Dynamic m6 A profiles reveal the role of YTHDC2-TLR2 signaling axis in Talaromyces marneffei infection.

Talaromyces marneffei (TM) immune evasion is an important factor leading to the high mortality rate of Penicilliosis marneffei. N6 -methyladenosine (m6 A) plays important roles in host immune response to various pathogen infections, yet its role in TM and HIV/TM coinfection remains largely unexplored. Here we reported genome-wide transcriptional m6 A profiles of TM mono-infection and HIV/TM coinfection. Our finding revealed dynamic alterations in global m6 A levels and upregulation of the m6 A reader YTH N6 -methyladenosine RNA binding protein C2 (YTHDC2) in TM-infected macrophages. Knockdown of YTHDC2 in TM-infected cells showed an elevated expression of TLR2 through m6 A-dependence, along with upregulation of TNF-α and IL1-ß. Overall, we characterized the m6 A profiles of the host and fungus before and after TM infection, and demonstrated that YTHDC2 mediates the key m6 A site of TLR2 to exert its function. These findings provide new insights into the underlying mechanisms and novel therapeutic approaches for TM diseases.

A bibliometric analysis of m6A methylation in viral infection from 2000 to 2022.

BACKGROUND: N6-methyladenosine (m6A) methylation has become an active research area in viral infection, while little bibliometric analysis has been performed. In this study, we aim to visualize hotspots and trends using bibliometric analysis to provide a comprehensive and objective overview of the current research dynamics in this field. METHODS: The data related to m6A methylation in viral infection were obtained through the Web of Science Core Collection form 2000 to 2022. To reduce bias, the literature search was conducted on December 1, 2022. Bibliometric and visual analyzes were performed using CiteSpace and Bibliometrix package. After screening, 319 qualified records were retrieved. RESULTS: These publications mainly came from 28 countries led by China and the United States (the US), with the US ranking highest in terms of total link strength.The most common keywords were m6A, COVID-19, epitranscriptomics, METTL3, hepatitis B virus, innate immunity and human immunodeficiency virus 1. The thematic map showed that METTL3, plant viruses, cancer progression and type I interferon (IFN-I) reflected a good development trend and might become a research hotspot in the future, while post-transcriptional modification, as an emerging or declining theme, might not develop well. CONCLUSIONS: In conclusion, m6A methylation in viral infection is an increasingly important topic in articles. METTL3, plant viruses, cancer progression and IFN-I may still be research hotspots and trends in the future.

Characteristics and risk factors for readmission in HIV-infected patients with Talaromyces marneffei infection.

OBJECTIVES: Talaromyces marneffei (T. marneffei) is an opportunistic fungal infection (talaromycosis), which is common in subtropical regions and is a leading cause of death in HIV-1-infected patients. This study aimed to determine the characteristics and risk factors associated with hospital readmissions in HIV patients with T. marneffei infection in order to reduce readmissions. METHODS: We conducted a retrospective study of admitted HIV-infected individuals at the Fourth People's Hospital of Nanning, Guangxi, China, from 2012 to 2019. Kaplan-Meier analyses and Principal component analysis (PCA) were used to evaluate the effects of T. marneffei infection on patient readmissions. Additionally, univariate and multifactorial analyses, as well as Propensity score matching (PSM) were used to analyze the factors associated with patient readmissions. RESULTS: HIV/AIDS patients with T. marneffei-infected had shorter intervals between admissions and longer lengths of stay than non-T. marneffei-infected patients, despite lower readmission rates. Compared with non-T. marneffei-infected patients, the mortality rate for talaromycosis patients was higher at the first admission. Among HIV/AIDS patients with opportunistic infections, the mortality rate was highest for T. marneffei at 16.2%, followed by cryptococcus at 12.5%. However, the readmission rate was highest for cryptococcus infection (37.5%) and lowest for T. marneffei (10.8%). PSM and Logistic regression analysis identified leukopenia and elevated low-density lipoprotein (LDL) as key factors in T.marneffei-infected patients hospital readmissions. CONCLUSIONS: The first admission represents a critical window to intervene in the prognosis of patients with T. marneffei infection. Leukopenia and elevated LDL may be potential risk factors impacting readmissions. Our findings provide scientific evidence to improve the long-term outcomes of HIV patients with T. marneffei infection.

Weighted gene co-expression network analysis revealed T cell differentiation associated with the age-related phenotypes in COVID-19 patients.

The risk of severe condition caused by Corona Virus Disease 2019 (COVID-19) increases with age. However, the underlying mechanisms have not been clearly understood. The dataset GSE157103 was used to perform weighted gene co-expression network analysis on 100 COVID-19 patients in our analysis. Through weighted gene co-expression network analysis, we identified a key module which was significantly related with age. This age-related module could predict Intensive Care Unit status and mechanical-ventilation usage, and enriched with positive regulation of T cell receptor signaling pathway biological progress. Moreover, 10 hub genes were identified as crucial gene of the age-related module. Protein-protein interaction network and transcription factors-gene interactions were established. Lastly, independent data sets and RT-qPCR were used to validate the key module and hub genes. Our conclusion revealed that key genes were associated with the age-related phenotypes in COVID-19 patients, and it would be beneficial for clinical doctors to develop reasonable therapeutic strategies in elderly COVID-19 patients.

CASA: a comprehensive database resource for the COVID-19 Alternative Splicing Atlas.

BACKGROUND: As a key process in transcriptional regulatory mechanisms, alternative splicing (AS) plays a crucial role in maintaining the diversity of RNA and protein expression, and mediates the immune response in infectious diseases, especially for the COVID-19. Therefore, urgent data gathering and more research of AS profiles in microbe-infected human cells are needed to improve understanding of COVID-19 and related infectious diseases. Herein, we have created CASA, the COVID-19 Alternative Splicing Atlas to provide a convenient computing platform for studies of AS in COVID-19 and COVID-19-related infectious diseases. METHODS: In CASA, we reanalyzed thousands of RNA-seq datasets generated from 65 different tissues, organoids and cell lines to systematically obtain quantitative data on AS events under different conditions. A total of 262,994 AS events from various infectious diseases with differing severity were detected and visualized in this database. In order to explore the potential function of dynamics AS events, we performed analysis of functional annotations and drug-target interactions affected by AS in each dataset. RNA-binding proteins (RBPs), which may regulate these dynamic AS events are also provided for users in this database. RESULTS: CASA displays microbe-induced alterations of the host cell splicing landscape across different virus families and helps users identify condition-specific splicing patterns, as well as their potential regulators. CASA may greatly facilitate the exploration of AS profiles and novel mechanisms of host cell splicing by viral manipulation. CASA is freely available at http://www.splicedb.net/casa/ .

Acceptance of COVID-19 vaccination and influencing factors among people living with HIV in Guangxi, China: a cross-sectional survey.

BACKGROUND: Vaccination has been proven to be an effective approach against the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to determine the acceptance rate and factors influencing acceptance of COVID-19 vaccination among people living with HIV (PLWH) in Guangxi, China. METHODS: A cross-sectional survey was carried out in five cities in Guangxi, China from May 7 to June 1, 2021. Questionnaires on the acceptance of COVID-19 vaccination and the related factors were conducted among PLWH recruited by simple random sampling. Univariate and multivariate logistic regression analyses were performed to identify factors associated with acceptance of COVID-19 vaccination. RESULTS: Of all valid respondents (n = 903), 72.9% (n = 658) were willing to receive COVID-19 vaccination. Fear of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was the main reason for being willing to receive vaccination (76.0%), while the main reasons for not willing were the concerns about vaccine safety (54.7%) and the vaccination's effect on antiretroviral therapy (ART) (50.6%). The most important factors influencing acceptance were the perception that vaccination is unsafe for HIV-infected people (aOR = 0.082, 95% CI = 0.024-0.282) and the poor efficacy in preventing SARS-CoV-2 infection in HIV-infected people (aOR = 0.093, 95% CI = 0.030-0.287). Other factors associated with acceptance included Zhuang ethnicity (aOR = 1.653, 95% CI = 1.109-2.465), highest education level of middle school, high school or above (aOR = 1.747, 95% CI = 1.170-2.608; aOR = 2.492, 95% CI = 1.326-4.682), and the vaccination having little effect on ART efficacy (aOR = 2.889, 95% CI = 1.378-6.059). CONCLUSIONS: Acceptance rate of the COVID-19 vaccination is relatively low among PLWH compared to the general population in China, although some patients refused vaccination due to concerns about vaccine safety and vaccination affecting ART efficacy. More research is needed to investigate the impact of the COVID-19 vaccines on ART efficacy and the effectiveness in preventing SARS-CoV-2 infection among PLWH.

The Role of Innate Immunity in Natural Elite Controllers of HIV-1 Infection.

The natural process of human immunodeficiency virus type 1(HIV-1) infection is characterized by high viral load, immune cell exhaustion, and immunodeficiency, which eventually leads to the stage of acquired immunodeficiency syndrome (AIDS) and opportunistic infections. Rapidly progressing HIV-1 individuals often die of AIDS several years after infection without treatment. The promotion of ART greatly prolongs the survival time of HIV-infected persons. However, some patients have incomplete immune function reconstruction after ART due to latent storage of HIV-infected cells. Therefore, how to achieve a functional cure has always been the focus and hot spot of global AIDS research. Fortunately, the emergence of ECs/LTNPs who can control virus replication naturally has ignited new hope for realizing a functional cure for AIDS. Recently, a special category of infected individuals has attracted attention that can delay the progression of the disease more rigorously than the natural progression of HIV-1 infection described above. These patients are characterized by years of HIV-1 infection, long-term asymptomatic status, and normal CD4+T cell count without ART, classified as HIV-infected long-term nonprogressors (LTNPs) and elite controllers (ECs). Numerous studies have shown that the host and virus jointly determine the progression of HIV-1 infection, in which the level of innate immunity activation plays an important role. As the first line of defense against pathogen invasion, innate immunity is also a bridge to induce adaptive immunity. Compared with natural progressors, innate immunity plays an antiviral role in HIV-1 infection by inducing or activating many innate immune-related factors in the natural ECs. Learning the regulation of ECs immunity, especially the innate immunity in different characteristics, and thus studying the mechanism of the control of disease progression naturally, will contribute to the realization of the functional cure of AIDS. Therefore, this review will explore the relationship between innate immunity and disease progression in ECs of HIV-1 infection from the aspects of innate immune cells, signaling pathways, cytokines, which is helpful to provide new targets and theoretical references for the functional cure, prevention and control of AIDS, and development of a vaccine.

Genome-Wide Profiling Reveals Alternative Polyadenylation of Innate Immune-Related mRNA in Patients With COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has caused many deaths worldwide. To date, the mechanism of viral immune escape remains unclear, which is a great obstacle to developing effective clinical treatment. RNA processing mechanisms, including alternative polyadenylation (APA) and alternative splicing (AS), are crucial in the regulation of most human genes in many types of infectious diseases. Because the role of APA and AS in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown, we performed de novo identification of dynamic APA sites using a public dataset of human peripheral blood mononuclear cell (PBMC) RNA-Seq data in COVID-19 patients. We found that genes with APA were enriched in innate immunity -related gene ontology categories such as neutrophil activation, regulation of the MAPK cascade and cytokine production, response to interferon-gamma and the innate immune response. We also reported genome-wide AS events and enriched viral transcription-related categories upon SARS-CoV-2 infection. Interestingly, we found that APA events may give better predictions than AS in COVID-19 patients, suggesting that APA could act as a potential therapeutic target and novel biomarker in those patients. Our study is the first to annotate genes with APA and AS in COVID-19 patients and highlights the roles of APA variation in SARS-CoV-2 infection.

Salient Object Detection With Purificatory Mechanism and Structural Similarity Loss.

Image-based salient object detection has made great progress over the past decades, especially after the revival of deep neural networks. By the aid of attention mechanisms to weight the image features adaptively, recent advanced deep learning-based models encourage the predicted results to approximate the ground-truth masks with as large predictable areas as possible, thus achieving the state-of-the-art performance. However, these methods do not pay enough attention to small areas prone to misprediction. In this way, it is still tough to accurately locate salient objects due to the existence of regions with indistinguishable foreground and background and regions with complex or fine structures. To address these problems, we propose a novel convolutional neural network with purificatory mechanism and structural similarity loss. Specifically, in order to better locate preliminary salient objects, we first introduce the promotion attention, which is based on spatial and channel attention mechanisms to promote attention to salient regions. Subsequently, for the purpose of restoring the indistinguishable regions that can be regarded as error-prone regions of one model, we propose the rectification attention, which is learned from the areas of wrong prediction and guide the network to focus on error-prone regions thus rectifying errors. Through these two attentions, we use the Purificatory Mechanism to impose strict weights with different regions of the whole salient objects and purify results from hard-to-distinguish regions, thus accurately predicting the locations and details of salient objects. In addition to paying different attention to these hard-to-distinguish regions, we also consider the structural constraints on complex regions and propose the Structural Similarity Loss. The proposed loss models the region-level pair-wise relationship between regions to assist these regions to calibrate their own saliency values. In experiments, the proposed purificatory mechanism and structural similarity loss can both effectively improve the performance, and the proposed approach outperforms 19 state-of-the-art methods on six datasets with a notable margin. Also, the proposed method is efficient and runs at over 27FPS on a single NVIDIA 1080Ti GPU.

Mortality risk in the population of HIV-positive individuals in Southern China: A cohort study.

To evaluate the mortality risk in the HIV-positive population, we conducted an observational cohort study involving routine data collection of HIV-positive patients who presented at HIV clinics and multiple treatment centers throughout Guangxi province, Southern China in 2011. The patients were screened for tuberculosis (TB) and tested for hepatitis B (HBV) and C (HCV) virus infections yearly. Following the registration, the cohort was followed up for a 60-month period till the end-point (December 31, 2015). Univariable and multivariable Cox proportional hazards regression models were used to analyze the hazard ratio (HR) and 95% confidence interval (95% CI) for mortality after adjusting for confounding factors stratified by patients' sociodemographic and behavioral characteristics. HRs were compared within risk-factor levels. With the median follow-up of 3.7-person years for each individual, 5,398 (37.8%) (of 14,293 patients with HIV/AIDS) died; among whom, 78.4% were antiretroviral therapy (ART)-naïve; 43.6% presented late; and 12.2% and 3.3% of patients had Mycobacterium tuberculosis (MTB) and HBV and HCV co-infection, respectively. Of individuals with CD4 counts, those with CD4 count >350 cells/µL formed 14.0% of those who died. Furthermore, gender [multivariable HR (95% CI):1.94 (1.68-2.25)], Han ethnicity [2.15 (1.07-4.32)], illiteracy [3.28 (1.96-5.5)], elementary education [2.91 (1.8-4.72)], late presentation [2.89 (2.46-3.39)], and MTB co-infection [1.28 (1.10-1.49)] strongly increased the all-cause mortality risk of HIV-positive individuals. The HR for ART-based stratification was 0.08 (0.07-0.09); and for HBV and HCV co-infection, HR was 1.02 (0.86-1.21). The findings emphasized that accessibility to HIV testing among high-risk populations and screening for viral hepatitis and TB co-infection are important for the survival of HIV-positive individuals. Initiating early ART, even for individuals with higher CD4 counts, is advisable to help increase the prolongation of lives within the community.

Opiate use inhibits TLR9 signaling pathway in vivo: possible role in pathogenesis of HIV-1 infection.

The molecular mechanism of opiate use promoting HIV-1 infection is not fully understood. TLR9 is expressed in many immune cells, including monocytes, macrophages, which can recognize viruses and viral products and consequently induce the production of antiviral factors and initiate immune responses. Previous studies have shown that chronic viral infections can overcome and impair TLR9 pathway. We aimed to explore whether opiate use enhances HIV infection through inhibition of TLR9 pathway via a population-based study. A total of 200 subjects were enrolled and divided into four groups as follows: Opiate+ HIV+ (50), Opiate- HIV+ (50), Opiate+ HIV- (50), and healthy control (Opiate- HIV-, 50). All HIV-infected subjects did not receive antiretroviral therapy while they were enrolled in the study. The results showed that opiate use was associated with higher viral load and lower CD4+ T cell count. Opiate use alone led to lower expression of TLR9, IRF7, and IFN-α at the protein level in PBMCs. Combined with HIV-1 infection, opiate use resulted in lower expression of MyD88, ISG56, and MxA. In addition, morphine treatment promoted HIV-1 replication in macrophages via inhibition of TLR9 pathway. Our data reveal that opiate use plays a cofactor role in pathogenesis of HIV-1 infection through inhibition of TLR9 pathway.

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.

Effects of high CD4 cell counts on death and attrition among HIV patients receiving antiretroviral treatment: an observational cohort study.

Current WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n = 49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with <350 CD4+ cells/mm3 at ART initiation, HIV patients with >500 CD4+ cells/mm3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40-0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03-1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation.

Commercial Sexual Behaviors Among Male Rural-to-Urban Migrants in Western China: Implications for HIV Prevention.

Rural-to-urban migrants are at high risk of HIV infection. The goal of this survey was to explore the commercial sexual behavior and condom use among male rural-to-urban migrants in western China. A cross-sectional survey on male rural-to-urban migrants in western China was conducted. Among all the subjects surveyed, 140 (7.4%) had commercial sexual behavior, which is associated with being aged older than 24 years, being of Han or other ethnic minorities, being divorced, separated, or widowed, having experienced drug abuse, having had heterosexual behavior, having had casual sexual partners, having had sex with a homosexual, and being from Xinjiang. A total of 31.4% of them never use condoms when buying sex. Not using condoms is associated with being from Chongqing, having a high school or above education, and having commercial sex monthly. Commercial sexual behavior and not using condoms are common among male rural-to-urban migrants in western China. Strategies and appropriate education should be developed to prevent HIV transmission due to high-risk sexual behaviors.

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.

Downregulation of autophagy-related gene ATG5 and GABARAP expression by IFN-λ1 contributes to its anti-HCV activity in human hepatoma cells.

Type-III interferon (IFN-λ), the most recently discovered family of IFNs, shares common features with type I IFNs, but also has many distinctive activities. It is not clear that whether IFN-λ has additional antiviral mechanisms. In this study, we investigated the effects of IFN-λ on autophagy, a cellular process closely related to hepatitis C virus (HCV) infection in human hepatoma Huh7 cells. Our results showed that IFN-λ1 treatment inhibit autophagic activity in Huh7 cells, as evidenced by the decreased expression of microtubule-associated protein 1 light chain 3B (LC3B)-II and conversion of LC3B-I to LC3B-II, decreased formation of GFP-LC3 puncta and accumulation of autophagosomes. IFN-λ1 could also inhibit HCV-induced or tunicamycin (a known inducer of autophagy with similar mechanism to HCV infection) -induced LC3B-II expression and autophagosome formation. Through PCR array, real time RT PCR, and western blot, two autophagy-related genes, ATG5 and GABARAP, were identified and verified to be down-regulated by IFN-λ1 treatment, either in HCV-uninfected Huh7 cells or in HCV JFH-1-infected cells. Overexpression of ATG5 and/or GABARAP could partly recover the IFN-λ1-inhibited HCV replication. Mechanism research demonstrated that IFN-λ1 could induce the expression of miR-181a and miR-214 (targeting ATG5 and GABARAP respectively), by which down-regulates ATG5 and GABARAP expression. Taken together, our results indicate that suppression of the autophagy response by IFN-λ1 contributes to IFN-λ1 anti-HCV activity. The results also provide a theoretical basis for improving the effectiveness of IFN treatment of HCV infection through inhibition of the HCV-induced autophagy response.

Dolutegravir(DTG, S/GSK1349572) combined with other ARTs is superior to RAL- or EFV-based regimens for treatment of HIV-1 infection: a meta-analysis of randomized controlled trials.

BACKGROUND: The first-generation integrase inhibitors (INIs) raltegravir (RAL) and elvitegravir (EVG) have shown efficacy against HIV infection, but they have the limitations of once-more daily dosing and extensive cross-resistance. Dolutegravir (DTG, S/GSK1349572), a second-generation drug that overcomes such shortcomings, is under spotlight. The purpose of this study is to review the evidence for DTG use in clinical settings, including its efficacy and safety. METHODS: PubMed, EMbase, Ovid, Web of Science, Science Direct, and related websites were screened from establishment until July 2013, and scientific meeting proceedings were manually searched. Two reviewers independently screened 118 citations repeatedly to identify randomized controlled trials comparing the efficacy and safety of DTG-based regimen with those of RAL- or elvitegravir-based regimens. Using the selected studies with comparable outcome measures and indications, we performed a meta-analysis based on modified intention-to-treat (mITT), on-treatment (OT), and as-treated (AT) virological outcome data. Independent data extraction and quality assessment were conducted. RESULTS: Four unique studies were included with the use of DTG in antiretroviral therapy-naive patients. In therapy-naive patients, DTG combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) resulted in a significantly better virological outcome with a mITT relative risk (RR)of 1.07 (95 % confidence interval (95 % CI 1.03-1.12). Evidence further supported use of DTG had a better virological suppression in the 50 mg once daily group (mITT RR 1.07; 95 % CI 1.03-1.12) as well as in the sub-analysis in dolutegravir/efavirenz(DTG/EFV) and dolutegravir/raltegravir (DTG/RAL) groups (RR 1.09, 95 % CI 1.03-1.15; RR 1.06, 95 % CI 0.98-1.15, respectively). In the matter of safety of DTG-based regimen, the risk of any event was RR 0.98 (95 % CI 0.94-1.01), the risk of serious adverse events (AEs) was RR 0.84 (95 % CI 0.62-1.15), and the risk of drug-related serious AEs was RR 0.33 (95 % CI 0.13-0.79). CONCLUSION: In general, DTG 50 mg given once daily combined with an active background drug is a better choice in terms of both efficacy and safety.

Application of a Combined Model with Autoregressive Integrated Moving Average (ARIMA) and Generalized Regression Neural Network (GRNN) in Forecasting Hepatitis Incidence in Heng County, China.

BACKGROUND: Hepatitis is a serious public health problem with increasing cases and property damage in Heng County. It is necessary to develop a model to predict the hepatitis epidemic that could be useful for preventing this disease. METHODS: The autoregressive integrated moving average (ARIMA) model and the generalized regression neural network (GRNN) model were used to fit the incidence data from the Heng County CDC (Center for Disease Control and Prevention) from January 2005 to December 2012. Then, the ARIMA-GRNN hybrid model was developed. The incidence data from January 2013 to December 2013 were used to validate the models. Several parameters, including mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE) and mean square error (MSE), were used to compare the performance among the three models. RESULTS: The morbidity of hepatitis from Jan 2005 to Dec 2012 has seasonal variation and slightly rising trend. The ARIMA(0,1,2)(1,1,1)12 model was the most appropriate one with the residual test showing a white noise sequence. The smoothing factor of the basic GRNN model and the combined model was 1.8 and 0.07, respectively. The four parameters of the hybrid model were lower than those of the two single models in the validation. The parameters values of the GRNN model were the lowest in the fitting of the three models. CONCLUSIONS: The hybrid ARIMA-GRNN model showed better hepatitis incidence forecasting in Heng County than the single ARIMA model and the basic GRNN model. It is a potential decision-supportive tool for controlling hepatitis in Heng County.

In vivo effects of methamphetamine on HIV-1 replication: A population-based study.

BACKGROUND: Although a number of in vitro studies have shown that methamphetamine (METH) can increase HIV-1 replication in human immune cells, a direct link between METH use and HIV-1 pathogenesis remains to be determined among HIV-1 patients. METHODS: According to the status of METH use and HIV-1 infection, we enrolled participants and divided them into four groups: METH+HIV+, METH-HIV+, METH+HIV-, and METH-HIV-. HIV viral loads and HIV-1-related cellular factors were measured and compared among different groups. RESULTS: A total of 60 participants were enrolled into this study, 15 within each group. HIV viral loads in METH+HIV+ group were significantly higher than those in METH-HIV+ group, while CD4+ T cell counts had an inverse trend between the two groups (p<0.05). METH users or HIV-1 infected patients had lower CCR5+, CXCR4+ percentages in CD4+ T cells than METH-HIV- subjects (p<0.01). However, METH use had little effect on CD3 expression in PBMCs and the levels of MIP-1α, MIP-1ß and IL-6 in PBMCs or plasma, which were increased by HIV-1 infection with or without METH. TLR-9 and IFN-α levels in PBMCs of METH users with or without HIV infection were higher than non-METH users (p<0.05). CONCLUSIONS: METH use is associated with higher viral loads and lower CD4+ T cell counts in HIV-infected individuals. This finding may be mediated by activation of innate immunity (TLR-9, IFN-α) by METH use.

Acceptability of Male Circumcision among College Students in Medical Universities in Western China: A Cross-Sectional Study.

BACKGROUND: Male circumcision (MC) has been shown to reduce the risk of female to male transmission of HIV. The goal of this survey was to explore MC's acceptability and the factors associated with MC among college students in medical universities in western China. METHODS: A cross-sectional study was carried out in three provinces in western China (Guangxi, Chongqing and Xinjiang) to assess the acceptability of MC as well as to discover factors associated with the acceptability among college students in medical universities. A total of 1,790 uncircumcised male students from three medical universities were enrolled in this study. In addition, 150 students who had undergone MC were also enrolled in the survey, and they participated in in-depth interviews. RESULTS: Of all the uncircumcised participants (n = 1,790), 55.2% (n = 988) were willing to accept MC. Among those who accepted MC, 67.3% thought that MC could improve their sexual partners' hygiene, 46.3% believed that HIV and sexually transmitted diseases (STDs) could be partially prevented by MC. The multivariable logistic regression indicates that MC's acceptability was associated with three factors: the redundant foreskin (OR = 10.171, 95% CI = 7.629-13.559), knowing the hazard of having a redundant foreskin (OR = 1.597, 95% CI = 1.097-2.323), and enhancing sexual pleasure (OR = 1.628, 95% CI = 1.312-2.021). The in-depth interviews for subjects who had undergone MC showed that the major reason for having MC was the redundant foreskin (87.3%), followed by the benefits and the fewer complications of having MC done. In addition, most of these participants (65.3%) said that the MC could enhance sexual satisfaction. CONCLUSIONS: MC's acceptance among college students in medical universities is higher than it is among other populations in western China. An implementation of an MC programme among this population is feasible in the future.