Objective To evaluate the efficacy and safety of orlistat combined with low calorie diet in the treatment of obesity with non-alcoholic fatty liver disease. Methods Orlistat 120 mg, three times a day, combined with low calorie diet for a cause of 24 weeks, were given to the 60 non-alcoholic fatty liver disease (NAFLD) patients whose body mass index (BMI) were between 27 and 40. Results ①The percentage of mean weight loss and mean decreased BMI were both (10.76? 4.52 )% of their initinal weight at 24 weeks treatment. ②ALT, AST, GGT and total bilirubin was significantly decreased ( P

Objective To study the expression of metabolism related genes in peripheral blood mononuclear cells in patients of non alcoholic fatty liver diseases (NAFLD)with cholelithiasis.Methods Patients who had BMI ≥ 27 were divided into obese ( n = 10),the NAFLD ( n = 7) and NAFLD with cholelithiasis (n= 16) groups.The subjects who had BM1<25 (n = 10) and cholelithiasis (n = 16) were served as controls.The expression of peroxisome proliferator-activated receptors (PPAR)α,sterol regulatory element-binding protein(SREBP)-lc and Leptin Rb in peripheral blood mononuclear cells were measured.Results The expressions of PPARα,SREBP-lc and Leptin Rb in peripheral blood mononuclear cells were different in five groups.The significant difference was found in expression of leptin Rb between NAFLD with cholelithiasis group and the obese group,NAFLD with cholelithiasis group and the cholelithiasis group,NAFLD with cholelithiasis group and NAFLD group,the obese group and controls (P values= 0.037,0.050,0.044and 0.038,respectively).The leptin Rb mRNA expression in NAFLD with choletethiasis group was the lowest.Conclusions The low expression of leptin Rb mRNA was found in NAFLD patients with cholelithiasis.Cholelithiasis may increase the extent of insulin resistance and cause NAFLD progression.

Objective:To develop an HPLC method for the determination of nintedanib in rabbit plasma and study the pharmacoki-netics of nintedanib in rabbits. Methods:The separation was performed on an Agilent ZORBAX SB-C18 column. A mixture of acetoni-trile-0. 1% trifluoroacetic acid-water (35∶ 20∶ 45) was used as the mobile phase at a flow rate of 1. 0 ml·min-1. The detection wavelength was set at 286 nm. Carbamazepine was used as the internal standard and nintedanib was extracted by ethyl acetate from plasma under basic condition. Totally 6 rabbits were given 20 mg·kg-1 nintedanib with intravenous administration. The blood samples were collected from the auricular vein at different time points after the administration. The concentration of nintedanib in plasma was detected by the HPLC method. The pharmacokinetics parameters were analyzed by DAS program. Results: An excellent linear rela-tionship was obtained within the range of 0. 05-10. 00 μg·ml-1(r=0. 999 8). The intra-day RSD was 5. 55%, 4. 53% and 2. 74%and inter-day RSD was 6. 15%, 5. 45% and 3. 15%, respectively for the three concentrations(0. 10, 2. 50 and 7. 50μg·ml-1), and the relative recovery was (98. 50 ± 5. 47)%, (100. 25 ± 4. 54)% and (99. 94 ± 2. 74)%, respectively. The main pharmacokinetics parameters of nintedanib were as follows: Cmaxwas (3.01 ±0.35) μg·ml-1, t1/2 was (4.38 ±1.53) h and AUC0-t was (11.67 ± 1. 71) μg·h·ml-1 . Conclusion:The method is simple, rapid and accurate, and can be used to determine the nintedanib concentra-tion in rabbit plasma and study its pharmacokinetics. Nintedanib is fitted the first-order elimination kinetics in rabbits.

Objective To evaluate the relationship between fatty liver disease and liver metastases from colorectal cancer.Methods Eight hundred and ninety patients with colorectal cancer,who were submitted to hospital from 1993 to 2002 and had complete clinical data,were retrospectively analyzed.Of 890 patients,127 were diagnosed as fatty liver(FL)by ultrasonography,and the other 763 who were without fatty liver were served as controls(NFL).The clinical data including pathology,liver matastasis or mortality after surgery were analyzed.The survival rate and liver matastasis after surgery were followed up and statistically analyzed.Results The liver metastases was lower in FL group than that in NFL group(7 cases vs 102 cases,P=0.012).The tumor size was smaller in FL group than that in NFL group[(4.15±1.80)crn vs(4.77±2.25)cm,P=0.0016].The Dukes B(247/732,33.74%)and C(232/732,31.83%)patients were more common in NFL group,whereas Dukes A(41/121,33.61 %)and B(40/121,32.77%)were more common in FL group with significant difference(P＜0.05).No significant difference was found in 7-year survival rate between two groups who had been followed up(P=0.3024).Conclusion The lower incidence of liver metastases is found in FL group,which indicate that fatty liver disease may inhibit liver metastases from colorectal cancer by underlying mechanisms.

In order to investigate the interactions between first- and second-order motion perception systems, 14 adult subjects with normal or correct to normal visual acuity were recruited and divided into two groups. Then these two groups were trained, in their parafovea, to discriminate the direction of first- and second-order motion gratings respectively. The spatial frequency of the gratings used in study was fixed at 2 cycles/degree and the temporal frequency was fixed at 8 Hz during training. Contrast sensitivity of subjects in these two training groups for first- and second- order motion was measured before and after 7 days' training to estimate the effects of training. In addition, the differences between the two training groups(14 subjects) and another control group (11 subjects) were studied. The results showed that: 1) the training with first-order motion gratings can improve subjects' performance in first-order motion direction discrimination but the improvement can't be transferred to the performance in second-order motion task; 2) the training with second-order motion gratings can improve subjects' performance in both first- and second-order motion direction discrimination tasks. In conclusion, an " asymmetric transfer" occurred between the training effect of first- and second-order motion gratings. These results indicate that there are two mechanisms for perceiving first- and second-order motion respectively. However, they are not completely different from each other but only partly separated.

ObjectiveTo explore the role of fatty acid on endoplasmic reticulum (ER) stress and to detect the influence of tauroursodeoxycholic acid (TUDCA) on the expression of ER related genes in steatosis hepatocytes by establishing different models of hepatic steatosis.MethodsHealthy adult hepatocyte cell line HL-7702 was taken as research object.The model of hepatic steatosis was established with palmitic acid alone or mixed fatty acids.The cell viability was measured and calculated through CCK-8 positive cell proliferation assay.The cell morphology and steatosis was observed.The intracellular triglyceride content was tested with the triglyceride determination kit.With TUDCA intervention,the relative expression of Glucose-regulated protein 78 (GRP78) and CCAAT/Enhancer binding protein homologous protein (CHOP) at mRNA level was determined by real-time PCR.ResultsThe viability of hepatocyte was influenced once the concentration of mixed fatty acid reached 0.5 mmol/L or palmitic acid was 0.125 mmol/L.The effect of palmitic acid alone was stronger than that of mixed fatty acid on hepatocyte injury.The content of intra-hepatocyte triglyceride gradually increased in mixed fatty acid group,which only significantly increased after treated for 12 hours in palmitic acid alone group and then there was no significant change.There was no significant difference in relative expression of GRP78 and CHOP at mRNA level in various concentrations and treated time of mixed fatty acid group.After treated with palmitic acid at 0.5 mmol/L,intra-hepatocyte relative expression of CHOP at mRNA level increased obviously,however there was no effect on GRP78mRNA expression.After treated with palmitic acid at 1.0 mmol/L,both intra-hepatocyte GRP78 and CHOP mRNA relative expression increased.There was no significant difference in GRP78 and CHOP mRNA relative expression before and after ER stress in TUDCA intervented low dose palmitic acid group.There was significant difference in CHOP mRNA relative expression before and after ER stress in TUDCA intervented high dose palmitic acid group (at 12hrs:8.6400 to 5.1032; at 24hrs:13.7948to 6.4928,P=0.042 and 0.017),while no significant difference in GRP78 mRNA expression.ConclusionAt same fatty acid concentration,the larger propotion palmitic acid has,the more severe injury hepatocyte has.The regulation of palmitic acid on intra-hepatic ER stress is a time and dose dependent manner.TUDCA may improve palmitic acid induced ER stress to some degree.

Objective To establish the normal parameters of psychometric measures such as the number connection tests A(NCT-A)and digit symbol tests(DST)in assessment of minimal hepatic en- cephalopathy(MHE).Methods One hundred and sixty healthy volunteers(aged 25 to 64 years;educa- tional level＞9 years)were divided into＜35 ys,35～44 ys,45～54 ys and 55～64 ys groups.All of the healthy volunteers were assessed with NCT-A and DST to establish the normal value of age-related parameters,which can be used for diagnosis of MHE in patients with liver cirrhosis.Two standard devi- ation of the normal mean was used as a diagnostic criterion for MHE.One hundred and six cirrhotic patients were assessed with these parameters.Results The parameters of NCT-A were(25.1?4.6) sec in＜35 ys group,(32.1?6.8) sec in 35～44 ys group,(38.6?7.1)sec in 45～54 ys group or (49.3?6.3)sec in 55～64 ys group.The scores of DST were 49.9?4.7 in＜35 ys group,44.6?4.8 in 35～44 ys group,38.5?5.0 in 45～54 ys group or 35.4?4.7 in 55～64 ys group.Thirty one out of 106 cirrhotic patients were diagnosed as MHE based on these parameters.Conclusion The NCT- A and DST are psychometric assessments for diagnosis of MHE.Age-based normal paramerters of NCT- A and DST are needed to be established.