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Introduction and aim. Hyponatremia is common in patients with decompensated cirrhosis and is associated with increased mortality. Tolvaptan, a vasopressor V2 receptor antagonist, can increase free water excretion, but its efficacy and safety in cirrhotic patients remain unclear. Material and methods. We studied the usage and safety of tolvaptan in cirrhotic patients in a real-life, non-randomized, multicenter prospective cohort study. Forty-nine cirrhotic patients with hyponatremia were treated with tolvaptan 15 mg daily, and 48 patients not treated with tolvaptan in the same period served as controls. Improvement in serum sodium level was defined as an increase in serum sodium from < 125 to ⩾ 125 mmol/L or from 125-134 to ⩾ 135 mmol/L on day 7. Results. Twenty-three (47%) patients in the tolvaptan group and 17 (35%) in the control group had normal serum sodium on day 7 (p = 0.25). Serum sodium improved in 30 (61%) patients in the tolvaptan group and 17 (35%) patients in the control group (p = 0.011). Adverse events occurred in 46-47% of patients in both groups, and tolvaptan was not associated with worsened liver function. No patient with normal serum sodium on day 7 died within 30 days of treatment, whereas 16% of those with persistent hyponatremia died (p = 0.0019). Conclusion. In conclusion, short-term tolvaptan treatment is safe and can improve serum sodium level in cirrhotic patients with hyponatremia. Normalization of serum sodium level is associated with better survival. [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. Methods: A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. Results: The mean decreases in the total symptom score at 4 weeks were estimated to be -18.1±13.8 in the combination therapy group and -15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were -8.4±6.6 in the combination therapy group and -6.8±5.9 in the monotherapy group (p=0.009). Conclusions: Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy. [ABSTRACT FROM AUTHOR]

The pathogenesis of autoimmune hepatitis (AIH) involves the intervention of the innate and adaptive immune responses. In the current study, the alterations in monocytes/Kupffer cells (KCs) were investigated in patients with AIH. A total of 21 patients with AIH at different stages of the disease, and 7 controls with non-alcoholic fatty liver disease were selected. The abundance of VAV1 and p21-activated kinase 1 (PAK1) in the liver and KCs was analyzed. In addition, the expression levels of HLA-DR and CD80 in the peripheral blood monocytes (PBMs) were measured, and phagocytosis of PBMs was assessed. KCs of AIH patients exhibited higher expression levels of VAV1 and PAK1. This upregulated expression was associated with disease progression. A reduced expression of HLA-DR and CD80, and reduced capacity of E. coli phagocytosis in PBMs was observed for patients with AIH. This downregulated expression was associated with disease progression. The results of the current study indicated that defective function of KCs and PBMs may be involved in the pathogenesis of AIH. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract is the most common location for primary extranodal non-Hodgkin lymphoma (NHL) with cases less commonly found in the intestine. The majority of primary intestinal B-cell lymphomas are exophytic, whereas enteropathy-associated T-cell lymphomas present predominantly as thickened plaques, ulcers or strictures. Crohn's disease (CD) is a chronic inflammatory disease of the intestines with fissures and ulcers, which is difficult for clinicians to diagnose based on endoscopic observations alone. Malignant lymphoma must be considered when clinically diagnosed CD is refractory to medication or when its clinical course becomes aggressive. The current study presents a rare case of primary colon T-cell lymphoma in a 16-year-old male with poor prognosis, as well as a case of gastrointestinal lymphoma occurring in the duodenum and colon in a 62-year-old male with a 10-year history of NHL. It was difficult to determine the diagnosis by a single endoscopic biopsy as the majority of biopsy specimens revealed mixed inflammation within which the lymphoma cells were difficult to identify. The present study indicated that it is important to recognize ulcerative or stenotic lymphoma and to differentiate it from CD as it exhibits a much more aggressive clinical behavior. The correct diagnosis may be confirmed by careful histopathological study and ancillary examination. [ABSTRACT FROM AUTHOR]

Background Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. Methods A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Results Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. Conclusions The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy. [ABSTRACT FROM AUTHOR]

Background Berberine, an isoquinoline alkaloid, has shown inhibitory effects on growth of several tumor cell lines in vitro. The aim of this study was to investigate chemopreventive effects of berberine on intestinal tumor development in Apcmin/+ mice. Methods Four-week old Apcmin/+ mice were treated with 0.05% or 0.1% berberine in drinking water for twelve weeks. The number and the size of tumors were measured to evaluate intestinal tumor development. Tissue sections were prepared for PCNA and Ki-67 immunostaining to detect cell proliferation, and TUNEL assay and cleaved caspase-3 immunostaining for apoptosis. Western blot analysis and immunostaining were performed to detect the activation of Wnt and epidermal growth factor receptor (EGFR) signaling pathways and COX-2 expression in the intestinal tumor cells. The prostaglandin E2 level in the small intestine was detected using ELISA. Results Compared with untreated Apcmin/+ mice, the total numbers of tumors in the small intestine and the colon were reduced by 39.6% and 62.5% in 0.05% and 0.1% berberine-treated mice, respectively. The numbers of tumors in proximal, middle, and distal segments of the small intestine in 0.1% berberine-treated mice were significantly reduced by 53.7%, 55.3%, and 76.5% respectively. Berberine treatment also decreased the numbers of all sizes of tumors (>2 mm, 1-2 mm, and <1 mm) in the small intestine. Berberine suppressed tumor cell proliferation and increased apoptosis. Furthermore, berberine decreased the activation levels of Wnt and EGFR signaling pathways, and down-regulated COX-2 expression in intestinal tumor cells and prostaglandin E2 production in the small intestine. Conclusions Berberine inhibits intestinal tumor development, which is correlated with its activity to suppress tumor cell proliferation and increase apoptosis in Apcmin/+ mice. Down-regulation of Wnt and EGFR signaling pathways and COX-2 expression by berberine may be involved in its anti-tumorigenic effects. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) results from dysregulation of intestinal mucosal immune responses to microflora in genetically susceptible hosts. A major challenge for IBD research is to develop new strategies for treating this disease. Berberine, an alkaloid derived from plants, is an alternative medicine for treating bacterial diarrhea and intestinal parasite infections. Recent studies suggest that berberine exerts several other beneficial effects, including inducing anti-inflammatory responses. This study determined the effect of berberine on treating dextran sulfate sodium (DSS)-induced intestinal injury and colitis in mice. Berberine was administered through gavage to mice with established DSS-induced intestinal injury and colitis. Clinical parameters, intestinal integrity, proinflammatory cytokine production, and signaling pathways in colonic macrophages and epithelial cells were determined. Berberine ameliorated DSS-induced body weight loss, myeloperoxidase activity, shortening of the colon, injury, and inflammation scores. DSSupregulated proinflammatory cytokine levels in the colon, including TNF, IFN-γ, KC, and IL-17 were reduced by berberine. Berberine decreased DSS-induced disruption of barrier function and apoptosis in the colon epithelium. Furthermore, berberine inhibited proinflammatory cytokine production in colonic macrophages and epithelial cells in DSS-treated mice and promoted apoptosis of colonic macrophages. Activation of signaling pathways involved in stimulation of proinflammatory cytokine production, including MAPK and NF-κB, in colonic macrophages and epithelial cells from DSS-treated mice was decreased by berberine. In summary, berberine promotes recovery of DSS-induced colitis and exerts inhibitory effects on proinflammatory responses in colonic macrophages and epithelial cells. Thus berberine may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders. [ABSTRACT FROM AUTHOR]

Tryptophan and its derivatives perform a variety of biological functions; however, the role and specific mechanism of many tryptophan derivatives in intestinal inflammation remain largely unclear. Here, we identified that an Escherichia coli strain (Ec-TMU) isolated from the feces of tinidazole-treated individuals, and indole-3-lactic acid (ILA) in its supernatant, decreased the susceptibility of mice to dextran sulfate sodium-induced colitis. Ec-TMU and ILA contribute to the relief of colitis by inhibiting the production of epithelial CCL2/7, thereby reducing the accumulation of inflammatory macrophages in vitro and in vivo. Mechanistically, ILA downregulates glycolysis, NF-κB, and HIF signaling pathways via the aryl hydrocarbon receptor, resulting in decreased CCL2/7 production in epithelial cells. Clinical evidence suggests that the fecal ILA level is negatively correlated with the progression indicator of inflammatory bowel diseases. These results demonstrate that ILA has the potential to regulate intestinal homeostasis by modulating epithelium-macrophage interactions. [ABSTRACT FROM AUTHOR]

This paper presents a novel minimally-invasive catheter-based acoustic interrogation device for real-time monitoring the dynamics of the lower esophageal sphincter (LES). Dysfunction of the LES could result gastrointestinal (GI) diseases, such as gastroesophageal reflux disease (GERD). A micro-oscillator actively emitting sound wave at 16 kHz is located at one side of the LES, and a miniature microphone is located at the other side of the LES to capture the sound generated from the oscillator. Thus, the dynamics of the opening and closing of the LES can be monitored. The device was tested in vitro by utilizing a custom-designed LES simulator, as well as in vivo in a pilot canine model. In the in vitro test, the sound was captured by the microphone and its strength was correlated with the level of LES opening and closing which was controlled by the simulator. The measurements showed statistically significant (p  <  0.05) Pearson correlation coefficients (0.905 on the average in quiet environment and 0.736 on the average in noisy environment, DOF  =  9). In the in vivo test, the LES was forced open and closed by a transoral endoscope, which was monitored in real-time by a transpyloric endoscope inserted from the duodenum and positioned into the distal stomach. Frame-by-frame video analysis validated the interrelation between the sound strength and the LES opening and closing. The LES dynamics monitored by the proposed device has the potential to become a valuable minimally-invasive technique for understanding LES dysfunction. [ABSTRACT FROM AUTHOR]

Prions are self-propagating protein conformers that cause a variety of neurodegenerative disorders in humans and animals. Mouse models have played key roles in deciphering the biology of prions and in assessing candidate therapeutics. The development of transgenic mice that form prions spontaneously in the brain has advanced our understanding of sporadic and genetic prion diseases. Furthermore, the realization that many proteins can become prions has necessitated the development of mouse models for assessing the potential transmissibility of common neurodegenerative diseases. As the universe of prion diseases continues to expand, mouse models will remain crucial for interrogating these devastating illnesses. [ABSTRACT FROM AUTHOR]

Background: The aim was to assess the clinical Glasgow-Blatchford score (GBS), Rockall score (CRS), and AIMS65 score in predicting outcomes (rebleeding, need for intervention, and length of stay) among patients with small bowel hemorrhage., Methods: We conducted a retrospective study of patients with small bowel bleeding (SBB). Rebleeding, need for intervention, and length of stay was investigated by 3 scoring systems. The area under the receiver operator characteristic curve was used to analyze the performance of 3 scoring systems., Results: Among 162 included patients, the scores of rebleeding, intervention, and length of stay ≥10 days groups were higher than no rebleeding, non-intervention, and length of stay <10 days groups, respectively (P < .05). The CRS, GBS, and AIMS65 scoring systems demonstrated statistically significant difference in predicting rebleeding (AUROC 0.693 vs. 0.790 vs. 0.740; all P < .01), intervention (AUROC: 0.726 vs. 0.825 vs. 0.773; all P < .01) and length of stay (AUROC 0.651 vs. 0.631 vs. 0.635; all P < .05). Higher cut-off scores achieved better sensitivity/specificity [rebleeding (CRS > 2, GBS > 7, AIMS65 > 0); need for intervention (CRS > 2, GBS > 7, AIMS65 > 0); length of stay (CRS > 0, GBS > 7, AIMS65 > 1)] in the risk stratification., Conclusions: The GBS system is reliable to be recommended for routine use in predicting rebleeding and the need for intervention for early decision making in patients with SBB. The 3 scoring systems are poorly useful in predicting length of stay.