Objective To investigate the association between the Adiponectin rs266729 and rs2241766 gene polymorphisms and nonalcoholic fatty liver disease in the Han Chinese population residing in Qingdao. Methods Adiponectin rs266729 and rs2241766 gene polymorphisms were genotyped in patients with NAFLD (n = 336) and healthy controls (n = 280) using polymerase chain reaction (PCR). Serum lipid profiles and adiponectin levels were determined using biochemical methods. Statistical analyses were performed using Pearson Chi square test, logistic regression analysis, t test, linear regression analysis. Results We found a significant association between the Adiponectin rs266729 genotype frequencies and allele frequencies between NAFLD pa-tients and controls (χ2= 9.929, P = 0.007; χ2= 9.809, P = 0.002). After adjustment of confounding factor, the rs266729 G allele was associated with an increased risk of NAFLD compared to the C allele (OR = 1.410, 95%CI: 1.082-1.831, P = 0.008) No significant differences were found in the rs2241766 genotype frequencies and allele frequencies between NAFLD population and the controls (OR = 1.410, 95%CI: 1.082-1.831, P = 0.008). Conclusion The Han Chinese in Qingdao carrying the rs266729 G allele are at increased risk of NAFLD.

Carcinoma, Hepatocellular ; Humans ; Lipase ; Liver Neoplasms ; Membrane Proteins ; Polymorphism, Genetic

Adult ; Female ; Hepatitis B, Chronic ; blood ; pathology ; Humans ; Liver Cirrhosis ; blood ; pathology ; Liver Function Tests ; Male ; Middle Aged ; Transforming Growth Factor beta ; blood ; Transforming Growth Factor beta1

Objective To investigate the association between (beta-parvin) PARVB gene rs5764455 polymorphism and susceptibility to non-alcoholic fatty liver disease (NAFLD). Methods A total of 230 patients with NAFLD (NAFLD, n = 230) and 230 control subjects (control, n = 330) were genotyped by PCR and direct sequencing. Clinical information was detected and compared in different groups. Genotypic frequency and gene frequency distribution in the two groups and relative risks to NAFLD susceptibility were assessed statistically , respectively. Results No statistical differences were observed between PARVB gene rs5764455 genotypic frequency with gene frequency distribution and the two groups, respectively (Genotypic frequency χ2 = 0.182, P = 0.913; gene frequency χ2 = 0.180, P = 0.672). Comparing C/T + T/T genotype carrier with C/C genotype carrier, there were no differences concerning the relative risks to NAFLD susceptibility (OR = 1.266, P =0.178;adjusted OR =1.631, P =0.096) before and after adjusting body mass, BMI and so on. In the latter group, there are significant differences in the increases of body mass, BMI, TG, ALT and AST (P < 0.05). Conclusion Non-relationship was observed between PARVB gene rs5764455 polymorphism and the risk of NAFLD in Qingdao Han Chinese.

ObjectiveTo investigate the mechanism of action of PNPLA3 I148M mutation in the development and progression of non-alcoholic fatty liver fibrosis. MethodsThe lentiviral vectors carrying the mutant or wild-type PNPLA3 I148M gene were constructed and transfected into rat hepatic stellate (HSC-T6) cells. Quantitative real-time PCR was applied to measure the mRNA expression of transforming growth factor β1 (TGF β1). The t-test was applied for statistical analysis. ResultsThe lentiviral vectors carrying the mutant or wild-type PNPLA3 I148M gene were successfully constructed and transfected into HSC-T6 cells, and a HSC-T6 cell line with stable expression of the mutant or wild-type PNPLA3 gene was established. Compared with the cell line carrying the wild-type gene, the cell line carrying the mutant gene showed significantly higher mRNA expression of TGF β1 (1.25±0.15 vs 0.48±0.07; t=11.826, P＜0001). ConclusionPNPLA3 I148M mutation can increase the expression of TGF β1 in HSC-T6 cells, which provides a new cell model and new research ideas for investigating the role of PNPLA3 I148M mutation in non-alcoholic fatty liver fibrosis.

OBJECTIVETo investigate the efficacy and safety of telbivudine for blocking mother-to-child transmission of hepatitis B virus (HBV) in pregnant women with high viremia.

METHODSA total of 128 pregnant women with high HBV load (HBV DNA ≥ 1.0*10⁷ copies/ml and positive for hepatitis B surface antigen (HBsAg)) were enrolled in the study from January 2009 to January 2013 and divided into the following three groups:group A (n=42) treated with telbivudine at 12 weeks of gestation until postpartum 12 weeks; group B (n=41) treated with telbivudine at 20 to 28 weeks of gestation until postpartum 12 weeks; group C (n=45; control group) with no telbivudine treatment.All study participants were given compound giyeyrrhizin for liver protection. All infants born to the women from the three groups were vaccinated with hepatitis B immunoglobulin (200 IU) and the HBV vaccine (20 tg) ager birth. The mother-to-infant transmission of HBV was indicated by the presence of HBsAg in infants at 7 months after birth.The maternal HBV DNA levels of the women in the three groups were statistically compared with the HBsAg positive rates in their neonates.

RESULTSThere were no significant differences in the HBV DNA levels between the three groups before treatment (P more than 0.05). The pre-delivery level of HBV DNA in group A (0.553 ± 1.588 log10 copies/ml) and in group B (0.486 ± 1.429 log10 copies/ml) was significantly decreased compared to that in group C (7.698 ± 0.255 log10 copies/ml) (both P < 0.01).The post-delivery (12 weeks) level of HBV DNA in group A (0.381 ± 1.116 log10 copies/ml) and in group B (0.335 ± 1.073 log10 copies/ml) was significantly decreased compared to that in group C (7.728 ± 0.277 log10 copies/ml) (both P < 0.01).There were no significant differences in the HBV DNA levels between group A and group B (P > 0.05). No infants in group A or group B were HBsAg-positive,while the HBsAg-positive rote was 17.4% in group C (P=0.012; P=0.015).

CONCLUSIONSTelbivudine treatment starting from the 12th week of gestation or from the 20-28th week of gestation can significantly decrease the serum HBV DNA level in peripheral blood of pregnant women with high viremia and reduce the infection rate of HBV in their neonates.

Female ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Immunoglobulins ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious ; Thymidine ; analogs & derivatives ; Viremia

ObjectiveTo investigate the association of KCNJ11 rs5210 single nucleotide polymorphism with nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population in Qingdao, China. MethodsA total of 246 patients with NAFLD who attended Qingdao Municipal Hospital from December 2018 to September 2019 were enrolled as NAFLD group, 201 patients with CAD were enrolled as CAD group, and 116 patients with NAFLD and CAD were enrolled as NAFLD+CAD group; 342 healthy individuals were enrolled as control group. Fasting venous blood samples were collected for biochemical analysis. Whole blood genomic DNA was extracted, and PCR was used to determine KCNJ11 rs5210 genotype. The chi-square test was used to analyze whether the distribution of KCNJ11 rs5210 gene frequencies met the Hardy-Weinberg equilibrium, in order to determine whether the tested samples could represent the population. The chi-square test was used to analyze the differences in sex and genotype/allele frequency between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Bonferroni method was used for further comparison between two groups. The unconditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval. ResultsThree genotypes (AA, GA, and GG) of KCNJ11 rs5210 were found by gene sequencing. There were no significant differences in rs5210 allele frequency and genotype distribution between the control group, the NAFLD group, the CAD group, and the NAFLD+CAD group (all P＞0.05), and there were still no significant differences after adjustment for sex, age, and body mass index (BMI) (all P＞0.05). For all subjects, the subjects with AA genotype had a higher level of alkaline phosphatase than those with GA genotype (P=0.048); in the NAFLD group, the patients with GA genotype had significantly higher BMI and total bilirubin than those with AA genotype (P=0.042 and 0.002). The unconditional logistic regression analysis showed that elevated BMI was associated with the risk of NAFLD (OR=1.35, P＜0.01), while decreased high-density lipoprotein (HDL) might indicate an increase in the risk of NAFLD (OR=0.33, P＜0.01); elevated fasting plasma glucose and decreased HDL might indicate an increase in the risk of CAD (OR=1.51 and 0.11, both P＜0.01) and NAFLD with CAD (OR=1.46 and 0.06, both P＜0.01). ConclusionThere is no significant association between KCNJ11 rs5210 polymorphism and the risk of NAFLD and CAD in the Chinese Han population in Qingdao.

ObjectiveTo investigate the association of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) rs8192678 single nucleotide polymorphism (SNP) with the risk of nonalcoholic fatty liver disease (NAFLD) and the influence of PPARGC1A rs8192678 SNP on NAFLD-related biochemical parameters. MethodsA total of 119 NAFLD patients who attended Qingdao Municipal Hospital Affiliated to Qingdao University from December 2017 to December 2018 were enrolled as NAFLD group, and 213 individuals who underwent physical examination during the same period of time were enrolled as control group. Clinical data and blood samples were collected from all subjects to measure related biochemical parameters and detect PPARGC1A rs8192678 SNP. The chi-square test was used to determine whether the genotype distribution of samples was in accordance with the Hardy-Weinberg equilibrium. The t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. A binary logistic regression analysis was used to investigate the risk factors for NAFLD. ResultsThere were no significant differences in the genotype and allele frequencies of PPARGC1A rs8192678 between the NAFLD group and the control group (χ2=0.011 and 0.015, P=0.918 and 0.904). The binary logistic regression analysis showed that CT genotype of PPARGC1A rs8192678 was not a risk factor for NAFLD (odds ratio=0.951, 95% confidence interval: 0.368-2.457, P=0.918). In the NAFLD group, the patients carrying CT genotype had a significantly higher level of gamma-glutamyl transpeptidase (GGT) than those carrying CC genotype (Z=-2.331, P=0.020). ConclusionPPARGC1A rs8192678 SNP does not increase the risk of NAFLD, while NAFLD patients carrying CT genotype tend to have a higher serum level of GGT.

Objective:Based on the regulatory effect of curcumin (Cur) on inflammation and iron death, to explore the mechanism of Cur protecting against cerebral ischemia-reperfusion injury (CIRI).Methods:A rat model of middle cerebral artery occlusion (MCAO) was established by the modified suture-occluded method. The modeled SD rats were randomly divided into the Sham group, CIRI group and Cur group. The neurobehavioral score of rats was measured by the Longa method. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the brain tissue of rats in each group. Furthermore, the contents of glutathione (GSH), malondialdehyde (MDA) and Fe 2+, as well as the levels of the inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in the ischemic cerebral cortex, were detected by corresponding testing kits. Western blotting was applied to detect the expression of glutathione peroxidase 4 (GPX4), a key regulatory protein of ferroptosis in the cerebral cortex. In addition, neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and ultrastructural changes in neurons in the cerebral cortex were observed under a transmission electron microscope. Results:Compared with the CIRI group, the Cur group showed decreased neurobehavioral scores, significantly reduced contents of MDA, Fe 2+, TNF-α, IL-1β and IL-6 (all P<0.05), but obviously increased content of GSH and protein expression of GPX4 (both P<0.05). Further pathological examination revealed edema, rupture and necrosis of neurons in the CIRI group, while mild edema and a small number of necrotic cells were observed in the Cur group only. The results of TUNEL staining indicated that the rate of neuronal apoptosis in the Cur group was lower than that in the CIRI group, with a statistically significant difference between groups [(23.6±3.5)% vs. (36.8±4.2)%; P<0.05]. In addition, under the transmission electron microscope, the CIRI group had a reduced volume of mitochondria, thickened double-layer membrane structure, and decreased or disappeared mitochondrial cristae, while the Cur group showed partial margination of nuclear chromatin and alleviated damage to mitochondria. Conclusions:Cur could attenuate CIRI, and its neuroprotective mechanism may be related to the inhibition of the inflammatory response and GPX4-mediated ferroptosis.

OBJECTIVETo investigate the association between two polymorphisms of the APOC3 gene (T-455C and C-482T) and hereditary risk of non-alcoholic fatty liver disease (NAFLD).

METHODSA total of 287 patients with NAFLD and 310 control subjects were genotyped by PCR and direct sequencing. Serum lipid profiles were also detected by standard biochemical

METHODSOne-hundred-and-eighty of the study participants were used to measure the APOC3 content by enzyme-linked immunosorbent assay. Inter-group differences and associations were assessed statistically using Chi square and t tests and logistic and linear regression analyses.

RESULTSThe frequencies of neither the genotypes or alleles were significantly different between the NAFLD cases and the controls. Compared with the most common genotypes-455TT or-482CC, none of the variants showed a significant increase in risk of NAFLD or for the clinical and biochemical parameters. The adjusted odds ratios (with 95% confidence intervals) of NAFLD were 1.25 (0.79-1.96) and 1.20 (0.76-1.89) for carriers of the APOC3-455C and-482 T variants respectively (P more than 0.05).

CONCLUSIONThe T-455C and C-482T polymorphisms of the APOC3 gene are not associated with risk of NAFLD, pathogenic changes in lipid profiles, or insulin resistance in Han Chinese.

Adult ; Aged ; Alleles ; Apolipoprotein C-III ; genetics ; Case-Control Studies ; Female ; Gene Frequency ; Genotype ; Humans ; Insulin Resistance ; Lipids ; blood ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; genetics ; metabolism ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Young Adult