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Backgrounds: Endoscopic submucosal dissection (ESD) has been widely performed in the treatment of early esophageal squamous cell carcinoma (ESCC). Few studies have compared the long-term outcomes of esophageal ESD based on absolute indications and relative indications. The aim of the current study was to investigate the safety and efficacy of ESD for early ESCC with relative indications. Methods: 297 patients with early ESCC who underwent ESD were retrospectively analyzed. They were divided into 3 groups: group A, the absolute indications group; group B, the relative indications without additional treatment after ESD group; and group C, the relative indications with additional treatment after ESD group. The baseline characteristics, therapeutic efficacy, complications, prognosis outcomes, and follow-up data were evaluated. Results: During the median follow-up period of 51.0 months (range 6–101 months), the incidence of local recurrence in groups A, B, and C was 1.63% (3/184), 4.23% (3/71), and 0 (0/42), respectively (p = 0.253). The 5-year overall survival rates were 97.83% (95% CI: 95.69–99.95%) in group A, 95.77% (95% CI: 90.95–100.00%) in group B, and 97.62% (95% CI: 92.81–100.00%) in group C with no significant differences among these 3 groups. Conclusions: ESD is a feasible and effective treatment for early ESCC with relative indications. Under the premise of sufficient preoperative assessment and scheduled postoperative endoscopic surveillance, additional treatment might not be necessary for patients with relative indications after ESD procedures. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that neuropsychiatric stabilizers have a place in resolving gastrointestinal disorders. Lithium carbonate (LC) is one of the most commonly used drugs for bipolar disorder clinically. Here, we estimate the therapeutic function of LC against colitis and investigate the mechanism of intestinal flora and metabolism modulation. A colitis model was constructed by continuously administering 2.5% dextran sodium sulfate (DSS) solution daily for 7 days. Analysis of gut microbiota was carried out by 16S rRNA gene high-throughput sequencing. Spectrum antibiotic cocktail (ABX) and faecal microbiota transplantation (FMT) were employed to evaluate the protective effect of intestinal flora. Colonic Treg cells and related immune responses were detected by flow cytometry. LC treatment significantly alleviated colon inflammation by regulating gut microbial diversity and altering flora composition. Notably, LC treatment upregulated short-chain fatty acid (SCFA)-producing bacteria, especially Akkermansia muciniphila (A. muciniphila), and transformed metabolite SCFA profiles. LC activated anti-inflammatory Treg cell responses in colonic lamina propria (LP) in a G-protein coupled receptor 43 (GPR43)-dependent mechanism. ABX, FMT and single bacteria gavage experiments were conducted to confirm the above mechanism. As an intestinal microbiome and metabolite modulator, LC alleviates colon inflammation in a GPR43-dependent manner through activating Treg cell responses. Therefore, the therapeutic strategy of the microbiome-metabolite-immune axis, as observed in the A. muciniphila -SCFA-Treg cell axis in our study, might provide a new direction for the treatment of IBD. [Display omitted] [ABSTRACT FROM AUTHOR]

• Protective autophagy induced by DDP decreases chemosensitivity in GC cells. • MGMT inhibited ATG4B to repress autophagy. • Inhibition of autophagy enhanced the chemosensitivity to DDP in GC xenograft model. • High MGMT expression and low ATG4B expression are significantly correlated with survival of GC. Cisplatin (DDP) is the first-line drug for the treatment of gastric cancer (GC). However, DDP resistance is common. Autophagy, which is closely related to chemoresistance, is a process of resolving and recycling proteins and damaged cellular organs. Additionally, O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for alkylating drug resistance. However, the relationship between autophagy and MGMT in response to DDP in GC is still unknown. In the present study, we determined that autophagy induced by DDP decreases chemosensitivity in GC cell lines. DDP may have induced autophagy in GC by inhibiting MGMT to increase autophagy-related gene (ATG) 4B. Inhibition of MGMT-mediated ATG4B suppression resulted in autophagy induction and DDP resistance. In vivo , combined DDP and autophagy inhibitor chloroquine (CQ) enhanced the anti-tumor effect of DDP; additionally, the negative correlation of MGMT and ATG4B was confirmed. High expression of MGMT and low expression of ATG4B were significantly correlated with favorable five-year survival rate (P < 0.05) in 66 clinicopathologically characterized GC cases. Our study demonstrate that DDP inhibits MGMT-mediated autophagy suppression to decrease chemosensitivity in GC, which provides a novel therapeutic strategy to promote DDP chemosensitivity in GC. [ABSTRACT FROM AUTHOR]