Current status of research on fibrates in treatment of primary biliary cholangitis / 临床肝胆病杂志

At present, ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are approved by FDA for the treatment of primary biliary cholangitis (PBC). New drugs are urgently needed for the patients who have inadequate response to UDCA or cannot tolerate pruritus, a common side effect of OCA. In recent years, a large number of basic experiments and clinical studies have shown that fibrates have a good clinical effect in the treatment of PBC. This article reviews the advances in the mechanism and clinical application of fibrates in the treatment of PBC.

Study on correlation between serum 25-hydroxyvitamin D3 level and esophageal variceal bleeding in cirrhotic patients / 中华肝脏病杂志

Objective@#To explore the correlation between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and esophageal variceal bleeding (EVB) in cirrhotic patients.@*Methods@#Eighty-three cases with liver cirrhosis hospitalized from November 2016 to January 2017 were collected. The patients were divided into bleeding group (51 cases) and non-bleeding group (32 cases) depending on the presence or absence of bleeding under gastroscopy. Serological tests were performed on both groups, including hemoglobin (Hb), albumin (ALB), alkaline phosphatase (ALP),γ-glutamyltransferase (GGT), interleukin-6 (IL-6), and 25-hydroxyvitamin D3 (25[OH]D3). Both groups were analyzed by univariate analysis. The differences between both groups were compared by t-test, after normality test. The other variables were compared by Mann-Whitney U test. The correlation between the relevant variables and EVB were analyzed by Spearman's rank correlation and a multivariate analysis. Cases with primary biliary cirrhosis were relatively low in number (four cases in bleeding group, accounting for 8%, 10 cases in non-bleeding group, accounting for 31%). The effects of ALP and GGT on serum 25(OH)D3 level were analyzed by stratified analysis. Moreover, ALP and GGT levels were divided into two and three groups: < 140 U/L and >140 U/L and < 30 U/L, > 30 U/L, and ~≤60 U/L.@*Results@#Bleeding group had low levels of hemoglobin (t= -2.827,P= 0.005), alkaline phosphatase (t= -3.097,P= 0.002), gamma-glutamyltransferase (t= -2.292,P= 0.022), and 25(OH)D3 (t= -3.134,P= 0.002) than non-bleeding group. Both groups (P> 0.05) had similar levels of albumin, interleukin-6, AAR, and FIB-4. Logistic regression analysis showed that 25(OH)D3, alkaline phosphatase and hemoglobin were independent risk factors for EVB. Spearman’s correlation coefficient analysis showed that 25(OH)D3was significantly positively and negatively correlated with interleukin-6 (r= 0.306,P= 0.005) and albumin (r= -0.327,P= 0.003). Stratified analysis showed that serum 25(OH)D3 level was lower in ALP≤140U/L group and the bleeding group, and the difference was statistically significant than non-bleeding group (P= 0.007), while the serum level of 25(OH)D3was decreased in both groups for alkaline phosphatase > 140 U/L group, and the difference was not statistically significant (P= 0.051). Furthermore, in the GGT > 60 U/L group, the serum level of 25(OH)D3was significantly lower in the bleeding group, and the difference was statistically significant in non-bleeding group (P= 0.003), while the difference between the two groups was not statistically significant (P> 0.05) in GGT≤30 U/ L, > 30 U/L, and ~≤60 U/L group.@*Conclusion@#Serum 25(OH)D3level was significantly lower in EVB cirrhotic patients, and it was an independent risk factor for EVB. Serum 25(OH)D3 low levels was more apparent with ALP normalization or GGT level > 60 U/L.

Long-term efficacy and prognostic factors of surgical treatment for gastric carcinoma with liver metastases: a Meta analysis / 中华消化外科杂志

Objective To evaluate systematically the long-term efficacy and prognostic factors of surgical treatment for gastric carcinoma with liver metastases (GCLM).Methods Database including Chinese Journal Full Text Database,Wan Fang Database,VIP database,Chinese Database of Literature on Biomedicine,Pubmed,EMBASE,Cochrane Library,Medline,Springerlink and Wiley Online Library were searched with“胃癌,胃月中瘤,肝转移,手术治疗,外科手术,肝切除术,生存率,预后因素,gastric cancer,gastric carcinoma,hepatic,resection,hepatic resection,hepatectomy,liver metastases,hepatic metastases,surgery,surgical,survival,prognostic factors.The time for retrieving was from January 1995 to August 2015.Literatures on longterm efficacy and prognostic factors of radical resection of gastric carcinoma combined with hepatectomy for GCLM were retrieved,and data were analyzed and evaluated by 2 independent researchers.The count data were presented by the relative risk (RR) and 95％ confidence interval (95％ CI).The group rate was merged by the formula RR/(1 + RR),corresponding 95％ CI upper limit values were transferred by the formula RR/(1 + upper limit value RR),and the lower limit values were transferred by the formula RR/(1 + lower limit value RR).The comparison of group rates was done by indirect comparison,Z =difference between group rate/√∑ni=1 (standard error of group rate)2.The heterogeneity was analyzed by I2.Results Eighteen literatures of cross-sectional studies were retrieved and the total sample size was 410 patients.The results of Meta analysis:(1) the summary RR of 3-year overall survival of surgical patients with GCLM was 0.47 (95％ CI:0.37-0.60) while the summary 3-year overall survival rate was 32.0％ (95 ％ CI:0.27-0.38).(2) The summary RR of 5-year overall survival of surgical patients with GCLM was 0.35 (95％ CI:0.27-0.45),summary RR of 5-year overall survival rate was 25.9％ (95％ CI:0.21-0.31).(3)The summary RR of overall recurrence of surgical patients with GCLM was 2.95 (95％CI:2.23-3.88) while the summary overall recurrence rate was 74.7％ (95％CI:0.69-0.80).(4)The summary RR of remnant liver recurrence of surgical patients with GCLM was 1.39 (95％ CI:0.91-2.15) while the summary RR of remnant liver recurrence rate was 58.2％ (95％ CI:0.48-0.68).(5)The summary 3-year survival rate of surgical patients with GCLM and primary carcinoma serosal invasion was 32.9％ (95％ CI:0.23-0.44),and summary 5-year survival rate was 25.9％ (95％ CI:0.16-0.40).The summary 3-year survival rate of surgical patients with GCLM and without primary carcinoma serosal invasion was 47.9％ (95％ CI:0.38-0.58),and summary 5-year survival rate was 38.3％ (95％ CI:0.29-0.49).The summary 3-year survival rate of surgical patients with synchronous hepatic metastases was 30.6％ (95 ％ CI:0.24-0.38),and summary 5-year survival rate was 24.2％ (95％ CI:0.18-0.32).The summary 3-year survival rate of surgical patients with metachronous hepatic metastases was 40.1％ (95％ CI:0.32 0.48),and summary 5-year survival rate was 32.9％ (95％ CI:0.25-0.41).The summary 3-year survival rate of surgical patients with solitary metastatic hepatic carcinoma was 47.6％ (95％ CI:0.40-0.56),and summary 5-year survival rate was 37.1％ (95 ％ CI:0.26-0.48).The summary 3-year survival rate of surgical patients with multiple metastatic hepatic carcinoma was 28.6％ (95％ CI:0.18-0.42),and summary 5-year survival rate was 15.3％ (95％ CI:0.07-0.30).The summary 3-year survival rate of surgical patients with GCLM and R0 resection was 28.6％ (95 ％ CI:0.19-0.40),and summary 5-year survival rate was 20.0％ (95％ CI:0.12-0.32).The summary 3-year survival rate of surgical patients with GCLM and without R0 resection was 0.0,and summary 5-year survival rate was 9.1％ (95 ％ CI:0.03-0.25).The summary 3-year survival rate of surgical patients with GCLM and resection margin ＜ 10 mm was 13.0％ (95 ％ CI:0.05-0.30),and summary 5-year survival rate was 8.3 ％ (95 ％ CI:0.02-0.28).The summary 3-year survival rate of surgical patients with GCLM and resection margin ≥ 10 mm was 34.6％ (95 ％ CI:0.21-0.52),and summary 5-year survival rate was 34.6％ (95％ CI:0.21-0.52).The summary 3-year survival rate of surgical patients with GCLM and chemotherapy was 45.9％ (95％ CI:0.29-0.64),and summary 5-year survival rate was 29.1％ (95 ％ CI:0.19-0.42).The summary 3-year survival rate of surgical patients with GCLM and without chemotherapy was 38.7％ (95 ％ CI:0.26-0.53),and the summary 5-year survival rate was 25.4％ (95％ CI:0.18-0.35).The 3-year survival rate of surgical patients without primary carcinoma serosal invasion and with metachronous hepatic metastases,solitary metastatic hepatic carcinoma,R0 resection and resection margin ≥10 mm was statistically significantly higher than that of surgical patients with primary carcinoma serosal invasion,synchronous hepatic metastases,multiple metastatic hepatic carcinoma and resection margin ＜ 10 mm and without R0 resection (Z =2.118,1.999,3.01 8,5.295,2.183,P ＜ 0.05).The 5-year survival rate of surgical patients with solitary metastatic hepatic carcinoma and resection margin ≥ 10 mm was statistically significantly higher than that of surgical patients with multiple metastatic hepatic carcinoma and resection margin ＜ 10 mm (Z =4.528,2.819,P ＜ 0.05).Conclusion Overall long-term efficacy of surgical patients with GCLM is not good enough,and there is the better prognosis in the surgical patients without primary carcinoma serosal invasion and with metachronous hepatic metastases,solitary metastatic hepatic carcinoma,R0 resection and resection margin≥ 10 mm.

Dietary Fiber and Ulcerative Colitis / 胃肠病学

Ulcerative colitis( UC)is a disease difficult to cure and easy to relapse. Although the pathogenic and recurrent factors for UC are not clear,dietary factors are thought to be associated with both of them and becoming the hot topic of UC-related studies. Traditionally,dietary fiber is considered beneficial to UC,however,some of the latest overseas studies raised doubts about it. In this article,the dietary fiber and its role in UC were reviewed.

Effects of 5-fluorouracil with 1-methyl tryptophan on myeloid-derived suppressor cells in gastric cancer bearing 615 mice / 中华普通外科杂志

Objective To investigate the effect of 1-MT in combination with 5-FU on the number of myeloid-derived supressor cells (MDSC) in gastric carcinoma beating mice.Methods By using the lipofectamine TM 2000,the eukaryotic expression plasmid pcDNA3.1-IDO and empty vector pcDNA3.1 (+) were transfected in a MFC cell line.Animal model of gastric cancer bearing 615 mice were established to give respectively normal saline (NS),1-MT,5-FU and 1-MT + 5-FU therapy.Flow cytometry and immunofluorescence were used to analyze MDSC expression in tumor tissue.Result (1) The expression of MDSC was detected in transplanted tumor.(2)The expression of MDSC in gastric cancer beating 615 mice (49.8％ ± 1.1％) was higher than the normal group (1.2％ ± 0.3％) (P ＜ 0.05).(3) Compared with normal group the MDSC expression in 1-MT + 5-FU group (18.5 ％ ± 0.5 ％) decreased significantly (P ＜ 0.05).Conclusions Combining 1-MT with 5-FU can reduce the number of MDSC in gastric cancer bearing 615 mice,improving tumor microenvironment.

Inhibition effect of 1-methyl-tryptophan on transplant hepatocellular carcinoma growth in mice subcutaneous / 中华肝胆外科杂志

ObjectiveTo investigate the inhibitory effect of 1-methyl-tryptophan (1-MT) on transplanted hepatocellular carcinoma in mice.MethodsHuman hepatocellular carcinoma subcutaneous tumor models were established in mice,and the mice were divided into hepG2 group,empty plasmid group,indoleamine 2,3-dioxygenase (IDO) saline group,IDO) 5-fluoropyrimidine (5-FU) group,IDO 1-MT group,and the group combining IDO 1-MT with 5-FU treatment (n=8 in each group).The tumor growth,tumor volume and pathological examination were observed and the expression of IDO in tumor tissues was determined by immunohistochemistry.ResultsCompared with hepG2 and the empty vector saline groups,IDO saline group had bigger tumor,faster growth,and the differences were statistically significant (P＜0.05).Compared with IDO saline group,5-FU group,1-MT group and combination treatment groups showed smaller tumor volume and weight,and the tumor inhibitory rates were 86.54％,79.95％,94.46％,respectively.There were significant differences between these groups (P＜0.05).However,there were no significant differences in tumor volumes between 5-FU group and 1-MT group (P＞0.05).HE pathological observation of ceils in each treatment group showed reduced density,increased necrotic area and significant decrease in peripheral blood alpha-fetoprotein (P＜0.05).ConclusionsIDO can promote the growth of liver cancer cells involved in immune escape.1-MT can inhibit the transplanted tumor growth in mice,and therefore may enhance the chemotherapeutic efficacy.

Effect of plasminogen activator inhibitor type-1 on transforming growth factor-beta 1 , hyaluronic acid and tissue inhibitor Of metalloproteinase-1 of hepatic stellate cells / 中国综合临床

Objective To study the effect of plasminogen activator inhibitor type-1 ( PAI-1 ) on the protein expression of transforming growth factor-beta 1 ( TGFβ1 ), hyaluronic acid ( HA ) and tissue inhibitor of metalloproteinase-1 (TIMP-1) of hepatic stellate cells(HSC). Methods Methyl thiazolyl tetrazolium (MTT)was performed to detect the effect of PAI-1 on the proliferation of LX-2 ,and to determine the perfect intervention concentration of PAI-1. After incubation with PAI-1 in LX-2 culture solution for 12 h,24 h,48 h,the protein expression of TGFβ1 ,TIMP-1 and HA was observed with enzyme linked immunosorbent assay (ELISA). Results A492 in the negative control was 0. 473 ± 0. 353, and 1. 249 ± 0. 440, 1. 636 ± 0. 315,1.283 ± 0. 413,0. 938 ±0. 263 and 0. 303 ±0. 125 when the concentration of PAI-1 was 5,10,20,40 and 80 μg/L,respectively,a concentration of 10 μg/L of PAI-1 showed the strongest stimulation remarkablely ( F = 11. 697, P ＜ 0. 01 ).After incubation with PAI-1 for 12 h,24 h,48 h,the protein expression of HA,TGFβ1 and TIMP-1 in the LX-2 supernatant significantly increased compared to negative control (F = 1566. 752,235. 632 and 67. 359,respectively,P ＜ 0. 01 or ＜ 0. 05 ). Conclusion PAI-1 may influence the development of hepatic fibrosis through promoting the protein expression of HA ,TGFβ1 and TIMP-1 of HSC.

The role of survivin in the process of colorectal carcinogenesis / 中国医师进修杂志

Objective To identify the role of survivin gene in colorectal carcinogenesis.Methods Using immunohistochemical method,expression of survivin gene were detected in colorectal mucosal tissues.Results Expression rates of survivin in four tissues were 62.5%,17.2%,0 and 0.there were significant differences between them(P0.05).Conclusion Survivin may play an important role in onset and progression of colorectal cancer.

Current status of research on fibrates in treatment of primary biliary cholangitis / 临床肝胆病杂志

At present, ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are approved by FDA for the treatment of primary biliary cholangitis (PBC). New drugs are urgently needed for the patients who have inadequate response to UDCA or cannot tolerate pruritus, a common side effect of OCA. In recent years, a large number of basic experiments and clinical studies have shown that fibrates have a good clinical effect in the treatment of PBC. This article reviews the advances in the mechanism and clinical application of fibrates in the treatment of PBC.