E3 ubiquitin ligase ring finger protein 5 protects against hepatic ischemia reperfusion injury by mediating phosphoglycerate mutase family member 5 ubiquitination.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear. APPROACH AND RESULTS: RNF5 expression was significantly down-regulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression of cell lines were subjected to hypoxia-reoxygenation challenge. Results showed that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, whereas RNF5 overexpression had the opposite effect. Furthermore, hepatocyte-specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage and cell apoptosis and activated hepatic inflammatory responses, whereas hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with phosphoglycerate mutase family member 5 (PGAM5) and mediated the degradation of PGAM5 through K48-linked ubiquitination, thereby inhibiting the activation of apoptosis-regulating kinase 1 (ASK1) and its downstream c-Jun N-terminal kinase (JNK)/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR. CONCLUSIONS: We revealed that RNF5 protected against HIR through its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR.

[Clinical features of children with colorectal polyps and the efficacy of endoscopic treatment: an analysis of 1 351 cases]. / å„¿ç«¥ç»“ç›´è‚ æ¯è‚‰1 351ä¾‹çš„ä¸´åºŠç‰¹å¾åŠå† é•œä¸‹æ²»ç–—æ•ˆæžœåˆ†æž.

OBJECTIVES: To study the clinical features of children with colorectal polyps and the efficacy of endoscopic treatment. METHODS: A retrospective analysis was performed on the medical data of 1 351 children with colorectal polyps who were admitted and received colonoscopy and treatment in the past 8 years, including clinical features and the pattern and outcomes of endoscopic treatment. RESULTS: Among the 1 351 children, 893 (66.10%) were boys and 981 (72.61%) had an age of 2-<7 years, and hematochezia (1 307, 96.74%) was the most common clinical manifestation. Of all the children, 89.27% (1 206/1 351) had solitary polyps, and 95.77% (1 290/1 347) had juvenile polyps. The polyps were removed by electric cauterization with hot biopsy forceps (6 cases) or high-frequency electrotomy and electrocoagulation after snare ligation (1 345 cases). A total of 1 758 polyps were resected, among which 1 593 (90.61%) were pedunculated and 1 349 (76.73%) had a diameter of <2 cm. Postoperative complications included bleeding in 51 children (3.77%), vomiting in 87 children (6.44%), abdominal pain in 14 children (1.04%), and fever in 39 children (2.89%), while no perforation was observed. The children aged <3 years had the highest incidence rates of postoperative bleeding and fever (P<0.0125), and the children with a polyp diameter of ≥2 cm had significantly higher incidence rates of postoperative bleeding, vomiting, and fever (P<0.05). CONCLUSIONS: Solitary polyps, pedunculated polyps, and juvenile polyps are common types of pediatric colorectal polyps. Electric cauterization with hot biopsy forceps or high-frequency electrotomy and electrocoagulation after snare ligation can effectively remove colorectal polyps in children, with good efficacy and few complications. Younger age and larger polyp diameter are associated with a higher risk of postoperative bleeding.

Efficacy of Lactobacillus-supplemented triple therapy for Helicobacter pylori infection in children: a meta-analysis of randomized controlled trials.

Therapy-related side effects and severe antimicrobial resistance still remain an obstacle to Helicobacter pylori eradication. This meta-analysis aimed to investigate the efficacy of Lactobacillus-supplemented triple therapy on H. pylori eradication rates and therapy-related side effects in children. Five studies involving 484 pediatric patients were included in our analysis. The pooled relative risk (RR) for eradication rates in the Lactobacillus group versus the control group was 1.19 [95% confidence interval (CI) 1.07-1.33]. In subgroup analyses based on dose and duration of Lactobacillus supplementation, the pooled RRs for eradication rates were 1.36 (95% CI 1.15-1.60) in the high-dose group, 1.08 (95% CI 0.86-1.35) in the low-dose group, 1.24 (95% CI 1.06-1.46) in the long-term group, and 1.17 (95% CI 0.96-1.44) in the short-term group. With respect to side effects, Lactobacillus supplementation significantly reduced the incidence of diarrhea (RR = 0.30, 95% CI 0.10-0.85).Conclusions: Lactobacillus, as an adjunct to triple therapy, can increase H. pylori eradication rates as well as reduce the incidence of therapy-related diarrhea in children. And a higher dose and a longer duration of supplementation may conduce to the positive impact of Lactobacillus on H. pylori eradication. What is Known: • Probiotics-supplemented triple therapy may be beneficial in improving H. pylori eradication rates and reducing therapy-related side effects in children. However, not all probiotics are beneficial to H. pylori eradication and the pooled outcomes based on different probiotics may be erroneously extrapolated to other ineffective strains. What is New: • Lactobacillus, as an adjunct to triple therapy, can increase H. pylori eradication rates as well as reduce the incidence of therapy-related diarrhea in children.