Epigenetic Regulation of Macrophage Polarization in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the leading cause of hospitalization and death worldwide, especially in developing countries. The increased prevalence rate and mortality due to CVDs, despite the development of several approaches for prevention and treatment, are alarming trends in global health. Chronic inflammation and macrophage infiltration are key regulators of the initiation and progression of CVDs. Recent data suggest that epigenetic modifications, such as DNA methylation, posttranslational histone modifications, and RNA modifications, regulate cell development, DNA damage repair, apoptosis, immunity, calcium signaling, and aging in cardiomyocytes; and are involved in macrophage polarization and contribute significantly to cardiac disease development. Cardiac macrophages not only trigger damaging inflammatory responses during atherosclerotic plaque formation, myocardial injury, and heart failure but are also involved in tissue repair, remodeling, and regeneration. In this review, we summarize the key epigenetic modifications that influence macrophage polarization and contribute to the pathophysiology of CVDs, and highlight their potential for the development of advanced epigenetic therapies.

A community-based comprehensive intervention to reduce syphilis infection among low-fee female sex workers in China: a matched-pair, community-based randomized study.

BACKGROUND: Low-fee female sex workers (FSWs) are at high risk of acquiring and spreading human immunodeficiency virus (HIV)/sexually transmitted diseases (STDs) in China. There is an urgent need to develop comprehensive intervention measures targeted towards low-fee FSWs to reduce HIV/STD infections. Thus, this study aimed to reduce HIV/STD infections among low-fee FSW through a matched-pair, community-based randomized intervention trial carried out in 12 cities in three provinces in China. METHODS: Four cities from Guangxi Zhuang Autonomous Region, four from Yunnan Province, and four from Hunan Province were paired and participants received either the intervention package (including condom promotion, HIV and syphilis testing, reimbursement for syphilis treatment costs, and free anti-retroviral therapy or the current standard of care. Venue-based, convenience sampling was used to recruit FSWs. A face-to-face interview and HIV and syphilis blood testing was conducted at baseline and follow-up intervals of 24 months. Generalized linear mixed models (GLMM) were used to evaluate the effect of the intervention package on reducing HIV/STD infection in the FSWs. RESULTS: A total of 1024 eligible FSWs were enrolled in the baseline survey and 843 in the follow-up. GLMM results showed that syphilis infection was reduced by 49% in the intervention group compared to the current standard of care group (P = 0.0378, OR = 0.51, 95% CI: 0.27-0.96). FSWs aged 35 years or older were 2.38 times more likely to get syphilis infection compared to those younger than 35 years old (P <  0.0001, OR = 2.38, 95% CI: 1.55-3.65). The risk of syphilis infection among more educated FSWs was 0.43 times less than those with lower levels of education (P <  0.05, OR = 0.43, 95% CI: 0.63-0.93). CONCLUSIONS: This study demonstrates that comprehensive interventions can lead to significant declines in syphilis infection amongst low-tier FSWs. Integrating both behavioral and biomedical intervention measures should be considered when developing programs for low-fee FSWs. TRIAL REGISTRATION: CHiCTR-TRC-12002655.

Genetic Characteristics of CRF01_AE Among Newly Diagnosed HIV-1-Infected 16- to 25-Year Olds in 3 Geographic Regions of Guangxi, China.

The aim of this study was to analyze the distribution of clusters and drug resistance of CRF01_AE among newly diagnosed, treatment-naïve HIV-infected teenagers and young adults in 3 major HIV-affected geographic regions of Guangxi Province, including the cities of Hezhou, Liuzhou, and Nanning. Samples were sequentially collected from newly diagnosed HIV-infected 16- to 25-year olds in these 3 regions from 2009 to 2013. The viral genome was extracted, and the partial pol gene was amplified and sequenced. Phylogenetic analyses were used to determine HIV-1 subtypes and CRF01_AE clusters. Transmitted drug resistance (TDR) mutations were identified using the 2009 WHO list of TDR mutations. A total of 216 sequences were obtained from CRF01_AE strains, which accounted for 83.1% of the 260 genotyped samples, of which 36 were from Hezhou, 147 from Liuzhou, and 33 in Nanning. Most (83.3%, 180/216) were from heterosexuals, followed by injection drug users (5.6%), homosexuals (4.2%), and unknown risk group (6.9%). Based on phylogenetic analyses by the maximum likelihood method, 5 distinct clusters (cluster 1-5) were identified with 213 (98.6%) sequences, whereas 3 (1.4%) sequences were ungrouped. In Hezhou, 88.9% (32/36) of CRF01_AE infections were caused by cluster 2, and 11.1% (4/36) were caused by cluster 1. In Liuzhou, 83.0% (122/147) of the CRF01_AE strains were found in cluster 1, 11.6% (17/147) from cluster 2, 1.4% (2/147) from cluster 3, 2.7% (4/147) from cluster 4, and 0.7% (1/147) from cluster 5. The distribution of CRF01_AE clusters was more even in Nanning than it was in the other 2 regions, with 18.2% (6/33) from cluster 1, 36.3% (12/33) from cluster 2, 9.1% (3/33) from cluster 3, 18.2% (6/33) from cluster 4, and 12.1% (4/33) from cluster 5. The most frequent TDR mutations were M46I (2) in the protease region and Y181C (2) from the reverse transcriptase fragment. Clusters 1 and 2 of CRF01_AE strains were prevalent in Liuzhou and Hezhou, respectively. However, multiple CRF01_AE clusters existed in Nanning. This can be partially explained by the high mobility of laborers in Nanning, the capital city of Guangxi. The prevalence of TDR was low.

[Investigation on the risk factors for HIV infection among elderly male clients of the commercial female sex-workers in Guangxi Zhuang Autonomous Region, in 2012].

OBJECTIVE: To monitor the current HIV prevalence, related risk behaviors and factors for HIV infection among the elderly male clients of the commercial female sex-workers (CFSW)in Guangxi. METHODS: Face to face interview on male clients aged ≥40 years old was carried out in April to July, 2012. Information on demography, awareness of HIV prevention, related risk behaviors, history on HIV testing etc. were collected, with 3-5 ml full blood collected for testing on HIV. Data was analyzed by SPSS 18.0 software. RESULTS: 4260 clients were surveyed at 14 surveillance sites in which 82.1% had received secondary or lower education, 72.0% experienced commercial sex in places with low-class sex trade. HIV awareness rate of clients was 74.2% in which the rate of clients who were HIV positive was 65.8%. Among all the clients, 73 were detected as HIV positive, with the HIV positive rate as 1.40% . Samples from voluntary counseling and testing sites showed higher risk to HIV infection than from other sources (OR = 23.672, 95%CI:4.984-112.434). Samples from middle class population showed lower risk to HIV infection than those at low class (OR = 0.410, 95%CI:0.190-0.885). Among those who were syphilis negative (OR = 0.255, 95%CI: 0.132-0.491) or hepatitis C virus (HCV)negative (OR = 0.154, 95% CI:0.059-0.401), the risk of getting HIV infected seemed to be low. Rate on condom use was low for clients among all of the sex-related behaviors regardless of the marriage status. In those lower-class sex trade places, lower rate on the condom use was seen. Rate for previous HIV testing for clients was only 4.6% . Among 41 clients who had received CD4 testing, 80.5% of them showed CD4 under 350 cell/µl, 61.0% were under 200 cell/µl. CONCLUSION: The HIV positive rate for elderly male clients of the CFSWs was high in Guangxi. Unprotective sexual contact with low class sex workers was the most important risk factor for HIV infection.

The effect of a structural intervention for syphilis control among 3597 female sex workers: a demonstration study in South China.

BACKGROUND: Syphilis has made a rapid resurgence in China, especially among high-risk groups including female sex workers (FSWs). METHODS: Two cities in each of 3 provinces in South China were chosen and allocated to intervention or control arms. The intervention consisted of enhancing community-based syphilis screening outreach intervention with comprehensive sexually transmitted infection services at designated clinics while the control maintained routine intervention activities. Generalized linear modeling was used to examine effect of the intervention on incident syphilis infection. RESULTS: A total of 8275 women were eligible, and 3597 women enrolled (n = 2011 in control arm, n = 1586 in intervention arm) in the study. The median follow-up duration was 375 days (interquartile range, 267­475). Syphilis incidence density in the intervention group was reduced by 70% (95% confidence interval, 53%­81%) compared with the incidence in the control arm. The syphilis prevention intervention benefits were robust among FSWs at low-tier venues, individuals with less than high school education, migrants, and women who did not report condom use during the last episode of sex. CONCLUSIONS: Integrated sexually transmitted infection and human immunodeficiency virus prevention strategies substantially reduce syphilis incidence among FSWs, especially among those at low-tier venues. This intervention suggests the need for scaling up comprehensive FSW programs in China.

Acceptability of hypothetical microbicides among women in sex establishments in rural areas in Southern China.

OBJECTIVES AND GOAL: The objectives of this study were to measure the potential acceptability of a hypothetical microbicide among women in sex establishments in rural areas of Southern China and demographic, behavioral, and social context factors likely to affect microbicide acceptability. STUDY DESIGN: This was a cross-sectional survey, using a quota sampling, among 300 women from sex establishments in 3 rural towns. An interviewer-administered standardized questionnaire was used to measure the acceptability score of hypothetical microbicides' characteristics, as well as sexual relationships and behaviors and other contextual factors. RESULTS: Findings showed a generally positive response to microbicides, indicated by an acceptability index score of 2.89 (SD, 0.56, scale of 1-4) in the overall sample. Multivariate analysis shows that the acceptability score varied significantly by study sites, type of sex-work establishments, marital status, sex partner type, vaginal product experience, locus of control by partners, and locus of control by chance. CONCLUSIONS: Microbicides may be acceptable among sex workers in rural settings in China; however, contextual factors should be carefully considered in education and promotion of microbicides in the future.