Damage-induced NAD release activates intestinal CD4+ and CD8+ T cell via P2X7R signaling.

BACKGROUND: Postoperative ileus (POI) is characterized by the activation of inflammation triggered by tissue damage. Damage-associated molecular patterns (DAMPs) reportedly induce local inflammation after injury. However, the impact of DAMPs on intestinal resident lymphocytes during POI remains poorly elucidated. METHODS: POI in mice was induced via intestinal manipulation (IM). The concentration of nicotinamide adenine dinucleotide (NAD) was detected after IM. The gastrointestinal motility of the mice was assessed after IM or NAD injection. Cytokine production and calcium influx in T cells were investigated after NAD stimulation using flow cytometry. RESULTS: The concentration of extracellular NAD significantly increased after IM administration, and NAD directly impaired gastrointestinal motility. Intraperitoneal injection of NAD promoted the expression of TNF-α in intestinal CD8+ and CD4+ T cells, but only IFN-γ production by CD8+ T cells was significantly promoted by NAD injection. Granzyme B production in CD8+ and CD4+ T cells decreased after administration. Concordantly, the same results were observed in NAD stimulation of intestinal CD3+ T cells in vitro. Blocking the P2X7R-related membrane enzyme ART2.2 significantly diminished the pro-inflammatory effect of NAD. CONCLUSION: IM includes the release of NAD derived from damaged tissues, consequently promoting pro-inflammatory cytokine production in intestinal CD4+ and CD8+ T lymphocytes. NAD-induced intestinal T cells activation may be associated with POI progression in the mouse.

Factors associated with overall survival in early gastric cancer patients who underwent additional surgery after endoscopic submucosal dissection.

BACKGROUND: Controversy exists about the benefit of additional surgery after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). AIM: To examine risk factors for overall survival (OS) after additional surgery in patients with EGC who initially underwent ESD. METHODS: This was a retrospective analysis of patients with EGC who underwent additional surgery after ESD at the Beijing Friendship Hospital affiliated to Capital Medical University between August 2012 and August 2019. OS was the primary outcome. Lymph node metastasis and residual tumor were secondary outcomes. Logistic regression models and Kaplan-Meier curves were used for further analysis. RESULTS: Forty-two patients were evaluated, including 35 (83.3%) males and 7(16.7%) females. The mean age was 62 (range, 32-82) years. Male sex [hazard ratio (HR) = 21.906, 95% confidence interval (CI): 3.762-229.250; P = 0.039), T1b invasion (HR = 3.965, 95%CI: 1.109-17.432; P = 0.047), undifferentiated tumor (HR = 9.455, 95%CI: 0.946-29.482; P = 0.049), lymph node metastasis (HR = 2.126, 95%CI: 0.002-13.266; P = 0.031), and residual tumor (HR = 4.275, 95%CI: 1.049-27.420; P = 0.043) were independently associated with OS. The follow-up duration was 4-81 mo (median: 50.7 mo). OS was 77.0 ± 12.1 mo (95%CI: 53.3-100.7 mo). The 3-year and 5-year OS rates were 94.1% and 85%, respectively. CONCLUSION: Male sex, T1b invasion, undifferentiated tumor, lymph node metastasis, and residual tumor are independently associated with OS in patients with EGC who underwent additional surgery after ESD.