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This study aimed to determine the risk factors and establish a risk score for post-transjugular intrahepatic portosystemic shunt (TIPS) overt hepatic encephalopathy (OHE).Altogether 299 and 62 cirrhotic patients receiving TIPS from January 2015 to March 2018 were divided into the derivation and validation cohorts, respectively. The data of the derivation cohort were analyzed for risk factors of post-TIPS OHE. A risk score was established from the derivation cohort and verified by the validation cohort.During a median follow-up of 112.6 weeks, 52 (17.4%) patients in the derivation cohort experienced post-TIPS OHE. Logistic regression showed that alcoholic cirrhosis (odds ratio [OR] 3.068, 95% confidence interval [CI] 1.423-6.613, P = 0.004), stent diameter of 10 mm (OR 12.046 [95% CI 2.308-62.862], P = 0.003), portal pressure gradient (PPG) decrement ≥60% (OR 3.548 [95% CI 1.741-7.230], P 0.001), model for end-stage liver disease (MELD) score ≥10 (OR 2.695 [95% CI 1.203-6.035], P = 0.016), blood ammonia (OR 1.009 [95% CI 1.000-1.018], P = 0.043) and notable hydrothorax (OR 4.393 [95% CI 1.554-12.415], P = 0.005) were associated with an increased risk of post-TIPS OHE. The risk score reached a promising risk evaluation of post-TIPS OHE when verified by the validation cohort (sensitivity 71.4%, specificity 70.7%, accuracy 71.0%).Alcoholic cirrhosis and notable hydrothorax are independent risk factors for post-TIPS OHE in liver cirrhosis, together with the stent diameter of 10 mm, PPG decrement ≥60%, MELD score ≥10 and blood ammonia. The established risk score is reliable to identify high-risk individuals of developing post-TIPS OHE.

Liver sinusoidal endothelial cells (LSECs) are ideally situated to sense stiffness and generate angiocrine programs that potentially regulate liver fibrosis and portal hypertension. We explored how specific focal adhesion (FA) proteins parlay LSEC mechanotransduction into stiffness-induced angiocrine signaling in vitro and in vivo.Primary human and murine LSECs were placed on gels with incremental stiffness (0.2 kPa vs. 32 kPa). Cell response was studied by FA isolation, actin polymerization assay, RNA-sequencing and electron microscopy. Glycolysis was assessed using radioactive tracers. Epigenetic regulation of stiffness-induced genes was analyzed by chromatin-immunoprecipitation (ChIP) analysis of histone activation marks, ChIP sequencing and circularized chromosome conformation capture (4C). Mice with LSEC-selective deletion of glycolytic enzymes (Hk2Glycolytic enzymes, particularly phosphofructokinase 1 isoform P (PFKP), are enriched in isolated FAs from LSECs on gels with incremental stiffness. Stiffness resulted in PFKP recruitment to FAs, which paralleled an increase in glycolysis. Glycolysis was associated with expansion of actin dynamics and was attenuated by inhibition of integrin β1. Inhibition of glycolysis attenuated a stiffness-induced CXCL1-dominant angiocrine program. Mechanistically, glycolysis promoted CXCL1 expression through nuclear pore changes and increases in NF-kB translocation. Biochemically, this CXCL1 expression was mediated through spatial re-organization of nuclear chromatin resulting in formation of super-enhancers, histone acetylation and NF-kB interaction with the CXCL1 promoter. Hk2Glycolytic enzymes are involved in stiffness-induced angiocrine signaling in LSECs and represent druggable targets in early liver disease.Treatment options for liver fibrosis and portal hypertension still represent an unmet need. Herein, we uncovered a novel role for glycolytic enzymes in promoting stiffness-induced angiocrine signaling, which resulted in inflammation, fibrosis and portal hypertension. This work has revealed new targets that could be used in the prevention and treatment of liver fibrosis and portal hypertension.

Background & aims Splenomegaly is usually taken as a consequence of liver cirrhosis. However, as a risk factor for cirrhosis, the impacts of spleen-liver axis on the development of cirrhosis are largely unknown. This study focused on the impacts of splenomegaly on the development of cirrhosis and assessment of the effects of celecoxib, a selective COX-2 inhibitor, on the splenomegaly and cirrhotic liver. Materials and methods Liver cirrhosis was induced by thioacetamide (TAA). Sixty rats were randomly divided into control, TAA-16w, TAA + celecoxib groups and normal, TAA + sham, TAA + splenectomy groups. Hepatic stellate cells (HSCs) or hepatocytes were co-cultured with splenocytes from those groups. Results Splenocytes of cirrhotic rats stimulated the HSCs activation and induced hepatocyte apoptosis via enhancing oxidative stress. The hepatic levels of NOX-4 and the in situ O2− were profoundly reduced in TAA + splenectomy group by 50.6% and 18.5% respectively, p Conclusion Splenomegaly contributed to the development of liver cirrhosis through enhancing oxidative stress in liver. Celecoxib could effectively ameliorate liver cirrhosis via reducing inflammatory cytokines and immune cells derived from spleen and suppressing oxidative stress.

Long intergenic non-coding RNA for kinase activation (Linc-A) has been reported to enhance the occurrence and progression of breast cancer. Nevertheless, whether Linc-A is related to the tumorigenesis of colorectal cancer (CRC) remains unknown. In this study, we aimed to evaluate the expression of Linc-A in colon adenocarcinoma and explore the correlation between Linc-A and prognosis of CRC. The expression of Linc-A in human colon tissues was evaluated by qRT-PCR, which contained 15 pairs of human colon adenocarcinoma and paracancerous tissues and other 65 colon adenocarcinoma tissues. A total of 80 patients were divided into low and high expression groups according to the Linc-A levels. The levels of Linc-A in colon adenocarcinoma was higher than that in paracancerous tissues (p = 0.047). Furthermore, high expression of Linc-A was associated with advanced TNM stage (p = 0.013), positive lymph nodes (p = 0.024), low 5-year survival rate (p = 0.024) and even 10-year survival rate (p = 0.007). Besides, Linc-A, advanced age, advanced TNM stage, deep infiltration degree and positive lymph nodes were also found to be positively related to poor overall 5-year survival by Kaplan–Meier survival analysis(p

// Can Gan 1, 2, * , Yan-Hua Chen 1, 2, * , Ling Liu 1, 2 , Jin-Hang Gao 1 , Huan Tong 1, 2 , Cheng-Wei Tang 1, 2 and Rui Liu 1 1 Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China 2 Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China * These authors contributed equally to this work and should be considered as co-first authors Correspondence to: Cheng-Wei Tang, email: shcqcdmed@163.com Rui Liu, email: lrui60@163.com Keywords: pancreatic enzyme replacement therapy, exocrine pancreatic insufficiency, efficacy, safety, standardization Received: July 12, 2017 Accepted: September 21, 2017 Published: October 07, 2017 ABSTRACT Background: Pancreatic enzyme replacement therapy (PERT) is widely applied to patients with exocrine pancreatic insufficiency (EPI), but its effect and safety has not been quantified. Therefore we performed a meta-analysis to determine the efficacy and tolerance of PERT on patients with EPI. Materials and Methods: PubMed, Medline, Cochrane library database, Evidence-based medicine/clinical trials published before December 2016 were searched by two independent reviewers to identify prospective randomized controlled trials (RCTs). Results: Seven RCTs, randomizing a total of 282 patients, were filtrated and assessed qualitatively (Jadad score). PERT increased CFA (WMD: 26.56, 20.35 to 32.76, I 2 = 79.6%, P < 0.001) compared with baseline, and CFA (WMD: 17.97, 12.61 to 23.34, I 2 = 76.7%, P < 0.001) vs. placebo. Meanwhile, CNA, SFE, SNE and SW were significantly improved in PERT compared with baseline and placebo, with no statistical differences in adverse events. Subgroup analysis indicated that standard forms of PERT displayed more effectiveness with significantly decreased heterogeneity, and large sample size also reduced the heterogeneity to some degree. Conclusions: PERT is demonstrated to be effective and tolerable in patients with EPI, especially using standard administration of PERT. Larger and higher quality studies on EPI are demanded to long-term effect of standard PERT treatment.

Hypoxia inducible factor 1 alpha subunit (HIF-1α) is induced in hypoxic conditions and plays a crucial role in the neoangiogenesis and metastasis of cancer. In this study, we aimed to evaluate the expression of HIF-1α in colon adenocarcinoma and to explore its clinicopathological characteristics and prognosis. A tissue microarray involving colon adenocarcinoma tissues and their corresponding paracancerous tissues from 92 patients was utilized to detect HIF-1α. The expression of HIF-1α in colon adenocarcinoma tissues was significantly higher than it was in the corresponding paracancerous tissues (P < 0.001). Furthermore, similar results were observed in HCT116 and RKO human colon adenocarcinoma xenografts in node mice (P < 0.05). Additionally, augmented HIF-1α expression was positively associated with TNM stage III-IV (P = 0.025), the presence of distant metastasis and vascular invasion (P = 0.048), and the presence of positive lymph nodes (P = 0.041). A Kaplan-Meier survival analysis showed that up-regulation of HIF-1α was associated with poor 5-year or 10-year survival (P < 0.05). A multivariable Cox regression analysis also found HIF-1α was an independent risk factor for poor prognosis in colon adenocarcinoma. Thus, targeting HIF-1α might be a viable strategy to treat patients with colon adenocarcinoma.

In the research area of text steganography, algorithms based on font format have advantages of great capacity, good imperceptibility and wide application range. However, little work on steganalysis for such algorithms has been reported in the literature. Based on the fact that the statistic features of font format will be changed after using font-format-based steganographic algorithms, we present a novel Support Vector Machine-based steganalysis algorithm to detect whether hidden information exists or not. This algorithm can not only effectively detect the existence of hidden information, but also estimate the hidden information length according to variations of font attribute value. As shown by experimental results, the detection accuracy of our algorithm reaches as high as 99.3% when the hidden information length is at least 16 bits.