目的 基于巨噬细胞自噬探讨参芩龙清肺培元颗粒的作用机制。方法 选择人类免疫缺陷病毒(HIV)/艾滋病(AIDS)合并肺部感染痰热壅肺证患者36例,应用流式细胞术检测治疗前后患者外周血T淋巴细胞亚群中CD4^(+)及CD8^(+)T淋巴细胞计数,巨噬细...目的 基于巨噬细胞自噬探讨参芩龙清肺培元颗粒的作用机制。方法 选择人类免疫缺陷病毒(HIV)/艾滋病(AIDS)合并肺部感染痰热壅肺证患者36例,应用流式细胞术检测治疗前后患者外周血T淋巴细胞亚群中CD4^(+)及CD8^(+)T淋巴细胞计数,巨噬细胞亚群CD11b、CD86、CD206的表达及巨噬细胞自噬探针CD11b+DALGreen、CD86+DALGreen、CD206+DALGreen的表达。ELISA法检测治疗前后血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-10、转化生长因子(TGF)-β1等炎性因子的表达。采用荧光定量PCR法检测治疗前后患者外周血中组蛋白去乙酰化酶(HDAC)2 m RNA、Unc-51样激酶1(ULK1)m RNA的表达。结果 治疗后,患者CD11b、CD206、CD11b+DALGreen、CD206+DALGreen、ULK1 m RNA表达明显升高(P<0.05);CD86、TNF-α、IL-1β、HDAC2 m RNA的表达明显下降(P<0.05);CD4^(+)T淋巴细胞计数、IL-10、TGF-β1表达呈上升趋势(P>0.05)。结论 参芩龙清肺培元颗粒可能通过调节HDAC2/ULK1信号轴,促进巨噬细胞自噬,调节M1/M2的平衡,抑制炎症反应,从而发挥治疗HIV/AIDS患者合并肺部感染的作用。展开更多
Debate regarding the premature aging of knee joints in acquired immune deficiency syndrome(AIDS)patients has remained contentious,with conjectures pointing towards its correlation with distinct antiviral regimes.Prote...Debate regarding the premature aging of knee joints in acquired immune deficiency syndrome(AIDS)patients has remained contentious,with conjectures pointing towards its correlation with distinct antiviral regimes.Protease inhibitors(PIs)stand as a prominent class of antiviral agents frequently utilized in AIDS management and have been significantly linked to premature senescence.This study aimed to investigate whether PI-containing regimens would accelerate osteoarthritis(OA)development and explore the molecular mechanisms underlying this association.A retrospective cohort of 151 HIV-infected individuals,categorized into PI and non-PI groups,was established.Patients in PI group exhibited lower KOOS and a higher prevalence of radiological knee OA than those in non-PI group.Additionally,25 anti-HIV drugs were screened and among all antiviral drugs,lopinavir had the most detrimental impact on cartilage anabolism,accelerating cartilage senescence and promoting mouse OA development.Mechanistically,lopinavir accelerated cellular senescence by inhibiting Zmpste24 and interfering nuclear membrane stability,which leads to decreased binding between nuclear membrane-binding protein Usp7 and Mdm2 and activates Usp7/Mdm2/p53 pathway.Zmpste24 overexpression reduces OA severity in mice.These findings suggest that PI-containing regimens accelerate cartilage senescence and OA development through Zmpste24 inhibition,which provides new insights into the selection of HIV regimens.展开更多
目的了解凉山州新报告HIV感染者或艾滋病病人(简称HIV/AIDS病例)性别比的特征,并探索性别比的影响因素。方法通过中国艾滋病综合防治信息系统收集2019—2022年凉山州新报告的报告年龄15岁及以上、传播途径为异性传播HIV/AIDS病例的基本...目的了解凉山州新报告HIV感染者或艾滋病病人(简称HIV/AIDS病例)性别比的特征,并探索性别比的影响因素。方法通过中国艾滋病综合防治信息系统收集2019—2022年凉山州新报告的报告年龄15岁及以上、传播途径为异性传播HIV/AIDS病例的基本信息,分析凉山州不同地区、人口学特征、疾病特征的男女性别比差异;采用SPSS 22.0软件进行卡方检验、Fisher确切概率法、linear by linear association检验,并建立线性混合模型,分析男女性别比的影响因素。结果2019—2022年凉山州新报告15周岁及以上异性传播HIV/AIDS病例9963例,占全部新报告病例的76.08%,其中非婚非商业性传播病例占71.55%。凉山州四年新报告异性传播HIV/AIDS病例的男女性别比为1.19∶1,布拖、昭觉、金阳和美姑连续4年的性别比均小于1∶1。多因素分析结果显示:年龄越小,民族为彝族,文化程度越低,婚姻状态为离异或丧偶、已婚有配偶,常住人口,异性传播表现形式为非婚非商、配偶阳性,首次CD4^(+)T淋巴细胞计数越高,性别比越小,倒置越明显。结论2019—2022年凉山州新报告HIV/AIDS病例以非婚非商业性传播为主,布拖、昭觉、金阳和美姑等县女性的HIV感染风险高于男性。应进一步发挥学校、多媒体的作用,做好宣传教育工作;加强育龄妇女管理、单阳家庭管理和抗病毒治疗等工作,降低当地女性的艾滋病传播风险,控制艾滋病的传播。展开更多
文摘目的 基于巨噬细胞自噬探讨参芩龙清肺培元颗粒的作用机制。方法 选择人类免疫缺陷病毒(HIV)/艾滋病(AIDS)合并肺部感染痰热壅肺证患者36例,应用流式细胞术检测治疗前后患者外周血T淋巴细胞亚群中CD4^(+)及CD8^(+)T淋巴细胞计数,巨噬细胞亚群CD11b、CD86、CD206的表达及巨噬细胞自噬探针CD11b+DALGreen、CD86+DALGreen、CD206+DALGreen的表达。ELISA法检测治疗前后血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-10、转化生长因子(TGF)-β1等炎性因子的表达。采用荧光定量PCR法检测治疗前后患者外周血中组蛋白去乙酰化酶(HDAC)2 m RNA、Unc-51样激酶1(ULK1)m RNA的表达。结果 治疗后,患者CD11b、CD206、CD11b+DALGreen、CD206+DALGreen、ULK1 m RNA表达明显升高(P<0.05);CD86、TNF-α、IL-1β、HDAC2 m RNA的表达明显下降(P<0.05);CD4^(+)T淋巴细胞计数、IL-10、TGF-β1表达呈上升趋势(P>0.05)。结论 参芩龙清肺培元颗粒可能通过调节HDAC2/ULK1信号轴,促进巨噬细胞自噬,调节M1/M2的平衡,抑制炎症反应,从而发挥治疗HIV/AIDS患者合并肺部感染的作用。
基金supported by Natural Science Foundation of China(82472476)Fundamental Research Funds for the Central Universities(YG2023ZD15)+2 种基金The Youth Talent Program from Shanghai Health System(2022YQ020)AI-Driven Reform of Research Paradigms Empowers Discipline Advancement Initiatives from Shanghai Municipal Education Commission(Grant No.JWAIZD-7)the Natural Science Foundation of Shanghai(23ZR1437300).
文摘Debate regarding the premature aging of knee joints in acquired immune deficiency syndrome(AIDS)patients has remained contentious,with conjectures pointing towards its correlation with distinct antiviral regimes.Protease inhibitors(PIs)stand as a prominent class of antiviral agents frequently utilized in AIDS management and have been significantly linked to premature senescence.This study aimed to investigate whether PI-containing regimens would accelerate osteoarthritis(OA)development and explore the molecular mechanisms underlying this association.A retrospective cohort of 151 HIV-infected individuals,categorized into PI and non-PI groups,was established.Patients in PI group exhibited lower KOOS and a higher prevalence of radiological knee OA than those in non-PI group.Additionally,25 anti-HIV drugs were screened and among all antiviral drugs,lopinavir had the most detrimental impact on cartilage anabolism,accelerating cartilage senescence and promoting mouse OA development.Mechanistically,lopinavir accelerated cellular senescence by inhibiting Zmpste24 and interfering nuclear membrane stability,which leads to decreased binding between nuclear membrane-binding protein Usp7 and Mdm2 and activates Usp7/Mdm2/p53 pathway.Zmpste24 overexpression reduces OA severity in mice.These findings suggest that PI-containing regimens accelerate cartilage senescence and OA development through Zmpste24 inhibition,which provides new insights into the selection of HIV regimens.
文摘目的了解凉山州新报告HIV感染者或艾滋病病人(简称HIV/AIDS病例)性别比的特征,并探索性别比的影响因素。方法通过中国艾滋病综合防治信息系统收集2019—2022年凉山州新报告的报告年龄15岁及以上、传播途径为异性传播HIV/AIDS病例的基本信息,分析凉山州不同地区、人口学特征、疾病特征的男女性别比差异;采用SPSS 22.0软件进行卡方检验、Fisher确切概率法、linear by linear association检验,并建立线性混合模型,分析男女性别比的影响因素。结果2019—2022年凉山州新报告15周岁及以上异性传播HIV/AIDS病例9963例,占全部新报告病例的76.08%,其中非婚非商业性传播病例占71.55%。凉山州四年新报告异性传播HIV/AIDS病例的男女性别比为1.19∶1,布拖、昭觉、金阳和美姑连续4年的性别比均小于1∶1。多因素分析结果显示:年龄越小,民族为彝族,文化程度越低,婚姻状态为离异或丧偶、已婚有配偶,常住人口,异性传播表现形式为非婚非商、配偶阳性,首次CD4^(+)T淋巴细胞计数越高,性别比越小,倒置越明显。结论2019—2022年凉山州新报告HIV/AIDS病例以非婚非商业性传播为主,布拖、昭觉、金阳和美姑等县女性的HIV感染风险高于男性。应进一步发挥学校、多媒体的作用,做好宣传教育工作;加强育龄妇女管理、单阳家庭管理和抗病毒治疗等工作,降低当地女性的艾滋病传播风险,控制艾滋病的传播。
