Background HIV testing is an essential gateway to HIV prevention and treatment thus controlling the HIV epidemic. More innovative interventions are needed to increase HIV testing among men who have sex with men (MSM) since their testing rate is still low. We proposed an online HIV test results exchange mechanism whereby the one without a certified online HIV report will be asked to test HIV for exchanging HIV report with others. The exchange mechanism is developed as an extension to the existing online HIV testing service system. Through the extended system, MSM can obtain certified online HIV reports and exchange their reports with friends via WeChat. This study aims to assess effectiveness of the exchange mechanism to increase the HIV testing rate among MSM. Methods This study will use a cluster randomized controlled trial (RCT) design. Participants are recruited based on the unit of individual social network, the sender and the receivers of the HIV report. An individual social network is composed of one sender (ego) and one or more receivers (alters). In this study, MSM in an HIV testing clinic are recruited as potential egos and forwarded online reports to their WeChat friends voluntarily. Friends are invited to participate by report links and become alters. Ego and alters serve as a cluster and are randomized to the group using the certified online HIV report with exchange mechanism (intervention group) or without exchange mechanism (control group). Alters are the intervention targeting participants. The primary outcome is HIV testing rate. Other outcomes are sexual transmitted infections, sexual behaviors, HIV testing norms, stigma, risk perception and HIV report delivery. The outcomes will be assessed at baseline and follow-up questionnaires. Analysis will be according to intention to treat approach and using mixed-effect models with networks and individuals as random effects. Discussion This is the first study to evaluate the effectiveness of an HIV test result exchange mechanism to increase the HIV testing among MSM. This assessment of the intervention will also provide scientific evidence on other potential effects. Findings from this study will yield insights for sustainability driven by communities' intrinsic motivation. Trail registration: ClinicalTrials.gov NCT03984136. Registered 12 June 2019.
TcpC is a multifunctional virulence factor of Uropathogenic Escherichia coli (UPEC). Macrophages can differentiate into two different subsets M1 and M2 that play distinct roles in anti-infection immunity. Here, we investigate the influence of TcpC on M1/M2 polarization and the potential mechanisms. Our data showed that M1 markers CD86 and iNOS were significantly inhibited, while the M2 markers CD163, CD206 and Arg-1 were enhanced in macrophages in kidneys from the TcpC-secreting wild-type CFT073 (CFT073wt)-infected pyelonephritis mouse model, compared with those in macrophages in kidneys from TcpC knockout CFT073 mutant (CFT073Δtcpc)-infected mice. CFT073wt or recombinant TcpC (rTcpC) treatment inhibits LPS + IFN-γ-induced CD80, CD86, TNF-α and iNOS expression, but promotes IL-4-induced CD163, CD206, Arg-1 and IL-10 expression in both human and mouse macrophage cell lines THP-1 and J774A.1. Moreover, rTcpC significantly attenuated LPS + IFN-γ-induced phosphorylation of p38, ERK, p50 and p65 but enhanced IL-4-induced phosphorylation of Akt and STAT6. These data suggest that TcpC inhibits M1 but promotes M2 macrophage polarization by down-regulation of p38, ERK/NF-κB and up-regulation of the Akt/STAT6 signaling pathway, respectively. Our findings not only illuminate the regulatory effects of TcpC on macrophage M1/M2 polarization and its related signaling pathways, but also provide a novel mechanism underlying TcpC-mediated immune evasion of macrophage-mediated innate immunity.
Preexposure prophylaxis (PrEP) is not available in China and the willingness to use PrEP among Chinese men who have sex with men (MSM) is not clear. The aim of this study was to better understand the association between PrEP comprehension and the willingness to use PrEP under varying conditions among MSM. An online survey investigating personal characteristics, PrEP comprehension, and PrEP willingness among MSM was conducted. A third of respondents (36.2%, 196 out of 541) reported that they would like to use PrEP. Compared with MSM with a basic level of PrEP comprehension, MSM with a high level were more likely to report clear choices: a willingness or unwillingness to use PrEP (82.4% versus 65.7%, p <0.01). Among 350 MSM willing to use PrEP or uncertain about uptake, those with a high level of PrEP comprehension were more likely to use PrEP daily (adjusted odds ratio [AOR] = 1.71, 95% confidence interval 1.04-2.80), and to use PrEP with mild or other side effects (AOR = 2.72 or 2.77). A high level of PrEP comprehension is a key factor in urging MSM to use PrEP under varying conditions. Our findings call attention to the need for health education to improve PrEP comprehension.
BackgroundThe decline in the quantity and quality of oocytes due to ovarian ageing in women is now a significant threat to reproductive health today as the concept of delayed fertility becomes widespread. However, the molecular mechanisms of natural ovarian ageing have not been fully elucidated.MethodHere, we used transcriptomic data from 180 normal ovarian tissues from GTEx V8 to analyze the expression profile of ovarian tissues from women with age segments of 20-29 (22 individuals), 30-39 (14 individuals), 40-49 (37 individuals), 50-59 (61 individuals), 60-69 (42 individuals), and 70-79 (4 individuals), respectively. XCELL was used to assess the infiltration score of 64 cell types of the ovary. WGCNA was used to characterize the co-expression network during the natural aging of the ovary. ClusterprofileR was used for functional enrichment analysis of co-expression modules. MsViper was used for master regulator analysis.ResultsThe infiltration score of endothelial cells and activated antigen-presenting cells during natural ovarian ageing increased significantly at ages 30-39, 40-49, and then decreased, whereas CD4+ Tcm increased with age. WGCNA identified six co-expression modules from ovarian tissue transcriptomic data species. The red module was significantly and positively correlated with senescence and CD4+ Tcm, and the turquoise module was significantly and positively correlated with Endothelial Cells. We further explored ovarian tissue for women aged 20-29 and 30-39 years. The GSEA results showed that the Chemokine signaling pathway was significantly activated in the 30-39-year-old group, while Oocyte meiosis was significantly inhibited. Finally, the results of msviper found that transcription factors such as KDM1A, PRDM5, ZNF726, PPARG, FOXJ2, and GLI2 were mainly activated in the 20-29 years group, while VAV1, RUNX3, ZC3H12D, MYCL, and IRF5 were mainly activated in the 30-39 years group and that these transcription factor activities were diagnostic of natural ovarian ageing (AUC: 0.65-0.71).ConclusionNatural ageing of the ovary is significantly correlated with immune cell infiltration and activation of inflammation-related signaling pathways, with inflammation levels reaching a maximum during early ovarian ageing (30-39, 40-49) and then gradually decreasing after that. These studies provide a research basis for exploring the mechanisms of natural ovarian ageing.
Pyroptosis, an inflammatory programmed cell death, is characterized by the caspase-mediated pore formation of plasma membranes and the release of large quantities of inflammatory mediators. In recent years, the morphological characteristics, induction mechanism and action process of pyroptosis have been gradually unraveled. As a malignant tumor with high morbidity and mortality, cervical cancer is seriously harmful to women's health. It has been found that pyroptosis is closely related to the initiation and development of cervical cancer. In this review the mechanisms of pyroptosis and its role in the initiation, progression and treatment application of cervical cancer are summarized and discussed.
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