INTRODUCTION: Intestinal metaplasia (IM) is an independent risk factor for gastric cancer (GC). However, the subtypes of IM as a risk factor for GC remain controversial. We performed a systematic review and meta-analysis to evaluate the relationship between IM subtypes and GC risk. METHODS: Systematic searches were conducted in PubMed, EMBASE, and the Cochrane Library for published cohort studies of patients with complete IM (type I) or incomplete IM (type II or type III) from inception to May 15, 2021. We extracted relevant data and calculated pooled risk ratios (RRs) and 95% confidence intervals (CIs) comparing the GC risk with IM subtypes. RESULTS: Twelve cohort studies comprising 6,498 individuals were included in the study. Compared with complete IM, the pooled relative risk of GC risk of patients with incomplete IM was 5.16 (95% CI, 3.28–8.12), and the GC risk of type III IM was the highest, with a pooled relative risk of 2.88 (95% CI, 1.37–6.04) compared with that of type II. Compared with complete IM, the pooled relative risk of dysplasia risk in patients with incomplete IM was 3.72 (95% CI, 1.42–9.72), and the dysplasia risk of type III IM was 11.73 (95% CI, 2.08–66.08) compared with that of type I. DISCUSSION: Patients with incomplete IM, especially type III, were at a higher risk of GC and dysplasia than those with complete IM. The current evidence indicates a potential correlation between IM subtypes and GC risk, which may support the use of IM subtypes in GC surveillance.

Background: Gastric cancer (GC) is a leading cause of mortality worldwide, particularly in China. Chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are recognized as precancerous conditions contributing to GC development. Qilianxiaopi formula (QLXP), a traditional Chinese medicine (TCM), has demonstrated significant therapeutic effects on CAG and IM; however, its underlying mechanisms remain poorly understood. Methods: This study utilized chromatography-mass spectrometry to identify the major compounds in QLXP. Network pharmacology was used to predict the associated targets of these components. Thermal proteome profiling (TPP) pinpointed the potential binding proteins of QLXP, which were validated by bioinformatic analyses. Bio-layer interferometry (BLI) was used to analyze the interactions between QLXP and its key target proteins, thereby determining their binding components. Molecular docking predicted the binding modes between the components and proteins. Results: ADAM17 was identified as a key binding protein for QLXP. Further investigation revealed that QLXP inhibits the enzymatic activity of ADAM17, thereby reducing the secretion of the pro-inflammatory cytokine TNF-α, contributing to the anti-inflammatory properties of QLXP. BLI confirmed direct and reversible binding interactions between QLXP and ADAM17. Narirutin, isolated from the ADAM17 binding fraction, displayed the highest affinity for QLXP. Conclusions: This study highlights ADAM17 as a key molecular target of QLXP and narirutin as its principal binding component. The integrated approach combining chromatography-mass spectrometry, network pharmacology, TPP, BLI, and molecular docking provides a robust framework for elucidating the mechanisms of action of TCM.