Objective:To observe the curative effects of the combined application of domperidone, pantoprazole and hydrotalcite tablets in the treatment of bile reflux gastritis ( BRG) and explore the underlying mechanism. Methods:Totally 80 patients with BRG were randomly divided into the treatment group and the control group with 40 cases in each. The treatment group was received panto-prazole, hydrotalcite tablets and domperidone, and the control group was treated by hydrotalcite tablets and domperidone. The efficacy was observed in both groups after 4 weeks. Results:The effective rate of symptom relief in the treatment group and the control group was respectively 92. 5% and 62. 5% (P<0. 05). After the 4 week treatment, the gastritis healing rate in the treatment group was higher than that in the control group (P<0. 05). The improvement of gastric mucosal hyperemia, edema and erosion in the treatment group was better than that in the control group with significant difference (P<0. 05). Cholic acid in gastric juice and gastric acid se-cretion were significantly reduced in both groups after the treatment, while the reduction of gastric acid secretion in the treatment group was more notable than that in the control (P<0. 05). Conclusion:Pantoprazole can be used to control BRG, and the combination of the three drugs shows better efficacy in the treatment of BRG.

Bleaching Agents ; Hydrogen Peroxide ; Immunohistochemistry ; Melanins

Objective To detect the expressions of angiotensin-receptor-1 (AT1R) and hypoxia-inducible factor (HIF)-1αin glomeruli and juxtaglomerular apparatus of different types of lupus nephritis (LN) patients, and analyze the correlation between them with systemic lupus erythematosus disease activity index (SLEDAI) complement 3, serum creatinine and 24-hour proteinuria in order to explore the role of the two factors in the pathogenesis of lupus nephritis (LN). Methods Between May 2010 and April 2016, a total of 90 patients with LN and 8 healthy controls were selected from Department of Rheumatology, Qujing Affiliated Hospital of Kunming Medical University and the First Affiliated Hospital of Kunming Medical University. The expressions of AT1R and HIF-1αin renal biopsy specimens were measured by streptavidin-perosidase (SP) of immunohistochemical stains. Pathological graphic analysis system was used for semi-quantitative estimate. Levels of SLEDAI, C3, serum creatinin and 24-hour proteinuria were also detected. Finally the relationshipbetween the two factors with clinical data was analyzed. The ANOVA test was used for intergroup comparison, and SNK-q test was used for the two groups comparison. Pearson's analysis was used for correlation analysis. Results The AT1R [(10.55 ±0.31)% vs (7.04 ±0.11)%] and HIF-1α [(10.51 ±0.52)% vs (8.96 ±0.31)%] in the glomeruli of typeⅠLN was significantly higher than healthy controls(all P<0.05). In the early phase of LN, RAS was activated and tissues were ischemic and hypoxic. The highest expression of AT1R (18.22 ± 2.11)% and HIF-1α (19.48 ±0.61)% in glomeruli was found in type Ⅳ LN, especially in juxtaglomerular apparatus, AT1R (19.98 ±0.21)% and HIF-1α(24.90 ±0.70)%. AT1R was positively correlated with HIF-1αin the glomer-ulus (r=0.949, P<0.01) and juxtaglomerular apparatus (r=0.762, P<0.05). AT1R and HIF-1αin juxtaglomerular apparatus was positively correlated with 24-hour proteinuria (r=0.756, P<0.05 and r=0.802, P<0.05). Conclusion High expressions of AT1R and HIF-1α have been shown in active LN biopsies. It proves that RAS is activated by ischemia and hypoxia, then it up-regulates HIF-1α expression. Our results suggest that the two factors may be associated with disease activity of LN.

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl₄, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl₄-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl₄-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.