Survival Analysis and Immune Differences of HIV Long-Term Non-progressors in Xinjiang China: A 12-Year Prospective Cohort Observation.

This 12-year cohort study of 80 long-term non-progressors (LTNPs) observed a cumulative follow-up duration of 628.5 person-years. Among them, 60 received antiretroviral therapy (ART) for a total of 418.6 person-years. Twenty-four deaths occurred during the follow-up period, with an average age of 42.36 years and a lowest 8-year survival rate of 0.90. Cox model analysis revealed that the risk of AIDS-related death was 1.47 times higher for non-marital, non-commercial heterosexual transmission than for injection drug use. Treatment initiation at ages 31-40 was correlated with an elevated risk of mortality, while treatment for 3-10 years reduced mortality risks in untreated LTNPs. Flow cytometry observed significant differences in the proportion of NK cells. Long-term ART (> 2 years) before LTNPs developed AIDS symptoms could lower mortality risk and potentially extend lifespan, especially when it was initiated at a younger age without affecting NK cell balance. Epidemiological and immunological studies on ART-treated LTNPs are vital for advancing HIV treatment and achieving functional cures for AIDS individuals.

RESUMEN: Este estudio de cohorte de 12 años con 80 no progresores a largo plazo (LTNPs) observó un total acumulado de 628.5 personas-año. De ellos, 60 recibieron terapia antirretroviral (TAR) durante un total de 418.6 personas-año. Se produjeron veinticuatro muertes durante el período del estudio, con una edad promedio de 42.36 años y una tasa de supervivencia más baja de 0.90 a los 8 años. El análisis del modelo de Cox identificó que la transmisión heterosexual no marital ni comercial presentaba un riesgo 1.47 veces mayor de muerte relacionada con el SIDA en comparación con el uso de drogas inyectables. Comenzar el tratamiento entre los 31-40 años mostró incrementos en los riesgos de mortalidad, mientras que 3-10 años de tratamiento redujeron los riesgos de mortalidad en LTNPs no tratados. Se observaron diferencias significativas en las proporciones de células NK desde el punto de vista inmunológico. La TAR a largo plazo (> 2 años) antes de la aparición de síntomas del SIDA en LTNPs podría disminuir el riesgo de mortalidad y potencialmente prolongar la vida, especialmente si se inicia a una edad más temprana sin afectar el equilibrio de las células NK. Los estudios epidemiológicos e inmunológicos sobre LTNPs tratados con TAR son fundamentales para el progreso del tratamiento del VIH y la cura funcional del SIDA.

Application of O-RADS US combined with MV-Flow to diagnose ovarian-adnexal tumors.

PURPOSE: This study aimed to explore the application of Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US) combined with MV-Flow (Samsung Medison Co., Ltd.) to diagnose ovarian-adnexal masses. METHODS: A total of 112 ovarian-adnexal masses (81 benign and 31 malignant) from 105 consecutive patients were analyzed. The O-RADS US and vascular index from MV-Flow (VIMV) were measured and compared with the reference standard. O-RADS US and MV-Flow were tested for consistency. RESULTS: Receiver operating characteristic curves were drawn for O-RADS US, MV-Flow, and their combination. The combined methods had the largest area under the curve (0.955), followed by O-RADS US (0.929) and MV-Flow (0.923). A mass was considered malignant when the O-RADS US classification was 5 and VIMV was ≥7.15. With this definition, MV-Flow had the highest sensitivity (87.10%), with consistent findings for the combined diagnostic methods and O-RADS US (83.87%). The specificity of the combined diagnostic methods (93.83%) was higher than that of MV-Flow (91.36%). O-RADS US had the lowest specificity (90.12%). The combined diagnostic methods had the highest coincidence rate (91.07%), and MV-Flow (90.18%) had a significantly higher coincidence rate than O-RADS US (88.39%). Both O-RADS US and MV-Flow showed good consistency among different physicians (former kappa, 0.974; latter intraclass correlation coefficient [ICC], 0.986). MV-Flow had a high consistency for the same physician (ICC, 1). CONCLUSION: O-RADS US and MV-Flow exhibited good diagnostic efficacy, and their combined diagnostic efficacy was higher than that of each individually. O-RADS US and MV-Flow can improve the diagnosis of benign and malignant ovarian-adnexal masses.

Identification of methylation markers for diagnosis of autism spectrum disorder.

Autism spectrum disorder (ASD) is a hereditary heterogeneous neurodevelopmental disorder characterized by social and speech dysplasia. We collected the expression profiles of ASD in GSE26415, GSE42133 and GSE123302 from the gene expression omnibus (GEO) database, as well as methylation data of GSE109905. Differentially expressed genes (DEGs) between ASD and controls were obtained by differential expression analysis. Enrichment analysis identified the biological functions and signaling pathways involved by common genes in three groups of DEGs. Protein-protein interaction (PPI) networks were used to identify genes with the highest connectivity as key genes. In addition, we identified methylation markers by associating differentially methylated positions. Key methylation markers were identified using the least absolute shrink and selection operator (LASSO) model. Receiver operating characteristic curves and nomograms were used to identify the diagnostic role of key methylation markers for ASD. A total of 57 common genes were identified in the three groups of DEGs. These genes were mainly enriched in Sphingolipid metabolism and PPAR signaling pathway. In the PPI network, we identified seven key genes with higher connectivity, and used qRT-PCR experiments to verify the expressions. In addition, we identified 31 methylation markers and screened 3 key methylation markers (RUNX2, IMMP2L and MDM2) by LASSO model. Their methylation levels were closely related to the diagnostic effects of ASD. Our analysis identified RUNX2, IMMP2L and MDM2 as possible diagnostic markers for ASD. Identifying different biomarkers and risk genes will contribute to the diagnosis of ASD and the development of new clinical and drug treatments.

HIV transmission in sero-discordant couples with the HIV-positive partner in Xinjiang: incidence and associated predictors.

INTRODUCTION: To control the spread of human immunodeficiency virus (HIV) among sero-discordant couples, we explored the HIV seroconversion and its contributing factors. METHODOLOGY: We recruited negative partners in HIV sero-discordant couples to established a prospective cohort between January 2010 and June 2015 from areas with severe HIV epidemic in Xinjiang. Follow up once every 3 months, serological tests and risk behavior surveys every 6 months. Variables were screened by LASSO regression and a Cox proportional hazards model was established. RESULTS: A total of 1162 negative partners of sero-discordant couples were recruited. The seroconversion occurred in 42 negative partners during follow-up period, with a seroconversion rate of 2/100 (95% CI = 1.21-2.27), and the median time for seroconversion was 0.92 years. The Cox model showed that frequency of sexual behavior for nearly six months, consistent condom use, knowledge of the transmission route for HIV, a history of sexually transmitted diseases, recent CD4 + T lymphocyte count were all significant contributing factors to the seroconversion in negative partner of HIV sero-discordant couples. In addition, the Cox model was used to evaluate the risk factors of seroconversion for HIV negative partners. CONCLUSIONS: The seroconversion rate of HIV negative partners in Xinjiang was lower. The LASSO Cox model may accurately predict the risk of HIV transmission in sero-discordant couples.

Identification of molecular mechanisms for achieving HIV-1 control in the absence of antiretroviral therapy.

AIMS: Antiretroviral therapy (ART) controls viral replication but cannot eradicate an infected virus and restore the immune response of patients. MATERIALS AND METHODS: The gene expression profiles of whole blood, PBMCs, CD4+ and CD8+ T cells were obtained from GSE108297. Coexpression analysis was carried out to evaluate differentially expressed genes (DEGs) between strong and weak responder HIV controllers (HICs). Enrichment analysis was used to explore the biological functions of DEGs. The key genes with common DEGs were screened using the Lasso Cox model. Then, the immune scores of HICs and HAART were calculated by ssGSEA. The content of CD4+ and CD8+ T cells, key genes were verified by flow cytometry, RT-PCR and Western blot analysis. KEY FINDINGS: DEGs were clustered into 24 coexpression modules. DEGs related to general immune responses had the highest correlation with strong responding HICs, while DEGs mainly related to the apoptotic process had the highest correlation with weak responder HICs. The hub genes CD8A and CCT2, as well as the key genes TMEM132C and S100A9, were DEGs in HICs and HARRT. The immune score and flow cytometry showed that CD4+ and CD8+ T cells of HICs were lower than those of HARRT in whole blood. Experiments confirmed the expression of key genes in HICs and HARRT. SIGNIFICANCE: The key genes identified in this study highlight the strong responder HICs features that to help the immune system control HIV-1 infection. These results will be useful for developing therapeutic targets.