Perfluorooctane sulfonate alternatives and metabolic syndrome in adults: New evidence from the Isomers of C8 Health Project in China.

Chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), are ubiquitous alternatives to perfluorooctane sulfonate (PFOS), a widely used poly- and perfluoroalkyl substance (PFAS). Despite in vivo and in vitro evidence of metabolic toxicity, no study has explored associations of Cl-PFESAs concentrations with metabolic syndrome (MetS) in a human population. To help address this data gap, we quantified 32 PFAS, including 2 PFOS alternative Cl-PFESAs (6:2 and 8:2 Cl-PFESAs) in serum from 1228 adults participating in the cross-sectional Isomers of C8 Health Project in China study. The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS and its various components were estimated using individual PFAS as a continuous or categorical predictor in multivariate regression models. The association between the overall mixture of PFAS and MetS was examined using probit Bayesian Kernel Machine Regression (BKMR-P). Greater serum PFAS concentrations were associated with higher odds of MetS and demonstrated a statistically significant dose-response trend (P for trend < 0.001). For example, each ln-unit (ng/mL) increase in serum 6:2 Cl-PFESA was associated with a higher prevalence of MetS (OR = 1.52, 95% CI: 1.25, 1.85). MetS was also 2.26 (95% CI: 1.59, 3.23) times more common in the highest quartile of serum 6:2 Cl-PFESA concentration than the lowest, and particularly high among women (OR = 6.41, 95% CI: 3.65, 11.24). The BKMR-P analysis showed a positive association between the overall mixture of measured PFAS and the odds of MetS, but was only limited to women. While our results suggest that exposure to Cl-PFESAs was associated with MetS, additional longitudinal studies are needed to more definitively address the potential health concerns of these PFOS alternatives.

Risk Factors for Adverse Pregnancy Outcomes among Zhuang Ethnic Pregnant Women: A Cohort Study in Guangxi, China.

Risk factors for adverse pregnancy outcomes among Zhuang ethnic pregnant women are unclear. This study analyzed the incidence and risk factors related to preterm birth (PB), low birth weight (LBW) and macrosomia in Zhuang population. We conducted a prospective cohort study of 9965 Zhuang pregnancy women in Guangxi, China. Information on mothers and newborns was obtained by using questionnaires and referring to medical records. Multivariate logistic regression analyses were used to evaluate the association between related factors and adverse pregnancy outcomes. Our results showed that the incidence of PB, LBW and macrosomia in Zhuang people was 5.55%, 5.64% and 2.19%, respectively. Maternal age ≥36 years (OR=2.22, 95% CI: 1.51-3.27) was related to a higher incidence of PB. Those with pre-pregnancy body mass index (BMI) <18.5 kg/m2 (OR=1.91, 95% CI: 1.45-2.51), and had a female fetus (OR=1.74, 95% CI: 1.36-2.23) were more likely to have LBW infants. Maternal age between 31 and 35 years (OR=1.76, 95% CI: 1.03-2.99) and pre-pregnancy overweight or obesity (OR=1.79, 95% CI: 1.15-2.80) were associated with a higher risk of macrosomia. The protective factors of macrosomia were maternal pre-pregnancy BMI <18.5 kg/m2 (OR=0.30, 95% CI: 0.15-0.60) and female fetus (OR=0.41, 95% CI: 0.28-0.59). Our study provided a reference for maternal and childcare administration among Zhuang population.

Serum levels of per- and polyfluoroalkyl substances alternatives and blood pressure by sex status: Isomers of C8 health project in China.

Several in vitro and in vivo studies have demonstrated the toxicity of perfluoroalkyl and polyfluoroalkyl substances (PFASs) alternatives, however, relevant epidemiological findings remain to be performed. In addition, the association between PFASs alternatives and blood pressure has not been explored. To address this gap, we quantified serum levels of alternatives and legacy PFAS in 1273 healthy Chinese, aged 34-94 years, from "isomers of C8 health project". Our results showed that an increase of serum PFASs levels was correlated with elevated blood pressure and higher prevalence of hypertension: per natural log unit (ng/mL) increase of 6:2 chlorinated polyfluorinated ether sulfonic acids (Cl-PFESA) elevated 1.31 (95%CI: 0.13, 2.50) mmHg of diastolic pressure (DBP). Adjusted odds ratios (aORs) for hypertension with per natural log increase of 6:2 and 8:2 Cl-PFESA were 2.57 (95%CI: 1.86, 3.56) and 1.18 (95%CI: 1.06, 1.32), respectively. When stratified by sex, the effects of PFASs alternatives on increased blood pressure and hypertension were stronger in women. Meanwhile, the association between 6:2 Cl-PFESA (aOR = 6.81; 95%CI: 3.54, 13.09) and hypertension was stronger than perfluorooctanoic acid (PFOA) (aOR = 2.32, 95%CI: 1.38, 3.91) in women. In conclusion, our pilot study demonstrates that serum concentrations of PFASs alternatives are positively associated with blood pressure. Moreover, women seem to be more susceptible, and alternatives exhibited stronger effects than legacy PFASs.

[Clinical effect of functional chewing training in treatment of oral motor dysfunction in children with cerebral palsy: a prospective randomized controlled clinical trial].

OBJECTIVE: To study the effect of functional chewing training (FuCT) on masticatory function, the severity of tongue thrust, and the severity and frequency of drooling in children with cerebral palsy. METHODS: A prospective study was performed for 48 children who were diagnosed with oral motor dysfunction from January 2019 to January 2020, and they were randomly divided into an FuCT group and an oral motor training group, with 24 children in each group. Both groups received FuCT or oral motor training for 12 weeks, and then they were evaluated in terms of the changes in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling. RESULTS: There were no significant differences between the two groups in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling before treatment (P>0.05). After the 12-week training, the FuCT group showed significant improvements in the masticatory function and the severity of tongue thrust and drooling (P<0.05), but with no improvement in the frequency of drooling (P>0.05), while the oral motor training group had no improvements in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling (P>0.05). After the 12-week training, the FuCT group had more significantly improvements in the severity of tongue thrust and the severity and frequency of drooling than the oral motor training group (P<0.05). CONCLUSIONS: FuCT can effectively improve the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling in children with cerebral palsy.

Incidence of ocular conditions associated with perfluoroalkyl substances exposure: Isomers of C8 Health Project in China.

The detrimental effects of perfluoroalkyl substances (PFASs) on several physiological systems have been reported, but the association of PFASs with eye, one of the most sensitive and exposed organ, has never been explored. To investigate the association between eye diseases including visual impairment (VI) and PFASs isomers, a cross-sectional stratified study was conducted in 1202 Chinese population, aged 22-96 years, from Shenyang, China. A standard protocol including Snellen vision chart, slit-lamp microscopy and direct ophthalmoscopy was used to examine eye diseases/conditions relating to anterior and posterior segment of eyes. In addition, we measured the blood concentrations of 19 linear and branched PFASs at one-time point. Results indicated that blood levels of PFASs were significantly higher in eye disease group than normal group. PFASs exposure were positively associated with both combined eye diseases and individual eye diseases. Among other PFASs, linear perfluorooctane sulfonate (n-PFOS; odds ratio [OR] = 3.37, 95% confidence interval [CI]: 2.50, 4.56), branched perfluorooctane sulfonate (Br-PFOS; OR = 2.25, 95% CI: 1.72, 2.93) and linear perfluorooctanoic acid (n-PFOA; OR = 1.79, 95% CI: 1.36, 2.37) significantly increases the odds of VI. Vitreous disorder was adversely associated with long-chain PFASs exposure. For example, perfluorotridecanoic acid (PFTrDA; OR = 1.86, 95% CI: 1.51, 2.29) and perfluorodecanoic acid (PFDA; OR = 1.79, 95% CI: 1.36, 2.36) showed the most significant association. In conclusion, this study suggests higher serum PFASs levels were associated with increase odds of VI and vitreous disorder in Chinese adults.

Alternatives of perfluoroalkyl acids and hepatitis B virus surface antibody in adults: Isomers of C8 Health Project in China.

Previous epidemiological and experimental studies have shown that legacy perfluoroalkyl acids (PFAAs) are immunotoxic. However, whether the immunosuppressive effects in PFAA alternatives which recently have been widely detected in the environment are unknown. To address this knowledge gap, we investigated the relationship of serum legacy PFAAs and PFAA alternatives with the antibody of hepatitis B virus in adults. We recruited 605 participants from a cross-sectional study, the Isomer of C8 Health Project in China. We measured two representative legacy PFAAs (perfluorooctane sulfonate, PFOS and perfluorooctanoic acid, PFOA), and three PFAA alternatives (two chlorinated polyfluorinated ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) in serum using ultra-performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS). We applied linear and logistic regression models to analyze associations between serum PFAAs and hepatitis B surface antibody (HBsAb) with multivariable adjustments. We found negative associations between serum PFAAs concentrations and HBsAb. Lower serum HBsAb levels (log mIU/mL) were observed for each log-unit increase in linear PFOS (ß = -0.31, 95% confidential interval: 0.84, -0.18), 6:2 PFESA (ß = -0.81, 95% CI: 1.20, -0.42), 8:2 PFESA (ß = -0.29, 95% CI: 0.43, -0.14) and PFBA (ß = -0.18, 95% CI: 0.28, -0.08). The association between PFAAs and HBsAb seronegative seemed to be higher for 6:2 PFESA (odds ratio = 3.32, 95% CI: 2.16, 5.10) than its predecessors, linear PFOS (OR = 1.96, 95% CI: 1.37, 2.81) and branched PFOS isomers (OR = 1.64, 95% CI: 1.05, 2.56). We report new evidence that exposure to PFAA alternatives are associated with lower HBsAb in adults. This association seems to be stronger in 6:2 PFESA than PFOS. Our results suggest that more studies are needed to clarify the potential toxicity of PFAA alternatives in human which will facilitate better chemical regulations for PFAAs.

Synthesis and antitumor, antityrosinase, and antioxidant activities of xanthone.

Ten substituted 1,3-dihydroxyxanthones were synthesized in one step. The yields ranged from 40 to 76%. Compounds 8-10 were first reported. Next, the compounds' in vitro anti-proliferative activities against nine human cancer cell lines, antityrosinase, and antioxidant activities were evaluated. Compounds 1, 4, 6-7, and 9-10 exhibited enhanced cytotoxicity against certain cancer cells. Compounds 2, 8, 9, and 10 inhibited tyrosinase activity to a certain extent. In addition, compound 4 exhibited the best antioxidant activity, which was consistent with theoretical calculations. These results demonstrated that compounds 1-2, 4, and 6-10 were promising leads for further investigation.

Genetic variants of cell cycle pathway genes predict disease-free survival of hepatocellular carcinoma.

Disruption of the cell cycle pathway has previously been related to development of human cancers. However, associations between genetic variants of cell cycle pathway genes and prognosis of hepatocellular carcinoma (HCC) remain largely unknown. In this study, we evaluated the associations between 24 potential functional single nucleotide polymorphisms (SNPs) of 16 main cell cycle pathway genes and disease-free survival (DFS) of 271 HCC patients who had undergone radical surgery resection. We identified two SNPs, i.e., SMAD3 rs11556090 A>G and RBL2 rs3929G>C, that were independently predictive of DFS in an additive genetic model with false-positive report probability (FPRP) <0.2. The SMAD3 rs11556090G allele was associated with a poorer DFS, compared with the A allele [hazard ratio (HR) = 1.46, 95% confidential interval (95% CI) = 1.13-1.89, P = 0.004]; while the RBL2 rs3929 C allele was associated with a superior DFS, compared with the G allele (HR = 0.74, 95% CI = 0.57-0.96, P = 0.023). Additionally, patients with an increasing number of unfavorable genotypes (NUGs) of these loci had a significant shorter DFS (Ptrend  = 0.0001). Further analysis using receiver operating characteristic (ROC) curves showed that the model including the NUGs and known prognostic clinical variables demonstrated a significant improvement in predicting the 1-year DFS (P = 0.011). Moreover, the RBL2 rs3929 C allele was significantly associated with increased mRNA expression levels of RBL2 in liver tissue (P = 1.8 × 10-7 ) and the whole blood (P = 3.9 × 10-14 ). Our data demonstrated an independent or a joint effect of SMAD3 rs11556090 and RBL2 rs3929 in the cell cycle pathway on DFS of HCC, which need to be validated by large cohort and biological studies.

Positive association between metabolic syndrome and serum uric acid in Wuhan.

BACKGROUND AND OBJECTIVES: The objective was to determine whether serum uric acid concentrations were associated with metabolic syndrome in a population from Wuhan. METHODS AND STUDY DESIGN: 5,628 subjects (2,838 men, 2,790 women) aged 18-80 years were recruited in Wuhan, China. Biochemical parameters of venous blood were measured by standard methods and metabolic syndrome was defined by Chinese Diabetes Society criteria. Association analysis was performed by logistic regression. RESULTS: 8.2% of the included subjects were confirmed as having metabolic syndrome and 14.4% were confirmed as having hyperuricemia. After multivariable adjustment, logistic regression showed the odds ratios of metabolic syndrome for subjects in the highest quartile of serum uric acid concentration was 2.84 (95% CI: 2.09-3.86) compared with those in the lowest quartile and no gender difference was found. For each component of metabolic syndrome, subjects in the highest quartile of serum uric acid concentrations had increased multivariable odds ratios for high BMI (OR: 3.29, 95% CI: 2.71-3.98), for hypertension (OR: 3.54, 95% CI: 2.93-3.86), for dyslipidemia (OR: 2.49, 95% CI: 1.98-3.14), but not for hyperglycemia (OR: 1.21, 95% CI: 0.87-1.67). CONCLUSIONS: Odd ratio of metabolic syndrome was significantly positively associated with serum uric acid concentration among the present sample of 5,628 subjects in Wuhan.

Positive association between the metabolic syndrome and white blood cell counts in Chinese.

BACKGROUND AND OBJECTIVES: The aim was to investigate the association between peripheral circulating white blood cell count (WBC) and the metabolic syndrome among populations in central China. METHODS AND STUDY DESIGN: In the present study, 5,278 subjects (2,412 women, 2,866 men) aged 18-75 years were recruited through a health check program in Wuhan, China. Biochemical and haematological parameters were measured by standard methods and the metabolic syndrome diagnosed as defined by the Chinese Diabetes Society criteria for Chinese. RESULTS: Both WBC counts and prevalence of metabolic syndrome were significantly higher in men than in women (p<0.01). Participants in the highest quartile of white blood cell count had significantly higher odds ratio of metabolic syndrome (3.79, 95% CI: 2.64, 5.44), compared with subjects in the lowest quartile. The trend remained significant after adjustment for confounding factors and in further subgroup-analyses. CONCLUSIONS: Metabolic syndrome prevalence was significantly and positively correlated with the total white blood cell count in this Chinese population.

Heat Shock Protein 90 Facilitates Latent HIV Reactivation through Maintaining the Function of Positive Transcriptional Elongation Factor b (p-TEFb) under Proteasome Inhibition.

The persistence of HIV in resting memory CD4+ T cells at a latent state is considered as the major barrier on the path to achieve a cure for HIV. Proteasome inhibitors (PIs) were previously reported as latency reversing agents (LRAs) but the mechanism underlying this function is yet unclear. Here we demonstrate that PIs reactivate latent HIV ex vivo without global T cell activation, and may facilitate host innate immune responses. Mechanistically, latent HIV reactivation induced by PIs is mediated by heat shock factor 1 (HSF1) via the recruitment of the heat shock protein (HSP) 90-positive transcriptional elongation factor b (p-TEFb) complex. Specifically, HSP90 downstream HSF1 gives positive feedback to the reactivation process through binding to cyclin-dependent kinase 9 (CDK9) and preventing it from undergoing degradation by the proteasome. Overall, these findings suggest proteasome inhibitors as potential latency reversing agents. In addition, HSF1/HSP90 involved in HIV transcription elongation, may serve as therapeutic targets in HIV eradication.

Relationships between cell cycle pathway gene polymorphisms and risk of hepatocellular carcinoma.

AIM: To investigate the associiations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma (HCC). METHODS: We enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospital of Guangxi Medical University and 1200 non-tumor patients from the First Affiliated Hospital of Guangxi Medical University. General demographic characteristics, behavioral information, and hematological indices were collected by unified questionnaires. Genomic DNA was isolated from peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom MassARRAY iPLEX genotyping method. The association between genetic polymorphisms and risk of HCC was shown by P-value and the odd ratio (OR) with 95% confidence interval (CI) using the unconditional logistic regression after adjusting for age, sex, nationality, smoking, drinking, family history of HCC, and hepatitis B virus (HBV) infection. Moreover, stratified analysis was conducted on the basis of the status of HBV infection, smoking, and alcohol drinking. RESULTS: The HCC risk was lower in patients with the MCM4 rs2305952 CC (OR = 0.22, 95%CI: 0.08-0.63, P = 0.01) and with the CHEK1 rs515255 TC, TT, TC/TT (OR = 0.73, 95%CI: 0.56-0.96, P = 0.02; OR = 0.67, 95%CI: 0.46-0.97, P = 0.04; OR = 0.72, 95%CI: 0.56-0.92, P = 0.01, respectively). Conversely, the HCC risk was higher in patients with the KAT2B rs17006625 GG (OR = 1.64, 95%CI: 1.01-2.64, P = 0.04). In addition, the risk was markedly lower for those who were carriers of MCM4 rs2305952 CC and were also HBsAg-positive and non-drinking and non-smoking (P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBsAg-negative and non-drinking (P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2B rs17006625 GG and were also HBsAg-negative (P < 0.05). CONCLUSION: Of 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2B polymorphisms may be associated with the risk of HCC.

Activation of autophagy improved the neurologic outcome after cardiopulmonary resuscitation in rats.

OBJECTIVE: Recent studies have shown the existence of autophagy in cerebral ischemia; however, there has been no research on the role of autophagy in cerebral injury after cardiopulmonary resuscitation (CPR). This study was conducted to determine the role of autophagy in an animal model of ventricular fibrillation (VF)/CPR. METHODS: Experiment 1: A total of 48 adult Wistar rats were untreated for 7 minutes after induction of VF using an external transthoracic alternating current, and subsequent CPR was performed to observe the existence of autophagy after the return of spontaneous circulation (ROSC). Experiment 2: A total of 72 rats were pretreated with intracerebroventricular injection of physiologic saline (control group), the autophagy inducer (rapamycin group), or the autophagy inhibitor 3-methyladenine (3-methyladenine group) before ROSC to evaluate the contribution of autophagy to neuronal injury after ROSC. RESULTS: The activation of autophagy was attenuated 2 to 4 hours after ROSC, which was related to the activity decrease of 5'-adenosine monophosphate-activated protein kinase after ROSC. Rapamycin treatment significantly increased the expressions of LC3-II and Beclin-1 after ROSC, attenuated the activation of caspase-3, promoted neuronal survival and decreased neuronal apoptosis, and improved the neurologic deficit score after CPR. CONCLUSIONS: The activation of autophagy after ROSC offered a remarkable tolerance to VF/CPR ischemic insult and improved the neurologic outcomes.

Heat Shock Factor 1 Mediates Latent HIV Reactivation.

HSF1, a conserved heat shock factor, has emerged as a key regulator of mammalian transcription in response to cellular metabolic status and stress. To our knowledge, it is not known whether HSF1 regulates viral transcription, particularly HIV-1 and its latent form. Here we reveal that HSF1 extensively participates in HIV transcription and is critical for HIV latent reactivation. Mode of action studies demonstrated that HSF1 binds to the HIV 5'-LTR to reactivate viral transcription and recruits a family of closely related multi-subunit complexes, including p300 and p-TEFb. And HSF1 recruits p300 for self-acetylation is also a committed step. The knockout of HSF1 impaired HIV transcription, whereas the conditional over-expression of HSF1 improved that. These findings demonstrate that HSF1 positively regulates the transcription of latent HIV, suggesting that it might be an important target for different therapeutic strategies aimed at a cure for HIV/AIDS.

[Small molecular agents against MERS-CoV infection].

Middle East respiratory syndrome coronavirus (MERS-CoV) has caused outbreaks of SARS-like disease with 35% case-fatality rate, mainly in the Middle East. A more severe outbreak of MERS occurred recently in the Republic of Korea, where 186 people contracted the infections, causing great concern worldwide. So far, there has been no clinically available drug for the treatment of MERS-CoV infection. The potential drugs against MERS-CoV mainly consist of monoclonal antibodies, peptides and small molecular agents. Small molecular agents have an advantage of easier synthesis, lower cost in production and relatively higher stability. There is better chance for those candidates to gain a quick development. This article reviews the progress of developing small molecular MERS-CoV agents.

[Relationship between IL6 -572G/C polymorphism and hepatocellular carcinoma in men].

To study the relationship between the interleukin (IL)6 -572G/C polymorphism and risk of hepatocellular carcinoma (HCC) in men.A hospital-based case-control study was conducted with 500 male HCC patients without tumor history in other organs and 590 healthy male controls without history of tumors or chronic diseases. All HCC cases were diagnosed by histopathology. The controls were recruited from the Department of Orthopedic Trauma and Ophthalmology at the same hospital. The IL-6 promoter -572G/C polymorphism and its genotype variants were detected by real-time fluorescence quantitative PCR. The Chi-squared test and unconditional logistic regression analyses were applied to determine the risk of HCC among men carrying the different genotype variants.The frequencies of alleles and distribution of genotypes in the -572G/C loci were not significantly different between the HCC cases and controls (P more than 0.05). The Chi-squared test indicated that the polymorphisms of the loci were not associated with HCC in our male population. However, after adjusting by multivariate logistic regression, the odds ratio (OR) of HCC for the G allele (CG + GG genotypes) carriers was 1.31 (95% confidence interval (CI): 1.00 - 1.71) compared with the CC genotype. Among the male HBV carriers, the CG genotype increased HCC risk significantly (OR = 1.60, 95% CI: 1.14 - 2.24) compared with the CC genotype. A trend test indicated that HCC risk was significantly increased with the numbers of G alleles (P trend less than 0.05). Breslow-Day tests of homogeneity of the ORs indicated an interaction between hepatitis B virus (HBV) infection and polymorphisms of IL-6 (P less than 0.05). The synthetic odds ratio (OReg) of HBV infection and harboring a G allele was 5.95 (95% CI: 3.99-8.87), which represented a super multiplication interaction.Polymorphism of the IL-6 promoter -572 loci may be associated with HCC occurrence in men. Moreover, there is a super multiplication interaction for HCC risk between HBV infection and harboring the IL-6 G allele.

[Correlation between polymorphism of sex hormone binding globulin and occurrence of hepatocellular carcinoma].

OBJECTIVE: This study aims to investigate the correlation between polymorphism of sex hormone-binding globulin (SHBG) Asp327Asn (rs6259) locus and occurrence of hepatocellular carcinoma (HCC). METHODS: 621 cases with HCC and 621 cancer-free controls from two hospitals of Guangxi were recruited from January, 2007 to June, 2010. Single nucleotide polymorphisms (SNP) of SHBG Asp327Asn were detected by ABI7500 Fast Real-Time fluorescence quantitative PCR. Multivariate unconditional logistic regression was applied to analyze risk of HCC among different genotypes carriers and their interaction with the exposure factors. The Kaplan-Meier survival analysis was used to detect the relationship between onset age of HCC and genotypes. RESULTS: The frequencies of Asp/Asp, Asp/Asn and Asn/Asn genotype in case group were 86.31% (536/621), 12.40% (77/621) and 1.29% (8/621), respectively; while those in control group were 81.00% (503/621), 17.39% (108/621) and 1.61% (10/621), respectively. Significant difference in the genotype frequencies distribution was found between case and control groups (χ2=6.465, P<0.05). Compared with those harboring Asp/Asp genotype, multivariate logistic regression analysis revealed that the HCC risk of Asn/Asn+Asp/Asn genotype carriers was significantly decreased (adjusted OR=0.63, 95%CI: 0.40-0.98). Interaction analysis showed that there was interaction between the polymorphisms and two exposure factors, drinking (adjusted OR=3.45, 95%CI: 1.74-6.83) and HBV infection (adjusted OR=40.77, 95%CI: 21.60-76.97). Among those male patients with history of drinking, survival analysis indicated that the mean age of onset of individuals harboring Asp/Asp genotypes ((47.99±0.75) years-old) was 6 years earlier than those with Asn/Asn or Asp/Asn genotypes ((53.68±2.07) years-old) (χ2=6.91, P<0.01). CONCLUSION: Polymorphism of SHBG (Asp327Asn) may be associated with both the risk of HCC occurrence and onset age of HCC.

TNF-α -863 polymorphisms and the risk of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common type of highly malignant tumor. Guangxi is an area of China characterized by a high incidence of HCC. Previous epidemiological studies have found that chronic infection with hepatitis B virus (HBV) is one of the major etiological risk factors for HCC in China. With the increased understanding of the host immune response against HBV and the pathogenesis of the virus, at present, greater attention is being given to the immune response of cytokine genes, as polymorphisms may have a major impact on the course and outcome of HBV infection. In the present study, we genotyped tumor necrosis factor-α (TNF-α) rs1800629 (-308G/A), rs1800630 (-863C/A); interleukin-1B rs1143627 (-31T/C); and transforming growth factor ß1 (TGF-ß1) rs1800469 (-509C/T) in a hospital-based study of 772 HCC cases and 852 cancer-free controls. The distribution of the frequency of TNF-α rs1800630 sites of CC, CA, AA were 65.67, 27.46 and 6.87% in the case group, respectively, as compared with 67.02, 29.58 and 3.40% in the controls, all with a statistical significance (P<0.05). The logistic regression analysis revealed that the variant rs1800630 AA genotypes were associated with a significantly increasing risk of HCC (OR=2.058, 95% CI 1.289-3.287), compared with the wild-type rs1800630 CC. Further stratified analyses showed that after stratification for history of alcohol drinking, in a subgroup of individuals without a history of drinking, the HCC risk in the group with the TNF-α rs1800630 A allele was 1.839 times higher than that in the group with TNF-α rs1800630 C (P<0.010). These findings suggest that TNF-α rs1800630 may contribute to the risk of HCC, however, these data require further validation.

[Study on the relationship between single-nucleotide polymorphisms in IL-6, IL-10 genes and HBV-related hepatocellular carcinoma].

OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) in cytokine IL-6, IL-10 genes and HBV-related hepatocellular carcinoma (HCC). METHODS: A hospital-based case-control study was conducted in 381 cases with HBV-related HCC, 340 HBsAg carriers and 359 non-tumor controls. Genotypes of -572 site of IL-6 gene and -819, -592 sites of IL-10 gene were determined by real-time polymorphism chain reaction. Unconditional logistic regression was used to estimate the odds ratios (ORs) and 95 confidence intervals (CIs). RESULTS: For the G/C alleles of -572 loci on IL-6 gene, there were significant differences between the three groups (P < 0.05). Compared with CC genotype, GG genotype increased the risk of HBV infection (OR = 2.171, 95%CI: 1.068 - 4.415), but did not seem to be associated with HCC. For the alleles of -819 and -592 site of IL-10 gene, there were significant differences between the three groups (P < 0.05). Compared with CC genotype, TT genotype increased the risks of both HCC (OR = 2.791, 95%CI: 1.326 - 5.874), and HCC in HBsAg carriers (OR = 3.522, 95%CI: 1.707 - 7.266). When compared with CC genotype on -592 site, the AA genotype reduced the risk of both HCC (OR = 0.389, 95%CI: 0.173 - 0.875), and HCC in HBsAg carriers (OR = 0.336, 95%CI: 0.154 - 0.734). CONCLUSION: The SNPs in -572 site of IL-6 gene might be associated with the risk of HBV infection. The SNPs in -819 site of IL-10 gene increased the risk of HCC, but -592 site of IL-10 gene decreased the risk of HCC.

[Association of XPC and XPG polymorphisms with the risk of hepatocellular carcinoma].

OBJECTIVE: To investigate whether the polymorphism of DNA repair genes XPC (Ala499Val and Lys939Gln) and XPG (His1104Asp) is associated with the susceptibility to hepatocellular carcinoma (HCC). METHODS: A hospital-based case-control study was conducted in 500 cases with HCC and 507 controls. Genotypes of XPC and XPG were determined by real-time polymerase chain reaction with the TaqMan MGB probe. RESULTS: Compared to the CC genotype, the CT genotype and the TT genotype of XPC Ala499Val were not associated with the susceptibility to HCC (adjusted OR = 1.34, 95% CI: 0.85-2.12; adjusted OR = 1.30, 95% CI: 0.68-2.51, respectively). Compared to the AA genotype, the AC genotype and the CC genotype of Lys939Gln were not associated with the susceptibility to HCC (adjusted OR = 1.20, 95% CI: 0.78-1.85; adjusted OR = 1.81, 95% CI: 0.88-3.73, respectively). Compared to the CC genotype, the CG genotype and the GG genotype of XPG His1104Asp were not associated with the susceptibility to HCC (adjusted OR = 0.85, 95% CI: 0.56-1.27; adjusted OR = 1.12, 95% CI: 0.67-1.87, respectively) However, the stratified analysis revealed that the females with the AC+CC genotype of XPC Lys939Gln had increased risk of HCC compared to those with AA genotype (OR = 2.17, 95% CI: 1.01-4.64). CONCLUSION: Our results suggest that XPC and XPG polymorphisms do not independently affect on the susceptibility to HCC, but the joint effect of C allele of XPC Lys939Gln and female may modify the risk of HCC.