Performance of HIV Infection Prediction Models in Men Who Have Sex with Men: A Systematic Review and Meta-Analysis.

Effective ways to identify and predict men who have sex with men (MSM) at substantial risk for HIV is a global priority. HIV risk assessment tools can improve individual risk awareness and subsequent health-seeking actions. We sought to identify and characterize the performance of HIV infection risk prediction models in MSM through systematic review and meta-analysis. PubMed, Embase, and The Cochrane Library were searched. Eighteen HIV infection risk assessment models with a total of 151,422 participants and 3643 HIV cases were identified, eight of which have been externally validated by at least one study (HIRI-MSM, Menza Score, SDET Score, Li Model, DHRS, Amsterdam Score, SexPro model, and UMRSS). The number of predictor variables in each model ranged from three to 12, age, the number of male sexual partners, unprotected receptive anal intercourse, recreational drug usage (amphetamines, poppers), and sexually transmitted infections were critical scoring variables. All eight externally validated models performed well in terms of discrimination, with the pooled area under the receiver operating characteristic curve (AUC) ranging from 0.62 (95%CI: 0.51 to 0.73, SDET Score) to 0.83 (95%CI: 0.48 to 0.99, Amsterdam Score). Calibration performance was only reported in 10 studies (35.7%, 10/28). The HIV infection risk prediction models showed moderate-to-good discrimination performance. Validation of prediction models across different geographic and ethnic environments is needed to ensure their real-world application.

GOLPH3 silencing inhibits adhesion of glioma U251 cells by regulating ITGB1 degradation under serum starvation.

GOLPH3, an oncoprotein, plays crucial roles in tumor etiology. Compelling evidences have demonstrated that GOLPH3 contributes to regulate tumor cell growth, migration and invasion under normal nutrient condition. However, the oncogenic activity of GOLPH3 under serum starvation remains largely unknown. In this study, we reported that GOLPH3 depletion led to marked reduction in adhesion of glioma U251 cells, particularly under serum deprivation. We found that silencing of GOLPH3 expression reduced the protein amount of ITGB1 only in serum-free medium. Further insights into the mechanism between GOLPH3 and ITGB1, we applied proteasome or lysosome inhibitor to block the degradation of ITGB1, and identified GOLPH3 silencing can prompt ITGB1 lysosomal degradation under serum starvation. Finally, we found the reductions in glioma cell adhesion and ITGB1 protein amount could be rescued by ITGB1 overexpression. Taken together, these results show that GOLPH3 contributes to the adhesion of glioma cells by regulating the lysosomal degradation of ITGB1 under serum starvation.

An integrated online-to-offline model for HIV post-exposure prophylaxis (O2O-PEP) scale-up among men who have sex with men (MSM): Protocol for developing a pilot randomized controlled trial.

Background: HIV post-exposure prophylaxis (PEP) is an evidence-based biomedical HIV prevention strategy consisting of a 28-day course of highly active antiretroviral therapy after recent potential exposure to HIV. However, awareness and uptake of PEP among men who have sex with men (MSM) are very low. Innovative and effective methods are needed to support PEP implementation among MSM. This work reports a protocol to design and evaluate an online-to-offline-based delivery model for HIV PEP uptake (O2O-PEP) in Chinese MSM. Methods and analysis: This will be a two-phase study. In phase 1, we will develop an O2O-PEP model delivered through the WeChat mini-app (an app built into the WeChat platform). The O2O-PEP model initially includes four core components: a gamification-based education package for PEP, an online HIV risk assessment tool, a free online booking system for PEP initiation, and offline PEP prescription in the study hospitals. In phase 2, a two-arm pilot stratified randomized controlled trial comparing the O2O-PEP group with the standard care group will be designed to assess the feasibility, usability, and preliminary evidence of the efficacy of the O2O-PEP model in increasing PEP uptake among Chinese MSM. Model feasibility and usability will be further explored for broader model implementation. Discussion: The O2O-PEP model is one of the first interventions in China aiming to promote PEP initiation in Chinese MSM. Components in the O2O-PEP model could assist MSM in better understanding their HIV infection risk and increasing accessibility of PEP. Moreover, coupled with online and offline recruitment, the O2O-PEP model has great potential to reach and engage MSM who are not involved in care by traditional methods. Clinical trial registration: No. ChiCTR2200062538.

Cinobufagin induces cell cycle arrest at the S phase and promotes apoptosis in nasopharyngeal carcinoma cells.

Emerging evidence suggests that cinobufagin, an active ingredient in Venenum Bufonis, inhibits cell proliferation in several tumor cells. However, the anti-tumor effect of cinobufagin on nasopharyngeal carcinoma and the underlying molecular mechanisms are still unclear. In this study, we found that cinobufagin significantly inhibits the proliferation of nasopharyngeal carcinoma HK-1 cells. Further analyses demonstrated that cinobufagin induces cell cycle arrest at the S phase in HK-1 cells through downregulating the levels of CDK2 and cyclin E. Moreover, cinobufagin significantly downregulates the protein level of Bcl-2 and upregulates the levels of Bax, subsequently increasing the levels of cytoplasmic cytochrome c, Apaf-1, cleaved PARP1, cleaved caspase-3, and cleaved caspase-9, leading to HK-1 apoptosis. Furthermore, we found that cinobufagin significantly increases ROS levels and decreases the mitochondrial membrane potential in HK-1 cells. Collectively, these data imply that cinobufagin induces cell cycle arrest at the S phase and induces apoptosis through increasing ROS levels, thereby inhibiting cell proliferation in HK-1 cells. Therefore, cinobufagin is a promising bioactive agent that may contribute to the development of treatment strategies of nasopharyngeal carcinoma.