Patterns of Sexually Transmitted Co-infections and Associated Factors Among Men Who Have Sex With Men: A Cross-Sectional Study in Shenyang, China.

Background: Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infections (STIs). We sought to describe patterns of sexually transmitted co-infections and explore factors associated with increased acquisition of STIs among MSM. Methods: We enrolled MSM in Shenyang, China, between July and December 2020 to test for four STIs, including human papillomavirus (HPV), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Treponema pallidum (TP). Data regarding demographic and behavioral characteristics of participants were collected through a self-administered digital questionnaire. We adopted the ordinal logistic regression model to identify factors associated with acquiring more STIs. Results: Overall, 177 participants with completed test results for all four STIs were analyzed. These participants had a median age of 29.0 (interquartile range: 23.0-38.0) years. The prevalence of STI co-infections was 23.7% [42/177; 95% confidence interval (CI), 17.8%-30.8%], among which HPV/CT (47.1%) and HPV/CT/NG (50.0%) co-infection were the predominant types among participants with dual and multiple infections, respectively. Participants who had a higher educational background [adjusted odds ratio (aOR), 0.46; 95% CI, 0.24-0.85; P = 0.014] and had a history of STIs (aOR, 2.53; 95% CI, 1.24-5.18; P = 0.011) were positively associated with acquiring more STIs. Conclusions: MSM in Shenyang suffer a substantial burden of sexually transmitted co-infections. An optimized multi-STI integration strategy targeting prevention, surveillance, screening, and treatment is warranted to reduce the prevalence of sexually transmitted co-infections, especially in less-educated MSM.

Association of HIV Preexposure Prophylaxis Use With HIV Incidence Among Men Who Have Sex With Men in China: A Nonrandomized Controlled Trial.

Importance: Evidence on HIV preexposure prophylaxis (PrEP) among Chinese men who have sex with men (MSM) is critical to guide its large-scale implementation in low- and middle-income countries. Objective: To evaluate incident HIV infection, adherence, safety, and changes in sexual behaviors among MSM using daily PrEP (D-PrEP) and event-driven PrEP (ED-PrEP) in 4 cities in China. Design, Setting, and Participants: This nonrandomized controlled trial was conducted among HIV-seronegative MSM from December 11, 2018, to November 30, 2020, in Beijing, Shenyang, Chongqing, and Shenzhen. Participants self-chose D-PrEP or ED-PrEP regimens at baseline and could switch regimens during the 12-month study period. HIV-negative MSM who declined to initiate PrEP (nonusers) in the same cities joined a separate parallel prospective cohort and served as control individuals. Interventions: PrEP consisted of coformulated tenofovir disoproxil fumarate, 300 mg, and emtricitabine, 200 mg. Main Outcomes and Measures: The main outcome was incident HIV infection. Poisson regression was used to obtain the HIV incidence rate ratio (IRR). Results: A total of 1530 MSM were included in the analysis (median age, 30 [IQR, 25-37] years). At baseline, 520 MSM chose D-PrEP (median age, 29 [IQR, 25-35] years) and 503 chose ED-PrEP (median age, 29 [IQR, 25-36] years). The median HIV Risk Index score was 18 (IQR, 12-22) among D-PrEP users and 18 (IQR, 11-22) among ED-PrEP users. Among 507 PrEP nonusers, the median age was 33 (IQR, 27-43) years, and the median HIV Risk Index score was 12 (IQR, 7-18). Although PrEP users had more baseline behaviors associated with HIV risk, the HIV incidence was lower among all PrEP users (adjusted IRR, 0.09 [95% CI, 0.04-0.21]), ED-PrEP users (adjusted IRR, 0.05 [95% CI, 0.01-0.22]), and D-PrEP users (adjusted IRR, 0.12 [95% CI, 0.04-0.33]) compared with PrEP nonusers. There was no difference in HIV incidence between D-PrEP users and ED-PrEP users (IRR, 0.33 [95% CI, 0.06-2.04]). Event-driven PrEP users consumed 40% fewer tablets than D-PrEP users during the study period. Adherence, defined as the proportion of self-reported days with sexual intercourse in which PrEP was taken according to prescription of at least 90%, increased over time among ED-PrEP users (from 57.4% to 77.8%; P < .001 for trend) and decreased over time among D-PrEP users (from 75.1% to 72.1%; P = .02 for trend). Daily PrEP users reported fewer adverse events than ED-PrEP users (193 of 520 [37.1%] vs 241 of 503 [47.9%]). Conclusions and Relevance: The findings of this study suggest that D-PrEP and ED-PrEP regimens are associated with lower incidence of HIV and a good safety profile among high-risk MSM in China. Trial Registration: Chinese Clinical Trial Registry number: ChiCTR-IIN-17013762.

High Human Papillomavirus Vaccine Acceptability and Cost-Effectiveness of the Chinese 2-Valent Vaccine Among Men Who Have Sex With Men: A Cross-Sectional Study in Shenyang, China.

Background: Despite the insupportable burden caused by the human papillomavirus (HPV) and high vaccine acceptability, vaccination programs are not currently available for men who have sex with men (MSM). We aimed to assess HPV infection by examining the willingness for vaccination among MSM and cost-effectiveness of the Chinese 2-valent HPV vaccine. Methods: We recruited MSM in Shenyang, China between July and December 2020 to conduct anal HPV testing and an online survey regarding HPV-related knowledge and vaccine acceptability. We performed a cost-effectiveness analysis to evaluate the incremental cost-effectiveness ratios (ICERs) of the Chinese 2-valent HPV vaccine. Results: A total of 234 participants completed the online survey; of those, 203 were successfully tested for HPV. The median age was 30 years [interquartile range (IQR): 23-38 years]. Most participants had at least undergraduate education (136/234, 58.1%). The acceptability rate for the free HPV vaccine was 57.7% (135/234). The prevalence of HPV types 16 and 18 was 14.9% (18/121) and 26.8% (22/82) in the willing and unwilling to vaccinate groups, respectively (P > 0.05). The prevalence of high-risk HPV among participants aged <30 and ≥50 years was 48.6 and 38.9%, respectively. Using the Chinese per capita gross domestic product (GDP) as a threshold, the Chinese 2-valent HPV vaccine would be a "very cost-effective" strategy, with an ICER value of USD 4,411. This evidence showed that the Chinese 2-valent HPV vaccine was more cost-effective than other imported vaccines. Conclusions: Targeted strategies should be utilized in MSM with different rates of vaccine acceptability. A pilot HPV vaccination program based on the Chinese 2-valent HPV vaccine for MSM is urgently warranted to reduce the burden of HPV and anal cancer.

Factors Influencing Clinicians' Willingness to Prescribe Pre-exposure Prophylaxis for Persons at High Risk of HIV in China: Cross-sectional Online Survey Study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is an effective HIV prevention measure. Clinicians play a crucial role in PrEP implementation, and their knowledge, attitudes, and career experience may affect their willingness to prescribe PrEP. However, little is known about the attitudes and willingness of clinicians to prescribe PrEP in countries without PrEP-specific guidelines. OBJECTIVE: We aimed to determine the factors associated with clinicians being willing to prescribe PrEP in China. METHODS: Between May and June 2019, we conducted an online cross-sectional survey of clinicians in 31 provinces across the six administrative regions in China on the WeChat smartphone app platform. Multivariable logistic regression was used to determine factors associated with willingness to prescribe PrEP. RESULTS: Overall, 777 HIV clinicians completed the survey. Most of the respondents had heard of PrEP (563/777, 72.5%), 31.9% (248/777) thought that PrEP was extremely effective for reducing the risk of HIV infection, and 47.2% (367/777) thought that it was necessary to provide PrEP to high-risk groups. After adjusting for age, gender, ethnicity, and educational background of the clinicians, the following factors significantly increased the odds of the clinicians being willing to prescribe PrEP: having worked for more than 10 years, compared to 5 years or less (adjusted odds ratio [aOR] 2.82, 95% CI 1.96-4.05); having treated more than 100 patients living with HIV per month, compared to 50 patients or fewer (aOR 4.16, 95% CI 2.85-6.08); and having heard of PrEP (aOR 7.32, 95% CI 4.88-10.97). Clinicians were less likely to be willing to prescribe PrEP if they were concerned about poor adherence to PrEP (aOR 0.66, 95% CI 0.50-0.88), the lack of PrEP clinical guidelines (aOR 0.47, 95% CI 0.32-0.70), and the lack of drug indications for PrEP (aOR 0.49, 95% CI 0.32-0.76). CONCLUSIONS: About half of all clinicians surveyed were willing to prescribe PrEP, but most surveyed had a low understanding of PrEP. Lack of PrEP clinical guidelines, lack of drug indications, and less than 11 years of work experience were the main barriers to the surveyed clinicians' willingness to prescribe PrEP. Development of PrEP clinical guidelines and drug indications, as well as increasing the availability of PrEP training, could help improve understanding of PrEP among clinicians and, thus, increase the number willing to prescribe PrEP.

Context and Barriers to the Prescription of Nonoccupational Postexposure Prophylaxis Among HIV Medical Care Providers: National Internet-Based Observational Study in China.

BACKGROUND: Nonoccupational postexposure prophylaxis (nPEP) is an effective HIV biomedical prevention strategy. The research and use of nPEP are mainly concentrated in the developed world, while little is known about the knowledge, attitudes, and practices of nPEP among HIV medical care providers in developing countries. OBJECTIVE: We aimed to assess the nPEP knowledge and prescribing practice among HIV medical care providers in mainland China. METHODS: HIV medical care providers were recruited in China during May and June 2019 through an online survey regarding nPEP-related knowledge, attitudes, and clinical prescription experiences. Multivariable logistic regression was performed to identify factors associated with prescribing nPEP among HIV medical care providers. RESULTS: A total of 777 eligible participants participated in this study from 133 cities in 31 provinces in China. Of the participants, 60.2% (468/777) were unfamiliar with nPEP and only 53.3% (414/777) of participants ever prescribed nPEP. HIV care providers who worked in a specialized infectious disease hospital (vs general hospital, adjusted odds ratio [aOR] 2.49; 95% CI 1.85-3.37), had practiced for 6-10 years (vs 5 or fewer years, aOR 3.28; 95% CI 2.23-4.80), had practiced for 11 years or more (vs 5 or fewer years, aOR 3.75; 95% CI 2.59-5.45), and had previously prescribed occupational PEP (oPEP, aOR 4.90; 95% CI 3.29-7.29) had a significantly positive association with prescribing nPEP. However, unfamiliarity with nPEP (aOR 0.08; 95% CI 0.05-0.11), believing nPEP may promote HIV high-risk behavior (aOR 0.53; 95% CI 0.36-0.77) or result in HIV drug resistance (aOR 0.53; 95% CI 0.36-0.77) among key populations, and self-reported having no written oPEP guideline in place (aOR 0.53; 95% CI 0.35-0.79) were negatively associated with nPEP prescription behavior. CONCLUSIONS: HIV medical care providers have insufficient nPEP knowledge and an inadequate proportion of prescribing, which may impede the scale-up of nPEP services to curb HIV acquisition. The implementation of tailored nPEP training or retraining to HIV medical care providers would improve this situation.

CircRNA Circ-ITCH Inhibits the Proliferation and Invasion of Glioma Cells Through Targeting the miR-106a-5p/SASH1 Axis.

Circ-ITCH, a novel circRNA, was generated from several exons of itchy E3 ubiquitin protein ligase (ITCH). Recently, circ-ITCH has been demonstrated to be involved in cancer development. However, there have been few investigations on the specific role of circ-ITCH in glioma. In this study, we performed quantitative real-time polymerase chain reaction analysis and identified that circ-ITCH was significantly downregulated in glioma tissues and cell lines. The function assays showed that upregulation of circ-ITCH inhibited glioma cell proliferation and invasion in vitro as well as reduced cell growth in vivo. Moreover, miR-106a-5p was found serving as a target of circ-ITCH and miR-106a-5p mimics could reverse the inhibitory effect of circ-ITCH on glioma cell proliferation and invasion. We also revealed that circ-ITCH increased SASH1 expression by sponging miR-106a-5p in glioma cells. In addition, SASH1 downregulation could abrogate the suppressive effect of circ-ITCH on glioma progression. Taken together, our results suggested that circ-ITCH could suppress glioma cell proliferation and invasion via regulating the miR-106a-5p/SASH1 axis, elucidating a novel molecular target for glioma treatment.

Correction: Risk-Taking Behaviors and Adherence to HIV Pre-Exposure Prophylaxis in Users of Geosocial Networking Apps: Real-World, Multicenter Study.

[This corrects the article DOI: 10.2196/22388.].

Risk-Taking Behaviors and Adherence to HIV Pre-Exposure Prophylaxis in Users of Geosocial Networking Apps: Real-World, Multicenter Study.

BACKGROUND: Over half of men who have sex with men (MSM) use geosocial networking (GSN) apps to encounter sex partners. GSN apps' users have become a unique large subpopulation among MSM for interventions concerning HIV prevention and control. Pre-exposure prophylaxis (PrEP) is a promising measure for HIV prevention, especially for MSM, but its effectiveness largely depends on medication adherence. However, little is known about PrEP adherence among GSN apps' users, which is critical to addressing the overall optimization of PrEP compliance outside of clinical trials in the context of large-scale implementation. OBJECTIVE: The objective of this study is to understand the correlation between GSN apps' use and medication adherence among MSM receiving PrEP, with the aim to increase their awareness about PrEP use in order to increase adherence. METHODS: This study based on the China Real-world Oral intake of PrEP (CROPrEP) project, a multicenter, real-world study of Chinese MSM on daily and event-driven PrEP. Eligible participants completed a detailed computer-assisted self-interview on sociodemographic, GSN apps' use, and sexual behavior. Then participants were followed up for 12 months and assessed for various characteristics (eg, PrEP delivery, adherence assessment, PrEP coverage of sexual activities, and regimens switch). A generalized estimation equation was used to analyze the predictors of medication adherence and regimen conversion among GSN apps' users and nonusers. RESULTS: At baseline, 756 of the 1023 eligible participants (73.90%) reported primarily using GSN apps to seek sexual partners, and GSN apps' users are more likely to have high-risk behaviors such as multiple sex partners and condomless anal intercourse than other nonusers (all P<.05). During follow-up, GSN apps' users had a significantly low level of pill-counting adherence than nonusers (adjusted odds ratio [aOR] 0.8, 95% CI 0.6-1.0, P=.038). In the event-driven group, GSN apps' users had marginally lower levels of self-reported adherence (aOR 0.7, 95% CI 0.4-1.0, P=.060) and lower PrEP coverage of sexual practices (aOR 0.6, 95% CI 0.4-1.0, P=.038). Additionally, GSN apps' users seemed more likely to switch from event-driven to daily regimen (aOR 1.8, 95% CI 0.9-3.3, P=.084). CONCLUSIONS: GSN apps' users are highly prevalent among MSM, despite their higher sexual risk and lower adherence levels, suggesting that eHealth needs to be introduced to the GSN platform to promote PrEP adherence. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IIN-17013762; https://tinyurl.com/yy2mhrv4. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12879-019-4355-y.

The long noncoding RNA ZFAS1 promotes the progression of glioma by regulating the miR-150-5p/PLP2 axis.

Numerous studies have reported that long noncoding RNA (lncRNA) dysregulation is involved in the progression of many malignant tumors, including glioma. The lncRNA ZNFX1 antisense RNA 1 (ZFAS1) plays an oncogenic role in various malignant tumors, such as gastric cancer and hepatocellular carcinoma. However, the underlying molecular mechanism of ZFAS1 in glioma has not been fully clarified. In this study, we found that the expression of ZFAS1 was upregulated in both glioma tissues and cell lines. Functional experiments revealed that ZFAS1 promoted glioma proliferation, migration and invasion, and increased resistance to temozolomide in vitro. By using online databases, RNA pull-down assays and luciferase reporter assays, ZFAS1 was demonstrated to act as a sponge of miR-150-5p. Furthermore, proteolipid protein 2 (PLP2) was shown to be the functional target of miR-150-5p. Rescue experiments revealed that ZFAS1 regulated the expression of PLP2 by sponging miR-150-5p. Finally, a xenograft tumor assay demonstrated that ZFAS1 promoted glioma growth in vivo. Our results showed that ZFAS1 promoted glioma malignant progression by regulating the miR-150-5p/PLP2 axis, which may provide a potential therapeutic target for the treatment of glioma.

Long non-coding RNA SNHG5 promotes glioma progression via miR-205/E2F3 axis.

In recent years, many studies have reported on the abnormal expression and correlation of long non-coding RNAs (lncRNAs) in tumours. However, the accurate molecular mechanism of lncRNAs in glioma is still in its infancy. In the present study, we aimed to explore the molecular mechanism of small nucleolar RNA host gene 5 (SNHG5) in glioma progression. First, we found that SNHG5 expression was higher in glioma and was related to glioma glucose uptake, migration and invasion. Second, through a series of assays, we concluded that SNHG5 acts as a sponge for miR-205, which inhibits tumour growth in glioma by targeting E2F transcription factor 3 (E2F3). Third, using a xenograft mouse model, we demonstrated that SNHG5 regulates tumourigenesis in vivo Taken together, our results show that the SNHG5/miR-205/E2F3 axis is involved in glioma progression and may provide a new therapeutic target for the diagnosis and therapy of glioma.

Long non-coding RNA HOTAIR acts as a competing endogenous RNA to promote glioma progression by sponging miR-126-5p.

LncRNA HOX transcript antisense intergenic RNA (HOTAIR) has been shown to play prominent roles in tumorigenesis. However, its precise molecular mechanism in glioma has not been completely elucidated. In this study, we found that HOTAIR was aberrantly up-regulated in glioma tissues and was negatively correlated with miR-126-5p expression. Next, we determined that HOTAIR promote glioma progression by sponging miR-126-5p. Subsequently, glutaminase (GLS) was confirmed to be a direct target of miR-126-5p using bioinformatics software and a luciferase reporter assay. Moreover, HOTAIR could modulate GLS expression by functioning as a competing endogenous RNA (ceRNA) for miR-126-5p. Taken together, our study clarified that the HOTAIR/miR-126/GLS pathway is involved in glioma progression and may potentially serve as a target for glioma therapy.

MiR-520b inhibits the development of glioma by directly targeting MBD2.

MicroRNAs play important roles in the process of cancer, which microRNA-520b (miR-520b) has been reported to play critical roles in tumor progression in many types of cancers. However, its role in glioma remains unknown. In this study, we found that miR-520b could inhibit growth and progression in glioma by targeting methyl-CpG-binding domain 2 (MBD2). First, we analyzed the expression of miR-520b in different glioma grades and different cell lines (U87, U251 and astrocyte). Then we assessed the effect of miR-520b on glucose metabolism, invasion, angiogenesis and chemosensitivity in U87 and U251 cells. By using an online database, miR-520b was found to directly bind to the 3'-untranslated regions (3'-UTR) of MBD2 and reduce its expression at the protein level, which further inhibits the development of glioma. MBD2 was also found to be over-expressed in human glioma tissues and in U87 and U251 cells and its level was inversely correlated with that of miR-520b. Furthermore, restoration of MBD2 partially rescued the miR-520b-induced inhibitory effect on glucose metabolism, invasion, angiogenesis and chemosensitivity in glioma cells. In summary, to date, this is the first study to demonstrate that miR-520b functions as a tumor suppressor in glioma by directly targeting MBD2, suggesting that MBD2 may be a potential therapeutic target for glioma.

MiR-421 inhibits the malignant phenotype in glioma by directly targeting MEF2D.

MicroRNA-421 (miRNA-421) dysregulation has been found in various human tumors, however, the biological function and molecular mechanism of miR-421 in glioma remain unclear. In this study, we investigated the potential biological roles of miR-421 in glioma cell lines. First, we demonstrated that compared with that of low grade gliomas (LGG), miR-421 expression is much lower in high grade gliomas (HGG) within the CGGA (Chinese Glioma Genome Atlas) database. MiR-421 expression in 5 normal brain tissues and 20 glioma tissues were in agreement with the result in the CGGA. Second, exogenous expression of miR-421 inhibited glucose metabolism, invasion, angiogenesis and enhanced the radiosensitivity in glioma cell lines. Third, through an online database, myocyte enhancer factor 2D (MEF2D) was identified as a target of miR-421. Interestingly, down-regulation of MEF2D led to an inhibitory effect on glioma glucose metabolism, invasion, angiogenesis and enhancing effect on radiosensitivity, which was similar to the effects of the up-regulation of miR-421. Simultaneously, overexpression of MEF2D partially restored the effect of miR-421 on the glioma cell lines. Finally, in a xenograft model, overexpression of miR-421 suppressed tumorigenicity. These data collectively suggested miR-421 may suppress tumor-associated activity in gliomas by targeting MEF2D.