H. pylori exhibits antibiotic resistance with regional differences. In this paper, we explored antibiotic resistance of H. pylori to five antibiotics in an area with a high risk of gastric cancer. H. pylori resistance rates to metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline were 78.0, 56.0, 31.0, 9.0, and 15.0%, respectively. Double, triple, quadruple, and quintuple resistance rates were 23, 20, 6, and 4%, respectively. The clarithromycin and multidrug resistance rates were significantly higher in males than females (clarithromycin: 44.4% vs 15.2%, respectively, P = 0.002; multidrug: 75.5% vs 37.2%, respectively; P < 0.001). During the three periods of 1998–1999, 2002–2004 and 2016–2017, the resistance rates to levofloxacin and amoxicillin were increasing (OR: 2.089, 95%CI: 1.142–3.821, P = 0.017; and OR: 5.035, 95%CI: 1.327–19.105, P = 0.018, respectively). The antibiotic resistance rates were unassociated with the host disease state. Metronidazole resistance was lower in the vacAs1m1/m2 group than the vacAs1m1m2 group (65% vs 85.7%, respectively; P = 0.026). As for levofloxacin resistance, it was higher with cagA + than cagA− (60.9% vs 23.1%, respectively; P = 0.020) but lower with slyD+ than slyD− (41.4% vs 68.5%, respectively; P = 0.009). Clarithromycin had a lower resistance rate with iceA++ than iceA−+ (19.7% vs 52.4%, respectively; P = 0.017). For amoxicillin, the iceA++ group had a lower resistance rate than the iceA−− group (1.6% vs 27.8%, respectively; P = 0.009). The total resistance rates of H. pylori to metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline were high in Zhuanghe. The resistanc rates to levofloxacin and amoxicillin increased over time. Clarithromycin resistance was associated with male and iceA. The resistance of metronidazole was related to vacA. Levofloxacin resistance was concerned with cagA and slyD and amoxicillin resistance was concerned with iceA. While, the antibiotic resistance of H. pylori had nothing to do with the status of gastric disease.

Increasingly, studies have focused on the relationship between Helicobacter pylori (H pylori) cytotoxin associated gene A protein (CagA) Glu-Pro-Ile-Tyr-Ala (EPIYA)-D motifs or multiple EPIYA-C phosphorylation sites and peptic ulcer disease (PUD) or gastric cancer (GC) risk. However, the conclusions have been inconsistent. The aim of this meta-analysis was to evaluate whether 1 CagA EPIYA-D motif or multiple EPIYA-C phosphorylation sites were associated with PUD or GC risk. A literature search was performed in PubMed, Web of Science, Wanfang Data, Excerpt Medica Database, and the Chinese National Knowledge Infrastructure database to identify eligible research. We analyzed the odds ratios (OR) and 95% confidence intervals (CI) to assess the strength of association. Compared with 1 EPIYA-C motif in Asian populations, 1 EPIYA-D site was associated with an increased GC risk (OR=1.91, 95% CI=1.19–3.07, P = .008). However, 1 EPIYA-D motif was not significantly associated with PUD (OR = 0.90, 95% CI = 0.46–1.76, P = .764), gastric ulcer (GU) (OR = 0.85, 95% CI = 0.27–2.63, P = .771), or duodenal ulcer (DU) (OR = 0.89, 95% CI = 0.25–3.16, P = .859) risk. Compared with no more than 1 EPIYA-C motif, multiple motifs were associated with increased PUD (OR = 2.33, 95% CI = 1.29–4.20, P = .005) and DU (OR = 2.32, 95% CI = 1.08–5.00, P = .031) risk in Asia and GC risk in the United States and Europe (OR = 3.28, 95% CI = 2.32–4.64, P < .001). Multiple EPIYA-C sites were not associated with GU risk (OR = 4.54, 95% CI = 0.95–21.83, P = .059). There was no publication bias identified in these comparisons. In Asia, 1 EPIYA-D motif was significantly associated with increased GC risk. Multiple EPIYA-C motifs were associated with increased PUD and DU risk, particularly in Asia. In the United States and Europe, multiple EPIYA-C motifs were associated with increased GC risk. Therefore, detection of polymorphic CagA EPIYA motifs may improve clinical prediction of disease risk.

Objective: This study mainly focused on revealing ceRNA network in gastric cancer (GC) with Hp infection after comparing with GC without Hp infection and exploring the biological function and prognostic relevance of related molecules.

Gastric cancer (GC) development trends have identified multiple processes ranging from inflammation to carcinogenesis, however, key pathogenic mechanisms remain unclear. Tissue microenvironment (TME) cells are critical for the progression of malignant tumors. Here, we generated a dynamic transcriptome map of various TME cells during multi-disease stages using single-cell sequencing analysis. We observed a set of key transition markers related to TME cell carcinogenic evolution, and delineated landmark dynamic carcinogenic trajectories of these cells. Of these, macrophages, fibroblasts, and endothelial cells exerted considerable effects toward epithelial cells, suggesting these cells may be key TME factors promoting GC occurrence and development. Our results suggest a phenotypic convergence of different TME cell types toward tumor formation processes in GC. We believe our data would pave the way for early GC detection, diagnosis, and treatment therapies.

To explore the mutation characteristics of H. pylori resistance‐related genes to antibiotics of clarithromycin (CAM), levofloxacin (LVX) and metronidazole, 23SrRNA, gyrA , gyrB , rdxA, and frxA genes were amplified and sequenced, respectively. Molecular docking study was performed to explore molecular interactions between chemotherapeutic agents and target proteins. In the CAM‐resistant strains, the mutation rate in site A2143G was 74.2% (n = 23). The interactions in sites of G1949A, C1953T, and G2211T with CAM were weaker after mutation. In the LVX‐resistant strains, the mutation rates in 87 (N to K/I) and 91 (D to N/Y/G) of gyrA were 28.6% (n = 16) and 12.5% (n = 7), respectively. We could infer by docking studies that N87 K/I, D91Y/G/N, D99N, and D143E mutations in GyrA protein all had weakened interaction with LVX. The mutation types of RdxA protein consisted of protein truncation caused by premature stop codons (n = 26, 33.3%), frameshift mutations (n = 8, 10.3%), FMN‐binding sites (n = 16, 20.5%), and the others (n = 11, 14.1%). Docking analysis showed that some mutations in those four types of RdxA protein could reduce interaction with MNZ, and play a significant role in antibiotic resistance. What's more, we performed natural transformation with some of these mutated DNA fragments to see if they really impact susceptibility to antibiotics. Our study suggested that in addition to the reported mutation sites, H. pylori antibiotic resistance in this region may also be associated with changes in some new sites. Our study provides novel ideas and methods for the identification of H. pylori resistance‐related mutations, and also clues and basis for further investigation on specific molecular mechanism.

Cellular senescence is widely acknowledged as having strong associations with cancer. However, the intricate relationships between cellular senescence-related (CSR) genes and cancer risk remain poorly explored, with insights on causality remaining elusive. In this study, Mendelian Randomization (MR) analyses were used to draw causal inferences from 866 CSR genes as exposures and summary statistics for 18 common cancers as outcomes. We focused on genetic variants affecting gene expression, DNA methylation, and protein expression quantitative trait loci (cis-eQTL, cis-mQTL, and cis-pQTL, respectively), which were strongly linked to CSR genes alterations. Variants were selected as instrumental variables (IVs) and analyzed for causality with cancer using both summary-data-based MR (SMR) and two-sample MR (TSMR) approaches. Bayesian colocalization was used to unravel potential regulatory mechanisms underpinning risk variants in cancer, and further validate the robustness of MR results. We identified five CSR genes (CNOT6, DNMT3B, MAP2K1, TBPL1, and SREBF1), 18 DNA methylation genes, and LAYN protein expression which were all causally associated with different cancer types. Beyond causality, a comprehensive analysis of gene function, pathways, and druggability values was also conducted. These findings provide a robust foundation for unravelling CSR genes molecular mechanisms and promoting clinical drug development for cancer.