HIV/AIDS病人生活质量评价及影响因素分析

目的评价艾滋病病毒感染者/艾滋病病人(HIV/AIDS病人)的生活质量,并探讨其影响因素。方法对在中国医科大学附属第一医院就诊的289名HIV/AIDS病人,用世界卫生组织生活质量简表(WHOQOL-BREF)进行生活质量评价,并与同期高危人群及健康人群进行对比,通过多元线性回归分析生活质量的相关影响因素。结果 HIV/AIDS病人生活质量的生理、心理、社会关系和环境四个维度的平均得分依次为44.5、58.1、62.6和57.7分。HIV/AIDS病人生活质量显著低于HIV阴性的高危人群以及健康人群(P<0.05)。多元线性回归分析显示,尚未接受抗病毒治疗者、男男性行为人群(MSM)、低收入、低文化程度、缺少家庭支持和食欲差,是HIV/AIDS病人较低生活质量的显著影响因素(P<0.05)。结论 HIV/AIDS病人生活质量较低,尤以MSM人群明显,高效抗病毒治疗可显著提高HIV/AIDS病人生活质量,同时应加强对低文化程度、低收入和缺少家庭支持的MSM人群的医疗和社会支持,提高其生活质量,降低死亡率。     

V4 region of the HIV-1 envelope gene mediates immune escape and may not promote the development of broadly neutralizing antibodies

To date, inducing the production of broadly neutralizing antibodies (bnAbs) against HIV-1 in humans has been unsuccessful. Several studies have explored the coevolution of HIV-1 and neutralizing antibodies (nAbs), but little is known about what affects the lack of bnAbs after long-term infection. A better understanding of the coevolution of the virus and nAbs in cases involving no bnAb production will help in the design of an effective HIV-1 vaccine. An individual with acute CRF01_AE HIV-1 infection who lacked bnAbs at just over 2 years post-infection (p.i.) was identified from a cohort of HIV negative men who have sex with men. The coevolution of the viral envelope gene and nAbs was studied over 741 days p.i. Strain-specific antibodies (ss-Abs) to the transmitted/founder (T/F) virus developed within 54 days p.i., but plasma collected at subsequent time points could not neutralize synchronous viruses until 557 days p.i., when the plasma acquired low-level synchronous but not heterologous neutralizing activity. The V4 region of envelope gene mutated firstly and continually evolve up to 2 years p.i. Multiple variations in the V4 region, including substitutions, deletions and glycosylation mutations, were driven by ss-Abs and mediated immune escape partially by impacting the binding of nAbs to the virus. The remarkable variations in the V4 region mediated immune escape from ss-Abs and contributed to the affinity maturation of ss-Abs against the T/F virus but may not promote the development of bnAbs. Thus, the V4 region might not be a good target for an HIV-1 vaccine.     

Analytical characterization of an assay designed to detect and identify diverse agents of disseminated viral infection

BackgroundDiverse viruses often reactivate in or infect cancer patients, patients with immunocompromising infections or genetic conditions, and transplant recipients undergoing immunosuppressive therapy. These infections can disseminate, leading to death, transplant rejection, and other severe outcomes.ObjectivesTo develop and characterize an assay capable of inclusive and accurate identification of diverse potentially disseminating viruses directly from plasma specimens.Study designWe developed a PCR/electrospray ionization mass spectrometry (PCR/ESI-MS) assay designed to simultaneously detect and identify adenovirus, enterovirus, polyomaviruses JC and BK, parvovirus B19, HSV-1, HSV-2, VZV, EBV, CMV, and herpesviruses 6–8 in plasma specimens. The assay performance was characterized analytically, and the results from clinical plasma samples were compared to the results obtained from single-analyte real time PCR tests currently used in clinical practice.ResultsThe assay demonstrated sensitivity and specificity to diverse strains of the targeted viral families and robustness to interfering substances and potentially cross reacting organisms. The assay yielded 94% sensitivity when testing clinical plasma samples previously identified as positive using standard-of-care real-time PCR tests for a single target virus (available samples included positive samples for 11 viruses targeted by the assay).ConclusionsThe assay functioned as designed, providing simultaneous broad-spectrum detection and identification of diverse agents of disseminated viral infection. Among 156 clinical samples tested, 37 detections were made in addition to the detections matching the initial clinical positive results.     

MicroR-760 suppresses cancer stem cell subpopulation and breast cancer cell proliferation and metastasis: By down-regulating NANOG

Background and objectiveEmerging evidences suggest that cancer stem cells are responsible for tumor aggressive, metastasis and therapeutic resistance. To data, the mechanism underlying breast cancer stem cell (BCSC) population within tumor metastasis remains to be fully elucidated. The current study was to investigate the potential role of microRNA-760 (miR-760) and its associated target gene in population and metastasis of BCSC.MethodsCharacteristic BCSCs surface markers (CD44⁺/CD24^−/low) were determined by flow cytometry in breast cancer MCF-7 and BT-549 cells. Quantitative RT-PCR was used to evaluate miR-760 and NANOG mRNA expression. Expression of NANOG protein was determined using western blot. Cell proliferation was determined by MTT assay. The model of breast cancer cell xenograft was used to evaluate the effect of miR-760 on tumor growth.ResultsBT-549 cell has substantially more CD44⁺/CD24^−/low subpopulation than MCF-7 cell. Moreover, BT-549 cell expressed lower level of miR-760 and higher level of NANOG than MCF-7cell. By result from cellular miR-760 modulation, we found that miR-760 overexpression suppressed CD44⁺/CD24^−/low population as well as inhibited cell proliferation and migration of BT-549. On the contrary, knockdown of miR-760 promoted CD44⁺/CD24^−/low population and migration of MCF-7 cells. By luciferase reporter assay, miR-760 was proved to be functional associated with NANOG via regulating its expression. This functional interaction was showed to be involved in controlling proliferation and migration of MCF-7 and BT-549 cell.ConclusionThese data suggest that the target of miR-760/NANOG axis may represent a new therapeutic approach to suppress breast cancer stem cell subpopulation thereby prevent cancer metastasis.     

Rapid Disease Progression in HIV-1-Infected Men Who Have Sex with Men Is Negatively Correlated with Peripheral Plasmacytoid Dendritic Cell Counts at the Early Stage of Primary Infection

To explore the relationship between absolute dendritic cell (DC) counts at the early stage of primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) and subsequent disease progression, we performed a prospective study of 16 rapid progressors (RPs) and 12 typical progressors (TPs) from a PHI cohort of men who have sex with men. Significantly decreased plasmacytoid DC (pDC) and myeloid DC (mDC) counts in the blood of RPs were observed at study entry as compared with TPs and healthy HIV-1-negative subjects. Low baseline pDC counts were significantly associated with rapid disease progression after adjustment for baseline CD4(+) T cell counts, mDC counts, and HIV-1 load. Kaplan-Meier survival analysis showed that low pDC counts were strongly associated with rapid disease progression. Our findings demonstrated the predictive value of blood absolute pDC counts at baseline in PHI for HIV-1 disease progression. Further studies are required to confirm this notion.     

HIV早期和慢性感染者不同亚群T细胞BTLA的表达

目的:对中国HIV早期和慢性感染者不同亚群T细胞BTLA表达水平及与疾病进展相关性进行研究,探讨BTLA表达在HIV感染中的作用。方法:选取21例HIV早期感染者、29例HIV慢性感染者及23例正常对照,应用流式细胞仪检测CD4+CD45RA+、CD4+CD45RA-、CD8+CD45RA+、CD8+CD45RA-及总CD4+、CD8+T细胞BTLA表达水平,同时分析CD4+HLA-DR+、CD4+CD38+、CD8+HLA-DR+、CD8+CD38+T细胞表达水平,分析不同亚群T细胞BTLA表达水平与疾病进展及免疫活化的相关性。结果:HIV早期感染组各亚群T细胞BTLA表达水平高于正常对照,其中CD4+CD45RA-、CD8+CD45RA-、总CD4+T细胞BTLA表达水平在两组之间差异具有统计学意义(P<0.01);HIV早期感染组各亚群T细胞BTLA表达水平高于慢性感染者,除CD8+CD45RA-T细胞外,其它亚群T细胞BTLA表达水平在两组之间差异具有统计学意义(P<0.01);慢性HIV感染者CD8+CD45RA+T细胞BTLA表达水平低于正常对照,差异显著(P<0.01),其余T细胞亚群BTLA表达水平在两组之间无明显差异。HIV感染者T细胞亚群BTLA表达水平与T细胞活化水平负相关:除CD8+CD45RA-T细胞外,各亚群T细胞BTLA表达百分率与T细胞活化(CD4+HLA-DR+T细胞表达)水平明显负相关(P<0.01);各亚群T细胞BTLA表达水平与CD4+CD38+、CD8+CD38+T细胞表达水平无明显相关性。HIV感染者总CD8+T细胞BTLA表达水平与CD4+T细胞数量明显正相关(P<0.01)。结论:中国HIV感染者T细胞BTLA表达与疾病进展及免疫活化状况显著相关,早期感染阶段BTLA表达升高,慢性感染期表达下降,为明确HIV的致病机制及免疫治疗提供线索。