Pan-cancer analysis of the prognostic and immunological roles of SHP-1/ptpn6.

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.

Using gut microbiota as a diagnostic tool for colorectal cancer: machine learning techniques reveal promising results.

Introduction. Increasing evidence suggests a correlation between gut microbiota and colorectal cancer (CRC).Hypothesis/Gap Statement. However, few studies have used gut microbiota as a diagnostic biomarker for CRC.Aim. The objective of this study was to explore whether a machine learning (ML) model based on gut microbiota could be used to diagnose CRC and identify key biomarkers in the model.Methodology. We sequenced the 16S rRNA gene from faecal samples of 38 participants, including 17 healthy subjects and 21 CRC patients. Eight supervised ML algorithms were used to diagnose CRC based on faecal microbiota operational taxonomic units (OTUs), and the models were evaluated in terms of identification, calibration and clinical practicality for optimal modelling parameters. Finally, the key gut microbiota was identified using the random forest (RF) algorithm.Results. We found that CRC was associated with the dysregulation of gut microbiota. Through a comprehensive evaluation of supervised ML algorithms, we found that different algorithms had significantly different prediction performance using faecal microbiomes. Different data screening methods played an important role in optimization of the prediction models. We found that naïve Bayes algorithms [NB, accuracy=0.917, area under the curve (AUC)=0.926], RF (accuracy=0.750, AUC=0.926) and logistic regression (LR, accuracy=0.750, AUC=0.889) had high predictive potential for CRC. Furthermore, important features in the model, namely s__metagenome_g__Lachnospiraceae_ND3007_group (AUC=0.814), s__Escherichia_coli_g__Escherichia-Shigella (AUC=0.784) and s__unclassified_g__Prevotella (AUC=0.750), could each be used as diagnostic biomarkers of CRC.Conclusions. Our results suggested an association between gut microbiota dysregulation and CRC, and demonstrated the feasibility of the gut microbiota to diagnose cancer. The bacteria s__metagenome_g__Lachnospiraceae_ND3007_group, s__Escherichia_coli_g__Escherichia-Shigella and s__unclassified_g__Prevotella were key biomarkers for CRC.

Factors Related to Smoking and Perceptions of a Behavioral Counseling and Messenger Service-Delivered Smoking Cessation Intervention for People With HIV in China: Qualitative Study.

BACKGROUND: China, 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. OBJECTIVE: This 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. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: We 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.

Integrated bioinformatics analysis for the identification of hub genes and signaling pathways related to circANRIL.

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.

Talaromyces marneffei promotes M2-like polarization of human macrophages by downregulating SOCS3 expression and activating the TLR9 pathway.

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.

Cardiopulmonary Bypass Duration and the Incidence of Pressure Injuries in Patients Undergoing Cardiovascular Surgery: A Retrospective Cohort Study.

PURPOSE: The purpose of our study was to investigate the association between cardiopulmonary bypass (CPB) duration and the incidence of pressure injuries (PIs) in patients undergoing cardiovascular surgery. DESIGN: Retrospective chart review. SUBJECTS AND SETTING: Two hundred and eighty-eight patients who underwent cardiovascular surgery with CPB from January 2016 through December 2016 in a 2000-bed general hospital, which integrates medical service, education, and research and in which 300 to 350 cardiovascular surgical procedures with CPB are performed each year. METHODS: We retrospectively collected data from patients' medical records. Univariate analysis and multivariate logistic regression analysis were performed to identify the independent risk factors for the development of PI. In addition, a simple linear regression model was conducted to assess the relationship between CPB duration and PI development. RESULTS: Of the 288 patients, 56 developed 80 PIs, with an incidence of 19.4% (95% confidence interval, 14.9%-24.3%). Multivariate logistic regression analysis showed that CPB duration, use of vasoactive drugs, and diabetes mellitus were independent risk factors for the development of PIs in patients receiving cardiovascular surgery. Median CPB duration was significantly longer in the group with PIs compared with the group without PIs (144 [range 48-415] minutes compared with 102.5 [range 16-678] minutes, P = .000). This result was consistent in the subgroup analysis of pediatric and adult patients. Pressure injuries also increased proportionally with CPB duration, from 12.2% at 60 minutes or shorter to 45.5% at more than 300 minutes (P = .002, R = 0.936). CONCLUSIONS: The CPB duration, use of vasoactive drugs, and presence of diabetes mellitus are independent risk factors for the development of PIs in patients undergoing cardiovascular surgery with CPB. Our findings indicated that PI incidence increased incrementally with the duration of CPB. We recommend implementing measures to prevent PIs in cardiovascular surgical patients, especially those undergoing prolonged CPB, receiving vasoactive drugs, and diagnosed with diabetes.

No Increase in HIV Drug Resistance Mutations among Injecting Drug Users on Methadone Maintenance Therapy: A Prospective Cohort Study.

BACKGROUND: Whether HIV-positive injecting drug users (IDUs) are at higher risk of developing drug resistance mutations (DRMs) after methadone maintenance therapy (MMT) than any other HIV-positive population is unclear. OBJECTIVE: To compare the incidence of new DRMs in two population groups: antiretroviraltreatment (ART) HIV-positive IDUs and non-drug users. METHODS: A prospective cohort of ART HIV-positive patients including IDUs who received MMT (MMT group) and non-drug users (N-MMT group) was established from April 2016 to December 2017 in Guangxi, China. RESULTS: Of the 80 participants, 43 were in the MMT group and 37 were in the N-MMT group. Compared with the N-MMT group, the HRs of PIs, NRTIs and NNRTIs for new DRMs in the MMT group was 1.55 (95%CI: 0.28-8.64; P = 0.616), 1.51 (95%CI: 0.44-5.20; P = 0.512) and 0.45 (95%CI: 0.15-1.35; P = 0.155), respectively. There was no dose-response relationship between MMT and new DRMs for PIs, NRTIs and NNRTIs (P > 0.05). The new DRM incidence for NRTIs (138.23 per 104 person-months) was higher than for PIs (94.16 per 104 person-months) and NNRTIs (95.41per 104 person-months) in the MMT group, while the new DRM incidence for NNRTIs (208.24 per 104 person-months) was higher than for PIs (44.13 per 104 person-months) and NRTIs (91.78 per 104 person-months) in the N-MMT group. CONCLUSION: Among ART HIV-positive patients, there is no significant difference in the incidence of new DRMs between IDUs receiving MMT and non-drug users. MMT has little impact on the development of DRMs among IDUs.

SLC1A1, SLC16A9, and CNTN3 Are Potential Biomarkers for the Occurrence of Colorectal Cancer.

BACKGROUND: This study is aimed at identifying unknown clinically relevant genes involved in colorectal cancer using bioinformatics analysis. METHODS: Original microarray datasets GSE107499 (ulcerative colitis), GSE8671 (colorectal adenoma), and GSE32323 (colorectal cancer) were downloaded from the Gene Expression Omnibus. Common differentially expressed genes were filtered from the three datasets above. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, followed by construction of a protein-protein interaction network to identify hub genes. Kaplan-Meier survival analysis and TIMER database analysis were used to screen the genes related to the prognosis and tumour-infiltrating immune cells of colorectal cancer. Receiver operating characteristic curves were used to assess whether the genes could be used as markers for the diagnosis of ulcerative colitis, colorectal adenoma, and colorectal cancer. RESULTS: A total of 237 differentially expressed genes common to the three datasets were identified, of which 60 were upregulated, 125 were downregulated, and 52 genes that were inconsistently up- and downregulated. Common differentially expressed genes were mainly enriched in the cellular component of extracellular exosome and integral component of membrane categories. Eight hub genes, i.e., CXCL3, CXCL8, CEACAM7, CNTN3, SLC1A1, SLC16A9, SLC4A4, and TIMP1, were related to the prognosis and tumour-infiltrating immune cells of colorectal cancer, and these genes have diagnostic value for ulcerative colitis, colorectal adenoma, and colorectal cancer. CONCLUSION: Three novel genes, CNTN3, SLC1A1, and SLC16A9 were shown to have diagnostic value with respect to the occurrence of colorectal cancer and should be verified in future studies.

Deguelin inhibits HCV replication through suppressing cellular autophagy via down regulation of Beclin1 expression in human hepatoma cells.

AIMS: Deguelin, a natural compound derived from Mundulea sericea (Leguminosae) and some other plants exhibits an activity to inhibit autophagy, a cellular machinery required for hepatitis C virus (HCV) replication. This study aimed to illuminate the impact of deguelin on HCV replication and mechanism(s) involved. METHODS: HCV JFH-1-Huh7 infectious system was used for the investigation. Real time RT-PCR, Western blot, fluorescent microscopy assay were used to measure the expression levels of viral or cellular factors. Overexpression and silencing expression techniques were used to determine the role of key cellular factors. RESULTS: Deguelin treatment of Huh7 cells significantly inhibited HCV JFH-1 replication in a dose- and time-dependent manner. Deguelin treatment suppressed autophagy in Huh7 cells, evidenced by the decrease of LC3B-II levels, the conversion of LC3B-I to LC3B-II, and the formation of GFP-LC3 puncta as well as the increase of p62 level in deguelin-treated cells compared with control cells. HCV infection could induce autophagy which was also suppressed by deguelin treatment. Mechanism research reveals that deguelin inhibited expression of Beclin1, which is a key cellular factor for the initiation of the autophagosome formation in autophagy. Overexpression or silencing expression of Beclin1 in deguelin-treated Huh7 cells could weaken or enhance the inhibitory effect on autophagy by deguelin, respectively, and thus partially recover or further inhibit HCV replication correspondingly. CONCLUSIONS: Deguelin may serve as a novel anti-HCV compound via its inhibitory effect on autophagy, which warrants further investigation as a potential therapeutic agent for HCV infection.

Berbamine exerts anticancer effects on human colon cancer cells via induction of autophagy and apoptosis, inhibition of cell migration and MEK/ERK signalling pathway.

PURPOSE: Berbamine is a plant-derived alkaloid with amazing and wide diversity of pharmacological properties which range from antimicrobial and anticancer. Nonetheless, the anticancer properties of Berbamine have not been thoroughly evaluated against colon cancer cells. This study was undertaken to evaluate the anticancer effects of Berbamine against human colon cancer cells (HT-29 colon cancer cells). Μethods: CCK-8 assay was used to determine the cell viability. DAPI and propidium iodide (PI) staining assays were used for the detection of apoptosis. Electron microscopy was used for the determination of autophagy. Wound healing assay was used to monitor cell migration. Protein expression was determined by western blotting. RESULTS: The results showed that Berbamine caused a remarkable decrease in the HT-29 cell viability with an IC50 of 14 µM, while the high IC50 of Berbamine against the normal CDD-18Co cells indicated low toxicity of this molecule against the normal cells. DAPI and PI staining assays showed nuclear fragmentation, indicative of apoptosis in HT-29 cells. Berbamine also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio. Electron microscopic analysis showed that Berbamine triggered the development of autophagic vesicles in the HT-29 cells which was concomitant with the increase in protein levels of LC3B-I, ATG-5, ATG-12 and Beclin-1. Wound healing assay showed that Berbamine decreased the migration potential of the HT-29 and also blocked the MEK/ERK signalling pathway in colon cancer cells. CONCLUSION: Berbamine may prove an efficient lead molecule for the development of more potent anticancer agents through semi-synthetic approaches.

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.

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.

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.

Assessment of Different Intervention Models of Male Circumcision and Their Preliminary Effectiveness in Reducing HIV Incidence Among Drug Users in Western China.

World Health Organization (WHO) and Joint United Nations Program on AIDS (UNAIDS) recommend male circumcision (MC) as an additional HIV prevention measure. This study aimed to assess three models of promoting MC and their effects on preventing HIV infection among drug users in western China. We carried out a cohort study in three provinces of western China. HIV seronegative male drug users were recruited from methadone maintenance therapy clinics and cluster randomized into three intervention models. At baseline, 6, and 9 months of follow-up, changes in MC knowledge, the acceptability of MC, MC surgery uptake, and the costs of model implementation were analyzed. Of 1,304 male drug users who were screened, 1,218 were enrolled in the study. The participants' knowledge about MC was significantly increased after interventions by all three models. The one-stage model led to the highest increase in MC acceptability and the greatest increase in MC uptake. Multivariable Cox regression analysis showed that the one-stage model was also the most effective method to promote MC uptake, compared with the two-stage model [rate ratio (RR) = 0.602; 95% confidence interval (CI), 0.420-0.862] and three-stage model (RR = 0.555; 95% CI, 0.382-0.807). The HIV incidence rate in the MC group was lower than that in the non-MC group (RR = 0.234; 95% CI, 0.056-0.974). Moreover, the one-stage model required the lowest cost per circumcision. The one-stage model is the most effective and the most cost-effective intervention to increase MC uptake among male drug users in western China and could decrease the HIV incidence rate, based on a short follow-up investigation.

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.

HIV pre-exposure prophylaxis interest among female sex workers in Guangxi, China.

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.

[The efficacy of antiviral therapy and drug resistance analysis among HIV/AIDS patients with heroin addiction in Guangxi Zhuang Autonomous Region].

OBJECTIVE: To investigate the impact of heroin for antiviral treatment, drug resistance, mutation types and frequency in HIV/AIDS patients in Guangxi Zhuang Autonomous Region. METHODS: HIV/AIDS patients were recruited in Methadone Maintenance Treatment Clinics, HIV/AIDS Clinic and HIV Voluntary Counseling and Testing Center Liuzhou and Baise city from April 2008 to October 2009. The patients were grouped by the situation of antiviral treatment and use of heroin. A total of 435 HIV/AIDS patients were recruited, among which 108 cases in antiviral treatment and heroin group, 93 cases in antiviral treatment and never using drug group, 105 cases in no antiviral treatment and using heroin group, 129 cases in no antiviral treatment and never using drug group. The effect of antiviral treatment was evaluated by questionnaire survey, viral load measurement and CD4(+) T lymphocyte count. HIV-1 RNA from plasma was extracted, and then the pol genes were amplified and sequenced. The sequences were analyzed for HIV-1 genotype drug-resistance. RESULTS: For the patients who received antiviral treatment, the viral load in heroin group was higher than that in never using drug group (lg (2.61 ± 1.24) vs lg (2.08 ± 0.80), t = 3.54, P < 0.05) , and the percentage of viral load lower than 1 000 copies/ml in heroin group was significantly less than that in never using drug group (63.9% vs 86.0%,χ(2) = 12.76, P < 0.05). For the patients who received antiviral treatment, the difference has no significance in CD4(+) T lymphocyte count between heroin group and never using drug group ((337.92 ± 181.66) vs (326.14 ± 254.98), t = 0.38, P = 0.703). For the patients who didn't receive antiviral treatment, the difference also has no significance in CD4(+) T lymphocyte count between heroin group and never using drug group ((373.73 ± 155.97) vs (337.53 ± 209.26), t = 1.47, P = 0.143). For the patients who received antiviral treatment, there was no difference in the percentage of the CD4(+) T lymphocyte count more than 350/ml between heroin group and never using drug group (48.1% vs 43.0%, χ(2) = 0.53, P = 0.466). 319 HIV-1 pol gene sequences were obtained. Among the patients who received antiviral treatment, the mutation frequency of M184V/I, T215Y/F, L210W and T69N/S in heroin abuser group were significantly higher than that in never using drug group (14.9% (11/74) vs 4.4% (3/68), 12.2% (9/74) vs 1.5% (1/68), 12.2% (9/74) vs 1.5% (1/68) and 10.8% (8/74) vs 1.5% (1/68) respectively) (P < 0.05). CONCLUSION: Using heroin may promote HIV replication, reducing the virological response to antiviral treatment and increasing the frequencies of drug resistance loci among HIV/AIDS patients.Heroin rehabilitation may benefit from the antiviral treatment and obtain better antiviral effect.

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.

Acceptance of male circumcision among male rural-to-urban migrants in western China.

To describe the acceptability of male circumcision (MC) and explore potential factors associated with MC acceptability among male rural-to-urban migrants in western China, a cross-sectional survey of MC acceptability was conducted with 1,904 subjects in three western provinces with high HIV prevalence (Guangxi, Chongqing, and Xinjiang) in China between June 2009 and November 2009. Through face-to-face interviews, the participants completed a self-administered questionnaire about demographics, MC knowledge, willingness and reasons to accept or refuse MC, sexual behaviors, and other psychosocial variables. Factors associated with acceptability of MC were identified by multiple logistic regression analysis. Of the participants (n=1,904), 710 men were willing to accept MC (37.3%); the reasons included promotion of the partners' genital hygiene (54.9%), redundant prepuce or phimosis (43.1%), enhancement of sexual pleasure (40.6%), prevention of penile inflammation or cancer (35.5%), and protection against HIV and sexual transmitted diseases (STDs)(31.1%). A multivariable logistic regression showed that four factors were associated with acceptability of MC, including education level (OR=1.286, 95% CI=1.025~1.614), redundant prepuce or phimosis (OR=13.751, 95% CI=10.087~18.745), having one or more circumcised friends (OR=2.468, 95% CI=1.953~3.119), and having sexual intercourse with a temporary partner in the past year (OR=1.543, 95% CI=1.101~2.162). Compared with previously published data among the general population in China or worldwide, the acceptability of MC (37.3%) was low among the male rural-to-urban migrants in western China. Nevertheless, appropriate education could greatly improve the acceptability of MC. More public campaigns and health education on MC are needed to increase the rate of MC in China.