Objective To investigate the protective effects of melatonin and possible mechanisms on rats with alco-holic fatty liver (AFL). Methods All rats were randomly divided into 4 groups: normal group (n = 10), model group (n = 12) and melatonin groups (10 mg / kg, 20 mg / kg; n = 10, respectively). The model of rats’ alcoholic fatty liver was induced by intragastric influsion of ethanol for 8 weeks. The melatonin groups’ rats received melato-nin by intraperitoneal injection after intragastric infusion of ethanol. Histopathological changes were evaluated by hematoxylin and eosin staining. The expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by immunohistochemical methods. The detection of aspartate aminotransferase (AST) levels and alanine transarninase (ALT) levels and the total bilirubin ( TBIL) levels in serum were provided by routine laboratory methods using an autoanalyzer. The levels of malondialdehyde ( MDA) and activities of glutathione peroxidase ( GPx) were measured by spectrophotometry. Results Compared with the normal group, the liver cells of the mod-el group showed obvious steatosis and significant swelling. However, less degree and less extensive of steatosis and swelling were observed in the melatonin groups. Compared with the normal group, the levels of ALT, AST and TBIL in serum and the levels of MDA in liver homogenates were significantly increased in the model group (P <0. 01), and the activities of GPx were distinctly decreased in the model group(P < 0. 01). But in the melatonin groups, the levels of ALT, AST and TBIL in serum and the levels of MDA in liver homogenates were decreased (P< 0. 01), and the activities of GPx were increased (P < 0. 01). Additionally, melatonin lessened the expression of TNF-α and IL-6 in liver obviously (P < 0. 01). Conclusion Melatonin may inhibit the development of alcoholic fatty liver and its possible mechanism is the ability to resist oxidative stress and lessen the expression of TNF-α and IL-6 and other relevant factors in liver.

Objective To explore the risk factors of esophageal gastric varices in patients with primary biliary cirrhosis (PBC ) .Methods From January 2008 to November 2014 ,112 PBC patients underwent gastroscopy examination and among them 24 received liver biopsy .The correlation between esophageal gastric varices and histological stage ,age ,gender ,anti‐centromere antibodies (ACA) ,platelet (PLT ) , albumin (Alb ) , total bilirubin (TBil ) , alkaline phosphatase (ALP ) , γ‐glutamyl‐transferase (GGT ) ,aspartate‐aminotransferase (AST ) ,alanine‐aminotransferase (ALT ) ,prothrombin time (PT ) and Mayo score was analyzed .Logistic regression analysis was used to identify independent risk factors predicting esophageal gastric varices in PBC patients .Results Among 112 patients with PBC ,varices was found in 62 patients (51 pure esophageal varices ,nine esophageal gastric varices and two pure gastric varices) .Among 24 patients with liver biopsy ,15 had varices (two at early histological stage Ⅰ and Ⅱ , 13 at later histological stage Ⅲ and Ⅳ ) .The ACA positive rate ,PT ,TBil and Mayo score of patients with varices were higher than those of patients without varices ;while Alb ,GGT and PLT were lower than those of patients without varices , and the differences were statistically significant (all P < 0 .01) . Multivariate Logistic regression analysis revealed that positive ACA (odds ratio (OR) = 8 .759 ,95%cofidence interval (CI) :1 .308 to 58 .637) ,Mayo score over 4 .52 (OR = 8 .941 ,95% CI :1 .145 to 69 .809) ,PLT count less than 96 .5 × 109 /L (OR = 10 .410 ,95% CI :2 .344 to 46 .224) ,TBil level over 26 .62 μmol/L(OR = 14 .348 ,95% CI :2 .945 to 69 .913) were independent risk factors predicting varices . Conclusion ACA positive ,PLT count less than 96 .5 × 109 /L ,TBil level over 26 .62 μmol/L and Mayo score over 4 .52 can help to predict esophageal gastric varices in patients with PBC .

Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin's protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat's alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-kappaB (NF-kappaB), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-kappaB p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-kappaB.
Alanine ; Alcoholics* ; Animals ; Aspartate Aminotransferases ; Bilirubin ; Cholesterol ; Diet, High-Fat ; Eosine Yellowish-(YS) ; Ethanol ; Fatty Liver ; Fatty Liver, Alcoholic* ; Glutathione Peroxidase ; Hematoxylin ; Humans ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; Interleukin-6 ; Lipid Peroxidation ; Liver ; Malondialdehyde ; Methods ; NF-kappa B ; Rats* ; Silymarin ; Spectrophotometry ; Superoxide Dismutase ; Triglycerides

OBJECTIVEProtein induced by vitamin K absence or antagonist II (PIVKA II), also called des-gamma carboxy prothrombin (DCP), is a sensitive marker for the diagnosis of hepatocellular carcinoma (HCC), in Japan and the United States since the sensitive kits were available (1998). PIVKA II is not used in clinical diagnosis in China so far. The aim of this study was to assess the diagnostic value of PIVKA II in Chinese patients with HCC.

METHODSSerum PIVKA II and alpha-fetoprotein (AFP) levels were determined in 60 patients with HCC and 30 patients with cirrhosis not carrying HCC.

RESULTSThe mean serum concentration of PIVKA II in HCC patients (784.3 +/- 1364.1 mean +/- s) was higher than that in cirrhosis patients (16.1 +/- 31.7); this difference was highly significant (P < 0.0001). When the cutoff level of 40 mAU/ml was used as the level of discriminating HCC from cirrhosis, 51.7% of patients (31/60) with HCC had PIVKA II values above this level (sensitivity). Only 4 patients with cirrhosis had such high PIVKA II levels. Thus, the specificity of this test was 86.7% (26/30). Total accuracy was 62.2% [(31 + 26)/(60 + 30)]. Seven of 19 small HCCs (36.84%) had PIVKA II values above the cutoff level. Concentrations of AFP above 20 ng/ml were observed in 34 of 60 patients with HCC (56.7%) and in 11 patients with cirrhosis (36.7%). Eleven of 26 patients with HCC (46.2%) without increased AFP had concentrations of PIVKA II greater than 40 mAU/ml. No significant correlation was found between serum levels of AFP and PIVKA II that were measured in 60 HCC patients (rs = 0.101, P = 0.247). Combining the information from PIVKA II and AFP showed an increase of approximately 21.6% over AFP and 26.7% over PIVKA II alone. For small HCC patients, combining the information from PIVKA II and AFP showed an increase of approximately 15.8% over AFP alone and 21.1% over PIVKA II alone.

CONCLUSIONPIVKA II is a useful early diagnostic marker for HCC and may be more sensitive when combined with AFP in Chinese patients.

Adult ; Aged ; Aged, 80 and over ; Biomarkers ; Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; diagnosis ; pathology ; Female ; Humans ; Liver Cirrhosis ; blood ; Liver Neoplasms ; blood ; diagnosis ; pathology ; Male ; Middle Aged ; Protein Precursors ; blood ; Prothrombin ; alpha-Fetoproteins ; analysis

Objective To investigate the inhibitory effect of melatonin on TGF-β1-stimulated HSC-T6 cells and its underling mechanism.Methods The HSC-T6 cells were divided into five groups:control group,model group and three experimental groups.After being cultured for 24 h,they were replaced with FBS-free medium and treated with transforming growth factor-β1 (TGF-β1,5 ng/ml) excepted the control group,and melatonin was added immediately with different concentrations (1 nmol/L,1 μmol/L,0.1 mmol/L) in three experimental groups.After drugs incubation for 48 h,MTT assay was performed to assess the cell proliferation,immunocytochemistry were used to assess the expression levels of Smad2/3,p-Smad2/3.Results Melatonin could significantly inhibited cells proliferation simulating with TGF-β1 (P ＜ 0.05).The expression of Smad2/3 and p-Smad2/3 in TGF-β1-treated group were dramatically elevated compared to the control group(P ＜ 0.01).After being added with different concentrations of melatonin,the expression of Smad2/3 and p-Smad2/3 were strongly attenuated compared with the model group (P ＜ 0.05).Conclusion Melatonin significantly mitigates HSCs'activation,which might be related to TGF-β1/Smad signaling pathway.

Objective : To investigate the effects of melatonin ( MEL) on the proliferation of hepatic stellate cells (HSCs) induced by platelet - derived growth factor (PDGF⁃BB) and explore its correlation with the regulation of autophagy levels . Methods : The HSC⁃T6 cells were divided into the following groups : control group , model group and MEL (low , medium and high) treatment groups . After 24 hours culture , the cells adhered to the wall and were changed into serum⁃free DMEM medium to synchronize the cells to the G0 stage . After 24 hours culture , all groups were given with PDGF ⁃ BB ( 10 ng/ml) excepted the control group . Besides , melatonin of different concentrations ( 1 nmol/L , 1 μmol/L and 0. 1 mmol/L) were added immediately in three treated groups . After incubated for 48 hours , the effect of MEL on the proliferation of hepatic stellate cells activated by PDGF⁃BB was detected by CCK8 method . The protein expression levels of LC3b and α ⁃SMA in hepatic stellate cells were determined by Western blot . The expression levels of LC3b mRNA and α ⁃SMA mRNA in hepatic stellate cells were determined by qRT⁃PCR . The ultrastructure of HSCs was observed by transmission electron microscopy to understand the autophagy level. Results : Compared with control group , PDGF⁃BB could induce the proliferation of HSCs ( P < 0. 01) . Compared with model group , MEL inhibited the proliferation of HSCs activated by PDGF⁃BB ( P < 0. 01) . Compared with the control group , LC3b and α ⁃SMA protein expressions significantly increased in the model group ( all P < 0. 05) , and LC3b mRNA and α ⁃SMA mRNA expressions significantly increased in the model group (P < 0. 05 , P < 0. 01) . Compared with the model group , MEL could inhibit such effects (LC3b : P < 0. 05 , P < 0. 01 ; α ⁃SMA : P < 0. 01) . Transmission electron microscopy ( TEM) showed that compared with the control group , autopolysosome significantly increased in the model group (P < 0. 05) . Compared with model group , autopolysosome significantly decreased in MEL treatment group (P < 0. 01) . Conclusion The up⁃regulation of autophagy level can promote the proliferation of hepatic stellate cells and the inhibition of hepatic stellate cell proliferation by MEL may be related to the down⁃regulation of autophagy level .

Objective: To evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym^®) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs. Methods: A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym^® group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated. Results: A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym^® group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly (P<0.001), while they were similar between groups (P>0.05). The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment (P<0.001), especially in the combined treatment group. Compared with Mosapride group, the scores in Combizym^® group decreased significantly after one or two weeks [discomfort intensity score: after one week, 4.0(2.5, 8.0) vs. 6.0(3.0, 10.0); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 6.0); all P<0.05. PDS score: after one week, 6.0(3.0, 9.0) vs. 7.0(3.5, 10.5); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 7.0); all P<0.05]. The efficacy rate in all patients after first week of treatment was over 15.0%. The efficacy rates after two weeks were 55.2%, 68.8% and 73.4% in Mosapride group, Combizym^® group and combined treatment group, respectively. After two week treatment, the efficacy rates in Combizym^® group (P=0.041) and combined group (P=0.006) were higher than that of Mosapride group. The recurrence rate of Mosapride group was 9.5%, which was significantly higher than that of Combizym^® group (1.8%, P<0.05) and combined treatment group (1.8%, P<0.05). There were no serious adverse effects in the three groups. Conclusions The efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients, with fewer adverse effects and low recurrence rate. Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.