hTERT rs2736098 genetic variants and susceptibility of hepatocellular carcinoma in the Chinese population: a case-control study.

BACKGROUND: The human telomerase reverse transcriptase (hTERT) gene encodes the catalytic subunit of telomerase, which mediates pleiotropic effects, including the regulation of senescence and proliferation and plays an important role in carcinogenesis. This study attempts to clarify the genetic predisposition to hepatocellular carcinoma (HCC), focusing on the hTERT gene rs2736098 polymorphism. METHOD: Four hundred patients with HCC and 400 non-cancer controls were genotyped to elucidate the potential association between hTERT rs2736098 polymorphism and HCC risks. RESULTS: Compared with the controls, the patients with HCC had a lower frequency of G/G genotype (33.3% vs 44.3%, P=0.001) and a higher frequency of G/A (51.5% vs 39.5%, P=0.001). Allele genotypic frequencies in the patients differed from those of the controls (P=0.040). The data of this study rs2736098[A] allele contributed significantly to HCC risk in female patients (OR=1.78, 95% CI, 1.17-2.72, P=0.007), patients with HCV infection (OR=2.89, 95% CI, 1.08-7.70, P=0.031), non-drinker patients (OR=1.32, 95% CI, 1.06-1.65, P=0.015), and patients not affected by HBV (OR=1.77, 95% CI, 1.30-2.40, P<0.001). CONCLUSIONS: rs2736098[A] may be an independent hereditary parameter in HCC, but some risk factors would cover up the association by more powerful hepatocarcinogenesis. These results are important guidance for further studies in detecting HCC-associated single nucleotide polymorphisms.

HIV incidence among men who have sex with men using geosocial networking smartphone application in Beijing, China: an open cohort study.

BACKGROUND: Sexual transmission among men who have sex with men (MSM) is the dominant route of HIV transmission in China. Extensive use of geosocial networking (GSN) smartphone application (app) has dramatically changed the pattern of sexual behaviors and HIV risk among MSM, but data on HIV incidence and the changing risk behaviors of GSN app-using MSM are limited. We aims to assess the HIV incidence and its correlates among gay GSN app-using MSM in China. METHODS: We constructed an open cohort which was initiated and maintained using a GSN app to assess the HIV incidence among app-using MSM, recruited from June 2017 to December 2018. MSM completed an online questionnaire on their sociodemographic characteristics, sexual behaviors, recreational drug use and sexually transmitted infections status. Then each man had an HIV test, and those tested negatives were enrolled into the cohort. Participants completed follow-ups with additional HIV tests though the app during the study period, and were censored at HIV seroconversion or study end date. HIV incidence was calculated by dividing the sum of observed HIV seroconversions by the observed person-time. Univariate (Chi-square test and Fisher's exact test) and multivariate (proportional hazards regression) analyses were used to examine correlates of HIV incidence. RESULTS: A total of 6957 HIV negative MSM were enrolled in the open cohort, 37 seroconversions occurred among 1937 men contributing 1065 observed person-years: HIV incidence was 3.47 per 100 person-years [95% confidence interval (CI): 2.37-4.57]. More than five sexual partners [hazard ratio (HR) = 2.65, 95% CI: 1.04-6.67], and sex with HIV positive partners (HR = 3.82, 95% CI: 1.16-12.64) in the preceding six months were positively associated with HIV seroconversion. Consistent condom use for anal sex (HR = 0.27, 95% CI: 0.07-0.96), and reporting insertive anal sex only (HR = 0.23, 95% CI: 0.08-0.62) in the preceding six months were protective factors for HIV seroconversion. CONCLUSIONS: Tailored interventions targeting app-using MSM are urgently needed given their high risk of HIV. As a new tool for accessing MSM at higher HIV risk, GSN smartphone app could play an important role in HIV research among MSM.

Proteome analysis of Neisseria meningitidis serogroup strains C associated with outbreaks in China.

OBJECTIVE: During 2003-2005, an outbreak of meningitis due to Neisseria meningitidis serogroup C occurred in China. With the aim to find strain clues result in the final epidemics, the ancestral strain 053442, a clinical isolate, and a carrier strain 053426 with different gene type were analyzed. METHODS: Clinical strain 053442 and carrier strain 053426 were cultured on GC agar plates under the same condition. Two-dimensional electrophoresis was performed using the pH 3-10 nonlinear IPG strips of 24 cm length, and all the protein spots were identified by matrix-assisted laser desorption/ionization time of flight spectrometry. RESULTS: 502 and 380 protein spots were identified in 053426 and 053442 respectively, relating to 266 and 202 different genes covering a wide range of cellular functions. The express volume and number of proteins involved in energy metabolism, protein synthesis and amino acid biosynthesis in 053426 were higher than in 053442. Virulence factor Opa, Opc and a series of proteins involved in pilus assembly and retraction were identified in 053442, which appear to be of primary importance in colonization and invasion of human cells. Compared to 053442, virulence protein species were less in 053426, with lower express volumes too. No Opa and Opc were detected in 053426. CONCLUSIONS: The different protein expression profiles of the clinical strain 053442 and carrier strain 053426 in the present study provide some clues of the different pathogenicity of the two strains, which may account for result in the final epidemics.

A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression.

BACKGROUND: The identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression. RESULTS: In this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method). This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS) and Progression Score (PS) in progression analysis, True Positive Rate (TPR) in gene pair analysis, and Pathway Enrichment Score (PES) in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From this research, several gene interaction networks inferred could provide clues for the mechanism of prostate cancer progression. CONCLUSION: The SIG method reliably identifies cancer progression correlated gene pairs, and performs well both in gene pair ontology analysis and in pathway enrichment analysis. This method provides an effective means of understanding the molecular mechanism of carcinogenesis by appropriately tracking down the process of cancer progression.

Cross-reactivity of anti-H pylori antibodies with membrane antigens of human erythrocytes.

AIM: To investigate whether anti-H pylori antibodies have cross-reaction with antigens of erythrocyte membrane. METHODS: Blood samples were collected from 14 volunteers (8 positive and 6 negative for H pylori detected by (13)C-urea breath test) of the general population. Erythrocyte membrane proteins of the subjects were examined by Western blot using anti-H pylori serum. The proteins related to the positive bands were identified by mass spectrum analysis. RESULTS: Anti-H pylori antibodies had cross-reaction with the proteins of about 50 kDa of erythrocyte membranes in all samples independent of H pylori infection. One protein in the positive band was identified as Chain S, the crystal structure of the cytoplasmic domain of human erythrocyte Band-3 protein. CONCLUSION: Anti-H pylori antibodies cross-react with some antigens of human erythrocyte membrane, which may provide a clue for the relationship between H pylori infection and vascular disorders.

Effect of antiallergic herbal agents on chloride channel-3 and immune microenvironment in nasal mucosal epithelia of allergic rhinitis rabbits.

BACKGROUND: Allergic rhinitis (AR) is a Th2 dominant cytokine response. Chloride channel-3 (ClC-3) plays an important role in nasal mucosal edema and inflammatory pathologic changes in AR. Antiallergic herbal agents (AHA) are antiallergic herbal products. In the previous study, we have demonstrated that AHA clearly inhibited allergic medium and relieved allergic reaction of AR. The aim of this study was to evaluate the function of ClC-3 and discuss the possible therapeutic effects of AHA on immune microenvironment in AR. METHODS: AHA were produced and used to treat AR. An animal model of an AR rabbit was established by ovalbumin (OVA). The rhinitis rabbits were randomly divided into three groups: AHA treated group (AHATG), model group (MG) and healthy control group (HCG). The expressions of ClC-3 protein were examined by immunohistochemical method. The mucosal epithelial cells of all the rabbit groups were primarily cultured with tissue culture method in vitro with or without rhIL-4 or rhIL-2. Furthermore, the expressions of ClC-3 mRNA were detected by real-time PCR. The levels of monocyte chemotactic factor-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) protein in culture supernatants were measured by ELISA. RESULTS: The expressions of ClC-3 mRNA increased more in mucosal epithelial cells of MG than those in AHATG and HCG (P < 0.01). The levels of ClC-3 mRNA, MCP-1 and VCAM-1 protein in culture supernatants of MG were significantly higher than those in the other two groups (P < 0.01). Those were significantly increased in MG untreated 12 hours later than those in other two groups (P < 0.01). The expressions of ClC-3 mRNA, MCP-1 and VCAM-1 protein in culture supernatants of MG and HCG treated with rhIL-4 were significantly higher than those in the AHATG treated with rhIL-4 (P < 0.01). The levels of ClC-3 mRNA, MCP-1 and VCAM-1 protein in culture supernatants of all groups treated with rhIL-2 showed no significant changes (P > 0.05). CONCLUSIONS: AHA can inhibit the secretions of ClC-3, MCP-1 and VCAM-1 in mucosal epithelia and improve inflammatory reaction of AR. ClC-3 plays an important role in the secretion of cytokines and mucosal inflammatory response in AR. RhIL-4 can enhance the secretion of ClC-3, MCP-1 and VCAM-1 in mucosal epithelial cells, especially during the AR process. These enhanced effects of rhIL-4 were significantly suppressed by AHA. The secretions of ClC-3, MCP-1 and VCAM-1 can not be induced obviously by rhIL-2 in mucosal epithelial cells in AR.