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Abstract SHP-1, a nonreceptor protein tyrosine phosphatase encoded by ptpn6, has been regarded as a regulatory protein of hematopoietic cell biology for years. However, there is now increasing evidence to support its role in tumors. Thus, the role of ptpn6 for prognosis and immune regulation across 33 tumors was investigated, aiming to explore its functional heterogeneity and clinical significance in pan-cancer. Differential expression of ptpn6 was found between cancer and adjacent normal tissues, and its expression was significantly correlated with the prognosis of tumor patients. In most cancers, ptpn6 expression was significantly associated with immune infiltration. This was further confirmed by ptpn6-related genes/proteins enrichment analysis. Additionally, genetic alterations in ptpn6 was observed in most cancers. As for epigenetic changes, it’s phosphorylation levels significantly altered in 6 tumors, while methylation levels significantly altered in 12 tumors. Notably, the methylation levels of ptpn6 were significantly decreased in 11 tumors, accompanied by its increased expression in 8 of them, suggesting that the hypomethylation may be related to its increased expression. Our results show that ptpn6 plays a specific role in tumor immunity and exerts a pleiotropic effect in a variety of tumors. It can serve as a prognostic factor for some cancers. Especially in LGG, KIRC, UCS and TGCT, the increased expression of ptpn6 is associated with poor prognosis and high immune infiltration. This aids in understanding the role of ptpn6 in tumor biology, and can provide insight into presenting a potential biomarker for poor prognosis and immune infiltration in cancers.

Abstract The close link between HIV-1 infection and the occurrence of pulmonary arterial hypertension (PAH). However, the underlying molecular mechanisms of their interrelation remain unclear. The microarray data of HIV-1 and PAH were downloaded from GEO database. We utilized WGCNA to identify shared genes between HIV-1 and PAH, followed by conducting GO and pathway enrichment analyses. Subsequently, differentially genes analysis was performed using external validation datasets to further filter hub genes. Immunoinfiltration analysis was performed using CIBERSORT. Finally, hub gene expression was validated using scRNA-seq data. We identified 109 shared genes through WGCNA, primarily enriched in type I interferon (IFN) pathways. By taking the intersection of WGCNA important module genes and DEGs, ISG15 and IFI27 were identified as pivotal hub genes. Immunoinfiltration analysis and scRNA-seq results indicated the significant role of monocytes in the shared molecular mechanisms of HIV-1 and PAH. In summary, our study illustrated the possible mechanism of PAH secondary to HIV-1 and showed that the heightened IFN response in HIV-1 might be a crucial susceptibility factor for PAH, with monocytes being pivotal cells involved in the type I IFN response pathway. This provides potential new insights for further investigating the molecular mechanisms connecting HIV-1 and PAH.

Abstract Background The studies on SARS-CoV-2 and human microbiota have yielded inconsistent results regarding microbiota α-diversity and key microbiota. To address these issues and explore the predictive ability of human microbiota for the prognosis of SARS-CoV-2 infection, we conducted a reanalysis of existing studies. Methods We reviewed the existing studies on SARS-CoV-2 and human microbiota in the Pubmed and Bioproject databases (from inception through October 29, 2021) and extracted the available raw 16S rRNA sequencing data of human microbiota. Firstly, we used meta-analysis and bioinformatics methods to reanalyze the raw data and evaluate the impact of SARS-CoV-2 on human microbial α-diversity. Secondly, machine learning (ML) was employed to assess the ability of microbiota to predict the prognosis of SARS-CoV-2 infection. Finally, we aimed to identify the key microbiota associated with SARS-CoV-2 infection. Results A total of 20 studies related to SARS-CoV-2 and human microbiota were included, involving gut (n = 9), respiratory (n = 11), oral (n = 3), and skin (n = 1) microbiota. Meta-analysis showed that in gut studies, when limiting factors were studies ruled out the effect of antibiotics, cross-sectional and case–control studies, Chinese studies, American studies, and Illumina MiSeq sequencing studies, SARS-CoV-2 infection was associated with down-regulation of microbiota α-diversity (P

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide, and gut microbes are associated with the development and progression of NAFLD. Despite numerous studies exploring the changes in gut microbes associated with NAFLD, there was no consistent pattern of changes.MethodWe retrieved studies on the human fecal microbiota sequenced by 16S rRNA gene amplification associated with NAFLD from the NCBI database up to April 2023, and re-analyzed them using bioinformatic methods.ResultsWe finally screened 12 relevant studies related to NAFLD, which included a total of 1,189 study subjects (NAFLD, n = 654; healthy control, n = 398; obesity, n = 137). Our results revealed a significant decrease in gut microbial diversity with the occurrence and progression of NAFLD (SMD = −0.32; 95% CI −0.42 to −0.21; p 0.7). The occurrence and progression of NAFLD are significantly associated with higher levels of LPS biosynthesis, tryptophan metabolism, glutathione metabolism, and lipid metabolism.ConclusionThis study elucidated gut microbes relevance to disease development and identified potential risk-associated microbes and functional pathways associated with NAFLD occurrence and progression.

BackgroundInternet-derived data and the autoregressive integrated moving average (ARIMA) and ARIMA with explanatory variable (ARIMAX) models are extensively used for infectious disease surveillance. However, the effectiveness of the Baidu search index (BSI) in predicting the incidence of scarlet fever remains uncertain. ObjectiveOur objective was to investigate whether a low-cost BSI monitoring system could potentially function as a valuable complement to traditional scarlet fever surveillance in China. MethodsARIMA and ARIMAX models were developed to predict the incidence of scarlet fever in China using data from the National Health Commission of the People’s Republic of China between January 2011 and August 2022. The procedures included establishing a keyword database, keyword selection and filtering through Spearman rank correlation and cross-correlation analyses, construction of the scarlet fever comprehensive search index (CSI), modeling with the training sets, predicting with the testing sets, and comparing the prediction performances. ResultsThe average monthly incidence of scarlet fever was 4462.17 (SD 3011.75) cases, and annual incidence exhibited an upward trend until 2019. The keyword database contained 52 keywords, but only 6 highly relevant ones were selected for modeling. A high Spearman rank correlation was observed between the scarlet fever reported cases and the scarlet fever CSI (rs=0.881). We developed the ARIMA(4,0,0)(0,1,2)(12) model, and the ARIMA(4,0,0)(0,1,2)(12) + CSI (Lag=0) and ARIMAX(1,0,2)(2,0,0)(12) models were combined with the BSI. The 3 models had a good fit and passed the residuals Ljung-Box test. The ARIMA(4,0,0)(0,1,2)(12), ARIMA(4,0,0)(0,1,2)(12) + CSI (Lag=0), and ARIMAX(1,0,2)(2,0,0)(12) models demonstrated favorable predictive capabilities, with mean absolute errors of 1692.16 (95% CI 584.88-2799.44), 1067.89 (95% CI 402.02-1733.76), and 639.75 (95% CI 188.12-1091.38), respectively; root mean squared errors of 2036.92 (95% CI 929.64-3144.20), 1224.92 (95% CI 559.04-1890.79), and 830.80 (95% CI 379.17-1282.43), respectively; and mean absolute percentage errors of 4.33% (95% CI 0.54%-8.13%), 3.36% (95% CI –0.24% to 6.96%), and 2.16% (95% CI –0.69% to 5.00%), respectively. The ARIMAX models outperformed the ARIMA models and had better prediction performances with smaller values. ConclusionsThis study demonstrated that the BSI can be used for the early warning and prediction of scarlet fever, serving as a valuable supplement to traditional surveillance systems.

BackgroundGut microbiota is the largest population of microorganisms and is closely related to health. Many studies have explored changes in gut microbiota in viral hepatitis. However, the correlation between gut microbiota and the occurrence and progression of viral hepatitis has not been fully clarified.MethodsPubMed and BioProject databases were searched for studies about viral hepatitis disease and 16S rRNA gene sequencing of gut microbiota up to January 2023. With bioinformatics analyses, we explored changes in microbial diversity of viral hepatitis, screened out crucial bacteria and microbial functions related to viral hepatitis, and identified the potential microbial markers for predicting risks for the occurrence and progression of viral hepatitis based on ROC analysis.ResultsOf the 1389 records identified, 13 studies met the inclusion criteria, with 950 individuals including 656 patient samples (HBV, n = 546; HCV, n = 86; HEV, n = 24) and 294 healthy controls. Gut microbial diversity is significantly decreased as the infection and progression of viral hepatitis. Alpha diversity and microbiota including Butyricimonas, Escherichia-Shigella, Lactobacillus, and Veillonella were identified as the potential microbial markers for predicting the risk of development of viral hepatitis (AUC>0.7). Microbial functions including tryptophan metabolism, fatty acid biosynthesis, lipopolysaccharide biosynthesis, and lipid metabolism related to the microbial community increased significantly as the development of viral hepatitis.ConclusionsThis study demonstrated comprehensively the gut microbiota characteristics in viral hepatitis, screened out crucial microbial functions related to viral hepatitis, and identified the potential microbial markers for predicting the risk of viral hepatitis.

Background: Existing researches have established a correlation between internet search data and the epidemics of numerous infectious diseases. This study aims to develop a prediction model to explore the relationship between the Pulmonary Tuberculosis (PTB) epidemic trend in China and the Baidu search index. Methods: Collect the number of new cases of PTB in China from January 2011 to August 2022. Use Spearman rank correlation and interaction analysis to identify Baidu keywords related to PTB and construct a PTB comprehensive search index. Evaluate the predictive performance of autoregressive integrated moving average (ARIMA) and ARIMA with explanatory variable (ARIMAX) models for the number of PTB cases. Results: Incidence of PTB had shown a fluctuating downward trend. The Spearman rank correlation coefficient between the PTB comprehensive search index and its incidence was 0.834 (P < 0.001). The ARIMA model had an AIC value of 2804.41, and the MAPE value was 13.19%. The ARIMAX model incorporating the Baidu index demonstrated an AIC value of 2761.58 and a MAPE value of 5.33%. Conclusions: The ARIMAX model is superior to ARIMA in terms of fitting and predicting accuracy. Additionally, the use of Baidu Index has proven to be effective in predicting cases of PTB.

BackgroundThe immune activation caused by microbial translocation has been considered to be a major driver of HIV infection progression. The dysbiosis of gut microbiota has been demonstrated in HIV infection, but the interplay between gut microbiota and its metabolites in the pathogenesis of HIV is seldom reported.MethodsWe conducted a case-controlled study including 41 AIDS patients, 39 pre-AIDS patients and 34 healthy controls. Both AIDS group and pre-AIDS group were divided according to clinical manifestations and CD4 + T cell count. We collected stool samples for 16S rDNA sequencing and untargeted metabolomics analysis, and examined immune activation and microbial translocation for blood samples.ResultsThe pre-AIDS and AIDS groups had higher levels of microbial translocation and immune activation. There were significant differences in gut microbiota and metabolites at different stages of HIV infection. Higher abundances of pathogenic bacteria or opportunistic pathogen, as well as lower abundances of butyrate-producing bacteria and bacteria with anti-inflammatory potential were associated with HIV severity. The metabolism of tryptophan was disordered after HIV infection. Lower level of anti-inflammatory metabolites and phosphonoacetate, and higher level of phenylethylamine and polyamines were observed in HIV infection. And microbial metabolic pathways related to altered metabolites differed. Moreover, disrupted metabolites contributed by altered microbiota were found to be correlated to microbial translocation and immune activation.ConclusionsMetabolites caused by dysbiosis of gut microbiota and related metabolic function are correlated to immune activation and microbial translocation, suggesting that the effect of microbiota on metabolites is related to intestinal barrier disruption in HIV infection.

Little is known about how Talaromyces marneffei, a thermally dimorphic fungus that causes substantial morbidity and mortality in Southeast Asia, evades the human immune system. Polarization of macrophages into fungal-inhibiting M1-like and fungal-promoting M2-like types has been shown to play an important role in the innate immune response against fungal pathogens. This mechanism has not been defined for T. marneffei. Here, we demonstrated that T. marneffei promotes its survival in human macrophages by inducing them toward M2-like polarization. Our investigations of the mechanism revealed that T. marneffei infection led to SOCS3 protein degradation by inducing tyrosine phosphorylation, thereby relieving the inhibitory effect of SOCS3 on p-STAT6, a key factor for M2-like polarization. Our SOCS3-overexpression experiments showed that SOCS3 is a positive regulator of M1-like polarization and plays an important role in limiting M2-like polarization. Furthermore, we found that inhibition of the TLR9 pathway partially blocked T. marneffei-induced M2-like polarization and significantly enhanced the killing activity of macrophages against T. marneffei. Collectively, these results reveal a novel mechanism by which T. marneffei evades the immune response of human macrophages.

BackgroundChina, where half of the adult male population smoke tobacco, has one of the highest global burdens of smoking. Smoking rates are even higher among people with HIV. People with HIV can be affected by smoking in multiple ways, including more severe HIV-related symptoms and worse antiretroviral therapy treatment outcomes. However, smoking cessation services targeted for people with HIV are not routinely integrated into HIV care in China. Given the widespread mobile phone ownership, an exploration of factors related to smoking among people with HIV in China who smoke could inform the design and implementation of mobile smoking cessation interventions that target the needs of this vulnerable population. ObjectiveThis study aims to explore the perspectives of smoking, barriers and facilitators to quitting, and perceptions related to a smoking cessation intervention delivered through behavioral counseling sessions and brief daily messenger service (WeChat)–delivered messages. MethodsWe recruited people with HIV from the People’s 4th Hospital of Nanning, Guangxi, China, and conducted semistructured face-to-face interviews. All interviews were audio-recorded, transcribed verbatim in Chinese, and translated into English for data analysis. We conducted a thematic analysis using a codebook, which was guided by a team-based consensus approach to identify 5 main themes. We also explored themes according to the demographic groups. ResultsA total of 24 participants were enrolled in the study. The mean age was 37.2 (SD=13.5) years. The participants had lived with HIV for a mean of 2.4 years. The majority were male (18/24, 75%) and lived in urban or metropolitan settings (19/24, 79%). We identified five main themes: variable knowledge of the harms of smoking, both related and unrelated to HIV; willpower perceived as the primary quitting strategy; a duality of the effect of social factors on quitting; perceptions about optimal features of the smoking cessation intervention (eg, messages should be brief and most frequent during the first few weeks); and the largely negative impact of their HIV diagnosis on smoking behaviors. In addition, some themes differed according to participant demographic characteristics such as age, sex, and education level. ConclusionsWe identified barriers to and facilitators of smoking cessation among people with HIV in China by conducting semistructured qualitative interviews. Owing to the adverse impact of smoking on HIV outcomes, targeting cessation interventions to the unique needs and preferences of people with HIV in China may be needed to increase the effectiveness of future interventions. A pilot clinical trial will be conducted in the future to evaluate this behavioral counseling and brief daily messenger service (WeChat)–delivered messages approach among people with HIV who smoke in China.

BackgroundNeurological diseases are difficult to diagnose in time, and there is currently a lack of effective predictive methods. Previous studies have indicated that a variety of neurological diseases cause changes in the gut microbiota. Alpha diversity is a major indicator to describe the diversity of the gut microbiota. At present, the relationship between neurological diseases and the alpha diversity of the gut microbiota remains unclear.MethodsWe performed a systematic literature search of Pubmed and Bioproject databases up to January 2021. Six indices were used to measure alpha diversity, including community richness (observed species, Chao1 and ACE), community diversity (Shannon, Simpson), and phylogenetic diversity (PD). Random-effects meta-analyses on the standardized mean difference (SMD) were carried out on the alpha diversity indices. Subgroup analyses were performed to explore the sources of interstudy heterogeneity. Meta-analysis was performed on articles by matching the age, sex, and body mass index (BMI) of the disease group with the control group. Meanwhile, subgroup analysis was performed to control the variability of the sequencing region, platform, geographical region, instrument, and diseases. The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was calculated to assess the prediction effectiveness of the microbial alpha diversity indices.ResultsWe conducted a meta-analysis of 24 published studies on 16S rRNA gene amplified sequencing of the gut microbiota and neurological diseases from the Pubmed and Bioproject database (patients, n = 1,469; controls, n = 1,289). The pooled estimate demonstrated that there was no significant difference in the alpha diversity between patients and controls (P < 0.05). Alpha diversity decreased only in Parkinson's disease patients, while it increased in anorexia nervosa patients compared to controls. After adjusting for age, sex, BMI, and geographical region, none of the alpha diversity was associated with neurological diseases. In terms of Illumina HiSeq 2000 and the V3-V5 sequencing region, the results showed that alpha diversity increased significantly in comparison with the controls, while decreased in Illumina HiSeq 2500. ROC curves suggested that alpha diversity could be used as a biomarker to predict the AD (Simpson, AUC= 0.769, P = 0.0001), MS (observed species, AUC= 0.737, P = 0.001), schizophrenia (Chao1, AUC = 0.739, P = 0.002).ConclusionsOur review summarized the relationship between alpha diversity of the gut microbiota and neurological diseases. The alpha diversity of gut microbiota could be a promising predictor for AD, schizophrenia, and MS, but not for all neurological diseases.

ObjectiveTalaromycosis is a serious regional disease endemic in Southeast Asia. In China, Talaromyces marneffei (T. marneffei) infections is mainly concentrated in the southern region, especially in Guangxi, and cause considerable in-hospital mortality in HIV-infected individuals. Currently, the factors that influence in-hospital death of HIV/AIDS patients with T. marneffei infection are not completely clear. Existing machine learning techniques can be used to develop a predictive model to identify relevant prognostic factors to predict death and appears to be essential to reducing in-hospital mortality.MethodsWe prospectively enrolled HIV/AIDS patients with talaromycosis in the Fourth People's Hospital of Nanning, Guangxi, from January 2012 to June 2019. Clinical features were selected and used to train four different machine learning models (logistic regression, XGBoost, KNN, and SVM) to predict the treatment outcome of hospitalized patients, and 30% internal validation was used to evaluate the performance of models. Machine learning model performance was assessed according to a range of learning metrics, including area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanations (SHAP) tool was used to explain the model.ResultsA total of 1927 HIV/AIDS patients with T. marneffei infection were included. The average in-hospital mortality rate was 13.3% (256/1927) from 2012 to 2019. The most common complications/coinfections were pneumonia (68.9%), followed by oral candida (47.5%), and tuberculosis (40.6%). Deceased patients showed higher CD4/CD8 ratios, aspartate aminotransferase (AST) levels, creatinine levels, urea levels, uric acid (UA) levels, lactate dehydrogenase (LDH) levels, total bilirubin levels, creatine kinase levels, white blood-cell counts (WBC) counts, neutrophil counts, procaicltonin levels and C-reactive protein (CRP) levels and lower CD3+ T-cell count, CD8+ T-cell count, and lymphocyte counts, platelet (PLT), high-density lipoprotein cholesterol (HDL), hemoglobin (Hb) levels than those of surviving patients. The predictive XGBoost model exhibited 0.71 sensitivity, 0.99 specificity, and 0.97 AUC in the training dataset, and our outcome prediction model provided robust discrimination in the testing dataset, showing an AUC of 0.90 with 0.69 sensitivity and 0.96 specificity. The other three models were ruled out due to poor performance. Septic shock and respiratory failure were the most important predictive features, followed by uric acid, urea, platelets, and the AST/ALT ratios.ConclusionThe XGBoost machine learning model is a good predictor in the hospitalization outcome of HIV/AIDS patients with T. marneffei infection. The model may have potential application in mortality prediction and high-risk factor identification in the talaromycosis population.

Background Antisense noncoding RNA in the INK4 locus (ANRIL) is located on human chromosome 9p21, and modulation of ANRIL expression mediates susceptibility to some important human disease, including atherosclerosis (AS) and tumors, by affecting the cell cycle circANRIL and linear ANRIL are isoforms of ANRIL. However, it remains unclear whether these isoforms have distinct functions. In our research, we constructed a circANRIL overexpression plasmid, transfected it into HEK-293T cell line, and explored potential core genes and signaling pathways related to the important differential mechanisms between the circANRIL-overexpressing cell line and control cells through bioinformatics analysis. Methods Stable circANRIL-overexpressing (circANRIL-OE) HEK-293T cells and control cells were generated by infection with the circANRIL-OE lentiviral vector or a negative control vector, and successful transfection was confirmed by conventional flurescence microscopy and quantitative real-time PCR (qRT-PCR). Next, differentially expressed genes (DEGs) between circANRIL-OE cells and control cells were detected. Subsequently, Gene Ontology (GO) biological process (BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the principal functions of the significant DEGs. A protein–protein interaction (PPI) network and competing endogenous RNA (ceRNA) network were constructed in Cytoscape to determine circularRNA (circRNA)- microRNA(miRNA)-messenger RNA (mRNA) interactions and hub genes, and qRT-PCR was used to verify changes in the expression of these identified target genes. Results The successful construction of circANRIL-OE cells was confirmed by plasmid sequencing, visualization with fluorescence microscopy and qRT-PCR. A total of 1745 DEGs between the circANRIL-OE group and control were identified, GO BP analysis showed that these genes were mostly related to RNA biosynthesis and processing, regulation of transcription and signal transduction. The KEGG pathway analysis showed that the up regulated DEGs were mainly enriched in the MAPK signaling pathway. Five associated target genes were identified in the ceRNA network and biological function analyses. The mRNA levels of these five genes and ANRIL were detected by qRT-PCR, but only COL5A2 and WDR3 showed significantly different expression in circANRIL-OE cells.

Abstract Objectives For migrant female sex workers (FSWs) at the Sino-Vietnamese border, the impact of work time in their current location on the spread of HIV/AIDS is not clear. Methods Data were collected from the Sino-Vietnamese border cities of Guangxi, China. Migrant FSWs working in these cities were studied. FSWs who worked less than 6 months in their current location were assigned to the short-term work group (ST FSWs), and FSWs who worked equal to or longer than 6 months in their current location were assigned to the long-term work group (LT FSWs). Logistic regression was performed to examine the impact of work time in the current location and factors associated with HIV infection. Results Among the 1667 migrant FSWs, 586 (35.2%) and 1081 (64.9%) were assigned to the ST FSW and LT FSW groups, respectively. Compared to LT FSWs, ST FSWs were more likely to be of Vietnamese nationality, be less than 18 years old when they first engaged in commercial sex work, and have a low-level of HIV-related knowledge and had higher odds of using condoms inconsistently, having more male clients, having no regular male clients, and having a history of male clients who used aphrodisiacs but lower odds of receiving free condoms distribution and education/HIV counselling and testing programme. The analysis of factors associated with HIV infection revealed that Vietnamese FSWs, less than 18 years old when they first engaged in commercial sex work, having no regular male clients, and having lower average charge per sex transaction were correlated with HIV infection. Conclusion FSWs with short-term work at the Sino-Vietnamese border had a higher risk of risky sex and were correlated with HIV risk factors. Vietnamese FSWs were at higher risk of HIV infection, and they were more likely to have short-term work. More targeted HIV prevention should be designed for new FSWs who recently began working in a locality to further control the spread of HIV, particularly cross-border FSWs.

IntroductionPretreatment drug resistance (PDR) is becoming an obstacle to the success of ART. This study investigated the prevalence of PDR and the transmission clusters (TCs) of drug resistance mutations (DRMs) in two cities where drug abuse used to be high to describe the local HIV-1 transmission dynamics.MethodsPlasma samples were obtained from 1,027 ART-naïve patients in Guangxi. Viral subtypes and DRMs were identified. Transmission network and related factors were also determined.ResultsA total of 1,025 eligible sequences were obtained from Qinzhou (65.8%) and Baise (34.2%) cities. The predominant HIV-1 genotype was CRF08_BC (45.0%), followed by CRF01_AE (40.9%). The overall prevalence of PDR was 8.3%, and resistance to NNRTI was the most common. Putative links with at least one other sequence were found in 543/1,025 (53.0%) sequences, forming 111 clusters (2–143 individuals). The most prevalent shared DRMs included V106I (45.35%), V179D (15.1%), and V179E (15.1%). Clusters related to shared DRMs were more frequent and larger in CRF08_BC. The prevalence of shared DRMs increased with time, while the proportion of PDR gradually decreased. Age > 50 years was associated with clustering. Subtype CRF08_BC was more likely to have DRMs, PDR propagation, and DRM sharing.ConclusionPDR prevalence is moderate in this region. The association between PDR and subtype CRF08_BC suggested that DRMs spreading from injection drug users (IDUs) to heterosexuals (HETs) might be the major source of PDR in this region. Our findings highlight the significance of continuous surveillance of PDR.

Abstract Previous studies investigating HIV-infected patients suggested a direct link between underweight and the mortality rate of AIDS. However, there was a lack of evidence showing the optimal range of initial body mass index (BMI) patients maintain during antiretroviral therapy (ART). We aimed to evaluate associations of the BMI values pre-ART and during the entire ART duration with mortality among HIV-positive individuals. In total, 5101 HIV/AIDS patients, including 1439 (28.2%) underweight, 3047 (59.7%) normal-weight, 548 (10.7%) overweight and 67 (1.3%) obese patients, were included in this cohort. The cumulative mortality of underweight, normal-weight, and overweight were 2.4/100 person-years (95% CI 1.9–2.9), 1.1/100 person-years (95% CI 0.9–1.3), and 0.5/100 person-years (95% CI 0.1–0.9), respectively. Cumulative mortality was lower in both the normal-weight and overweight populations than in the underweight population, with an adjusted hazard ratio (AHR) of 0.5 (95% CI 0.4–0.7, p

Abstract Objective This study aimed to investigate the prevalence of HIV late presentation and advanced HIV disease and to identify the factors associated with HIV late presentation and advanced HIV disease among patients with newly diagnosed HIV/AIDS in the Guangxi Zhuang Autonomous Region, in Southwestern China. Methods Patients with newly diagnosed HIV registered in the HIV surveillance system of Guangxi Centers for Disease Control between January 2012 and December 2016 were included in this study. Results Of 45,118 newly diagnosed patients, 70.2% had late presentation, and 45.1% had advanced HIV disease. A higher prevalence of late presentation and advanced HIV disease was found in male heterosexuals and female people who use drugs (PWID). Heterosexuals (OR 2.11 [95% CI 1.90–2.34]) and PWID (OR 1.55 [95% CI 1.30–1.84]) had a higher risk of late presentation than men who have sex with men (MSM). Blood testing of the blood receivers (OR 1.75 [95% CI 1.36–2.26]) and diagnosed in hospital (OR 1.74 [95% CI 1.65–1.84]) had an increased risk of late presentation compared to those who diagnosis in voluntary counseling and testing (VCT). Heterosexuals (OR 2.86 [95% CI 2.51–3.27]), PWID (OR 2.23 [95% CI 1.83–2.71]), blood testing of the blood receivers (OR 1.58 [95% CI 1.29–1.94]) and diagnosed in hospital (OR 1.85 [95% CI 1.76–1.94]) were also independent risk factors associated with advanced HIV disease. Older age, lower level of education and being divorced or widowed were also associated with late presentation and advanced HIV disease. Conclusions Late presentation and advanced HIV disease were very common among patients with newly diagnosed HIV in Guangxi, China during 2012–2016. Targeted programs are urgently required to reduce HIV late diagnosis in Guangxi, especially for male heterosexuals, PWID, and patients with characteristics such as older age, lower level of education, divorced or widowed.

ABSTRACTThe dimorphic fungus Talaromyces marneffei (TM) is a common cause of HIV-associated opportunistic infections in Southeast Asia. Cotrimoxazole (CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi and has been used to prevent several opportunistic infections among HIV/AIDS patients. We question whether CTX is effective in preventing TM infection. To investigate this question, we conducted an 11-year (2005–2016) retrospective observational cohort study of all patients on the Chinese national antiretroviral therapy (ART) programme in Guangxi, a province with high HIV and TM burden in China. Survival analysis was conducted to investigate TM cumulative incidence, and Cox regression and propensity score matching (PSM) were used to evaluate the effect of CTX on TM incidence. Of the 3359 eligible individuals contributing 10,504.66 person-years of follow-up, 81.81% received CTX within 6 months after ART initiation, and 4.73% developed TM infection, contributing 15.14/1,000 person-year TM incidence rate. CTX patients had a significantly lower incidence of TM infection than non-CTX patients (4.11% vs. 7.53%; adjusted hazard ratio (aHR) = 0.50, 95% CI 0.35–0.73). CTX reduced TM incidence in all CD4+ cell subgroups (

BackgroundNew evidence implies that the imbalance of gut microbiota is associated with the progression of alcoholic liver disease (ALD) and that the composition of gut microbiota is altered in ALD patients. However, the predominant bacterium in patients involved in the progress of ALD has not been identified. The purpose of this study is to investigate the predominant bacterium in the early and end-stages of ALD as well as the relationship between the bacterium and the degree of liver injury.MethodsWe enrolled 21 alcoholic fatty liver (AFL) patients, 17 alcoholic liver cirrhosis (ALC) patients and 27 healthy controls, and sequenced the 16S rRNA gene of their fecal microbiota. The gut microbiota composition and its relationship with the indicators of clinical hepatic function were assessed using canonical correspondence analysis (CCA), spearman correlation heatmap and multivariate association with linear (MaAsLin) Models.ResultsThe composition and structure of gut microbiota changed greatly in different stages of ALD, and the degree of disorder was aggravated with the progression of ALD, even in the early stage. Moreover, the relative abundance of Streptococcus was highly enriched only in patients with ALC (P

Background: Many studies have explored changes in the gut microbiome associated with HIV infection, but the consistent pattern of changes has not been clarified. Men who have sex with men (MSM) are very likely to be an independent influencing factor of the gut microbiome, but relevant research is still lacking.Methods: We conducted a meta-analysis by screening 12 published studies of 16S rRNA gene amplicon sequencing of gut microbiomes related to HIV/AIDS (six of these studies contain data that is relevant and available to MSM) from NCBI and EBI databases. The analysis of gut microbiomes related to HIV infection status and MSM status included 1,288 samples (HIV-positive (HIV+) individuals, n = 744; HIV-negative (HIV–) individuals, n = 544) and 632 samples (MSM, n = 328; non-MSM, n = 304), respectively. The alpha diversity indexes, beta diversity indexes, differentially enriched genera, differentially enriched species, and differentially enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways related to gut microbiomes were calculated. Finally, the overall trend of the above indicators was evaluated.Results: Our results indicate that HIV+ status is associated with decreased alpha diversity of the gut microbiome. MSM status is an important factor that affects the study of HIV-related gut microbiomes; that is, MSM are associated with alpha diversity changes in the gut microbiome regardless of HIV infection, and the changes in the gut microbiome composition of MSM are more significant than those of HIV+ individuals. A consistent change in Bacteroides caccae, Bacteroides ovatus, Bacteroides uniformis, and Prevotella stercorea was found in HIV+ individuals and MSM. The differential expression of the gut microbiome may be accompanied by changes in functional pathways of carbohydrate metabolism, amino acid metabolism, and lipid Metabolism.Conclusions: This study shows that the changes in the gut microbiome are related to HIV and MSM status. Importantly, MSM status may have a far greater impact on the gut microbiome than HIV status.

Innate immunity is the first line of defense against invading pathogens and may mediate HIV-1 resistance in HIV-1–exposed seronegative (HESN) individuals. This study aims to identify components of innate immunity that confer natural HIV-1 resistance in Chinese HESN individuals. Specifically, we compared the expression levels of Toll-like receptors (TLRs) and associated pathway molecules in peripheral blood mononuclear cells (PBMCs), monocytes/macrophages, and plasma obtained from HESN and control individuals. HESN individuals had higher expression of TLR9, IRF7, IFN-α/β, RANTES, and MIP-1α/1β in PBMCs and plasma than control subjects. Upon TLR9 stimulation, significantly higher expression of TLR9 and IRF7, as well as higher production of IFN-α/β, RANTES, and MIP-1α/1β, was observed in PBMCs and monocytes/macrophages from HESN individuals than in the corresponding cells from control individuals. More importantly, both with and without TLR9 stimulation, the levels of HIV-1 replication in monocyte-derived macrophages (MDMs) from HESN individuals were significantly lower than those in MDMs from control individuals. These data suggest that increased TLR9 activity and subsequent release of antiviral factors contribute to protection against HIV-1 in HESN individuals.

Abstract Background Female sex workers (FSW) are a population that are at high risk for HIV infection, and their HIV/AIDS knowledge levels and sexual behaviors are of concern. This study describes changes in HIV prevalence and factors associated among female sex workers in Guigang City, Guangxi, one of the highest HIV prevalence areas in China. Methods Data were derived from an annual cross-sectional venue-based survey, 2008 to 2015, in the form of sentinel surveillance. The participants were recruited using cluster sampling. FSW aged 16 years and above who completed a questionnaire and HIV testing. Both descriptive and multi-level analyses were used to explore factors associated with changes in HIV prevalence. Results Seven thousand four hundred ninety-six FSW were recruited in this study. HIV prevalence among FSW in Guigang City fell into two periods, one with an increasing trend (2008–2011) and one with a decline (2012–2015). Differences between these time periods included age, relationship status, HIV knowledge, consistent condom use, lifetime illicit drug use, history of sexually transmitted infection in the past year, HIV testing, receipt of a condom distribution and education program or HIV counseling and testing, and peer education services. Conclusions Since 2012, a reduction in HIV prevalence among FSW in Guigang City has been observed. The decline of HIV prevalence was associated with coinciding changes in demographic characteristics of FSW, improvement of HIV knowledge and safer sexual behaviors, and a program that promotes condom use, HIV counseling & testing, and peer education.

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.

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.

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.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.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.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.

BackgroundNearly 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.MethodsA 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.ResultsSeven 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, PConclusionThese results show that PrEP is an effective strategy for reducing new HIV infections in high risk populations.

OBJECTIVES: Acceptability of pre-exposure prophylaxis (PrEP) and willingness to participate in a clinical trial for both safety and efficacy of PrEP were investigated among female sex workers (FSWs) in Guangxi, China. METHODS: A cross-sectional study was performed in three cities in Guangxi. Structured, self-administered questionnaires were used to assess the acceptability of PrEP and the willingness to participate in a clinical trial. Multivariable logistic regression models were fitted to identify predictors. RESULTS: Among 405 participants, 15.1% had heard of PrEP. If PrEP was deemed to be effective, safe and provided for free, 85.9% reported that they would accept it, and 54.3% of those who accepted PrEP said that they would participate in a clinical trial. The increased acceptability of PrEP was associated with working in male dominated venues, higher income, a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, not being forced to use condoms by the gatekeepers, consistent use of condoms, and use of drugs to prevent STD infection. The increased willingness to participate in a clinical trial was associated with a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, a willingness to adhere to daily PreP use, and not being concerned about discrimination by others. The main reason for rejecting PrEP or participating in a clinical trial was the concern about the side effects of PrEP. CONCLUSIONS: Acceptability of PrEP among Guangxi FSWs is relatively high, indicating that PrEP intervention programs may be feasible for Chinese FSWs. Given the fact that most of the participants had never heard of PrEP before, and that family, gatekeepers, and social discrimination could significantly affect its acceptability, a comprehensive mix of multiple interventions is necessary for the successful implementation of a PrEP program among this population in Guangxi.

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.