Genetic Predisposition to Disease ; Humans ; Non-alcoholic Fatty Liver Disease ; diagnosis ; genetics ; therapy

Elasticity Imaging Techniques ; Fatty Liver ; diagnostic imaging ; Humans

Objective To explore the prevalence,subtype,distribution characteristics and risk factors of IBS met ROME Ⅲ criteria in local adult residents of Shanghai Songjiang area.Methods With multi-stage,stratified cluster random sampling method,from April to May in 2010,residents of45 shanghai Songjiang communities were interviewed by questionnaire survey.IBS diagnosis was based on Rome Ⅲ criteria,and the subtypes were according to Bristol stool scale.Self-rating anxiety scale (SAS),self-rating depression scale (SDS) and Athens insomnia scale (AIS) were also simultaneously finished. Results There were 7648 individuals who completed the survey with qualified questionnaires; the efficient rate was 90％. The sample size accounted about 1.62％ of total population in Shanghai Songjiang area.Total 970 patients were detected,who met the Rome Ⅲ criteria,of those 492 males and 478 females.The adjusted prevalence of IBS was 13.1％,13.8％ in males and 12.7％ in females.The ratio of male to female was 1 ∶ 0.92.There was no significant difference in detection rate between males and females (P＞0.05).The prevalence was highest in the 18 to 29 years age group (18.2％,P=0.000).IBS unsubtyped (IBS-U) was the most common type in patients who met the Rome Ⅲ criteria (45.3 ％),IBS with diarrhea (IBS-D) type was more common in male (27.0％) and IBS with constipation (IBS-C) was more common in female (19.5％).The IBS prevalence of obesity group (x2 =4.046,P=0.044),higher education group (x2=31.210,P=0.000),mental group (x2 =8.409,P =0.015),unmarried group(x2 =26.933,P =0.000) and no abdominal surgery history group(x2 =5.894,P=0.015) was higher than that of control group.The risk of IBS prevalence in those who had the history of gastrointestinal infection,abdominal surgery,taking antibiotics or analgesics increased by 5.105,3.388,2.949 and 2.811 times respectively(P=0.000).Multivariate analysis indicated that the risk of IBS prevalence was increased by 1.69 times if took more spicy food,however high-protein diet was a protective factor (OR=0.900,P=0.000).Anxiety (OR=2.452,P=0.000) and insomnia (OR=1.923,P=0.000) were also risk factors of IBS.Conclusion IBS is a common and frequently occurring disease in Shanghai Songjiang community.The history of gastrointestinal infection,abdominal surgery,taking antibiotics or analgesics,intake of more spicy food,anxiety and insomnia may be risk factors of IBS.

Objective To explore the clinical characteristics of chronic hepatitis B patients with metabolic syndrome (MS).Methods A total of 127 patients with untreated chronic hepatitis B infection were recruited.The patients were divided into two groups according to the diagnosis of MS,with 45 in MS group and 82 in non-MS group.Age,gender,body mass index (BMI),waist-to-hip ratio (WHR),fasting blood glucose (FBG),triglyceride (TG),total cholesterol (TC),aspartate aminotransferase (AST),alanine aminotransferase (ALT),hepatitis B e antigen (HBeAg),hepatitis B virus deoxyribonucleic acid (HBV DNA) were compared between groups.Liver biopsy was performed in 94 patients,including 31 in MS group and 63 in non-MS group,to compare the histological characteristics of liver between two groups.A chi-square test and t test were used for the data analysis.Results BMI,WHR,TG,TC,and FBG results of patients in MS group and nonMS group were (28.88±3.00) kg/m2,0.93±0.03,(2.77±0.17) mmol/L,(6.51±0.95) mmol/L,(6.67±0.45) mmol/L,and (24.64± 2.21) kg/m2,0.91±0.04,(1.50±0.65) mmol/L,(4.38±0.71) mmol/L,(4.91±0.92) mmol/L,respectively.Patients in MS group had higher BMI,WHR,FBG,TG and TC compared with those in non-MS group (t=9.109,3.245,2.642,3.762 and 2.586,respectively; all P＜0.05).No statistical significant differences were found in age,ALT or AST between two groups (t=2.224,0.703 and 0.141,respectively; all P＞0.05).Neither any statistical difference was found in gender,the positive rate of HBeAg and HBV DNA between two groups (x2 =1.662,0.037 and 0.944,respectively; all P＞0.05).In inflammation activity comparison,the result of liver biopsy showed that 48.39 ％ (15/31) were classified as G0-G1 and 51.61％(16/31) as G2-G4 in MS group,and those in non MS group were 49.21％(31/63) and 50.79％(32/63),respectively.No statistical significance was reached (x2 =0.006,P＞0.05).In fibrosis stage comparison,patients in MS group classifies as S0-S1 and S2-S4 were 32.26％ (10/31) and 67.74％(21/31),respectively,and those in non-MS group were 60.32％ (38/63)and 39.68％ (25/63),respectively.The liver fibrosis in MS group was significantly more severe than that in non-MS group (x2 =6.546,P＜0.05).Conclusions The CHB patients with MS have higher BMI,WHR,FBG,TG and TC.The presence of MS may promote the progress of liver fibrosis in CHB patients.

Objective To explore the effects of lead acetate on free radicals and lipid peroxidation in the cerebral cor?tex, cerebellum, and hippocampus in rat brains. Methods SD rats (n=48), who were just weaned, were randomly divided in?to 4 groups base on their weight. Then the rats were fed with lead acetate in drinking water at the final concentrations of 0 mg/L (deionized water), 200 mg/L, 400 mg/L, 800 mg/L respectively. Blood lead level as well as the hydroxyl free radical inhibiting activity, the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA) in cerebral cortex, cerebellum, and hippocam?pus were measured 60 days after lead contamination in water. Results Upon lead exposure, blood lead levels increased sig?nificantly as compared with the control. The hydroxyl free radical inhibiting activity in cerebral cortex, cerebellum, and hip?pocampus decreased significantly in a dose dependent manner of lead(P < 0.05). And they all correlated negatively with blood lead level (r=-0.505,-0.414,-0.448, P<0.05). By contrast, blood lead level was positively correlated with H2O2 and MDA in these brain tissues (r=0.301, 0.411, 0.378, and 0.404, 0.324, 0.510,P < 0.05). Conclusion Lead exposure can lead to lipid peroxidation of rat brain tissues through inducing free radicals.

Objective: To observe the cellular damage of low-dose combined exposure to Hg, Pb and Cd on hippocampal neurons in rat. Methods: SH-SY5Y cells were randomly divided into 8 groups by 2×2×2 factorial design: control group, Pb exposure group, Hg exposure group, Pb+Hg exposure group, Pb+Cd exposure group, Hg+Cd exposure group and Pb+Cd+Hg exposure group. And the cell viabilities were measured. On this basis, an animal model was established. Twenty eight-week-old SD pregnant rats were randomly divided into four groups by random number table, and five in each group: the control group(distilled water), 1-fold metal mixture exposure group (1×MM, poisoning solution containing mercury chloride 0.15 mg/L, lead acetate trihydrate 25 mg/L, cadmium chloride 7.5 mg/L), 5-fold metal mixture exposure group (5×MM, poisoning solution containing mercury chloride 0.75 mg/L, lead acetate trihydrate 125.00 mg/L, cadmium chloride 37.50 mg/L), 10-fold metal mixture exposure group (10×MM, poisoning solution containing mercury chloride 1.50 mg/L, lead acetate trihydrate 250.00 mg/L, cadmium chloride 75.00 mg/L). Pregnant rats drank water until delivery. Twenty male pups were selected and exposed to these metals through breast milk until weaned. The heavy metals dose of poisoning water was adjusted, and then the weaned rats were exposed to heavy metals via drinking poisoning water until adulthood (postnatal day 83). The blood samples and brain hippocampus samples were collected to observe the ultrastructural changes of hippocampus, and to determine the levels of Hg, Pb and Cd in blood. In addition, apoptosis rate and fluorescence intensity of reactive oxygen species and intracellular free calcium concentration ([Ca²⁺]_i) in hippocampal neurons were measured. Results: Cellular factorial design analysis showed that Hg+Pb+Cd (at no observed adverse effect level, 1.0, 0.5 and 0.1 μmol/L, respectively)had a interaction on cell viability after 48 or 72 hours of combined exposure (P<0.05). The results of ultrastructure showed that mitochondria decreased, ridges and matrixes gradually dissolved in rat hippocampal neurons of 5×MM group; nuclear chromatin aggregated, more ridges and matrixes dissolved and the mitochondria also decreased in rat hippocampal neurons of 10×MM group. The concentration of Hg, Pb and Cd in the blood of 1×MM group, 5×MM group and 10×MM group were higher than those in the control group, and the differences were statistically significant (P<0.001). There was no significant difference in apoptosis rate between the 1×MM group and the control group. The apoptosis rate of 5×MM group and 10×MM group was higher than that in the control group, and the differences were statistically significant (P<0.001). There was no statistically significant difference in the fluorescence intensity of reactive oxygen species in hippocampal neurons of the 1×MM group and the control group. The fluorescence intensity of reactive oxygen species in the 5×MM group and the 10×MM group was higher than that in the control group, the difference was statistically significant (P<0.05). There was no significant difference in the fluorescence intensity of [Ca²⁺]_i between the 1×MM group and the control group. The fluorescence intensity values of [Ca²⁺]_i in the 5×MM group and the 10×MM group were higher than the control group, the differences were statistically significant (P<0.001). Conclusion Low-level combined exposure to Hg, Pb, and Cd caused synergistic neurotoxic damage, and the process may be related to the changes of neuronal apoptosis, reactive oxide species, and [Ca²⁺]_i levels.

OBJECTIVETo evaluate the controlled attenuation parameter (CAP) assessment of fatty liver and choose a cut-off value of hepatic steatosis more than 5%.

METHODSConsecutive patients, 18 years or older, who had undergone percutaneous liver biopsy and CAP measurement were recruited from five liver healthcare centers in China. All enrollees were categorized as hepatic steatosis grade S0 (<5%) or S1 (5%). An M-probe equipped FibroScan 502 was used to capture CAP values. Receiver operating characteristic (ROC) curves were plotted, and the areas under (AU) the curves were calculated to determine the diagnostic efficacy. The CAP cut-off values at the optimal thresholds were defined by maximum Youden indices; sensitivity and specificity were also calculated.

RESULTSA total of 332 patients were enrolled in the study, including 67 patients with non-alcoholic fatty liver disease (NAFLD) and 265 with chronic hepatitis B (CHB) viru: infection. The median age (inter quartile range, IQR) of the study cohort was 39.0 (32.0-50.5) years-old. There were 46 males (68.7%) in the NAFLD group, with a median age of 37.0 (28.0-45.0) years-old, and 182 males (68.7%) in the CHB group; the differences between the two groups in median age and male: female ratio did not reach statistical significance. Multivariate linear regression analysis identified steatosis grade and body mass index (BMI) as independently associated with CAP. The median (IQR) CAP values among patients with S0 and S1 grade steatosis were 215.0 (190.0-241.0) dB/m and 294.0 (255.0-325.5) dB/m (P<0.001), respectively. For all patients, when BMI was <25 kg/m2, the ability of the AUROC of the CAP to discriminate hepatic steatosis more than or equal to 5% was 0.853, and the optimal cut-off value was 244.5 dB/m; however, when BMI≥25 kg/m2, the AUROC was 0.835 and the optimal cut-off value 269.5 dB/m.

CONCLUSIONCAP can identify hepatic steatosis more than or equal to 5% and is applicable for the diagnosis of fatty liver if it is adjusted for BMI.

Adult ; Area Under Curve ; Bile ; Biopsy ; Body Mass Index ; China ; Fatty Liver ; Female ; Hepatitis B, Chronic ; Humans ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; ROC Curve ; Tissue Extracts

Objective: To investigate the serum lipidomic profile in patients with nonalcoholic fatty liver disease (NAFLD), and to analyze the lipid metabolism characteristics of NAFLD. Methods: The subjects were divided into control group (23 patients) and pathologically confirmed NAFLD group (42 patients), and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure serum lipidomic metabolites. The partial least squares-discriminant analysis (PLS-DA) model was established to analyze the differences in lipid metabolism with reference to the univariate analysis. The t-test and Mann-Whitney U test were used for data analysis. Results: A total of 239 lipids were identified and qualitative and quantitative analyses were performed. The PLS-DA model (R2 = 0.753, Q2 = 0.456) and the univariate analysis showed that 77 lipids were metabolized differentially between the NAFLD group and the control group (VIP > 1, P < 0.05), including free fatty acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylinositol (LPI), choline plasmalogen (PlsCho), ethanolamine plasmalogen (PlsEtn), ceramide (Cer), sphingomyelin, and triglyceride (TG). Compared with the control group, the NAFLD group had significant increases in monounsaturated fatty acids (increased by 39%, t = -3.954, P < 0.05) and TGs (increased by 36%, Z = -2.662, P < 0.05), mainly TGs with low numbers of carbon atoms and unsaturated bonds, while there were reductions in TGs with high numbers of carbon atoms and unsaturated bonds. In addition, compared with the control group, the NAFLD group had significant increases in the levels of LPI (increased by 223%, t = -3.858, P < 0.05) and Cer (increased by 21%, t = -2.481, P < 0.05) and significant reductions in PlsCho (reduced by 18%, t = 3.184, P < 0.05) and PlsEtn (reduced by 20%, t = 2.363, P < 0.05). Conclusion There is a significant difference in lipid metabolism profile between NAFLD patients and healthy people, and a serum lipidomic analysis of NAFLD helps to further clarify the characteristics of lipid metabolism in patients with NAFLD.

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*