Effects of transjugular intrahepatic portosystemic shunt treatment of patients with liver cirrhosis and portal hypertension: Case series.

RATIONALE: Transjugular intrahepatic portosystemic shunt (TIPS) is well established as an effective treatment tool for portal hypertension. However, the effects of TIPS in patients with liver cirrhosis and portal hypertension have not been adequately verified in clinical trials. PATIENT CONCERNS: To evaluate the effects of TIPS in patients with liver cirrhosis and portal hypertension with or without portal vein thrombosis (PVT). INTERVENTIONS: A total of 55 patients with liver cirrhosis and portal hypertension received TIPS treatment from December 2014 to April 2018 were enrolled. Clinical data, including portal pressure, Child-Pugh score, and relevant complications were recorded. OUTCOMES: TIPS was successfully performed in 54 patients. The overall technical success rate was 98.19% without serious technical complications. After TIPS treatment, portal pressure was significantly reduced from 38.13 ±â€Š4.00 cmH2O to 24.14 ±â€Š3.84 cmH2O (P < 0.05). In addition, symptoms including gastrointestinal bleeding and ascites were improved after TIPS treatment. During the 6 to 21-month follow up, hepatic encephalopathy in 15 patients (27.8%), shunt dysfunction in 5 patients (9.3%), rebleeding in 12 patients (22.2%) and deterioration of liver function in 2 patients (3.7%) were recorded. Moreover, there were no significant differences in the rates of rebleeding and hepatic encephalopathy between patients with PVT and the non-PVT group, whereas the occurrence rate of TIPS dysfunction was higher in the PVT group, but not statistically significant. LESSONS: TIPS treatment could alleviate the symptoms of liver cirrhosis and portal hypertension in individuals with or without PVT. However, complications during follow-up should be appropriately noted and addressed with corresponding treatments.

Phosphorylated­myosin light chain mediates the destruction of small intestinal epithelial tight junctions in mice with acute liver failure.

Tight junction dysregulation and epithelial damage contribute to intestinal barrier loss in patients with acute liver failure (ALF); however, the regulatory mechanisms of these processes remain poorly understood. The aim of the present study was to investigate the changes of intestinal tight junction and intestinal mucosa in mice with ALF and their mechanisms. In the present study, ALF was induced in mice through an intraperitoneal injection of D­galactosamine and lipopolysaccharide (D­GalN/LPS), and the morphological changes of the liver or small intestine were analyzed using hematoxylin and eosin staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The intestinal tissues and isolated serum were analyzed using western blotting, immunofluorescence staining and ELISA. D­GalN/LPS­induced mice exhibited signs of hepatocyte necrosis, alongside inflammatory cell infiltration into the liver tissue and partial microvilli detachment in the small intestinal mucosa. TEM demonstrated that the intestinal epithelial tight junctions were impaired, whereas SEM micrographs revealed the presence of abnormal microvilli in D­GalN/LPS­induced mice. In addition, the expression levels of phosphorylated (p)­myosin light chain (MLC), MLC kinase (MLCK) and Rho­associated kinase (ROCK) were significantly increased in the D­GalN/LPS­induced mice compared with those in the control mice, whereas the subsequent inhibition of MLCK or ROCK significantly reduced p­MLC expression levels. Conversely, the expression levels of occludin and zonula occludens­1 (ZO­1) were significantly decreased in the D­GalN/LPS­induced mice, and the inhibition of MLCK or ROCK significantly increased occludin and ZO­1 protein expression levels compared with those in the control group. Changes in the serum levels of tumor necrosis factor­α (TNF­α) and interleukin (IL)­6 were similar to the trend observed in p­MLC expression levels. In conclusion, the findings of the present study suggested that in a D­GalN/LPS­induced ALF model, TNF­α and IL­6 signaling may increase MLCK and ROCK expression levels, further mediate phosphorylation of MLC, which may result in tight junction dysregulation and intestinal barrier dysfunction.

Effect of Kruppel-like factor 4 on Notch pathway in hepatic stellate cells.

The relationship between Kruppel-like factor 4 (KLF4) and the Notch pathway was determined to investigate the effect of KLF4 on the activation of hepatic stellate cells and underlying mechanisms. Fifty SPF BALB/c mice were randomly divided into two groups. A liver fibrosis model was established in 25 mice as the experimental group, and the remaining 25 mice served as controls. On the day 0, 7, 14, and 35, liver tissues were removed for immunofluorescent detection. The Notch pathway inhibitor DAPT was added to the primary original hepatic stellate cells, and KLF4 and Notch-associated factor expression was detected by qRT-PCR. Additionally, the hepatic stellate cell line LX-2 was used to establish control and experimental groups, and was cultured in vitro. LX-2 cells in the experimental groups were treated with DAPT and the Notch activator transforming growth factor-beta 1 separately, whereas those in the control group were given isotonic culture medium. After 48 h, KLF4 expression was examined by Western blotting. After transient transfection of LX-2 cells to increase KLF4, the expression of Notch factor was examined. Immunofluorescence analysis showed that, with the aggravation of liver fibrosis, the absorbance (A) values of KLF4 were decreased (day 0: 980.73±153.19; day 7: 1087.99±230.23; day 14: 390.95±93.56; day 35: 245.99±87.34). The expression of Notch pathway- related factors (Notch-1, Notch-2, and Jagged-1) in the hepatic stellate cell membrane was negatively correlated to KLF4 expression. With the increase of KLF4 expression, Notch-2 (0.73±0.13) and Jagged-1 (0.43±0.12) expression decreased, whereas Notch-1 level was not detectable. When the Notch pathway was inhibited, KLF4 levels generally increased (18.12±1.31). Our results indicate that KLF4 expression is negatively correlated to the Notch pathway in hepatic stellate cells, which may provide a reference for the treatment of hepatic fibrosis.

Pancreatic neuroendocrine carcinoma diagnosed using endoscopic ultrasound-guided fine needle aspiration: A case report and literature review.

Pancreatic neuroendocrine carcinoma (NEC) is a rare pancreatic neoplasm. In this study, we report the case of a 67-year-old male who was admitted with epigastric pain, which began during the previous week. The planar imaging of the magnetic resonance imaging sequence detected oval shapes in the neck and tail of the pancreas. Endoscopic ultrasonography showed low-echo lumps at these sites. Endoscopic ultrasound-guided fine needle aspiration was performed on the pancreatic masses. Pathology results indicated that the tissue taken from the pancreas was consistent with small cell NEC. We also review the current published literature on pancreatic NEC.

Visualizing hepatitis B virus with biarsenical labelling in living cells.

BACKGROUND: Study on viruses has greatly benefited from visualization of viruses tagged with green fluorescent protein (GFP) in living cells. But GFP tag, as a large inserted fragment, is not suitable for labelling Hepatitis B virus (HBV) that is a compact virion with limited internal space. AIM: To visualize HBV in living cells, we constructed several recombinant HBV fluorescently labelled with biarsenical dye to track the behaviour of HBV in the cytoplasm of infected cells. METHODS: By mutagenesis, a smaller size tetracysteine (TC) tag (C-C-P-G-C-C) that could be bound with a biarsenical fluorescent dye was genetically inserted at different cell epitopes of HBV core protein expressed in transfected cells. RESULT: Confocal microscopy and transmission electron microscopy (TEM) observations showed that TC-tagged core proteins bound with biarsenical dye could specifically fluoresce in cells and be incorporated into nucleocapsid to form fluorescent virions. The recombinant fluorescent HBV virions retained their infectivity as wild-type ones. Moreover, tracking of fluorescent HBV particles in living cells reveals microtubule-dependent motility of the intracellular particles. CONCLUSION: To the best of our knowledge, this is the first time to generate fluorescent HBV virions with biarsenical labelling and to visualize their trafficking in living cells. The fluorescent HBV may become one highly valuable tool for further studying detailed dynamic processes of HBV life cycle and interaction of HBV with host in live-imaging approach.