Objective To investigate clinical and pathological features of chronic hepatitis B ( CHB) with nonalcoholic fatty liver disease(NAFLD).Methods The clinical and pathological data of 70cases of CHB and 68 cases of CHB with NAFLD and 42cases of NAFLD were analyzed and compared .Results In this patients with CHB overlapped NAFLD , plasma ALT,AST,GGT con-centrations were higher than that in CHB and NAFLD groups ( P <0.05 , P <0.01 ) , compared with CHB group ,the levels of serum TC,TG,FBS,INS and IRI on patients with CHB overlapped NAFLD were increased ( P <0.05, P <0.01), Compared to patients B groups, serum hepatitis B virus DNA titer in patients with steatosis was significantly lower ( P <0.05) and reduced sharply with the increasea degree of hepatic steatosis ( P <0.05 ) .hepatic inflammation grade and fibrosis stage between CHB patients with and with-out steatosis ( P >0.05 ) .Conclusions The reverse association of hepatitis B virus titer with the degree of hepatic steatosis needs further investigation .Hepatic steatosis is associated with metabolic factors than virus factors .The existence of hepatic fatty degeneration dose not exacerbate liver inflammation or fibrosis .

Objective To study the effect of FSH on the secretion of gastrin in the rat stomach,offering experimental evidence for reproductive endocrine hormone regulating digestive function. Methods The FSH was directly injected into the stomach of rats to observe the change of density of gastrin immunoreactive positive cells in the stomach by immunohistochemical SABC method and the gastrin level in circulating blood and gastric liquid by ELISA. Results Compared with the control group,which was injected with saline into the stomach,the density of immunoreactive positive cells was significantly increased in the stomach with FSH treatment group(P

Objective To investigate the mutations of basal core promoter (BCP) and precore (PreC) region of hepatitis B virus (HBV) and the association with the development of hepatocellular carcinoma in patients with chronic HBV infection.Methods Totally 381 untreated HBV patients were recruited from the Department of Infectious Diseases,People's Hospital of Shangyu from Jan 2003 to Dec 2010,which included patients with chronic hepatitis B (CHB,n =166),cirrhotic hepatocellular carcinoma (cirrhotic-HCC,n =158) and noncirrhotic hepatocellular carcinoma (noncirrhotic-HCC,n=57).The mutations in HBV BCP and PreC and the genotypes of HBV were determined by polymerase chain reaction (PCR) and direct sequencing.Data were analyzed by chi square test and Logistic regression.Results The HBV genotype of most cases was genotype B (CHB,n =124;cirrhotic-HCC,n=126 ; noncirrhotic-HCC,n=50).In univariant analysis,BCP V1753 (x2 =7.927,P=0.005),BCP T1762/A1764 (x2 =12.796,P＜0.01),PreC A1896 (x2 =6.890,P=0.009) and PreC A1899 (x2=11.850,P =0.001) mutations were more frequently detected in cirrhotic-HCC patients than those in CHB patients.PreC A1896 (x2 =27.310,P＜0.01) and A1899 (x2=7.575,P=0.006) mutations were highly detected in noncirrhotic-HCC patients than those in CHB patients.Multivariate Logistic regression analysis revealed that in HBeAg positive patients,BCP T1762/A1764 (wald=6.180,P=0.016,OR=8.883) and PreC A1899 (wald=10.279,P=0.001,OR=7.475) mutations were independently associated with the development of cirrhotic-HCC; PreC A1896 (wald=4.324,P=0.038,OR=4.439) and PreC A1899 (wald=4.850,P=0.028,OR=6.010)mutations were independently associated with the development of noncirrhotic-HCC.While in HBeAg negative patients,PreC A1896 mutation (wald=15.448,P＜0.01,OR=12.128) was independently associated with the development of noncirrhotic-HCC.Conclusions BCP T1762/A1764 mutations are associated with the development of cirrhotic-HCC in HBeAg positive patients.PreC A1896 mutation is associated with the development of noncirrhotic-HCC in HBeAg positive and HBeAg negative patients.PreC A1899 mutation is associated with the development of cirrhotic-HCC and noncirrhotic-HCC in HBeAg positive patients.

Objective To compare the pre-existing mutations in reverse transcription region of HBV in patients with different HBV infection stages.Methods Totally 474 patients with chronic HBV infections,including 205 with chronic hepatitis B (CHB),153 with liver cirrhosis and 116 with hepatocellular carcinoma (HCC),were enrolled from the People' s Hospital of Shangyu and the First Affiliated Hospital of Zhejiang University during January 2011 and June 2013.All patients had not received nucleos (t)ide analogues treatment.HBV RT region mutations and genotypes were determined by PCR followed by sequencing.SPSS14.0 was used for statistical analysis.Results There were 387 (81.6％) patients with HBV genotype B,in which 156 were with CHB,124 were with liver cirrhosis,and 107 were with HCC.Nucleos(t)ide analogues-related mutations were observed in all the above 387 patients.rtS106C mutation was more popular in CHB and liver cirrhosis (14.1％ and 14.5％) patients than that in patients with HCC (4.7％) (x2 =6.126,6.207,P ＜0.05); And the positive rates of rtD134E/G/N/S mutations were also higher in CHB and cirrhotic patients (21.8％ and 20.2％) than that in HCC patients (10.3％,x2 =5.933,4.263,P ＜ 0.05).rtD134E/G/N/S and rtS106C mutations were correlated with HBeAg (P ＜0.01) and gender (P ＜ 0.05),but not with HBV virus load and age (P ＞ 0.05).The mutation frequencies in A-B interdomain were higher in CHB and cirrhotic patients (5.3％ and 5.6％) than that in HCC patients (3.5％,x2 =9.018,11.018,P ＜ 0.01).Conclusions Nucleos (t) ide analogues-related mutations exist in various HBV infection stages.rtSl06C and rtD134E/G/N/S mutations may be involved in necro-inflammation,and A-B interdomain mutations may be correlated with necro-inflammation,immune response and fibrosis in chronic liver diseases.

Objective To observe the localization and distribution of follicle stimulating hormone receptor(FSHR) in the rat submandibular gland and stomach. Methods Immunohistochemical SABC method was used in the experiment. Results The serous glandular cells,granular convoluted epithelial cells and all other duct epithelial cells in the submandibular gland and the parietal cells of gastric gland showed FSHR positive immunoreactivity.The positive substance was distributed in the cytoplasm with negative nuclei.Conclusion The function of rat submandibular gland and gastric gland might be regulated by follicle stimulating hormone(FSH) through FSHR.

Objective To compare the diagnostic efficacies of narrow-band imaging (NBI) in distinguishing neoplastic from non-neoplastic colorectal lesions with routine endoscopy and with magnifying endoscopy. Methods Patients with colorectal lesions detected by NBI from September 2008 to February 2010 were enrolled in the study. These lesions were classified by pit pattern and capillary pattern, which was then assessed by reference to histopathology. Results A total of 100 patients with colorectal lesions were enrolled, and the lesions were observed by NBI with ordinary endoscopy (n =64) and NBI with magnifying endoscopy (n =36), respectively, and 7 cases (5 in NBI with ordinary endoscopy and 2 in NBI with magnifying endoscopy) which did not meet the diagnostic criteria were excluded. The overall diagnostic accuracy of NBI endoscopy in distinguishing neoplastic from non-neoplastic colorectal lesions was 91.4% ( 85/93 ), in which NBI with ordinary endoscopy and magnifying endoscopy was 89. 8% (53/59) and 94. 1% (32/34),respectively, with both significantly higher than that of conventional colonoscopy reported in the literature (79. 1% ) (P ＜ 0. 05 ). However, no significant difference was detected between 2 methods ( P ＞ 0. 05 ).Conclusion Similar with NBI magnifying endoscopy, NBI endoscopy without high magnification may also be useful to distinguish neoplastic from non-neoplastic colorectal lesions.

Objective To compare the 2-year efficacy of de novo combination therapy with lamivudine (LAM) and adefovir dipivoxil (ADV) to that of entecavir (ETV) monotherapy in treatment of patients with hepatitis B virus ( HBV )-related decompensated cirrhosis.Methods A total of 120 naive patients with HBV-related decompensated cirrhosis admitted to Shangyu People's Hospital and the First Affiliated Hospital of Zhejiang University from January 2007 to April 2008 were enrolled,in which 60 were treated with LAM and ADV combination therapy,and other 60 patients were treated with ETV monotherapy.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time (PT),and ultrasonography or CT scan of liver were performed every 1-3 months.Repeated measure ANOVA and x2test were used to compare the efficacy,side effects and accumulated survival rates at 12 and 24 month in two groups.Results Forty-five patients in each group were followed-up for 24 months.There was no significant difference in HBV DNA negative rates and ALT normalization rates at month 12 (x2 =2.12 and 2.88,P ＞0.05 ) and month 24 between two groups (x2 =3.21 and 3.24,P ＞ 0.05); while HBeAg seroconversion rate in LAM + ADV group at month 24 was significantly higher than that in ETV group (43.5％ vs.36.4％,x2 =4.09,P＜0.05).Viral breakthrough occurred in 2 cases (4.4％) by month 12 and 3 cases (6.7％) by month 24 in LAM + ADV group,and no viral mutation was observed; while in ETV group,viral breakthrough occurred in 1 case ( 2.2％ ) by month 12 and 2 cases (4.4％) by month 24,and viral mutation was observed in 1 case (2.2％) by month 24.At the end of month 24,increase of AIb (F=18.9 and 17.3,P＜0.05),decrease of TBil and ALT (F=16.5,17.1 and 23.7,24.8,P ＜0.05 ),shortening of PT ( F =22.7 and 24.5,P ＜ 0.05 ),and the improvements of CTP and MELD scores (F=18.5,17.8 and 24.2,23.8,P＜0.05) were observed in both groups.The accumulative rates of mortality or liver transplantation were 16.7％ ( 10/60 ) and 18.3％ ( 11/60 ) in LAM + ADV and ETV groups,respectively.No blood creatinine increased above the normal upper limit was observed in both groups.Conclusion Both LAM + ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,decrease mortality and viral resistance,but the 24-month HBeAg seroconversion rate in combination therapy group is higher than that in monotherapy group.

Objective To investigate the distribution of nerve growth factor(NGF) and epidermal growth factor(EGF) and their colocalization with follicle-stimulating hormone(FSH) in rat submaxilary glands,and to study the effects of FSH on the secretion of NGF and EGF by submandibular gland tissue in vitro.Methods Immunohistochemical colocalization method was used in the experiment.Submandibular tissues of rats were incubated in vitro and different concentration of FSH was added.Enzyme link immunoassay was used to measure EGF and NGF in supernatant.Results The serous glandular cells,granular convoluted epithelial cells and all other duct epithelial cells in the submandibular gland showed FSH,NGF or EGF positive immunoreactivity.The positive substance was distributed in the cytoplasm with negative nuclei.Both FSH and NGF or EGF positive products were co-located in rat submandibular gland.When the concentration of FSH was more than 10-5-10-6 IU/L,the secretion of EGF and NGF lessened with the decreased concentration of FSH;when the concentration of FSH was less than 10-5-10-6 IU/L,the secretion of EGF and NGF increased with the decreased concentration of FSH.Conclusion FSH has the same bidirectional regulation effects on EGF and NGF in vitro.FSH may regulate the function of endocrine of rat submandibular gland.

Objective To observe the effect of Kadsura coccinea on the expression of Bcl-2, Bax and proliferating cell nuclear antigen (PCNA) in liver tissue of experimental hepatic fibrosis rats, to further discuss the mechanism of anti-liver fibrosis. Methods Sixty SD rats were randomly divided into normal control group, model control group, colchicine group, low-dose Kadsura coccinea group (2.5 g·kg-1) and high-dose Kadsura coccinea group (5 g·kg-1) (n = 12) . All groups except the normal control group were treated with CCl4, rich fat and poor protein to establishexperimental hepatic fibrosis animal model. The second day after modeling, drug treatmentwas started, till the end of the sixth week. Pathological section of the rat' s liver was examined in order to observe its tissue under a optical microscope. Liver tissues were taken to examine the degree of liver fibrosis by HE and Masson staining, and the expression of Bcl-2, Bax and PCNA protein were detected by immunohistochemistry. Results Kadsura coccinea relieved the degree of necrosis of liver cells, liver fat' s degeneration and collagen fiber hyperplasia significantly. Compared with the model control group, expression of Bax in low-,high-dose Kadsura coccinea group and colchicine group were significantly decreased, and the expression of PCNA in hepatic fibrosis rats were enhanced(P<0.05 or P<0.01) . Conclusion Kadsura coccinea has a certain inhibitory effects on experimental hepatic fibrosis in rats, and its mechanism may be related to inhibiting the expression of Bax protein and promoting the expression of PCNA protein in liver tissues.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.