen Department of Pharmacy Xijing HospitalFourth Military Medical University

OBJECTIVE: To determine the cardioprotective effect of magnesium lithospermate B (MLB) on myocardial ischemia/reperfusion (MI/R) injury and to investigate the antioxidant potential in vivo and in vitro. METHODS: MI/R injury was induced by the occlusion of left anterior descending coronary artery for 30 min followed by reperfusion for 3 h in rats. After reperfusion, hearts were harvested to assess infarct size, histopathological damages, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and malondialdehyde (MDA). Blood samples were col- lected to determine serum levels of creatine kinase-MB (CK-MB), cardiac troponin (cTnI) and lactate dehydrogenase (LDH). Furthermore, simulatedischemia/reperfusion (SI/R) injury in vitro was established by oxygen and glucose deprivation (OGD) for 2 h followed by 24-hour recovery period in cardiomyocytes. The activity of LDH in the cultured supernatant and the levels of intracellular reactive oxygen species (ROS), SOD and MDA in cardiomyocytes were also measured. Finally, cardiomyocytes apoptosis was determined with flow cytometry. RESULTS: MLB significantly limited infarct size, ameliorated histopathological damages and prevented leakage of CK-MB, cTnI and LDH. Additionally, SOD, CAT, GPx and GSH activities were notably increased by MLB, along with the MDA content decreased as compared with the model group in rats. In vitro study, MLB also decreased LDH activity in the cultured supernatant, increased SOD activity in cardiomyocytes, reduced intracellular ROS and MDA levels, and significantly suppressed cardiomyocytes apoptosis. CONCLUSION: MLB possessed remarkably cardioprotective effects on MI/R injury in vivo and in vitro. The protection of MLB may contribute to its antioxidant properties.

关键词：缺血再灌注损伤心肌细胞凋亡抗氧化性能丹酚酸B 体外体内谷胱甘肽过氧化物酶镁盐

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高内涵筛选技术在中药作用机制及物质基础研究中的应用进展

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中药药理与临床 2024年第4期40卷 121-128页

作者：李星雨王婧陈思凯高峰欧莉李敏奚苗苗董泰玮卫培峰陕西中医药大学咸阳712046 陕西中医药大学第二附属医院咸阳712021 西安天工生物医药研究所西安710032

中药的现代化研究一直存在药效物质基础筛选复杂且筛选不全面,作用机制研究靶点多且认识不深入的问题,致使其研究结果存在不确定性及不充分性,无法得到国际认可。而高内涵筛选技术(High-content screening,HCS)又称高内涵分析技术(High-... 详细信息

中药的现代化研究一直存在药效物质基础筛选复杂且筛选不全面,作用机制研究靶点多且认识不深入的问题,致使其研究结果存在不确定性及不充分性,无法得到国际认可。而高内涵筛选技术(High-content screening,HCS)又称高内涵分析技术(High-content analysis,HCA),作为一项高通量、多靶点、多通道、全自动化的分析技术,能够量化分析大量细胞对药物的特异性反应图像,可在中药的现代化研究中以匹配中药及其复方多靶点作用的应用特性,对其进行作用机制及物质基础研究,以提高中药疗效、扩大用药范围、保障用药安全并使其结果具有相当的国际认可度。文章简要介绍了高内涵筛选的原理及其在中药作用机制及物质基础研究中的应用进展,从实例中,思考其优势与限制及对中药现代化研究做出的贡献。

关键词：高内涵分析技术高内涵筛选技术中药物质基础作用机制信号采集安全性评价

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Salvianolic acid B regulates macrophage polarization in ischemic/reperfused hearts by inhibiting mTORC1-induced glycolysis

Salvianolic acid B regulates macrophage polarization in isch...

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2019中国生理学会学术年会暨张锡钧基金第十五届全国青...

作者：赵美娜 miaomiao xi Aidong Wen Jingwen Wang Department of Pharmacy Xijing HospitalFourth Military Medical University

Macrophages play important roles in the healing and remodeling of cardiac tissues after myocardial ischemia/reperfusion（MI/R） injury.Here we investigated the potential effects of salvianolic acid B（SalB）, one of the abundant and bioactive compounds extracted from Chinese herb Salvia Miltiorrhiza（Danshen）, on macrophage-mediated inflammation after MI/R and the underlying mechanisms.In primary cultured bone marrow-derived macrophages（BMDMs）, SalB attenuated lipopolysaccharide（LPS）-induced M1 biomarkers（IL-6, iNOS, CCL2 and TNF-α） mRNA expression in a concentration-dependent manner.In contrast, M2 biomarkers（Arg1, Clec10 a and Mrc） mRNA levels following interleukinin-4（IL-4） stimulation were significantly upregulated by SalB.In addition, LPS stimulation potently induced transcriptional upregulation of RagD, an important activation factor of mammalian target of rapamycin complex 1（mTORC1）.Interestingly,SalB inhibited RagD upregulation and mTORC1 activation, decreased glycolysis, and reduced inflammatory cytokine production in LPS-stimulated macrophages,all of which were blunted in RagD knockdown macrophages.In mice subjected to MI/R, SalB treatment decreased cardiac M1-macrophages and increased M2-macrophages at 3 days post-MI/R, followed by decreased collagen deposition and ameliorated cardiac dysfunction at 7 days post-MI/R.Collectively, our data have shown that SalB decreases M1-polarized macrophages in MI/R hearts via inhibiting mTORC1-dependent glycolysis, which might contribute to alleviated inflammation and improved cardiac dysfunction afforded by SalB after MI/R.

关键词： Macrophage polarization Myocardial ischemia/reperfusion injury Salvianolic acid B MTORC1

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The serum metabolomic study of intervention effects of the traditional Chinese medicine Radix salviae miltiorrhizae and Lignum dalbergiae odoriferae in the treatment of myocardial ischemia/reperfusion injury in rats

The serum metabolomic study of intervention effects of the t...

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2016年中国药学大会暨第十六届中国药师周

作者： FEI MU JIALIN DUAN HAIXU BIAN RUI LIN MEINA ZHAO AIDONG WEN YONG YANG miaomiao xi Department of Pharmacy Xijing HospitalFourth Military Medical University Department of Pharmacy Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital

. Radix salviae miltiorrhizae（SM） and Lignum dalbergiae odoriferae（DO） are both traditional Chinese medicinal herbs for the treatment of ischemic heart disease and other cardiovascular diseases, but few of literature is about the systematic studies. Sprague-Dawley rats were pretreated with SM, aqueous extract of DO（DOA） and volatile oil of DO（DOO）, either as monotherapy or in combination for 7 days, then subjected to 30 min of ischemia followed by 180 min of reperfusion. Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time-of-flight mass spectrometry（GC/TOF-MS） were used to identify the therapeutic effect of these traditional Chinese medicines. The results showed that SM, DOA and DOO ameliorated cardiac function respectively, and this effect was further strengthened by their combinations. Among all combinations, SM+DOO showed predominant potential（P＜0.01） to improve electrocardiogram and heart rate, reduce heart weight index and myocardial infarct size, decrease the levels of CK-MB and LDH. Moreover, metabonomics-based findings such as the principal component analysis（PCA） and partial least squares discriminant analysis（PLS-DA） score plot of metabolic state in rat serum correlated well to the preceding results, confirming that SM+DOO exerted synergistic therapeutic efficacies to exhibit better effect on MI/R injury rats compared with other pretreatment groups. Furthermore, the maximum effective point of SM+DOO was 30 min and the minimum effective point was 180 min. In addition, SM+DOO group markedly（P＜0.01） reduced the number of TUNEL-positive cells, the levels of TNF-α, IL-6 and MDA, while increased the activity of SOD both in serum and tissue. These results indicated that SM+DOO have combined effects that are highly effective than single pretreatment against MI/R injury rats. This effect might be achieved partly through anti-apoptosis, anti-oxidant and anti-inflammatory. Thus SM+DOO might be an effective and promising medicine for both prophylaxis and treatment of ischemic he

关键词： Myocardial ischemia/reperfusion injury Radix salviae miltiorrhizae Lignum dalbergiae odoriferae The maximum and minimum effective points Cardioprotection Metabonomics

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Cardioprotective effects and mechanism of Radix salviae miltiorrhizae and Lignum dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury

Cardioprotective effects and mechanism of Radix salviae milt...

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中国药学会第十三届青年药学科研成果交流会

作者： Fei Mu JiaLin Duan HaiXu Bian Ying Yin YanRong Zhu Guo Wei Yue Guan YanHua Wang Chao Guo AiDong Wen Yong Yang miaomiao xi Department of Pharmacy Xijing HospitalFourth Military Medical University Department of Pharmacy Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital

Objective Radix salviae miltiorrhizae（SM） and Lignum dalbergiae odoriferae（DO） are both traditional Chinese medicinal herbs for the treatment of ischemic heart disease and other cardiovascular diseases,but few of literature is about the systematic studies.Sprague-Dawley rats were pretreated with SM,aqueous extract of DO（DOA） and volatile oil of DO（DOO）,either as monotherapy or in combination for 7 days,then subjected to 30 min of ischemia followed by 180 min of reperfusion.Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time-of-flight mass spectrometry（GC/TOF-MS） were used to identify the therapeutic effect of these traditional Chinese medicines.The results showed that SM,DOA and DOO ameliorated cardiac function respectively,and this effect was further strengthened by their combinations.Among all combinations,SM+DOO showed predominant potential（P＜0.01） to improve electrocardiogram and heart rate,reduce heart weight index and myocardial infarct size,decrease the levels of CK-MB and LDH.Moreover,metabonomics-based findings such as the principal component analysis（PCA） and partial least squares discriminant analysis（PLS-DA） score plot of metabolic state in rat serum correlated well to the preceding results,confirming that SM+DOO exerted synergistic therapeutic efficacies to exhibit better effect on MI/R injury rats compared with other pretreatment groups.Furthermore,the maximum effective point of SM+DOO was 30 min and the minimum effective point was 180 min.In addition,SM+DOO group markedly（P＜0.01） reduced the number of TUNEL-positive cells,the levels of TNF-α,IL-6 and MDA,while increased the activity of SOD both in serum and tissue.These results indicated that SM+DOO have combined effects that are highly effective than single pretreatment against MI/R injury rats.This effect might be achieved partly through anti-apoptosis,anti-oxidant and anti-inflammatory.Thus SM+DOO might be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease.

关键词： Myocardial ischemia/reperfusion injury Radix salviae miltiorrhizae Lignum dalbergiae odoriferae The maximum and minimum effective points Cardioprotection Metabonomics

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乌鲁木齐市MSM对生态瞬时评估法调查性行为的依从性研究

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中国艾滋病性病 2023年第4期29卷 413-417页

作者：席苗苗陈珍余文慧张国珍戴江红新疆医科大学公共卫生学院乌鲁木齐830011

目的了解乌鲁木齐市MSM对生态瞬时评估法(EMA)调查性行为的依从性及影响因素。方法依托乌鲁木齐市社会组织通过网络招募MSM,基线调查问卷收集一般人口学特征及过去14天性行为特征,再连续14天通过生态瞬时评估调查问卷一日两次实时收集... 详细信息

目的了解乌鲁木齐市MSM对生态瞬时评估法(EMA)调查性行为的依从性及影响因素。方法依托乌鲁木齐市社会组织通过网络招募MSM,基线调查问卷收集一般人口学特征及过去14天性行为特征,再连续14天通过生态瞬时评估调查问卷一日两次实时收集MSM性行为信息。采用Kappa一致性检验分别对EMA调查与基线调查和传统调查问卷的行为进行一致性分析;通过EMA问卷应答率反映MSM依从性,将问卷应答率≥80%的研究对象视为高依从性者,采用多因素Logistic回归探讨影响MSM对EMA调查性行为依从性的因素。结果招募MSM 150名,78.67%的MSM为高依从性者,EMA调查MSM性行为的问卷应答率为80.48%,EMA调查提醒后3 h内的EMA问卷完成率为81.95%。≥30岁MSM对EMA调查性行为高依从性的可能是0.4)。结论新疆乌鲁木齐市MSM对连续14天EMA调查性行为的依从性较高,短时间采用生态瞬时评估法调查MSM性行为具有较高的可行性,尤其是30岁及以上、不吸烟的MSM对EMA调查性行为的应答率较高。

关键词：男男性行为者生态瞬时评估法依从性

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单味中药治疗心肌梗死的药效物质及作用机制:基于网络药理学和多靶标分子对接方法

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南方医科大学学报 2022年第1期42卷 13-25页

作者：赵石刘珂娣段佳林陶星茹李伟红白杨卫培峰奚苗苗杨红莲陕西中医药大学药学院陕西咸阳712046 西北工业大学医学研究院陕西西安710072 陕西中医药大学第二附属医院国家药物临床试验机构陕西咸阳712021 西安天工生物医药研究所陕西西安710032 陕西中医药大学附属医院临床医学研究中心陕西咸阳712099

目的应用网络药理学及分子对接技术,发现治疗心肌梗死(MI)效果较优的中药,并进一步探讨其药效物质及作用机制。方法通过TCMSP数据库,根据指定的标准,筛选含有治疗MI的活性成分较多的中药。利用Genecards、OMIM、PharmGkb、PharmMapper... 详细信息

目的应用网络药理学及分子对接技术,发现治疗心肌梗死(MI)效果较优的中药,并进一步探讨其药效物质及作用机制。方法通过TCMSP数据库,根据指定的标准,筛选含有治疗MI的活性成分较多的中药。利用Genecards、OMIM、PharmGkb、PharmMapper数据库获取中药与MI的相关靶标,采用Venny2.1.0软件建立药物靶标与疾病靶标的共同靶标网络。通过R语言对共同靶标进行GO及KEGG信号通路富集分析;通过STRING数据库对共同靶标进行蛋白蛋白相互作用网络构建;通过Cytoscape3.7.2软件中的cytoHubba工具对PPI网络涉及的靶标进行分析并确定关键靶标;通过R语言对关键靶标进行GO及KEGG信号通路富集分析。应用SYBYL-X2.1.1软件对潜在药效物质及关键靶标进行分子对接,以Total Score≥6为参考,筛选药效物质并验证其与关键靶标的对接结合性。复制人脐静脉内皮细胞氧糖剥夺模型,通过蛋白质免疫印迹检测对潜在药效物质与治疗MI的关键靶标进行验证。结果本研究筛选出丹参、降香含有治疗MI的活性成分较多,涉及PTGS2、KDR等治疗MI的关键靶标16个,主要涉及炎症反应、血管新生、能量代谢与氧化应激等生物过程,HIF-1、VEGF、TNF等信号通路,丹参中的香紫苏醇与PTGS2、降香中的芒柄花黄素与KDR对接Total Score最高。Western blot结果显示,低、中、高计量的紫苏醇与芒柄花黄素分别能够抑制PTGS2与促进KDR的表达,且呈剂量-效应依赖关系,其中中、高剂量组差异具有统计学意义(P<0.05)。结论中药丹参、降香治疗MI的疗效较优,其作用机制可能与丹参、降香中的潜在药效物质香紫苏醇及芒柄花黄素调控PTGS2与KDR的表达,调节炎症反应、血管新生、氧化应激与能量代谢,进而发挥心肌保护作用有关。

关键词：网络药理学分子对接心肌梗死药效物质中药

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外置拱形耗能装置的节段拼装钢管混凝土桥墩抗震性能分析

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中南大学学报（自然科学版） 2024年第2期55卷 690-705页

作者：王城泉宗延威孙苗苗周子健黄毅方吴熙浙大城市学院工程学院浙江杭州310015 城市基础设施智能化浙江省工程研究中心浙江杭州310015 浙江省城市盾构隧道安全建造与智能养护重点实验室浙江杭州310015 江南大学环境与土木工程学院江苏无锡214122 浙江工业大学土木工程学院浙江杭州310014 浙江大学工程师学院工程创新与训练中心浙江杭州310015

为了进一步推广可恢复功能的预制装配式桥梁结构在中、高烈度地区的应用,减少桥墩的震后损伤及修复成本,提出一种外置拱形耗能装置的节段拼装钢管混凝土(concrete-filled steel tube,CFST)桥墩。基于ABAQUS有限元分析软件建立无耗能装... 详细信息

为了进一步推广可恢复功能的预制装配式桥梁结构在中、高烈度地区的应用,减少桥墩的震后损伤及修复成本,提出一种外置拱形耗能装置的节段拼装钢管混凝土(concrete-filled steel tube,CFST)桥墩。基于ABAQUS有限元分析软件建立无耗能装置、外置拱形钢板、外置竖直钢板、外置拱形耗能装置的四节段预制拼装CFST桥墩模型,并在往复位移加载作用下对各模型的抗震性能进行对比分析。研究结果表明:外置拱形耗能装置的预制节段拼装CFST桥墩具有较好的水平承载力、较高的初始刚度以及较强的耗能能力,与外置竖直钢板的节段拼装CFST桥墩相比,其抗侧承载力提升了约11.9%,初始刚度提升了约2.5%;与外置拱形钢板的节段拼装CFST桥墩相比,其抗侧承载力、初始刚度以及耗能能力分别提升了约28.8%、4.6%和13倍;与无耗能装置的预制拼装CFST桥墩相比,其抗侧承载力、初始刚度以及耗能能力分别提升了约39.4%、10.4%和18.1倍;外置拱形耗能装置的预制节段拼装CFST桥墩在整个位移加载阶段残余位移均保持在1 mm之内,偏移率不超过1%,且损伤集中在拱形耗能装置上,能够实现震后的快速修复。

关键词：桥梁抗震性能节段拼装钢管混凝土桥墩拱形耗能装置震后修复拟静力分析

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乌鲁木齐市男男性行为者多性伴及性传播疾病感染状况

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中国艾滋病性病 2022年第3期28卷 281-285页

作者：刘礼荣张泽文张国珍席苗苗戴江红新疆医科大学公共卫生学院乌鲁木齐830011 新疆伊宁市疾病预防控制中心新疆维吾尔自治区伊宁835000

目的了解新疆乌鲁木齐市MSM多性伴和STD感染情况。方法用滚雪球的方法招募MSM,收集血液进行HIV、梅毒、HBsAg和HCV抗体检测。近6个月同性性伴≥5人者定义为多性伴男男性行为者(MSMM),分别使用Poission回归和χ^(2)检验比较MSMM和非多性... 详细信息

目的了解新疆乌鲁木齐市MSM多性伴和STD感染情况。方法用滚雪球的方法招募MSM,收集血液进行HIV、梅毒、HBsAg和HCV抗体检测。近6个月同性性伴≥5人者定义为多性伴男男性行为者(MSMM),分别使用Poission回归和χ^(2)检验比较MSMM和非多性伴MSM的STD感染和行为特征差异。结果招募622名MSM,平均年龄为(32.43±8.69)岁,其中MSMM 71名(11.41%),非多性伴MSM 551名(88.59%)。相比非多性伴MSM,MSMM近1个月性交次数更多,近6个月在互联网上寻找性伴更常见,有时或偶尔使用安全套、使用毒品和有女性性伴的占比更高(P均<0.05)。622名MSM中HIV、梅毒、HBsAg和HCV抗体中至少检出一种阳性的有70人(11.25%),HIV、HBsAg、梅毒和HCV抗体的阳性率分别3.70%、4.98%、3.05%和0.64%;HIV和梅毒合并感染率为0.80%。其中MSMM的STD感染率(18.31%,13/71)高于非多性伴MSM(10.34%,57/551)(χ^(2)=3.995,P=0.046),MSMM的HIV和梅毒感染率及HIV和梅毒的合并感染率均高于非多性伴MSM(P均<0.05)。结论乌鲁木齐市MSM社区中MSMM较常见,相比非多性伴MSM,MSMM具有更高的高危性行为,HIV和梅毒的感染率更高。

关键词：男男性行为者多性伴性传播疾病多性伴男男性行为者

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