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 ; Helicobacter Infections/diagnostic imaging* ; Female ; Male ; Gastroscopy/methods* ; Child ; Helicobacter pylori ; Retrospective Studies ; Child, Preschool ; Adolescent ; Gastric Mucosa/pathology* ; Infant ; Logistic Models

OBJECTIVES: To investigate the causal relationship between Helicobacter pylori (Hp) infection and immune thrombocytopenia (ITP) using Mendelian randomization (MR), as well as the association between Hp infection and chronic ITP (cITP) through a clinical study. METHODS: The datasets from genome-wide association studies were used to select the single nucleotide polymorphism loci significantly associated with Hp infection as genetic instrumental variables. The MR analysis model was used to investigate the causal relationship between ITP and Hp infection. A retrospective analysis was conducted on the medical data of 316 children with newly diagnosed ITP at the First Affiliated Hospital of Xinjiang Medical University from January 2020 to December 2023. The children were followed up for 1 year, and a multivariate logistic regression analysis was used to investigate the risk factors for cITP. RESULTS: The inverse variance weighted analysis revealed that Hp infection was significantly associated with an increased risk of ITP (OR=1.280, 95%CI: 1.098-1.492, P=0.002). There was no heterogeneity or pleiotropy in this MR study (P>0.05), and the model was stable. The "leave-one-out" sensitivity analysis verified the reliability of the results. The multivariate logistic regression analysis demonstrated that Hp infection was an independent risk factor for progression to cITP (OR=7.916, 95%CI: 3.327-18.832, P<0.001). CONCLUSIONS Hp infection is a risk factor for the onset of ITP and is an independent risk factor for cITP in children.
Humans ; Helicobacter Infections/complications* ; Purpura, Thrombocytopenic, Idiopathic/etiology* ; Child ; Male ; Female ; Helicobacter pylori ; Prognosis ; Child, Preschool ; Logistic Models ; Retrospective Studies ; Risk Factors ; Polymorphism, Single Nucleotide ; Adolescent ; Infant

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* ; Helicobacter Infections/metabolism* ; Epithelial Cells/metabolism* ; Gastric Mucosa/metabolism* ; Chemokines/metabolism* ; Cell Line ; Gene Knockout Techniques ; Myelin Proteins

BACKGROUND: Owing to the high prevalence of antibiotic resistance in Helicobacter pylori ( H. pylori ) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs . esomeprazole for H. pylori eradication in a patient population in China. METHODS: This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori , evaluated using a 13 C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%. RESULTS: The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P  = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P  = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles. CONCLUSION: Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China. TRIAL REGISTRATION ClinicalTrials.gov , NCT04198363.
Humans ; Esomeprazole/therapeutic use* ; Double-Blind Method ; Helicobacter Infections/drug therapy* ; Male ; Female ; Middle Aged ; Helicobacter pylori/pathogenicity* ; Pyrroles/therapeutic use* ; Sulfonamides/therapeutic use* ; Adult ; Clarithromycin/therapeutic use* ; Amoxicillin/therapeutic use* ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Pyrrolidines/therapeutic use* ; Drug Therapy, Combination ; Proton Pump Inhibitors/therapeutic use*

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Gastric cancer (GC) is a globally prevalent malignancy with a particularly heavy burden in China. Helicobacter pylori ( H. pylori ) is a Group I carcinogen for GC, with a higher seroprevalence rate indicating a higher GC incidence. However, only approximately 3% of the individuals with H. pylori infection eventually develop GC, and about 2.6% still progress to GC even 10-20 years after the eradication of H. pylori . Thus, the pathogenic mechanism of H. pylori for GC must be elucidated, and high-risk individuals precisely identified. Furthermore, GC can occur even in individuals who have never been infected with H. pylori . As H. pylori infection rates decline, the proportion of H. pylori -negative GC cases is increasing annually, gaining significant research attention. In this review, potential pathogenic mechanisms of H. pylori infection are explored from the aspects of H. pylori virulence factors and host factors (genetic susceptibility and immune microenvironment). Possible risk factors for H. pylori -negative GC include infections by other microorganisms (e.g., bacteria, fungi, and viruses), autoimmune gastritis, bile reflux, genetic mutations, and environmental factors. We aim to review the potential mechanisms for GC with varying H. pylori infection statuses, identify the high-risk individuals, and pose questions that need to be addressed. In the future, as the prevalence of H. pylori infection gradually decreases, GC prevention and management must evolve to address host-specific factors and the growing challenge of H. pylori -negative GC by integrating multidisciplinary perspectives.
Stomach Neoplasms/genetics* ; Humans ; Helicobacter Infections/complications* ; Helicobacter pylori/pathogenicity* ; Risk Factors

A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) method was established for simultaneous determination of seven characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rat plasma, including galangin, kaempferol, kaempferide, pinocembrin, 1,7-diphenyl-4-en-3-heptanone, 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA), and 7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-4-en-3-heptanone(DPHB). The new developed HPLC-MS/MS method was applied to study the pharmacokinetics of the 7 characteristic components in rats with Helicobacter pylori gastritis. A Waters Sunfire C_(18) column(2.1 mm×150 mm, 3.5 μm) was used. The acetonitrile-aqueous solution(containing 0.1% formic acid) was adopted as the mobile phase for gradient elution. Seven components and internal standard(chlorogenic acid) were separated within 12 min. Mass spectrometric detection was performed in multiple reaction monitoring(MRM) mode using electrospray ionization(ESI) source with fast switching between positive and negative ions. The method was verified by specificity, linearity, precision, accuracy, recovery, matrix effect, and stability and met the requirements of pharmacokinetic study on the 7 components in rat plasma. Pharmacokinetic results showed that the average peak time(T_(max)) of the 7 components was 0.31-2.19 h, their elimination half-life(t_(1/2)) was 5.26-16.65 h, and the average residence time(MRT) was 6.29-31.03 h after the oral administration of the active fraction of Alpiniae Officinarum Rhizoma to rats with H. pylori gastritis. The plasma exposure levels of galangin and DHPA were higher than those of the other components. The concentration-time curves of four detected flavonoids showed obvious double peaks. This study elucidated the pharmacokinetic characteristics of 7 characteristic components from the active fraction of Alpiniae Officinarum Rhizoma in rats with H. pylori gastritis, providing a scientific basis for the identification of the pharmacodynamic substances of Alpiniae Officinarum Rhizoma for treatment of H. pylori gastritis and the clinical application of Alpiniae Officinarum Rhizoma in the prevention and treatment of H. pylori gastritis.
Animals ; Rats ; Chromatography, High Pressure Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Helicobacter pylori/drug effects* ; Alpinia/chemistry* ; Rats, Sprague-Dawley ; Gastritis/metabolism* ; Helicobacter Infections/metabolism* ; Flavonoids/blood* ; Rhizome/chemistry* ; Liquid Chromatography-Mass Spectrometry

Salvia miltiorrhiza (Danshen) is a traditional Chinese herb that is commonly known for its cardiovascular and hepatoprotective benefits. Recent studies have confirmed that Danshen and its bioactive components can influence gut microbial homeostasis, thereby affecting Helicobacter pylori (HP) colonization in the human stomach. HP is a bacterial pathogen associated with various gastrointestinal diseases. Current HP treatments mainly involve antibiotics and proton pump inhibitors. However, their efficacy is strongly compromised by the rapid emergence of antibiotic resistance in HP and genetic heterogeneity among patients. The interaction between Danshen and gut microbial status provides a novel perspective for HP treatment. Understanding the medical properties of Danshen in altering gut microbiota and eliminating HP, as well as the underlying mechanisms, is important for improving human gastrointestinal healthcare. This review investigates the interaction between Danshen and gut microbiota and its impact on HP infection using databases including Web of Science, PubMed, and Google Scholar. We explored the unconventional intersection between Danshen, gut microbiota, and HP infection, shedding light on their intricate interplay and potential therapeutic implications. A comprehensive understanding of this interaction provides valuable insights into developing novel therapeutic strategies that target the gut microbiota to mitigate HP-associated gastrointestinal disorders. Please cite this article as: Li SJ, Miao JX, Wang F, Wang HY, Ma YW, Jiang Y, Xue X. Salvia miltiorrhiza components and gut microbiota interactions in Helicobacter pylori infection. J Integr Med. 2025; 23(5):462-470.
Salvia miltiorrhiza/chemistry* ; Gastrointestinal Microbiome/drug effects* ; Humans ; Helicobacter Infections/microbiology* ; Helicobacter pylori/drug effects* ; Drugs, Chinese Herbal/therapeutic use*

Helicobacter pylori is a bacterium that can cause chronic gastritis, peptic ulcers, and other gastrointestinal diseases. The World Health Organization has classified H. pylori as a group Ⅰ carcinogen. Antibiotics are the primary clinical approach for eradicating H. pylori. However, incomplete eradication of H. pylori by antibiotics can lead to persistent infection, which is a major risk factor for the high incidence of gastric cancer. The widespread use of antibiotics has led to the emergence of multidrug resistance in H. pylori, contributing to treatment failures of chronic gastric diseases and increasing the risk of spreading resistant strains. Multidrug-resistant H. pylori has become a serious challenge in the diagnosis and treatment of gastrointestinal diseases. This paper reviews the global trends in the development of multidrug resistance in H. pylori, the underlying mechanisms, the challenges it poses to clinical diagnosis, and its impact on drug development, drawing on relevant literature and the research findings from our group. It proposes using cgt expression as a novel method for determining viable bacteria, identifying intracellularization as a new form of resistance in H. pylori, and exploring the potential of O-glycans as a therapeutic approach against H. pylori to address multidrug resistance. It provides new insights into understanding the mechanisms of H. pylori multidrug resistance and its prevention strategies, offering promising directions for future clinical treatments and antimicrobial drug development.
Helicobacter pylori/genetics* ; Humans ; Drug Resistance, Multiple, Bacterial ; Helicobacter Infections/microbiology* ; Anti-Bacterial Agents/therapeutic use* ; Gastrointestinal Diseases/drug therapy*

Helicobacter pylori ( H. pylori ) infects approximately half of the population worldwide and causes chronic gastritis, peptic ulcers, and gastric cancer. Test-and-treat strategies have been recommended for the prevention of H. pylori -associated diseases. Advancements in high-throughput sequencing technologies have broadened our understanding of the complex gastrointestinal (GI) microbiota and its role in maintaining host homeostasis. Recently, an increasing number of studies have indicated that the colonization of H. pylori induces dramatic alterations in the gastric microbiota, with a predominance of H. pylori and a reduction in microbial diversity. Dysbiosis of the gut microbiome has also been observed after H. pylori infection, which may play a role in the development of colorectal cancer. However, there is concern regarding the impact of antibiotics on the gut microbiota during H. pylori eradication. In this review, we summarize the current literature concerning how H. pylori infection reshapes the GI microbiota and the underlying mechanisms, including changes in the gastric environment, immune responses, and persistent inflammation. Additionally, the impacts of H. pylori eradication on GI microbial homeostasis and the use of probiotics as adjuvant therapy are also discussed. The shifts in the GI microbiota and their crosstalk with H. pylori  may provide potential targets for H. pylori -related gastric diseases and extragastric manifestations.
Helicobacter Infections/microbiology* ; Humans ; Helicobacter pylori/pathogenicity* ; Gastrointestinal Microbiome/drug effects* ; Probiotics/therapeutic use* ; Anti-Bacterial Agents/therapeutic use*