Despite effective antiretroviral therapy(ART),many individuals with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)achieve viral suppression but fail to fully restore cluster of differentia...Despite effective antiretroviral therapy(ART),many individuals with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)achieve viral suppression but fail to fully restore cluster of differentiation 4(CD4)^(+)T lymphocyte(CD4 cell)counts—a condition known as immunological non-response(INRs).INRs are associated with elevated health risks,including increased susceptibility to AIDS-related and non-AIDS-related complications.The pathogenesis of INRs remains incompletely understood,and no established therapeutic interventions exist,posing a major challenge in contemporary HIV/AIDS management.Emerging evidence indicates that INRs exhibit significant alterations in gut microbiota composition.Dysbiosis of the gut microbiota may contribute to persistent immune activation,cytokine imbalance,and cellular pyroptosis,all of which could impair immune reconstitution in people living with HIV/AIDS.Traditional Chinese medicine(TCM)has demonstrated potential immunomodulatory effects and is increasingly utilized in the management of INRs.Targeting the gut microbiota and elucidating the mechanisms by which TCM modulates this microbial ecosystem may offer new avenues for preventing and treating INRs.This review explores the interplay between gut microbiota and TCM,examines the association between gut dysbiosis and INRs,discusses the mechanistic pathways through which microbiota imbalance contributes to INRs development,and highlights how TCM interventions regulate gut microbiota to promote immune recovery.By focusing on the gut microbiota as a therapeutic interface,this article provides novel insights into TCM-based strategies for improving outcomes in INRs and supports the development of innovative treatment approaches.展开更多
目的探讨AIDS相关T淋巴母细胞淋巴瘤(AIDS-related T lymphoblastic lymphoma,AR-T-LBL)患者的临床病理特征,并文献复习。方法选取2015—2024年首都医科大学附属北京佑安医院AIDS相关淋巴瘤(AIDS-related lymphoma,ARL)患者的临床及病...目的探讨AIDS相关T淋巴母细胞淋巴瘤(AIDS-related T lymphoblastic lymphoma,AR-T-LBL)患者的临床病理特征,并文献复习。方法选取2015—2024年首都医科大学附属北京佑安医院AIDS相关淋巴瘤(AIDS-related lymphoma,ARL)患者的临床及病理资料,筛选出AR-T-LBL病例,总结其临床病理特征,结合国内外报道的文献分析影响患者预后的因素。结果共纳入ARL患者143例,其中T细胞淋巴瘤6例,AR-T-LBL仅1例,患者32岁,男性,HIV感染史长,多处淋巴结累及,治疗2个疗程后去世,总生存期为7个月;结合文献报道的6例,AR-T-LBL均为男性,多伴骨髓受累,治疗方案不一,预后较差。结论AR-T-LBL病例罕见,易误诊,需及时活检进行病理学检查,早期明确诊断有利于患者治疗方案的选择。展开更多
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
目的探讨AIDS患者经外周置入中心静脉导管(peripherally inserted central catheter,PICC)所致的导管相关血栓(catheter related thrombosis,CRT)的发生现状及其影响因素。方法回顾性选取2019年12月至2024年12月首都医科大学附属北京佑...目的探讨AIDS患者经外周置入中心静脉导管(peripherally inserted central catheter,PICC)所致的导管相关血栓(catheter related thrombosis,CRT)的发生现状及其影响因素。方法回顾性选取2019年12月至2024年12月首都医科大学附属北京佑安医院接受PICC置管治疗的AIDS患者265例,依据血管超声结果分为血栓组(n=55)和无血栓对照组(n=210)。采用多因素logistic回归分析AIDS患者发生PICC-CRT的影响因素,采用ROC曲线评估相关影响因素对AIDS患者发生PICC-CRT的预测效能。结果265例患者中,男256例、女9例,年龄20~80岁,平均(44.0±13.3)岁。发生PICC-CRT者55例,发生率为20.75%,其中仅11例为有症状血栓,其余44例仅在超声检查时发现血栓。多因素logistic回归分析结果显示,携带导管天数越长(OR=1.008,95%CI:1.002~1.014,P=0.009)、D-二聚体水平越高(OR=1.001,95%CI:1.000~1.001,P=0.015)、HIV病毒载量越大(OR=2.782,95%CI:1.930~4.008,P<0.001)的AIDS患者发生PICC-CRT的风险越高。ROC曲线分析结果显示,HIV病毒载量预测PICC-CRT的AUC为0.903(95%CI:0.858~0.949,P<0.001),其预测效能优于D-二聚体水平和携带导管天数。结论AIDS患者PICC-CRT的发生率较高,且具有较强的临床隐匿性。携带导管天数、D-二聚体水平及HIV病毒载量是AIDS患者发生PICC-CRT的影响因素。临床应加强风险评估与动态监测,尤其对高危人群开展规律性超声筛查和早期干预,构建前瞻性防控体系,以降低PICC-CRT的发生风险,改善患者预后。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
基金supported by the National Natural Science Foundation of China(No.82274474)。
文摘Despite effective antiretroviral therapy(ART),many individuals with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)achieve viral suppression but fail to fully restore cluster of differentiation 4(CD4)^(+)T lymphocyte(CD4 cell)counts—a condition known as immunological non-response(INRs).INRs are associated with elevated health risks,including increased susceptibility to AIDS-related and non-AIDS-related complications.The pathogenesis of INRs remains incompletely understood,and no established therapeutic interventions exist,posing a major challenge in contemporary HIV/AIDS management.Emerging evidence indicates that INRs exhibit significant alterations in gut microbiota composition.Dysbiosis of the gut microbiota may contribute to persistent immune activation,cytokine imbalance,and cellular pyroptosis,all of which could impair immune reconstitution in people living with HIV/AIDS.Traditional Chinese medicine(TCM)has demonstrated potential immunomodulatory effects and is increasingly utilized in the management of INRs.Targeting the gut microbiota and elucidating the mechanisms by which TCM modulates this microbial ecosystem may offer new avenues for preventing and treating INRs.This review explores the interplay between gut microbiota and TCM,examines the association between gut dysbiosis and INRs,discusses the mechanistic pathways through which microbiota imbalance contributes to INRs development,and highlights how TCM interventions regulate gut microbiota to promote immune recovery.By focusing on the gut microbiota as a therapeutic interface,this article provides novel insights into TCM-based strategies for improving outcomes in INRs and supports the development of innovative treatment approaches.
文摘目的探讨AIDS相关T淋巴母细胞淋巴瘤(AIDS-related T lymphoblastic lymphoma,AR-T-LBL)患者的临床病理特征,并文献复习。方法选取2015—2024年首都医科大学附属北京佑安医院AIDS相关淋巴瘤(AIDS-related lymphoma,ARL)患者的临床及病理资料,筛选出AR-T-LBL病例,总结其临床病理特征,结合国内外报道的文献分析影响患者预后的因素。结果共纳入ARL患者143例,其中T细胞淋巴瘤6例,AR-T-LBL仅1例,患者32岁,男性,HIV感染史长,多处淋巴结累及,治疗2个疗程后去世,总生存期为7个月;结合文献报道的6例,AR-T-LBL均为男性,多伴骨髓受累,治疗方案不一,预后较差。结论AR-T-LBL病例罕见,易误诊,需及时活检进行病理学检查,早期明确诊断有利于患者治疗方案的选择。
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。
文摘目的探讨AIDS患者经外周置入中心静脉导管(peripherally inserted central catheter,PICC)所致的导管相关血栓(catheter related thrombosis,CRT)的发生现状及其影响因素。方法回顾性选取2019年12月至2024年12月首都医科大学附属北京佑安医院接受PICC置管治疗的AIDS患者265例,依据血管超声结果分为血栓组(n=55)和无血栓对照组(n=210)。采用多因素logistic回归分析AIDS患者发生PICC-CRT的影响因素,采用ROC曲线评估相关影响因素对AIDS患者发生PICC-CRT的预测效能。结果265例患者中,男256例、女9例,年龄20~80岁,平均(44.0±13.3)岁。发生PICC-CRT者55例,发生率为20.75%,其中仅11例为有症状血栓,其余44例仅在超声检查时发现血栓。多因素logistic回归分析结果显示,携带导管天数越长(OR=1.008,95%CI:1.002~1.014,P=0.009)、D-二聚体水平越高(OR=1.001,95%CI:1.000~1.001,P=0.015)、HIV病毒载量越大(OR=2.782,95%CI:1.930~4.008,P<0.001)的AIDS患者发生PICC-CRT的风险越高。ROC曲线分析结果显示,HIV病毒载量预测PICC-CRT的AUC为0.903(95%CI:0.858~0.949,P<0.001),其预测效能优于D-二聚体水平和携带导管天数。结论AIDS患者PICC-CRT的发生率较高,且具有较强的临床隐匿性。携带导管天数、D-二聚体水平及HIV病毒载量是AIDS患者发生PICC-CRT的影响因素。临床应加强风险评估与动态监测,尤其对高危人群开展规律性超声筛查和早期干预,构建前瞻性防控体系,以降低PICC-CRT的发生风险,改善患者预后。
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.
