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Evidence showed preventive impacts of the highly active antiretroviral therapy (HAART) on the Human Immunodeficiency Virus (HIV) transmission amomg heterosexual population, however, that is of deficit among men who have sex with men (MSM). The aim was to systematically examine the efficacy of HAART on HIV transmission and the association between the HAART initiation and unprotected anal intercourse (UAI) in MSM population. Three electronic databases were fully searched for articles published in peer-reviewed journals between 1996 and 2017. Of 1616 identified articles, fifteen articles were eligible for meta-analyses. The summary incidence rate (IR) of HIV was 6.63/100 person-year (95%CI 2.06–11.20/100 person-year)(p = 0.004). The pooled per-contact rate (PCR) of HIV was 0.42% (95% CI 0.21–0.63%)(p 0.05). In the stratified analysis, participants with no less than 6 months recall period was slightly more likely to engage in UAI (OR 1.32; 95% CI 1.01–1.74)(p

The number of poly-drug users who mix use heroin and synthetic drugs (SD) is increasing worldwide. The objective of this study is to measure the risk factors for being infected with hepatitis C (HCV), human immunodeficiency virus (HIV) and syphilis among SD-only users, heroin-only users and poly-drug users. A cross-sectional study was conducted in 2015 from a national HIV surveillance site in Southwest China, 447 poly-drug, 526 SD-only and 318 heroin-only users were recruited. Poly-drug users have higher drug-use frequency, higher rates of drug-sharing and unsafe sexual acts than other users (p p

There is ample evidence indicating that epicardial adipose tissue (EAT) volume and thickness is positively associated with coronary artery disease (CAD). However, the exact pathological changes in the human EAT after myocardial ischemia remains largely unclear. In the current study, we applied a comparative quantitative proteomics to elucidate the altered biological processes in the EAT of ischemic cardiomyopathy (ICM) patients. A total of 1649 proteins were successfully quantified in our study, among which 165 proteins were significantly changed (ratio 1.2 fold and p

Strategies that enhance the function of T cells are critical for immunotherapy. One negative regulator of T-cell activity is ligand PD-L1, which is expressed on dentritic cells (DCs) or some tumor cells, and functions through binding of programmed death-1 (PD-1) receptor on activated T cells. Here we described for the first time a non-viral mediated approach to reprogram primary human T cells by disruption of PD-1. We showed that the gene knockout of PD-1 by electroporation of plasmids encoding sgRNA and Cas9 was technically feasible. The disruption of inhibitory checkpoint gene PD-1 resulted in significant reduction of PD-1 expression but didn’t affect the viability of primary human T cells during the prolonged in vitro culture. Cellular immune response of the gene modified T cells was characterized by up-regulated IFN-γ production and enhanced cytotoxicity. These results suggest that we have demonstrated an approach for efficient checkpoint inhibitor disruption in T cells, providing a new strategy for targeting checkpoint inhibitors, which could potentialy be useful to improve the efficacy of T-cell based adoptive therapies.

The number and subtype composition of N-methyl-d-aspartate receptor (NMDAR) at synapses determines their functional properties and role in learning and memory. Genetically increased or decreased amount of GluN2B affects hippocampus-dependent memory in the adult brain. But in some experimental conditions (e.g., memory elicited by a single conditioning trial (1 CS-US)), GluN2B is not a necessary factor, which indicates that the precise role of GluN2B in memory formation requires further exploration. Here, we examined the role of GluN2B in the consolidation of fear memory using two training paradigms. We found that GluN2B was only required for the consolidation of memory elicited by five conditioning trials (5 CS-US), not by 1 CS-US. Strikingly, the expression of membrane GluN2B in CA1was training-strength-dependently increased after conditioning and that the amount of membrane GluN2B determined its involvement in memory consolidation. Additionally, we demonstrated the increases in the activities of cAMP, ERK and CREB in the CA1 after conditioning, as well as the enhanced intrinsic excitability and synaptic efficacy in CA1 neurons. Up-regulation of membrane GluN2B contributed to these enhancements. These studies uncover a novel mechanism for the involvement of GluN2B in memory consolidation by its accumulation at the cell surface in response to behavioral training.

Strategies that enhance the function of T cells are critical for immunotherapy. One negative regulator of T-cell activity is ligand PD-L1, which is expressed on dentritic cells (DCs) or some tumor cells and functions through binding of programmed death-1 (PD-1) receptor on activated T cells. Here we described for the first time a non-viral mediated approach to reprogram primary human T cells by disruption of PD-1. We showed that the gene knockout of PD-1 by electroporation of plasmids encoding sgRNA and Cas9 was technically feasible. The disruption of inhibitory checkpoint gene PD-1 resulted in significant reduction of PD-1 expression but didn’t affect the viability of primary human T cells during the prolonged in vitro culture. Cellular immune response of the gene modified T cells was characterized by up-regulated IFN-γ production and enhanced cytotoxicity. These results suggest that we have demonstrated an approach for efficient checkpoint inhibitor disruption in T cells, providing a new strategy for targeting checkpoint inhibitors, which could potentialy be useful to improve the efficacy of T-cell based adoptive therapies.

The health impacts of polycyclic aromatic hydrocarbons (PAHs), the most concerning organic pollutants, depend not only on the locations and strengths of emission sources, but also on individual susceptibility. Moreover, trans-boundary transport makes them a global concern. In this study, a comprehensive analysis of the global health impacts of polycyclic aromatic hydrocarbons (PAHs) in ambient air is presented. Model resolution is critical in exposure modelling. Globally, incremental lifetime lung cancer risk (ILCR) induced by ambient PAH exposure is 3.1 × 10(-5). If the individual susceptibility was not taken into consideration, the overall risk would be underestimated by 55% and the proportion of highly vulnerable population would be underestimated by more than 90%. Emphasizing on individual susceptibility, our study provides an instrumental revision of current risk assessment methodology. In terms of lung cancer risk, the most important sources are combustion of biomass fuels (40%) and fossil fuels (14%) in the residential/commercial sector, coke (13%) and aluminium (12%) production, and motor vehicles (9%). PAHs can travel long distance globally especially within the Eurasian continent. Still, the risk is dominantly contributed by local.