Chronic atrophic gastritis (CAG) with intestinal metaplasia (IM) is a key precancerous lesion that may progress to intestinal-type gastric adenocarcinoma. Piwei Peiyuan Pill (PPP) has shown significant clinical efficacy in ameliorating CAG with IM, but its active components and underlying mechanisms remain unclear. High-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) were used to identify the components of PPP and the active ingredients in PPP-containing serum. The therapeutic efficacy and potential mechanisms of PPP were further investigated via transcriptomic sequencing and experimental validation. UHPLC-HRMS analysis of PPP-containing serum identified several bioactive components, including esculin, lithospermic acid, and atractylenolide III. In CAG rats, PPP significantly ameliorated gastric mucosal damage and reduced serum IL-6 and TNF-α levels. Transcriptomic results showed that IRAK1 was highly expressed in CAG patients with IM and associated with activation of the NF-κB pathway. PPP intervention dose-dependently suppressed hyperactivation of the Pellino1/IRAK1/NF-κB axis and decreased the expression of intestinal metaplasia markers CDX1 and MUC2. Additionally, PPP improved immune function by increasing the proportion of CD4[+] T cells and decreasing the proportion of CD8[+] T cells in CAG model rats. Taken together, these findings suggest that PPP mitigates CAG and attenuates IM at least in part by suppressing the Pellino1/IRAK1/NF-κB signaling pathway, indicating that it may serve as a promising therapeutic strategy for reducing inflammation-associated gastric carcinogenesis.

A 64-year-old Chinese man visited our clinic's health-screening center. The patient tested negative for Helicobacter pylori (HP) infection in his home country, but at this visit, anti-HP antibodies of 5 U/mL and a urea breath test (UBT) result of 48.6‰ were detected. Upper gastrointestinal endoscopy showed no atrophic gastritis, and a regular arrangement of collecting venules was observed. Since a false-positive UBT was also considered, Smart Gene testing was performed, which confirmed the HP positivity. As no clarithromycin resistance mutation was detected, Japan's first-line eradication regimen was prescribed. The eradication test result was a UBT of 0.1‰, confirming successful HP eradication.

This study investigated the therapeutic efficacy of Sijunzi Decoction on chronic atrophic gastritis(CAG) in rats and its potential mechanism of action in mitigating gastric mucosal injury through the "gut microbiota-hepcidin-ferroptosis" pathway. Specific pathogen-free(SPF) grade male Wistar rats were randomly divided into a normal group, a model group, a positive drug vatacoenayme group, and low-, medium-, and high-dose Sijunzi Decoction groups. A CAG model was established using a composite modeling method combining multiple pathogenic factors with irregular feeding. Gut microbiota composition and functional changes were analyzed by 16S rRNA high-throughput sequencing. Hepcidin expression in gastric tissues was assessed by immunofluorescence. Western blot was performed to measure the expression of ferroportin 1(FPN1) and ferroptosis-related proteins, including glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11). The levels of ferrous iron(Fe~(2+)), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione peroxidase(GSH-Px) were determined by colorimetric assay. Histopathological alterations in gastric tissue were observed via hematoxylin-eosin(HE) staining. The 16S rRNA sequencing results indicated a significant gut microbiota dysbiosis in the model group compared to the normal group. The model group exhibited significant enrichment of Prevotella, Allobaculum, Bacteroides, Enterococcus, and members of Enterobacteriaceae, whereas the normal group was relatively enriched with Turicibacteraceae/Turicibacter, Roseburia, and Veillonellaceae. Following pharmacological intervention, the vitaminazyme group showed enrichment of Clostridiaceae and Bifidobacterium. Distinct microbial signatures were observed across different doses of Sijunzi Decoction: the low-dose group was enriched with Bacteroides, Prevotella, and Veillonellaceae; the medium-dose group was enriched in Turicibacter and Actinobacteria; and the high-dose group was enriched with Sutterella, Allobaculum, and Blautia. Overall, the microbiota structure in all treatment groups shifted back towards that of the normal group compared to the model group. Functional prediction indicated that Sijunzi Decoction could upregulate metabolic pathways related to the degradation of aromatic compounds. In gastric tissues, the model group exhibited significant iron overload, oxidative stress, and ferroptosis activation, manifested as elevated Fe~(2+) and MDA levels, reduced GSH-Px and SOD activities, upregulated hepcidin expression, and markedly downregulated FPN1 and the key ferroptosis proteins GPX4 and SLC7A11. Sijunzi Decoction intervention effectively reversed these changes, restored iron homeostasis and redox balance, significantly upregulated the expression of FPN1, GPX4, and SLC7A11, and notably ameliorated gastric mucosal atrophy, glandular structural damage, and inflammatory cell infiltration in CAG rats. In summary, Sijunzi Decoction may improve gastric tissue injury and oxidative stress in CAG by remodeling the structure and function of the gut microbiota, downregulating hepcidin expression, promoting iron export, and inhibiting ferroptosis.

The article "Identification of LGR5 and TFF2 as Biomarkers in High-Risk Chronic Atrophic Gastritis: From Multi-Omics Mining to Clinical Validation" [Digestion. 2026; https://doi.org/10.1159/000549887] by Qingqing Zhang, Di Wu, Fengyun Guo, Shengnan Yang, Lijing Bao, Ruiying Zhang and Ping Wang has been retracted by the Publisher and the Editor.Post-publication concerns were raised regarding the integrity of the clinical cohort data reported in the article. The data presented in Table 1 shares the same subgroup size, gender distributions and H. pylori infection rates across all three subgroups to those reported in a previously published article by the same research group [1]. Additionally, the images in Figure 4b and d of this article are published as Figure 2a and b in [1]. The previous publication was not cited in this article.When asked about the similarities between the cohorts, the authors stated that they were two independent cohorts and that the similarities were coincidental. The Editors did not find the authors' explanation sufficient to resolve their concerns, and as a result have lost confidence in the reliability and originality of the reported cohort data.The authors did not respond to our correspondence about the retraction of this article within the timeframe specified.

Collagenous gastritis (CG) is a rare fibroinflammatory disorder that may present with heterogeneous endoscopic findings. We report a 35-year-old woman with a 7-year history of refractory dyspepsia who had previously received a provisional diagnosis of seronegative AIG at another hospital because of Helicobacter pylori-negative, corpus-predominant gastric atrophy, iron deficiency, vitamin B12 deficiency, and concomitant thyroid autoimmunity. Persistent symptoms despite vitamin B12 and iron supplementation prompted referral to our center for further evaluation. Comprehensive reassessment revealed diffuse gastric atrophic-appearing changes, together with several findings discordant with established AIG, including persistent hypogastrinemia and magnifying endoscopic features inconsistent with typical AIG. Magnifying endoscopy with narrow-band imaging showed effacement of the surface microarchitecture and disorganized microvessels rather than the typical "cast-off skin" appearance of AIG, while acetic acid-enhanced imaging revealed residual central pits within the atrophic mucosa. Histopathological review with Masson trichrome staining demonstrated thickened subepithelial collagen bands with entrapped capillaries in both corpus and antral biopsies, confirming CG. After initiation of proton pump inhibitor therapy, the patient reported marked symptomatic improvement within 8 weeks. This case highlights CG as an overlooked differential diagnosis in unexplained diffuse gastric atrophic-appearing changes; nodular mucosal changes, atypical magnifying NBI findings, and subtle subepithelial pink material on routine histology should prompt collagen-specific staining to avoid diagnostic anchoring to more common forms of atrophic gastritis.

Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory and gastrointestinal protective effects in clinical practice; however, its active constituents and mechanisms of action against CAG remain undefined. This study aimed to clarify the absorbed bioactive components of LHHZ and explore its therapeutic mechanism for CAG. Methods: Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was employed to identify the absorbed components of LHHZ in the gastric and intestinal tissues of mice. The therapeutic effects of LHHZ on CAG were assessed through histopathological staining, ultrastructural observation, and evaluation of serum and gastric functional indicators. Network pharmacology, molecular docking, and molecular dynamics simulations were integrated to predict the core targets and key signaling pathways, while the regulatory effects on the interleukin-17 (IL-17) signaling pathway were further validated by immunofluorescence staining, real-time quantitative polymerase chain reaction, and Western blotting. Additionally, 16S ribosomal RNA gene sequencing and targeted metabolomics were applied to investigate the effects of LHHZ on gut microbiota composition and short-chain fatty acid (SCFA) metabolism. Results: The results revealed that 55 and 48 absorbed components were identified in the gastric and intestinal tissues, respectively, predominantly derived from Coptis chinensis Franch. and Pogostemon cablin (Blanco) Benth. LHHZ significantly alleviated gastric mucosal lesions, reduced intestinal metaplasia, restored the ultrastructure of gastric mucosal cells, improved gastric functional indicators including pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (GAS-17), and decreased the levels of pro-inflammatory cytokines. Network pharmacology combined with in vitro and in vivo experiments demonstrated that the core bioactive components of LHHZ can target and regulate interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), attenuate activation of the IL-17 signaling pathway, and suppress the secretion of downstream pro-inflammatory factors. Furthermore, LHHZ enhanced the alpha diversity of gut microbiota, reduced the Firmicutes to Bacteroidetes (F/B) ratio, restored the abundance of SCFA-producing bacteria such as Bacteroidales and Oscillospirales, and normalized the aberrant levels of eight SCFAs. Significant correlations were also observed between gut microbiota composition and SCFA metabolism. Conclusions: These findings suggest that LHHZ alleviates CAG by inhibiting inflammation via the IL-17 signaling pathway and by modulating the gut microbiota-SCFA axis, thereby providing preclinical evidence supporting its further investigation and development for multi-target therapeutic strategies against CAG.

Intestinal metaplasia (IM), a precancerous precursor lesion to gastric cancer, can be subtyped as complete or incomplete, with the latter associated with a higher cancer risk. This article provides an in-depth evaluation of gross/endoscopic and microscopic findings and the role of special stains in distinguishing complete from incomplete IM. The authors also examine controversies surrounding IM subtyping, its impact on risk stratification, and its role in guiding surveillance. The article addresses the potential significance of IM subtyping in cancer progression and present arguments for its de-emphasis in clinical practice.