Objective To explore the clinical efficacy of different course of colloidal bismuth pectin quadruple therapy for Helicobacter pylori (Hp) eradication in patients with peptic ulcer (PU) and the condition of digestive tract symptom improvement by a single-center,prospective,random-control study,and to provide theoretic evidence for clinicians on the selection of the schedule upon unti-PU Hp infection.Methods 90 active stage PU initial treated patients with Hp infection diagnosed by gastroscope were enrolled randomly.The patients were given oral unti-Hp treatment including rabeprazole sodium (20mg,2/day),clarithromycin (0.5 g,2/day),amoxicillin (1 g,2/day) and colloidal bismuth subcitrate (0.6g,2/day),and were divided into three groups with different course of treatment randomly acconding to the digital table:A group (7 days),B group (10 days) and C group (14 days),each group including 30 cases.The condition of digestive symptom improvement and adverse effect were recorded during treatment.After the quadruple therapy,and at least 4 weeks without using proton pump inhibitor (PPI) and antibiotics,the outcome of Hp eradication was evaluated by 14C carbamide breath test (14C-UBT).The difference of Hp eradication among the three groups was analyzed.The clinical efficacy of different course was evaluated and the cost/effect was calculated.Results The Hp eradication rates of the A group,B group and C group were 46.67％,73.33 ％ and 76.67％,respectively,the differences was statistically significant (x2 =7.184,P =0.028).After treatment,the scores of the digestive symptom of the three groups were lower than before treatment (A group:t =3.272,P =0.038;B group:t =6.424,P ＜ 0.001;C group:t =8.086,P ＜ 0.001),and the scores of the B group and C group were lower than A group (F =3.110,P =0.028),while the three groups showed no obvious difference in the incidence of adverse effects(x2 =0.274,P =0.872).The C/E of the A group,B group and C group were 4.7,4.3 and 5.7,respectively.Conclusion The 10-day and 14-day course of colloidal bismuth pectin quadruple therapy including rabeprazole sodium,clarithromycin,amoxicillin and colloidal bismuth subcitrate demonstrated better clinical efficacy of unti-PU Hp infection than the 7-day treatment,with obvious improvement of digestive symptom,and the 10-day quadruple therapy has the best economical advantage.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis. However, which molecule regulates macrophage polarization in NAFLD remains unclear. Herein, we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) expression in hepatic macrophages concomitantly with elevated M1 polarization. Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet (HFD) for 6 weeks revealed that lipid metabolism pathways were notably changed. Furthermore, 17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis, insulin resistance and liver injury. Mechanistically, 17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content, thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines. In addition, to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD, fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity. Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production, and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages. In conclusion, our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment.