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.

This study aimed to explore the effects of akebiaquinata and dandelion extracts in impro-ving intestinal redox homeostasis in weaned rabbits.In the trial,120 35-day-old Ira rabbits weig-hing(1.22±0.08)kg were randomly divided into 4 groups according to the two-factor design,namely group C(basal diet),group D(basal diet+0.5％dandelion extract),group A(basal diet+0.5％akebiaquinata extract),and group DA(basal diet+0.5％dandelion extract+0.5％akebia-quinata extract),with 10 replicates in each group.The adapt period was one week and the experi-mental period was four weeks.At the last day,serum,liver tissue,jejunum and ileal mucosa samples were collected and stored for measurement.The results showed that:(1)First week,the average daily weight gain of group C was significantly lower than that of group D and group A(P＜0.05),and the feed weight ratio was significantly higher than that of group D and group A(P＜0.05).(2)The content of reactive oxygen species(ROS)in liver and serum was significantly reduced in akebiaquinata extract(P＜0.01),and the content of serum ROS in dandelion extract was significantly reduced(P＜0.01),and there were significant and extremely significant interac-tions in liver and serum,respectively.Extracts of akebiaquinata and dandelion were effective in re-ducing the levels of oxidative damage markers in tissues and serum,but increasing the content of malondialdehyde in liver tissues.(3)Akebiaquinata extract significantly increased the activity of glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)in serum(P＜0.01),and significantly reduced the activity of T-AOC in liver(P＜0.01)and superoxide dismutase in je-junum and liver(P＜0.05).Dandelion extract significantly increased the activity of T-AOC in ser-um and GSH-Px in jejunum(P＜0.05).The extracts of akebiaquinata and dandelion had a signifi-cant interaction effect on peroxidase in serum(P＜0.05).(4)The expression of Kelch-like ECH-as-sociated protein 1(Keap1)and NAD(P)H:quinone oxidoreductase 1(NQO1)genes in the jejunum was significantly and extremely significantly reduced by akebiaquinata extract.The extracts of ake-biaquinata and dandelion had significant interaction effects on ileal NQO1,Heme oxygenase1 and Superoxide dismutase 2(P＜0.05)and Keap1(P＜0.01).The expression of NQO1 gene in liver tis-sue was significantly reduced by akebiaquinata extract(P＜0.05).Dandelion and Akebiaquinata ex-tracts can reduce the content of reactive oxygen species in vivo and alleviate oxidative damage.At the same time,dandelion and akebiaquinata extract can work together to regulate antioxidant gene expression and antioxidant enzyme activity through the Nrf2-Keap1 signaling pathway to maintain intestinal redox homeostasis and relieve intestinal oxidative stress.

Objective:To explore the role of epithelial-mesenchymal transition(EMT) in fusion of the secondary palatal shelves to form the intact secondary palate induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).Methods:Twelve C57BL/6 J pregnant mice on gestation day (GD) 10.5 were divided into two groups: one group was conducted through gastric tubes with one dose of 28 μg/kg TCDD (experimental group) and the other group was operated through gastric tubes with equal volume corn oil (control group). Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 15.5) and the morphology of palatal tissue was observed. Primary media edge epithelial(MEE) were divided into experimental group and control group. MEE were treated with medium containing TCDD, 5 nmol/L, 10 nmol/L, 20 nmol/L and normal medium respectively. The expression of cytokeratin 19(CK-19) protein and vimentin protein in MEE were detected by immunofluorescence laser confocal microscopy and Western blotting after 72 hours. Statistical comparisons were made using one-way ANOVA.Results:A total of 36 fetuses were obtained in the experimental group, including 3 dead fetuses and absorbed fetuses. The incidence of cleft palate was 100% (33/33); the incidence of complete cleft palate was 84.8% (28/33), and the incidence of partial cleft palate was 15.2% (5/33); 40 fetuses were obtained in the control group, including 2 dead fetuses and resorbed fetuses, and the incidence of cleft palate was 0 (0/38). After 72 hours, the shape of MEE changed from uniform pebble-like to star-like or irregular shape with pseudopodia. The expressions of CK-19 protein were(0.739 ± 0.120, 0.483 ± 0.023, 1.007 ± 0.109, 1.086 ± 0.145) and fluorescence intensities were (53.384±5.785, 36.818 ± 8.250, 64.575±8.323, 76.898 ± 3.711) in control group and TCDD (5 nmol/L), TCDD (10 nmol/L) and TCDD (20 nmol/L) groups, respectively. The expressions of vimentin protein were (0.527 ± 0.112, 0.781 ± 0.095, 0.284 ± 0.046, 0.216 ± 0.040) and fluorescence intensities were (63.672±6.135, 82.632 ± 4.474, 52.608±7.525, 42.664 ± 7.659). Compared with the control group, the low-dose experimental group (5 nmol/L) had a decrease in CK-19 and an increase in vimentin; the high-dose experimental group (10 nmol/L, 20 nmol/L) had an increase in CK-19 and a decrease in vimentin, and the expression difference was statistically significant ( P<0.05), while there was no statistical significance among high-dose groups ( P>0.05). Conclusions:EMT process of MEE was identified in vitro and was a spontaneous procedure. TCDD-induced cleft palate may be related to the inhibition of the EMT process in MEE and with the increased dose of TCDD, the effects of EMT inhibiton were sustainable.

Objective:To explore the role of epithelial-mesenchymal transition(EMT) in fusion of the secondary palatal shelves to form the intact secondary palate induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).Methods:Twelve C57BL/6 J pregnant mice on gestation day (GD) 10.5 were divided into two groups: one group was conducted through gastric tubes with one dose of 28 μg/kg TCDD (experimental group) and the other group was operated through gastric tubes with equal volume corn oil (control group). Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 15.5) and the morphology of palatal tissue was observed. Primary media edge epithelial(MEE) were divided into experimental group and control group. MEE were treated with medium containing TCDD, 5 nmol/L, 10 nmol/L, 20 nmol/L and normal medium respectively. The expression of cytokeratin 19(CK-19) protein and vimentin protein in MEE were detected by immunofluorescence laser confocal microscopy and Western blotting after 72 hours. Statistical comparisons were made using one-way ANOVA.Results:A total of 36 fetuses were obtained in the experimental group, including 3 dead fetuses and absorbed fetuses. The incidence of cleft palate was 100% (33/33); the incidence of complete cleft palate was 84.8% (28/33), and the incidence of partial cleft palate was 15.2% (5/33); 40 fetuses were obtained in the control group, including 2 dead fetuses and resorbed fetuses, and the incidence of cleft palate was 0 (0/38). After 72 hours, the shape of MEE changed from uniform pebble-like to star-like or irregular shape with pseudopodia. The expressions of CK-19 protein were(0.739 ± 0.120, 0.483 ± 0.023, 1.007 ± 0.109, 1.086 ± 0.145) and fluorescence intensities were (53.384±5.785, 36.818 ± 8.250, 64.575±8.323, 76.898 ± 3.711) in control group and TCDD (5 nmol/L), TCDD (10 nmol/L) and TCDD (20 nmol/L) groups, respectively. The expressions of vimentin protein were (0.527 ± 0.112, 0.781 ± 0.095, 0.284 ± 0.046, 0.216 ± 0.040) and fluorescence intensities were (63.672±6.135, 82.632 ± 4.474, 52.608±7.525, 42.664 ± 7.659). Compared with the control group, the low-dose experimental group (5 nmol/L) had a decrease in CK-19 and an increase in vimentin; the high-dose experimental group (10 nmol/L, 20 nmol/L) had an increase in CK-19 and a decrease in vimentin, and the expression difference was statistically significant ( P<0.05), while there was no statistical significance among high-dose groups ( P>0.05). Conclusions:EMT process of MEE was identified in vitro and was a spontaneous procedure. TCDD-induced cleft palate may be related to the inhibition of the EMT process in MEE and with the increased dose of TCDD, the effects of EMT inhibiton were sustainable.

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.