The changes of inflammation and metabolism are two features in nonalcoholic steatohepatitis (NASH). However, how they interact to regulate NASH progression remains largely unknown. Our works have demonstrated the importance of solute carrier family 7 member 11 (SLC7A11) in inflammation and metabolism. Nevertheless, whether SLC7A11 regulates NASH progression through mediating inflammation and metabolism is unclear. In this study, we found that SLC7A11 expression was increased in liver samples from patients with NASH. Upregulated SLC7A11 level was also detected in two murine NASH models. Functional studies showed that SLC7A11 knockdown or knockout had augmented steatohepatitis with suppression of inflammatory markers in mice. However, overexpression of SLC7A11 dramatically alleviated diet-induced NASH pathogenesis. Mechanically, SLC7A11 decreased reactive oxygen species (ROS) level and promoted α-ketoglutarate (αKG)/prolyl hydroxylase (PHD) activity, which activated AMPK pathway. Furthermore, SLC7A11 impaired expression of NLRP3 inflammasome components through AMPK-mitophagy axis. IL-1β release through NLRP3 inflammasome recruited myeloid cells and promoted hepatic stellate cells (HSCs) activation, which contributed to the progression of liver injury and fibrosis. Anti-IL-1β and anakinra might attenuate the hepatic inflammatory response evoked by SLC7A11 knockdown. Moreover, the upregulation of SLC7A11 in NASH was contributed by lipid overload-induced JNK-c-Jun pathway. In conclusions, SLC7A11 acts as a protective factor in controlling the development of NASH. Upregulation of SLC7A11 is protective by regulating oxidation, αKG and energy metabolism, decreasing inflammation and fibrosis.

Background and Aim: Bowel preparation is an important determinant of the quality of colonoscopy. The traditional split-dose regimen of 4 L polyethylene glycol (PEG) solutions for bowel preparation is effective but poorly tolerated. The aim of this was to study the efficacy and tolerability of using linaclotide as an adjunctive agent with low-volume PEG for bowel preparation. Methods: This was an endoscopist-blinded, randomized, controlled trial of 432 patients randomly assigned to three groups: 2 L PEG, 4 L PEG and 2 L PEG + 290 µg linaclotide (2 L PEG + L group). The primary outcome measure was efficacy of bowel preparation according to the Boston Bowel Preparation Scale (BBPS), with secondary outcomes of patients’ tolerance, defecating frequency, complications, sleeping quality, cecal intubation rate, preparation-to-colonoscopy interval, withdrawal time, cecal intubation time, and adenoma and polyp detection rates. Results: The percentage of adequate bowel preparation in the 2 L PEG + L group was higher than that of the 2 L PEG group (87.9% vs. 77.0%; P = 0.017), but not the 4 L PEG group (87.9% vs. 91.4%; P = 0.339). In terms of the mean (SD) BBPS score for the total and segmental colons, the bowel cleansing efficacy of 2 L PEG + L was superior to that of 2 L PEG and similar to that of 4 L PEG. Patient’s tolerance (including complications, willingness to repeat and sleeping quality) were compatible between the 2 L and 2 L + L group, and the 4 L group was the worst among these three groups. Conclusion: Two liters of PEG combined with 290 µg linaclotide was an effective and well-tolerated bowel preparation regimen.

Patients with ulcerative colitis (UC) face a heightened risk of colorectal cancer (CRC), though the estimated risk levels differ across UC populations. This study aims to provide updated, population-based estimates of CRC incidence, standardised incidence ratios (SIR), and prevalence in patients with UC. We searched PubMed, Embase, and Cochrane Library to April 12, 2025, for population-based studies on patients with UC reporting CRC risk. Study quality was assessed using the Newcastle–Ottawa Scale. The primary outcome was CRC risk in UC, evaluated through incidence, SIR, and prevalence. A random-effects model was used for meta-analysis, and meta-regression evaluated the impact of study characteristics. Publication bias was assessed using funnel plots and statistical tests. PROSPERO: CRD42025634800. From 7991 records, 13 population-based studies involving 161,157 patients with UC were included. Most studies were conducted in Europe, with others from North America and Asia. All studies were of good quality, with scores greater than 5 on the NOS quality assessment scale. The pooled CRC incidence was 1.47 per 1000 person-years (95% CI 1.30–1.67; I² = 66.2%), the SIR was 2.48 (95% CI 1.64–3.76; I² = 91.7%), and the prevalence was 1.54% (95% CI 1.14–1.99; I² = 96.1%). Subgroup analyses revealed similar CRC risk in male (SIR 2.14, 95% CI 0.85–5.38) and female (SIR 2.20, 95% CI 1.52–3.19) patients and an increased risk with extensive colitis, with an SIR of 3.95 (95% CI 2.56–6.09). This systematic review and meta-analysis provides population-based estimates of CRC risk in patients with UC, based on high-quality studies with rigorous methodology. The results offer reliable reference values for incidence, SIR, and prevalence, which are applicable to the broader UC population and relevant to clinical decision-making and public health planning. Nonetheless, substantial heterogeneity across studies and limited geographic representation—particularly from Asia, South America, Africa, and Oceania—highlight the need for additional population-based research in underrepresented regions to improve the global applicability of CRC risk estimates in UC. This study was supported by State key Laboratory of Digestive Health.

AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22 (rIL-22) on L-arginine-induced acute severe pancreatitis (SAP)-associated lung injury and the possible signaling pathway involved. METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase (MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin (HE) staining. Expression of B cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL and IL-22RA1 mRNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group (P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-xL mRNAs in the SAP group was decreased markedly, while the IL-22RA1 mRNA expression was increased significantly relative to the normal control group (P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-xL or IL-22RA1 mRNA (P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the rIL-22 group were significantly lower than those in the SAP group (P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, rIL-22 stimulated the expression of Bcl-2, Bcl-xL and IL-22RA1 mRNAs in the lung (P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the rIL-22 group was significantly higher than that in the PBS group (P < 0.05). CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.

Background: Mitochondria play central roles in metabolic diseases including nonalcoholic steatohepatitis (NASH). However, how mitochondria regulate NASH progression remains largely unknown. Our previous findings demonstrate that mitochondrial general control of amino acid synthesis 5 like 1 (GCN5L1) is associated with mitochondrial metabolism. Nevertheless, the roles of GCN5L1 in NASH are unclear.Aims and methods: The GCN5L1 expression was detected in the fatty livers of NASH patients and animals. Hepatocyte‐specific GCN5L1 deficiency or overexpression mice were used to induce NASH models by feeding with a high‐fat/high‐cholesterol or methionine‐choline deficient diet. The molecular mechanisms underlying GCN5L1‐regulated NASH were further explored and verified in mice.Results and conclusions: GCN5L1 expression was increased in NASH patients. Upregulated GCN5L1 level was also illustrated in NASH mice. Mice with hepatocyte‐specific GCN5L1 conditional knockout improved the inflammatory response compared to GCN5L1^flox/flox mice. However, overexpression of mitochondrial GCN5L1 augmented the inflammatory response. Mechanically, GCN5L1 acetylated CypD and enhanced its binding with ATP5B, which induced the opening of mitochondrial permeability transition pores and the release of mitochondrial ROS into the cytoplasm. The increased ROS promoted ferroptosis of hepatocytes and induced accumulation of high mobility group box 1 in the microenvironment, which recruited neutrophils and induced the generation of neutrophil extracellular traps (NETs). NETs block impaired GCN5L1‐induced NASH progression. Furthermore, the upregulation of GCN5L1 in NASH was contributed by lipid overload‐induced endoplasmic reticulum stress. Together, mitochondrial GCN5L1 has a vital function in promoting NASH progression by regulating oxidative metabolism and the hepatic inflammatory microenvironment. Thus, GCN5L1 might be a potential intervention target in NASH treatment.

Previous studies have demonstrated the rejuvenating and restorative actions of mesenchymal stem cells (MSCs) in multiple diseases, but their role in reversing chronic atrophic gastritis (CAG) is not well understood owing to their low efficiency in homing to the stomach. In this work, we investigated the therapeutic effect of umbilical cord-derived MSCs (UC-MSCs) on CAG by endoscopic submucosal injection and preliminarily explored possible mechanisms in vitro. MSCs and normal saline (NS) were injected into the submucosa of the stomach in randomly grouped CAG rabbits. Therapeutic effects on serum indices and histopathology of the gastric mucosa were analyzed in vivo at 30 and 60 days after MSCs injection. GES-1 cells were co-cultured with MSCs in vitro using a Transwell system and cell viability, proliferation, and migration ability were detected. Additionally, in view of the potential mechanisms, the relative protein expression levels of apoptosis, autophagy and inflammation in vitro were explored by Western Blotting. We found that submucosal injection of MSCs up-regulated serum indices (G-17, PGI and PGI/PGII) and alleviated histopathological damage to the gastric mucosa in CAG rabbits. Co-culture of GES-1 cells with MSCs improved cell viability, proliferation, and migration ability, while suppressing apoptosis. We also observed a reduction in the expression of apoptosis indicators, including Bax and cleaved caspase-3, in GES-1 cells after co-culture with MSCs in vitro. Our findings suggest that submucosal injection of MSCs is a promising approach for reversing CAG, and attenuating apoptosis plays a potential role in this process.