Chuanyi Ning

Pre-Exposure Prophylaxis for the Prevention of HIV Infection in High Risk Populations: A Meta-Analysis of Randomized Controlled Trials

Background Nearly ten randomized controlled trials (RCTs) of pre-exposure prophylaxis (PrEP) have been completed or are ongoing worldwide to evaluate the effectiveness of PrEP in HIV transmission among HIV-uninfected high risk populations. The purpose of this study was to evaluate the role of PrEP to prevent HIV transmission through a Mata-analysis. Methods A comprehensive computerized literature search was carried out in PubMed, EMbase, Ovid, Web of Science, Science Direct, Wan Fang, CNKI and related websites to collect relevant articles (from their establishment date to August 30, 2013). The search terms were “pre-exposure prophylaxis”, “high risk population”, “HIV infection”, “reduction”, “relative risk” and “efficacy”. We included any RCT assessing PrEP for the prevention of HIV infection in high risk populations. Interventions of the studies were continuously daily or intermittent doses of single or compound antiretrovirals (ARVs) before HIV exposure or during HIV exposure. A meta-analysis was conducted using Stata 10.0. A random-effects method was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CI) for all studies included. Results Seven RCTs involving 14,804 individuals in high risk populations were eligible for this study. The number of subjects in the experimental groups was 8,195, with HIV infection rate of 2.03%. The number of subjects in the control groups was 6,609, with HIV infection rate of 4.07%. The pooled RR was 0.53 (95% CI = 0.40∼0.71, P<0.001). The re-analyzed pooled RR were 0.61 (95% CI = 0.48∼0.77, P<0.001), 0.49 (95% CI = 0.38∼0.63, P<0.001), respectively, by excluding the largest study or two studies without statistical significance. Publication bias analysis revealed a symmetry funnel plot. The fail-safe number was 1,022. Conclusion These results show that PrEP is an effective strategy for reducing new HIV infections in high risk populations.

Comparison of Three Intervention Models for Promoting Circumcision among Migrant Workers in Western China to Reduce Local Sexual Transmission of HIV

Objective Three models for promoting male circumcision (MC) as a preventative intervention against HIV infection were compared among migrant worker populations in western China. Methods A cohort study was performed after an initial cross-sectional survey among migrant workers in three provincial level districts with high HIV prevalence in western China. A total of 1,670 HIV seronegative male migrants were cluster-randomized into three intervention models, in which the dissemination of promotional materials and expert- and volunteer-led discussions are conducted in one, two, and three stage interventions. Changes in knowledge of MC, acceptability of MC, MC surgery uptake, and the costs of implementation were analyzed at 6-month and 9-month follow-up visits. Results All three models significantly increased the participants’ knowledge about MC. The three-stage model significantly increased the acceptability of MC among participants and led to greatest increase in MC uptake. At the end of follow-up, 9.2% (153/1,670) of participants underwent MC surgery; uptake among the one-, two-, and three-stage models were 4.9%, 9.3%, and 14.6%, respectively. Multivariable Cox regression analysis showed that three-stage model was the most effective method to scale up MC, with RR = 2.0 (95% CI, 1.3-3.1, P=0.002) compared to the on-site session model. The two-stage intervention model showed no significant difference with either the on-site session model (RR=1.5, 95% CI, 0.92-2.4, P=0.12) or three-stage model (P=0.10). Conclusions A three-stage intervention with gradual introduction of knowledge led to the significantly increase in MC uptake among migrant workers in western China, and was also the most cost-effective method among the three models.

Suppression of autophagy by mycophenolic acid contributes to inhibition of HCV replication in human hepatoma cells

Previous studies have shown that mycophenolic acid (MPA) has an anti-HCV activity. However, the mechanism of MPA-mediated inhibition of HCV replication remains to be determined. This study investigated whether MPA has an effect on autophagy, a cellular machinery required for HCV replication, thereby, inhibits HCV replication in Huh7 cells. MPA treatment of Huh7 cells could suppress autophagy, evidenced by decreased LC3B-II level and conversion of LC3B-I to LC3B-II, decreased autophagosome formation, and increased p62 level compared to MPA-untreated cells. Tunicamycin treatment or HCV infection could induce cellular autophagy, however, MPA also exhibited its inhibitory effect on tunicamycin- or HCV infection-induced autophagy. The expression of three autophagy-related genes, Atg3, Atg5, and Atg7 were identified to be inhibited by MPA treatment. Over-expression of these genes could partly recover HCV replication inhibited by MPA; however, silencing their expression by siRNAs could enhance the inhibitory effect of MPA on HCV. Collectively, these results reveal that suppression of autophagy by MPA plays a role in its anti-HCV activity. Down-regulating the expression of three autophagy-related genes by MPA involves in its antiviral mechanism.

Accuracy of rapid diagnosis of Talaromyces marneffei: A systematic review and meta-analysis

Background To examine the accuracy of Rapid Diagnosis of Talaromyces marneffei (RDTM) in order to improve diagnosis and treatment for clinical measures and reduce the mortality due to associated infections. Methods In this systematic review and meta-analysis, we screened PubMed, Ovid (Cochrane library) and Web of Science, Chinese database CNKI and Wanfang for articles published between 1956 and December, 2017. Data were taken from cross-sectional studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with T. marneffei and a control cohort or a cohort with standard fungus culture. Data were extracted by two authors and checked by three for accuracy. For quality assessment, modified QUADAS-2 criteria were used. Results The 26 included diagnostic studies enrolled 5,594 objectives in 632 patients with T. marneffei infections and 2,612 negative controls between 1996 and 2017 in Thailand, Vietnam and China. The total combined sensitivity and specificity of rapid diagnosis of T. marneffei was 0.82 (95% CI: 0.68–0.90) and 0.99 (95% CI: 0.98–1.00). According to the experimental method, the included studies can be divided into three subgroups, including PCR-based, ELISA-based and others. The results showed these three subgroups had a highly pooled specificity of 1.00 (95% CI: 0.99–1.00), 0.99 (0.98–1.00) and 0.97 (95% CI: 0.91–1.00), respectively, while combined sensitivity was 0.84 (95% CI: 0.37–0.98), 0.82 (95% CI: 0.64–0.92) and 0.77 (95% CI: 0.54–0.91), respectively. Conclusions Although serological methods with a high specificity is essential for potential rapid diagnostic, false-negative results can be obtained in the serum samples, there is no suitable rapid serological test to refer to as is the case with TM infection.

Impact of Educational Interventions on Acceptance and Uptake of Male Circumcision in the General Population of Western China: A Multicenter Cohort Study

To compare different intervention models for promoting male circumcision (MC) to prevent HIV transmission in Western China. A total of 1690 male participants from multiple study sites were cluster randomly allocated to three-stage (Model A), two-stage (Model B), and one-stage (Model C) educational interventions. In all three interventions models, knowledge about MC significantly increased and the reported willingness to accept MC increased to 52.6% (255/485), 67.0% (353/527), and 45.5% (219/481) after intervention, respectively (P < 0.05). Rate of MC surgery uptake was highest (23.7%; 115/485) among those who received Model A intervention, compared to those who received Model B (17.1%; 90/527) or Model C (9.4%; 45/481) interventions (P < 0.05). Multivariable Cox regression analysis identified that Model A or Model B had twice the effect of Model C on MC uptake, with relative risks of 2.4 (95%CI, 1.5–3.8) and 2.2 (95%CI, 1.3–3.6), respectively. Model B was the most effective model for improving participants’ willingness to accept MC, while Model A was most successful at increasing uptake of MC surgery. Self-reported attitude towards MC uptake was not strongly correlated with actual behavior in this study focusing on the general male population in Western China.

Alcohol attenuates anti-HCV function of IFN-λ1 through up-regulation of PLASy expression in human hepatic cells

Alcohol could compromise the anti‐hepatitis C virus (HCV) function of interferon‐alpha (IFN‐α). However, little information is available about the effect of alcohol on interferon‐lambda (IFN‐λ, type III IFN), a novel candidate for development of therapy for HCV infection. Huh7 cells were infected with HCV JFH‐1 virus, then treated with alcohol, and/or IFN‐λ1. RT‐PCR and Western blot were used to detect the levels of HCV and key cellular factors. Overexpression or silencing expression was performed to verify the role of key factors in alcohol‐attenuated anti‐HCV function of IFN‐λ1. Alcohol treatment compromised anti‐HCV effect of IFN‐λ1 in HCV JFH‐1‐infected Huh7 cells, evidenced by the significantly increased levels of HCV RNA, and HCV core protein in alcohol‐/IFN‐λ1‐treated cells compared to cells with IFN‐λ1 treatment alone. Investigation of the mechanisms responsible for the alcohol action revealed that alcohol enhanced the expression of protein inhibitor of activated STAT (PIASy). Overexpression of PIASy compromised anti‐HCV ability of IFN‐λ1, whereas silencing expression of PIASy partly restored the alcohol‐attenuated anti‐HCV effect of IFN‐λ1. More importantly, overexpression of PIASy significantly down‐regulated the level of IFN‐λ1‐indcued phosphorylation of STAT1 (p‐STAT1), an important adaptor in IFN‐λ pathway, as well as reduced the expression of IFN‐λ1‐induced IFN‐stimulated genes 56 (ISG56), and myxovirus resistance 1 (Mx1), two antiviral effectors in in IFN‐λ pathway. These findings indicate that alcohol, through inducing the expression of negative regulator in IFN‐λ pathway, inhibits IFN‐λ‐mediated anti‐HCV action in human hepatic cells, which may lead to the poor efficacy of IFN‐λ‐based therapy against HCV infection.

mircoRNA-3162-3p is a potential biomarker to identify new infections in HIV-1-infected patients

BACKGROUND Identification of new HIV infections (HIV incidence) is critical for monitoring AIDS epidemic and assessing the effectiveness of intervention measures. However, current methods for distinguishing new infections from newly diagnosed HIV-1 patients are still imperfect. We explored utilizing miRNAs as biomarker to identify HIV new infections. METHODS According to the HIV-1 status and the estimated duration of infection (EDI), we enrolled participants and divided them into three groups: healthy control, new infection (within 1 year), and old infection (longer than 1 year). Participants were assigned into screening set or validation set. miRNA microarray was performed in screening set and the differentially expressed miRNAs were screened out. The differentially expressed miRNAs were further confirmed in validation set and HIV-1 IIIB-MT2 cells infection system. RESULTS In screening set, 5 miRNAs including miR-1291, miR-3609, miR-3162-3p, miR-874-5p and miR-4258 were screened out for their differential expression in plasma among three groups. In validation set, down- trend of miR-3162-3p was validated from healthy control, new infection to old infection groups. In HIV-1 IIIB-MT2 system, the levels of miR-3162-3p also decreased along with infection duration in vitro. Sensitivity and specificity for miR-3162-3p to distinguish new infection from old infection were 100.0% and 71.43%, respectively, with the cut-off value of 0.916. CONCLUSION miR-3162-3p in plasma could be a potential microRNA biomarker to identify HIV new infections in HIV-1 infected patients.

Alcohol-induced autophagy via upregulation of PIASy promotes HCV replication in human hepatoma cells

Both alcohol and hepatitis C virus (HCV) infection could induce cellular autophagy in liver cells, which is considered to be essential for productive HCV replication. However, whether alcohol-induced autophagy is involved in the pathogenesis of HCV infection is still poorly understood. Alcohol treatment could induce autophagy in Huh7 cells (a hepatoma cell line that supports HCV JFH-1 replication), evidenced by the increase of LC3B-II levels, the conversion of LC3B-I to LC3B-II, and the formation of GFP-LC3 puncta as well as the decrease of p62 level in alcohol-treated cells compared with control cells. Alcohol treatment also significantly increased PIASy (a member of the PIAS family) expression, which can act as a SUMO (small ubiquitin-like modifier protein) E3 ligase to regulate a broader range of cellular processes including autophagy. Overexpression or the silencing expression of PIASy in alcohol-treated Huh7 cells could increase or decrease autophagic activation caused by alcohol treatment, respectively, and thus affect HCV replication correspondingly. In the absence of alcohol, overexpression or silencing expression of PIASy increase or decrease the level of cellular autophagy, judged by the changes of LC3B-II and p62 levels in the presence or absence of chloroquine (CQ), a lysosome inhibitor. More importantly, in the presence of 3-methyladenine (3-MA), an inhibitor in the early stage of autophagy, the effects of overexpression or silencing expression of PIASy on HCV replication were largely blocked. Furthermore, PIASy could selectively drive the accumulation of SUMO1-conjugated proteins, along with upregulation of the expression of several important autophagy factors, including ATG7 and ATG5–ATG12. In conclusion, alcohol promotes HCV replication through activation of autophagy in Huh7 cells, which partly attributes to its induction of PIASy expression. PIASy-enhanced accumulation of SUMO1-conjugated proteins may contribute to its inducing effect of autophagy. Our findings provide a novel mechanism for the action of alcohol-promoting HCV replication in the context of cellular autophagy.

Western Blot-Based Logistic Regression Model for the Identification of Recent HIV-1 Infection: A Promising HIV-1 Surveillance Approach for Resource-Limited Regions

Objectives Identifying recent infections is necessary to monitor HIV/AIDS epidemic; however, it needs to be further developed. Methods and Results Participants were defined as having recent infection or older infection according to the estimated duration of HIV-1 infection and further assigned into training set and validation set according to their entering time points. Western blot (WB) confirmatory test and BED-CEIA were performed. The performance of the two methods on recent HIV-1 diagnosis was evaluated and compared. 81 subjects were enrolled in the training set and 72 in the validation set. Relative grey ratios of p24, p39, p31, p66, gp41, and gp160 were significantly higher in older infected patients of the training set. The present status of p55 was more frequently missing in recently infected patients in both sets. The logistic stepwise regression analysis of WB method shows sensitivity, specificity, and accuracy of 93.02%, 92.11%, and 92.59%. For BED-CEIA, they were 76.74%, 86.84%, and 81.48%. In the validation set, overall agreement rate, sensitivity, and specificity were 88.46%, 84.78%, and 86.11% in the WB-based method and 50.00%, 84.78%, and 72.22% in the BED-CEIA method. Conclusions WB-based method is a promising approach to predict recent HIV-1 infection, especially in resource-limited regions.

A New Hybrid Model Using an Autoregressive Integrated Moving Average and a Generalized Regression Neural Network for the Incidence of Tuberculosis in Heng County, China

It is a daunting task to eradicate tuberculosis completely in Heng County due to a large transient population, human immunodeficiency virus/tuberculosis coinfection, and latent infection. Thus, a high-precision forecasting model can be used for the prevention and control of tuberculosis. In this study, four models including a basic autoregressive integrated moving average (ARIMA) model, a traditional ARIMA-generalized regression neural network (GRNN) model, a basic GRNN model, and a new ARIMA-GRNN hybrid model were used to fit and predict the incidence of tuberculosis. Parameters including mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE) were used to evaluate and compare the performance of these models for fitting historical and prospective data. The new ARIMA-GRNN model had superior fit relative to both the traditional ARIMA-GRNN model and basic ARIMA model when applied to historical data and when used as a predictive model for forecasting incidence during the subsequent 6 months. Our results suggest that the new ARIMA-GRNN model may be more suitable for forecasting the tuberculosis incidence in Heng County than traditional models.