ObjectiveTo investigate the changes in gut microbiota after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients with mild hepatic encephalopathy (MHE) in different prognosis groups. MethodsA total of 28 MHE cirrhotic patients who were hospitalized and underwent TIPS in Xijing Hospital of Digestive Diseases from July 2016 to July 2017 were enrolled. Fecal samples and related clinical data were collected on days 1-3 before surgery and at 1 month after surgery. According to the prognosis after surgery, the patients were divided into none-hepatic encephalopathy (HE) group with 8 patients, MHE group with 12 patients, and overt hepatic encephalopathy (OHE) group with 8 patients. Fecal samples were analyzed by 16S rRNA sequencing to obtain the relative abundance of gut microbiota, and SPSS and R packages were used to analyze the biodiversity, postoperative changes, and differences in such changes of gut microbiota at the genus level between groups. The chi-square test was used for comparison of categorical data between groups; the Kruskal-Wallis H test was used for comparison of continuous data between three groups; the Bonferroni method was used for multiple comparisons of multiple samples; the Wilcoxon signed-rank test was used for comparison before and after surgery within each group. For microbiome beta-diversity analyses, a principal coordinate analysis (PCoA) was performed based on Bray-Curtis distance matrix, and the Adonis method (PerMANOVA) was used for comparison between groups. ResultsPCoA based on Bray-Curtis distance matrix showed that only the MHE group had a significant change in beta diversity after surgery (F=2.71, P=0.049). After surgery, the non-HE group had significant increases in the abundance of the native flora Dialister, Coprococcus, Ruminococcaceae_uncultured, Flavonifractor, and Clostridium_sensu_stricto_1 (Z=2.521, 2.1, 2.1, 2.1, and 1.96, all P＜0.05); the MHE group had significant reductions in the abundance of the harmful flora Granulicatella（Z=2.521,P=0.012）, Enterococcus（Z=2.51,P=0.012）, Streptococcus（Z=2.432,P=0.015）, and Rothia（Z=2.001,P=0.045） and significant increases in the abundance of Veillonella（Z=2.353,P=0.019） and Megasphaera（Z=1.955,P=0.05）; the OHE group only had a significant increase in the abundance of Veillonella after surgery (Z=2.38, P=0.017). There was a significant difference in the change in gut microbiota (postoperative abundance/preoperative abundance) between the non-HE group, the MHE group, and the OHE group ［2.00 (1.11-91.61) vs 1.21 (0.26-679) vs 0.09 (0.01-0.92), χ2=6.249, P=0.043］. ConclusionThere is a significant difference in the change in gut microbiota after TIPS between patients with different prognoses, and the increase in the abundance of native flora may have a certain influence on the remission of MHE.

Coactosin-like protein 1 (Cotl1), a member of the actin-depolymerizing factor (ADF)/cofilin family, was first purified from a soluble fraction of Dictyostelium discoideum cells. Neuronal migration requires cytoskeletal remodeling and actin regulation. Although Cotl1 strongly binds to F-actin, the role of Cotl1 in neuronal migration remains undescribed. In this study, we revealed that Cotl1 overexpression impaired migration of both early- and late-born neurons during mouse corticogenesis. Moreover, Cotl1 overexpression delayed, rather than blocked, neuronal migration in late-born neurons. Cotl1 expression disturbed the morphology of migrating neurons, lengthening the leading processes. This study is the first to investigate the function of Cotl1, and the results indicate that Cotl1 is involved in the regulation of neuronal migration and morphogenesis.
Actins ; Animals ; Dictyostelium ; Humans ; Mice ; Morphogenesis ; Neurons

Objective To understand the incidence and risk factors of warfarin related hemorrhagic events during anticoagulation therapy with warfarin in patients with cirrhosis and portal vein thrombosis (PVT)after transjugular intrahepatic portosystemic shunt (TIPS). Methods The patients with liver cirrhosis who were treated with warfarin after TIPS due to portal hypertension were followed up from January 2012 in Xijing Hospital of Digestive Diseases,Air Force Military Medical University. The data of medical records and follow-up records up to the end of December 2015 in patients undergoing TIPS were collected and retrospectively analyzed. Cumulative incidence of hemorrhagic events related to warfarin treatment was calculated by Kaplan-Meier method. The patients were divided into warfarin-related bleeding group (bleeding group ) and non warfarin-related bleeding group (non-bleeding group ). The risk factors of hemorrhagic events related to warfarin treatment were analyzed using Cox regression model and the hazard ratio (HR)and the 95% confidence interval (CI)were calculated. Results A total of 179 patients were enrolled,including 117 males and 62 females with ages of 25-79 years and average age of (52 ± 12)years;the bleeding group comprised 47 patients (26.3%)and the non-bleeding group comprised 132 patients (73.7%). The follow-up time after discharge ranged 1-74 months and the average time was (28 ± 21) months. The average portal pressure gradient dropped from (25.4 ± 5.2)to (8.7 ± 3.7)mmHg before and after TIPS (P＜0.001). The median dose of oral warfarin in patients in the bleeding group was 2.5 (ranged from 2.5 to 3.75)mg and the median INR was 3.12 (ranged from 2.04 to 9.41);the median dose of oral warfarin in patients in the non-bleeding group was 1.8 (ranged from 0.63 to 2.5)mg and the median INR was 1.85 (ranged from 1.5 to 3.38). Fifty eight cases of hemorrhagic events occurred in 47 patients in the bleeding group,including 24 cases of gingival bleeding,16 cases of epistaxis,8 cases of cutaneous purpura, 4 cases of conjunctival hemorrhage,2 cases of hemorrhage of digestive tract,2 cases of intracranial hemorrhage,1 cases of hematuria,and 1 cases of menorrhagia. Nine of the 47 patients in the bleeding group had bleeding from multiple sites. The results of Kaplan-Meier analysis showed that the 1-,2-,3-,4-,5-and 6-year cumulative incidences of hemorrhagic events related to warfarin treatment after operation were 19%,23%,24%,30%,41%,and 45%,respectively. Warfarin was stopped in 11 patients and given at reduced doses in 36 patients among the 47 patients in the bleeding group. After that,43 patients'hemorrhagic symptoms disappeared and 3 patients' symptoms relieved,and then warfarin treatments were continued,except that 1 patient with a long history of hypertension died of intracranial hemorrhage. Multiple Cox regression analysis showed that the baseline serum creatinine level ＞115 μmol/L was an independent risk factor for hemorrhagic events related to warfarin treatment (HR＝1.82,95%CI:1.01-3.28,P＝0.045). Conclusions It is relatively safe for patients with liver cirrhosis and PVT receiving warfarin anticoagulation therapy after TIPS. Elevated serum creatinine is an independent risk factor for hemorrhagic events related to warfarin treatment.

Objective To understand the incidence and risk factors of warfarin related hemorrhagic events during anticoagulation therapy with warfarin in patients with cirrhosis and portal vein thrombosis (PVT)after transjugular intrahepatic portosystemic shunt (TIPS). Methods The patients with liver cirrhosis who were treated with warfarin after TIPS due to portal hypertension were followed up from January 2012 in Xijing Hospital of Digestive Diseases,Air Force Military Medical University. The data of medical records and follow-up records up to the end of December 2015 in patients undergoing TIPS were collected and retrospectively analyzed. Cumulative incidence of hemorrhagic events related to warfarin treatment was calculated by Kaplan-Meier method. The patients were divided into warfarin-related bleeding group (bleeding group ) and non warfarin-related bleeding group (non-bleeding group ). The risk factors of hemorrhagic events related to warfarin treatment were analyzed using Cox regression model and the hazard ratio (HR)and the 95% confidence interval (CI)were calculated. Results A total of 179 patients were enrolled,including 117 males and 62 females with ages of 25-79 years and average age of (52 ± 12)years;the bleeding group comprised 47 patients (26.3%)and the non-bleeding group comprised 132 patients (73.7%). The follow-up time after discharge ranged 1-74 months and the average time was (28 ± 21) months. The average portal pressure gradient dropped from (25.4 ± 5.2)to (8.7 ± 3.7)mmHg before and after TIPS (P＜0.001). The median dose of oral warfarin in patients in the bleeding group was 2.5 (ranged from 2.5 to 3.75)mg and the median INR was 3.12 (ranged from 2.04 to 9.41);the median dose of oral warfarin in patients in the non-bleeding group was 1.8 (ranged from 0.63 to 2.5)mg and the median INR was 1.85 (ranged from 1.5 to 3.38). Fifty eight cases of hemorrhagic events occurred in 47 patients in the bleeding group,including 24 cases of gingival bleeding,16 cases of epistaxis,8 cases of cutaneous purpura, 4 cases of conjunctival hemorrhage,2 cases of hemorrhage of digestive tract,2 cases of intracranial hemorrhage,1 cases of hematuria,and 1 cases of menorrhagia. Nine of the 47 patients in the bleeding group had bleeding from multiple sites. The results of Kaplan-Meier analysis showed that the 1-,2-,3-,4-,5-and 6-year cumulative incidences of hemorrhagic events related to warfarin treatment after operation were 19%,23%,24%,30%,41%,and 45%,respectively. Warfarin was stopped in 11 patients and given at reduced doses in 36 patients among the 47 patients in the bleeding group. After that,43 patients'hemorrhagic symptoms disappeared and 3 patients' symptoms relieved,and then warfarin treatments were continued,except that 1 patient with a long history of hypertension died of intracranial hemorrhage. Multiple Cox regression analysis showed that the baseline serum creatinine level ＞115 μmol/L was an independent risk factor for hemorrhagic events related to warfarin treatment (HR＝1.82,95%CI:1.01-3.28,P＝0.045). Conclusions It is relatively safe for patients with liver cirrhosis and PVT receiving warfarin anticoagulation therapy after TIPS. Elevated serum creatinine is an independent risk factor for hemorrhagic events related to warfarin treatment.

Objective:To study the effect of interference TIPE3 on the colon cancer cell growth by transfecting SW480 colon cancer cells with the TIPE3 interference plasmid were detected.Methods:Transfecting the constructed TIPE3-shRNA-pSIREN-RetroQ plasmid to SW480 cells.To determine the highest interference efficiency plasmid ,the mRNA and protein levels of recombined plasmid were detected by RT-PCR and Western blot separately and tested the cell proliferation with CCK 8.Meanwhile,apoptosis rate of SW480 cells was determined by flow cytometry assay with AnnexinV-FITC/PI.To further determined the effects of recombined plasmid on cell development ,the level of protein involved in proliferation and apoptosis were detected by Western blot .Results:The most effecient in-terference plasmids were successfully constructed.We found that the cell survival rate decreased when interference TIPE 3 gene express-ing in colorectal cancer cells .Flow cytometry indicated that interefering the expression of TIPE 3 would increase the sensitivity of SW 480 cell to apoptosis induced by aDR5ScFv.The results of Western blot showed that low expression of TIPE 3 would activate caspase3 and downregulate the expression of p-AKT,p-PDK1 and PCNA.Conclusion:Interference TIPE3 could promote apoptosis and inhibit prolif-eration in SW480 colon cancer cells .

OBJECTIVETo assess the efficacy and safety of bilateral versus unilateral biliary drainage in malignant hilar obstruction.

METHODSTopically relevant studies,regardless of randomized or observational design, were searched for in PubMed, EmBase and the Cochrane Library database. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to compare the effect of the two treatments.

RESULTSThree randomized trials and 7 observational studies were included, involving 894 patients with malignant hilar obstruction. The meta-analysis assessment of primary outcomes showed that the stent patency rate was better in bilateral drainage than in unilateral drainage (Rr=2.03,95% CI [1.16-3.56], P=0.01), but there were no significant differences in successful drainage rate (Rr=1.07,95% CI [0.97-1.18], P=0.20) and patient survival rate (Rr=-0.16,95% CI [-0.40-0.08], P=0.20). In the analysis of secondary outcomes,there were also no significant differences in the technical success rate (Rr=1.05,95% CI [0.98-1.17], P=0.34),the early complication rate (Rr=1.15, 95% CI [0.75-1.76], P=0.52), late complication rate (Rr=1.09,95% CI [0.75-1.60], P=0.60) and 30-day mortality rate (Rr=0.68,95% CI [0.38-1.23], P=0.20).

CONCLUSIONAlthough the cumulative stent patency was better for the bilateral than the unilateral drainage approach, based on the available data, there is not enough data to support bilateral drainage for malignant hilar obstruction. Well-designed randomized controlled trials are necessary to confirm it.

Objective To analyze the risk factors of 30-day mortality in patients with malignant hilar obstruction (MHO) after percutaneous transhepatic biliary metal stent deployment. Methods One hundred and fifty-nine consecutive patients with MHO caused by cholangiocarcinoma or gallbladder carcinoma were enrolled in this study. Percutaneous transhepatic biliary stent (PTBS) implantation was carried out in all the patients. Independent predictors for 30-day mortality were evaluated by logistic regression analysis. Covariates that were incorporated into the multivariate analysis were the variables that reached statistical significance (P < 0.1) in univariate analysis. Two-tailed, P value of less than 0.05 was considered to be statistically significant. Results The 30-day mortality of patient with MHO after metal stent deployment was 9.4%. Univariate analysis indicated that the differences in WBC (OR = 1.224.95%CI [1.07 - 1.44], P < 0.01), INR (OR=78.75, 95%CI [5.02-1 235.70], P<0.01), PT(OR=1.55, 95%CI [1.18-2.04], P<0.01), BUN (OR=1.19, 95%CI [1.02- 1.38], P < 0.05), CRE(OR = 1.02, 95%CI [1.000 - 1.041], P < 0.1) and lymph nodes metastasis(OR = 0.334. 95%CI[0.105 - 1.131], P < 0.1) were statistically significantly between 30-day mortality group and non-30-day mortality group. Multivariate analysis showed that statistically significant differences in WBC (OR = 1.19, 95%CI[1.026 - 1.380], P < 0.05), INR(OR = 151.5, 95%CI [3.13 - 5 440.7], P < 0.05) and CRE (OR = 1.025, 95%CI [1.002 - 1.048], P < 0.05) also existed palliative treatment for patients with malignant hilar obstruction. Active preoperative measures to improve hepatic and renal functions as well as to control infection are necessary in order to reduce 30-day mortality.

Since intra-arterial chemotherapy with the help of implantation of port-catheter system (PCS) was first used in the surgical field in 1981, PCS has been widely employed in the field of interventional radiology. Intra-arterial chemotherapy by implantation of PCS has some certain advantages such as minimal invasion, no need of general anesthesia, etc. Ten randomized clinic trails have been already reported, which indicate that intra- arterial chemotherapy with PCS is obviously superior to systemic chemotherapy in treating hepatic metastasis form colorectal cancer. As for the treatment of advanced biliary tract cancer, pancreatic carcinoma and hepatocellular carcinoma, the relevant reports can be found only in several phaseⅠ/Ⅱclinical trials or in some retrospective cohort studies. This paper aims to make a comprehensive review about the indications, clinical applications and complications of PCS in treating abdominal tumors in order to improve the clinical practice.