1.Research progress of traditional Chinese medicine in regulating "inflammation-cancer" transformation in gastric mucosa based on NLRP3 inflammasome.
Liu-Hong YANG ; Jia LIU ; Lan LIANG ; Jie LIN
China Journal of Chinese Materia Medica 2025;50(9):2334-2348
Gastric cancer is one of the most common malignant tumors in the digestive tract, which has the characteristics of high morbidity and mortality. However, gastric cancer is not achieved overnight but is gradually developing through the interaction of many factors. Therefore, actively delaying or blocking the "inflammation-cancer" transformation in gastric mucosa is the key to treatment. Nod-like receptor protein 3(NLRP3) inflammasome is a multi-protein signal complex and one of the important innate immune signal receptors. Inflammation plays an important role in the occurrence and development of gastric cancer, and continuous inflammation mediation will trigger the transformation from inflammation to cancer. Therefore, the significance of NLRP3 inflammasome to gastric mucosa lies in the transformation between inflammation and cancer. Traditional Chinese medicine(TCM) has the functions of multi-components, multi-targets, and few adverse reactions. A large number of studies show that TCM and related monomers have significant effects in treating liver, kidney, and immune diseases through mediating NLRP3 inflammasome, but there is less research on the "inflammation-cancer" transformation in gastric mucosa. By combing the NLRP3-related nuclear factor-κB transcription factor(NF-κB), hypoxia inducible factor-1α(HIF-1α), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), and other signal pathways, this paper clarified their mechanisms in the "inflammation-cancer" transformation in gastric mucosa, delayed the process of "inflammation-cancer" transformation in gastric mucosa through four aspects: energy metabolism, pyroptosis, immune response, and vascular endothelial growth factor, and prevented and treated "inflammation-cancer" transformation in gastric mucosa from three aspects: TCM monomer, TCM compound prescription, and other therapies, so as to provide ideas for the subsequent treatment of "inflammation-cancer" transformation in gastric mucosa with TCM.
Humans
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Inflammasomes/metabolism*
;
Gastric Mucosa/metabolism*
;
Stomach Neoplasms/pathology*
;
Animals
;
Drugs, Chinese Herbal/pharmacology*
;
Medicine, Chinese Traditional
;
Inflammation/drug therapy*
;
Signal Transduction/drug effects*
2.Diagnostic value of endoscopic findings under white light gastroscopy for Helicobacter pylori infection in children.
Ren-Min ZHOU ; Ying CHEN ; Qiong LIN
Chinese Journal of Contemporary Pediatrics 2025;27(4):438-443
OBJECTIVES:
To explore the clinical value of endoscopic findings under white light gastroscopy in diagnosing Helicobacter pylori (Hp) infection in children.
METHODS:
A retrospective analysis was conducted on the clinical data of 340 children who underwent gastroscopy and gastric mucosa tissue Hp culture from July 2022 to June 2023 in the Department of Gastroenterology at Wuxi Children's Hospital due to upper gastrointestinal symptoms. Based on the results of Hp culture, the children were categorized into an Hp-infected group (146 cases) and a non-infected group (194 cases). The detection rates of various endoscopic findings in the gastric mucosa between the two groups were compared, and the association between each endoscopic finding and different Hp infection statuses was analyzed, as well as the diagnostic value of each endoscopic finding under different Hp infection statuses.
RESULTS:
The proportions of white mucus, diffuse redness, mucosal edema, enlarged folds, chicken skin-like changes, and ulcers in the Hp-infected group were higher than those in the non-infected group (P<0.05), while the proportions of regular arrangement of collecting venules (RAC) and ridge-like redness were lower in the Hp-infected group compared to the non-infected group (P<0.05). Multivariate logistic regression analysis showed that diffuse redness, enlarged folds, mucosal edema, and chicken skin-like changes were closely associated with Hp infection (P<0.05), while RAC and ridge-like redness were closely associated with the absence of Hp infection (P<0.05). Receiver operating characteristic curve analysis indicated that the area under the curve for diffuse redness, enlarged folds, mucosal edema, and chicken skin-like changes in predicting Hp infection was 0.798, 0.731, 0.782, and 0.760, respectively (P<0.05). The area under the curve for RAC and ridge-like redness in predicting the absence of Hp infection was 0.861 and 0.589, respectively (P<0.05).
CONCLUSIONS
Endoscopic findings under white light gastroscopy are associated with Hp infection in children, with diffuse redness, mucosal edema, chicken skin-like changes, and enlarged folds showing significant diagnostic value for Hp infection.
Humans
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Helicobacter Infections/diagnostic imaging*
;
Female
;
Male
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Gastroscopy/methods*
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Child
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Helicobacter pylori
;
Retrospective Studies
;
Child, Preschool
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Adolescent
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Gastric Mucosa/pathology*
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Infant
;
Logistic Models
3.Scleromitrion diffusum reverses epithelial-mesenchymal transi-tion of gastric mucosa in rats with gastric precancerous lesions.
Luping MA ; Xin ZUO ; Weikai ZHU ; Jiyan LI ; Yanyan ZHAO ; Jingyuan ZHANG ; Hui SHEN
Journal of Zhejiang University. Medical sciences 2025;54(3):342-349
OBJECTIVES:
To investigate the effect of Scleromitrion diffusum on gastric mucosal epithelial-mesenchymal transition (EMT) in rats with gastric precancerous lesion.
METHODS:
Fifty SD rats were randomly divided into blank control group (n=11), model control group (n=13), Scleromitrion diffusum (SD) group (n=13) and vitase group (n=13). Gastric precancerous lesion animal model was prepared by 1-methyl-3-nitro-1-nitrosoguanidine complex polyfactor method, and the drugs were administrated by gavage once a day for 6 weeks. The pathological changes of gastric mucosa were observed with hematoxylin and eosin staining, the expression of EMT marker proteins were detected with immunohistochemical staining and Western blotting.
RESULTS:
Compared with the model control group, the gastric mucosal injury was significantly attenuated in the Scleromitrion diffusum group, the mucosal tissue structure gradually recovered, the saccular expansion area was reduced, and the inflammatory infiltration was ameliorated. The expression of epithelial cadherin was higher, and the expression of neural cadherin and vimentin in the Scleromitrion diffusum group were lower than those of model control group (all P<0.05).
CONCLUSIONS
Scleromitrion diffusum can ameliorate gastric mucosal injury in rats with gastric precancerous lesion by reversing the EMT.
Animals
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Rats
;
Rats, Sprague-Dawley
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Epithelial-Mesenchymal Transition/drug effects*
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Precancerous Conditions/metabolism*
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Gastric Mucosa/metabolism*
;
Stomach Neoplasms/drug therapy*
;
Male
;
Cadherins/metabolism*
4.Effect of CMTM6 on PD-L1 in Helicobacter pylori infected gastric epithelial cells.
Wei FU ; Jing NING ; Weiwei FU ; Jing ZHANG ; Shigang DING
Journal of Peking University(Health Sciences) 2025;57(2):245-252
OBJECTIVE:
To explore the changes of CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) and programmed death-ligand 1 (PD-L1) expression in gastric mucosal epithelial cells after Helicobacter pylori infection and the regulation of CMTM6 on PD-L1, and to analyze the mRNA expression differences before and after CMTM6 gene knock-out in helicobacter pylori infected gastric epithelial cells by microarray analysis.
METHODS:
The standard Helicobacter pylori strain ATCC 26695 was co-cultured with human gastric epithelial cell GES-1 for 6, 24 and 48 hours, and the mRNA and protein levels of CMTM6 and PD-L1 were detected by real-time quantitative PCR and Western blot. Using CRISPR/Cas9 to construct CMTM6 gene knockout plasmid and knockout CMTM6 gene of GES-1 cells. Helicobacter pylori was co-cultured with CMTM6 gene knockout and wild type GES-1 cells for 48 hours to detect PD-L1 transcription and protein level changes, and CMTM6 gene knockout GES-1 cells were treated with the proteasome inhibitor MG-132 to detect the changes in PD-L1 protein levels. Agilent Human ceRNA Microarray 2019 was used to detect the differentially expressed genes in CMTM6 gene knockout and wild-type GES-1 cells co-cultured with Hp for 48 hours, and the signal pathway of differentially expressed genes enrichment was analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) database.
RESULTS:
The mRNA and protein levels of CMTM6 and PD-L1 in GES-1 cells were significantly up-regulated after Helicobacter pylori infection, and CMTM6 mRNA was most significantly up-regulated 48 hours after infection. After CMTM6 gene knockout, the CD274 gene transcription level of Helicobacter pylori infected GES-1 cells did not change significantly, but PD-L1 protein level was significantly down-regulated, and the PD-L1 level increased after the application of proteasome inhibitor MG-132. After CMTM6 gene knockout, 67 genes had more than two times of differential expression. The transcription levels of TMEM68, FERMT3, GPR142, ATP6V1FNB, NOV, UBE2S and other genes were significantly down-regulated. The transcription levels of PCDHGA6, CAMKMT, PDIA2, NTRK3, SPOCK1 and other genes were significantly up-regulated. After CMTM6 gene knockout, ubiquitin-conjugating enzyme E2S (UBE2S) gene expression was significantly down-regulated, which might affect protein ubiquitination degradation. After CMTM6 gene knockout, adrenoceptor alpha 1B (ADRA1B), cholinergic receptor muscarinic 1 (M1), CHRM1, platelet activating factor receptor (PTAFR) gene expression was significantly up-regulated.
CONCLUSION
Helicobacter pylori infection up-regulates the expression level of CMTM6 in gastric mucosa cells, and CMTM6 can stabilize PD-L1 and maintain the protein level of PD-L1. CMTM6 gene knockout may affect biological behaviors such as protein ubiquitination and cell surface receptor expression.
Humans
;
MARVEL Domain-Containing Proteins/metabolism*
;
Helicobacter pylori/physiology*
;
B7-H1 Antigen/genetics*
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Helicobacter Infections/metabolism*
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Epithelial Cells/metabolism*
;
Gastric Mucosa/metabolism*
;
Chemokines/metabolism*
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Cell Line
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Gene Knockout Techniques
;
Myelin Proteins
5.Revolutionizing Gastric Cancer Prevention: Novel Insights on Gastric Mucosal Inflammation-Cancer Transformation and Chinese Medicine.
Lin LIU ; Xiao-Hui FAN ; Xu-Dong TANG
Chinese journal of integrative medicine 2025;31(10):942-952
The progression from gastric mucosal inflammation to cancer signifies a pivotal event in the trajectory of gastric cancer (GC) development. Chinese medicine (CM) exhibits unique advantages and holds significant promise in inhibiting carcinogenesis of the gastric mucosa. This review intricately examines the critical pathological events during the transition from gastric mucosal inflammation-cancer transformation (GMICT), with a particular focus on pathological evolution mechanisms of spasmolytic polypeptide-expressing metaplasia (SPEM). Moreover, it investigates the pioneering applications and advancements of CM in intervening within the medical research domain of precancerous transformations leading to GC. Furthermore, the analysis extends to major shortcomings and challenges confronted by current research in gastric precancerous lesions, and innovative studies related to CM are presented. We offer a highly succinct yet optimistic outlook on future developmental trends. This paper endeavors to foster a profound understanding of forefront dynamics in GMICT research and scientific implications of modernizing CM. It also introduces a novel perspective for establishing a collaborative secondary prevention system for GC that integrates both Western and Chinese medicines.
Stomach Neoplasms/pathology*
;
Humans
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Cell Transformation, Neoplastic/pathology*
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Gastric Mucosa/pathology*
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Medicine, Chinese Traditional
;
Inflammation/pathology*
;
Animals
6.Capsaicin (CAP) exerts a protective effect against ethanol-induced oxidative gastric mucosal injury by modulating the chemokine receptor 4 (CCR4)/Src/p47phox signaling pathway both in vitro and in vivo.
Zhiru YANG ; Haolin GUO ; Pengfei ZHANG ; Kairui LIU ; Junli BA ; Xue BAI ; Shiti SHAMA ; Bo ZHANG ; Xiaoning GAO ; Jun KANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(2):191-202
Ethanol (EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin (CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4 (CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65 (NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.
Ethanol/toxicity*
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Animals
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Gastric Mucosa/metabolism*
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Signal Transduction/drug effects*
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Oxidative Stress/drug effects*
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Capsaicin/pharmacology*
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Male
;
NADPH Oxidases/genetics*
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Mice
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Humans
;
src-Family Kinases/genetics*
7.Clinical Features of Collagenous Gastritis.
Long-Jiao CAI ; Yuan LIU ; Ai-Min LENG
Acta Academiae Medicinae Sinicae 2023;45(6):902-911
Objective To analyze the clinical characteristics of collagenous gastritis (CG) and provide evidence for the precise diagnosis and treatment of CG.Methods Published case reports and case series were collected from PubMed,CNKI,and Wanfang Med Online with the key words of collagenous gastritis,collagenous gastroduodenitis,collagenous gastrointestinal diseases,and gastric mucosal nodules.The demographic and clinical information of each case was collected.Results According to the extent of collagen deposition in the digestive tract,94 CG cases included in this study were assigned into upper digestive tract (UDT)-CG,total digestive tract (TDT)-CG and other groups.The UDT-CG group included 52 cases (57.69% females and 42.31% males) with a median age of 14.50 (11.00,25.75) years old.There were 17 cases in the TDT-CG group,including 70.59% females and 29.41% males,with a median age of 15.00 (9.50,48.50) years old.The other group contained 25 cases,(64.00% females and 36.00% males) with a median age of 25.00 (15.50,59.50) years old.The main clinical manifestations in the UDT-CG group were anemia (59.62%) and diarrhea (17.31%),and those in the TDT-CG group were anemia (29.41%) and diarrhea (94.12%).The nodular appearance of gastric mucosa was observed in 75.00% cases in the UDT-CG group and 35.29% cases in the TDT-CG group.In the initial treatment,symptomatic therapy and hormonal therapy respectively relieved the symptoms in 75.00% (30/40) and 100% (3/3) cases in the UDT-CG group and 57.14% (4/7) and 83.33% (5/6) cases in the TDT-CG group.In the retreatment,symptomatic therapy and hormone therapy respectively achieved the remission rates of 100.00% (3/3) and 88.89% (8/9) in the UDT-CG group and 80.00% (4/5) and 66.67% (2/3) in the TDT-CG group.Conclusions CG,a rare disease of gastric collagen deposition,mainly occurs in young patients,and females are more susceptible than males.The clinical manifestations of CG are nonspecific,and anemia,abdominal pain,diarrhea,weight loss,and gastrointestinal bleeding are the common symptoms of CG.Nodular appearance of gastric mucosa is a relatively specific endoscopic feature of CG.There is no standardized treatment for CG.Symptomatic treatment is commonly adopted to improve the quality of life of the patients,and hormones can be added when necessary.
Male
;
Female
;
Humans
;
Quality of Life
;
Gastritis/diagnosis*
;
Gastric Mucosa
;
Collagen
;
Anemia/etiology*
;
Diarrhea/complications*
8.Pathological features of early gastric cancer and its background mucosa after eradication of Helicobacter pylori and their implications for biopsy diagnosis.
Xiao Yu SUN ; Jing LI ; Bing YUE ; Rui XU ; Mei JIA ; Yang GAO ; Guang Yong CHEN
Chinese Journal of Pathology 2023;52(5):460-465
Objective: To investigate the clinicopathological changes of early gastric cancer, especially its background mucosa, after the eradication of Helicobacter pylori (H. pylori), and to investigate the causes of underdiagnosis in preoperative biopsy pathology. Methods: Ninety cases of early gastric cancer after H. pylori eradication and 120 cases of endoscopic submucosal dissection (ESD) specimens without H. pylori eradication and their corresponding biopsy specimens were collected from Beijing Friendship Hospital Affiliated to Capital Medical University during 2016-2021. The clinicopathological data of the patients were analyzed, and the histopathological characteristics and immunophenotypic results compared. Results: Compared with the early gastric cancer without H. pylori eradication history, the histopathological type of early gastric cancer after H. pylori eradication was differentiated adenocarcinoma, with staggered distribution of cancerous and non-cancerous epithelium in the tumor area. The morphologic characteristics of gastric mucosa in the background of early gastric cancer after H. pylori eradication, were distinctive, including widening of the opening of enterosylated glandular ducts, serrated change of luminal margin, eosinophilic and microvesicular cytoplasm of enterosylated epithelium. Low-grade atypia existed in gastric cancer epithelial cells after sterilization, which might lead to underdiagnosis or missed diagnosis in biopsy pathology. Conclusions: Early gastric cancer and its background mucosa after H. pylori eradication have unique morphological characteristics, which can be used as a clue for pathological diagnosis, improve the accuracy of biopsy pathology and reduce the underdiagnosis.
Humans
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Helicobacter pylori
;
Helicobacter Infections/drug therapy*
;
Stomach Neoplasms/pathology*
;
Gastric Mucosa/pathology*
;
Biopsy
10.Risk factors for complications of endoscopic full-thickness resection of upper gastrointestinal submucosal tumors.
Liu Jing NI ; Wen Xin ZHU ; Chen Tao ZOU ; Guo Ting XU ; Chao WANG ; Ai Rong WU
Chinese Journal of Gastrointestinal Surgery 2023;26(4):365-371
Objective: To analyze the risk factors for complications of endoscopic full-thickness resection (EFTR) of upper gastrointestinal submucosal tumors (SMTs). Methods: This was a retrospective observational study. The indications for EFTR included: (1) SMTs originating from the muscularis propria layer and growing out of the cavity or infiltrating the deep part of the muscularis propria layer; (2) SMTs diameter <5 cm; and (3) tumor identified as closely adherent to the serous layer during endoscopic submucosal dissection or endoscopic mucosal resection. This study included patients with SMTs originating from the muscularis propria layer in upper digestive tract, diagnosed preoperatively by endoscopic ultrasonography or computed tomography, who were successfully treated with EFTR. Those with incomplete clinical data were excluded. The clinical data of 154 patients with upper gastrointestinal SMTs who underwent EFTR at the Department of Gastroenterology, First Affiliated Hospital of Soochow University from January 2016 to January 2022 were retrospectively analyzed. Post-EFTR complications (such as delayed perforation, delayed bleeding, and postoperative infection, including electrocoagulation syndrome) were monitored and the risk factors for them were analyzed. Results: Among the 154 study patients, 33 (21.4%) developed complications, including delayed bleeding in three (1.9%), delayed perforation in two (1.3%), and postoperative infection in 28 (18.2%). One patient with bleeding was classified as having a major complication (hospitalized for more than 10 days because of complication). According to univariate analysis, complication was associated with tumor diameter >15 mm, operation time >90 minutes, defect closure method(purse string suture), and diameter of resected specimen ≥20 mm (all P<0.05). Multivariate logistic regression analysis showed that operation time >90 minutes (OR=6.252, 95%CI: 2.530-15.446, P<0.001) and tumor diameter >15 mm (OR=4.843, 95%CI: 1.985-11.817, P=0.001) were independent risk factors for complications after EFTR in patients with upper gastrointestinal SMTs. The independent risk factors for postoperative infection in these patients were operation time>90 minutes (OR=4.993, 95%CI:1.964-12.694, P=0.001) and purse string suture (OR=7.142, 95%CI: 1.953-26.123, P=0.003). Conclusion: Patients with upper gastrointestinal SMTs undergoing EFTR with tumor diameter >15 mm or operation time >90 minutes have a significantly increased risk of postoperative complications. Postoperative monitoring is important for these patients with SMTs.
Humans
;
Stomach Neoplasms/surgery*
;
Endoscopic Mucosal Resection/methods*
;
Gastroscopy/methods*
;
Retrospective Studies
;
Endosonography/adverse effects*
;
Postoperative Complications/etiology*
;
Treatment Outcome
;
Gastric Mucosa/surgery*

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