Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates.

BACKGROUND: Resistance to clarithromycin (CLA) and levofloxacin (LFX) of Helicobacter pylori (H. pylori) is increasing in severity, and successful eradication is essential. Presently, the eradication success rate has greatly declined, leaving a large number of patients with previous treatment histories. AIM: To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy. METHODS: We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023. Participants underwent a string test after an overnight fast. The gastric juice was obtained and transferred to vials containing storage solution. Subsequently, DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction (qPCR). Demographic information was also analyzed as part of the study. Based on these results, the participants were administered susceptibility-guided treatment. Efficacy was compared with that of the empiric treatment group. RESULTS: A total of 132 individuals tested positive for the H. pylori ureA gene by qPCR technique. CLA resistance rate reached a high level of 82.6% (n = 109), LFX resistance rate was 69.7% (n = 92) and dual resistance was 62.1% (n = 82). Gastric symptoms [odds ratio (OR) = 2.782; 95% confidence interval (95%CI): 1.076-7.194; P = 0.035] and rural residence (OR = 5.152; 95%CI: 1.407-18.861; P = 0.013) were independent risk factors for secondary resistance to CLA and LFX, respectively. A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment, respectively. The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5% (77/102) and 59.0% (59/411) by the intention-to-treat (ITT) analysis and 90.6% (77/85) and 70.2% (59/84) by the per-protocol (PP) analysis, respectively. The eradication rates of these two treatment strategies were significantly different in both ITT (P = 0.001) and PP (P = 0.012) analyses. CONCLUSION: H. pylori presented high secondary resistance rates to CLA and LFX. For patients with previous treatment failures, treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Antibiotic resistance characteristics and risk factors analysis of Helicobacter pylori strains isolated from patients in Liaoning Province, an area in North China.

Background: The prevalence of Helicobacter pylori (H. pylori) keeps rising while the eradication rate continues to decline due to the increasing antibiotic resistance. Regional variations of antimicrobial resistance to H. pylori have been recommended by guidelines in recent years. This study aims to investigate the antibiotic resistance rate of H. pylori and its association with infected subjects' characteristics in Liaoning Province, an area in north China. Methods: Gastric tissues from 178 H. pylori positive participants without previous antibiotic use within four weeks were collected for H. pylori culture. Antibiotic susceptibility to furazolidone (AOZ), tetracycline (TC), levofloxacin (LFX), metronidazole (MET), clarithromycin (CLA), and amoxicillin (AMX) were examined with the agar dilution method. Associations between H. pylori resistance and patient characteristics were further analysed. Results: No resistance was observed in AOZ or TC. For LFX, MET, CLA, and AMX, the overall resistance rates were 41.10%, 79.14%, 71.78%, and 22.09% respectively. There were significant differences between resistance to CLA and MALToma (P = 0.021), and between resistance to MET and age (P < 0.001). Conclusions: The primary resistant rates of LEX, MET, CLA, and AMX were relatively high in Liaoning. Treatment effectiveness improvement could be achieved by prior antimicrobial susceptibility tests before antibiotic prescription.

Comprehensive analysis of expression signature and immune microenvironment signature of biomarker Endothelin Receptor Type A in stomach adenocarcinoma.

Background: EDNRA (Endothelin Receptor Type A) is closely associated with tumor progression in many tumor types. However, the functional mechanism of EDNRA in stomach adenocarcinoma (STAD) remains to be elucidated. Methods: ENDRA expression levels in STAD were assessed. A Receiver Operating Characteristic (ROC) curve was constructed to measure the diagnostic value of EDNRA. The correlation between ENDRA expression levels and patient clinical-pathological characteristics was analyzed. The survival and prognostic significance were validated using Kaplan-Meier and Cox regression and confirmed by the immunohistochemistry cohorts. Differentially expressed genes of EDNRA in STAD were determined, and EDNRA related functional enrichment and biological pathways involved in STAD were obtained by Gene-Set Enrichment Analysis (GSEA). The correlation between EDNRA expression in STAD and immune cell infiltration was assessed using the CIBERSORT and Spearman correlation analysis, and the correlation between EDNRA and TMB, MSI, IC50, and immune checkpoints was examined. Results: EDNRA expression was significantly higher in STAD than in normal tissues (P < 0.001) and associated with worse overall survival (OS). EDNRA expression was significantly associated with T stage, histological type, histologic grade, and TP53 status. Cox regression analysis revealed that primary therapy outcome, age, tumor status, and EDNRA were independent prognostic factors for OS. Multivariate analysis revealed that EDNRA expression, tumor status, age, and primary therapy outcome influenced patient prognosis. GSEA was significantly enriched in several pathways and biological processes, which include Immunoregulatory, Hedgehog, WNT, PI3K-AKT.NK cells, Tem, macrophages, and mast cells were substantially positively correlated with EDNRA expression in the STAD microenvironment. Notably, high EDNRA expression may promote M2 macrophages to block PD-1-mediated immunotherapy and induce immunosuppression. In addition, patients with high expression of EDNRA might be resistant to the treatment of several anti-tumor drugs. Conclusion: Our results suggest that EDNRA was closely related to clinicopathologic characteristics, poor prognosis, and promoted macrophage differentiation and synergistic role in immunosuppression.

Establishment and Validation of a Genetic Label Associated With M2 Macrophage Infiltration to Predict Survival in Patients With Colon Cancer and to Assist in Immunotherapy.

BACKGROUND: Colon cancer is a malignant tumor with high morbidity and mortality. Researchers have tried to interpret it from different perspectives and divided it into different subtypes to facilitate individualized treatment. With the rise in the use of immunotherapy, its value in the field of tumor has begun to emerge. From the perspective of immune infiltration, this study classified colon cancer according to the infiltration of M2 macrophages in patients with colon cancer and further explored the same. METHODS: Cibersort algorithm was used to analyze the level of immune cell infiltration in patients with colon cancer in The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA), Consensus Clustering analysis, Lasso analysis, and univariate Kaplan-Meier analysis were used to screen and verify the hub genes associated with M2 macrophages. Principal component analysis (PCA) was used to establish the M2 macrophage-related score (M2I Score). The correlation between M2I Score and somatic cell variation and microsatellite instability (MSI) were analyzed. Furthermore, the correlation between M2 macrophage score and differences in immunotherapy sensitivity was also explored. RESULTS: M2 macrophage infiltration was associated with poor prognosis. Four hub genes (ANKS4B, CTSD, TIMP1, and ZNF703) were identified as the progression-related genes associated with M2 macrophages. A stable and accurate M2I Score for M2 macrophages used in colon adenocarcinoma was determined based on four hub genes. The M2I Score was positively correlated with the tumor mutation load (TMB). The M2I Score of the group with high instability of microsatellites was higher than that of the group with low instability of microsatellites and microsatellite-stable group. Combined with the Cancer Immunome Atlas database, we concluded that patients with high M2I Scores were more sensitive to programmed cell death protein 1 (PD-1) inhibitors and PD-1 inhibitors combined with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors. The low-rating group may have better efficacy without immune checkpoint inhibitors or with CTLA4 inhibitors alone. CONCLUSION: Four prognostic hub genes associated with M2 macrophages were screened to establish the M2I Score. Patients were divided into two subgroups: high M2I Score group and low M2I Score group. TMB, MSI, and sensitivity to immunotherapy were higher in the high-rated group. PD-1 inhibitors or PD-1 combined with CTLA-4 inhibitors are preferred for patients in the high-rated group who are more sensitive to immunotherapy.

A novel prognostic model based on epithelial-mesenchymal transition-related genes predicts patient survival in gastric cancer.

BACKGROUND: Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. METHODS: Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. RESULTS: Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. CONCLUSIONS: We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis.

Differential Proteomic Analysis Reveals Protein Networks and Pathways that May Contribute to Helicobacter pylori FKBP-Type PPIase-Associated Gastric Diseases.

PURPOSE: Though Helicobacter pylori (H. pylori) has been classified as class I carcinogen, key virulence factor generated by H. pylori that causes gastric cancer remains to be fully determined. Recently, we identified a gastric cancer-associated H. pylori gene, peptidylprolyl isomerase-FK506 binding protein (PPIase-FKBP), and showed that PPIase-FKBP was capable of inducing oncogenic transformation of gastric epithelial cells. But its mechanism was unclear. EXPERIMENTAL DESIGN: We carried out a comparative proteomic analysis of human gastric epithelial cells that either express PPIase-FKBP or green fluorescent protein using 2-DE and then MALDI-TOF-MS/MS. RESULTS: Our results identified 28 differentially expressed proteins induced by PPIase-FKBP. These proteins participate in some cellular biological processes, such as cell proliferation, cell apoptosis and DNA replication, mRNA splicing, and protein biosynthesis. Ingenuity Pathway Analysis categorized the 28 proteins into two molecular interaction networks, involved primarily in cancer and gastrointestinal diseases. CONCLUSIONS AND CLINICAL RELEVANCE: Our results provided insight on the protein interaction networks and signaling pathways that may contribute to PPIase-FKBP-associated gastric diseases and may lead to a better understanding of the mechanisms indicating the oncogenic effects of H. pylori PPIase-FKBP.

HpSlyD inducing CDX2 and VIL1 expression mediated through TCTP protein may contribute to intestinal metaplasia in the stomach.

Helicobacter pylori infection is the most important risk factor for gastric intestinal metaplasia (IM). Our previous study demonstrated that infection with H. pylori HpslyD-positive strains associated with IM. To further investigate the signalling pathway involved in HpSlyD-induced IM, CDX2 and VIL1 expressions were determined before and after HpSlyD application. TCTP was knocked down by siRNA or overexpressed by plasmid transfection. An HpSlyD binding protein was used to block HpSlyD's enzymatic activity. The expression of CDX2 and TCTP in gastric diseases was measured by immunohistochemistry. Our results showed HpSlyD induced CDX2 and VIL1 expressions. TCTP protein expression was markedly increased after application of HpSlyD and in an HpSlyD-expressing stable cell line. Downregulation of TCTP protein led to decreased HpSlyD-induced CDX2 and VIL1. Overexpression of TCTP protein improved the expression of CDX2 and VIL1. Co-application of HpSlyD and FK506 led to significant reductions in CDX2, VIL1, and TCTP expression. Immunohistochemistry demonstrated that CDX2 and TCTP expression was higher in HpslyD-positive specimens compared with HpslyD-negative ones. Expression of CDX2 was positively correlated with TCTP in HpslyD-positive cells. Our study is the first to show that HpSlyD induction of CDX2 and VIL1 expression mediated through TCTP may contribute to IM in the stomach.

Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer.

Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival.

An inverse association of Helicobacter pylori infection with oral squamous cell carcinoma.

BACKGROUND: Few studies have focused on the relationship between Helicobacter pylori (H. pylori) infection and oral diseases. In this study, we explored the correlation between H. pylori infection and oral squamous cell carcinoma (OSCC). METHODS: A total of 68 patients with OSCC and 104 age- and sex- matched healthy control subjects were retrospectively enrolled in this study. The H. pylori immunoglobin (Ig) G antibodies in serum were detected by enzyme-linked immunosorbent assay (ELISA) method to assess the status of H. pylori infection of our study sample. Polymerase chain reaction (PCR) was also employed using H. pylori genus-specific 16S rRNA primers in fasting blood, and OSCC specimens were analyzed by histochemical stain of each enrolled subject. The strength of correlation between H. pylori and the development of OSCC was estimated by Spearman's correlation coefficient. RESULTS: According to the three methods for detecting prevalence of H. pylori infection in the patients with OSCC, it was statistically lower than that in the healthy controls (35.3% vs. 54.8%, P = 0.012). An inverse correlation was observed between H. pylori infection and OSCC development (Spearman's correlation coefficient = -0.191, P = 0.012). In stratification analysis, we also found a statistical association between H. pylori infection and OSCC in the subpopulation with age ≥ 60 years (P = 0.037). CONCLUSION: Our findings suggested that H. pylori infection may be negatively related to OSCC. A reverse association of H. pylori infection with OSCC risk in the subpopulation with age ≥ 60 years was also found.

Helicobacter pylori FKBP-type PPIase promotes gastric epithelial cell proliferation and anchorage-independent growth through activation of ERK-mediated mitogenic signaling pathway.

Though Helicobacter pylori (H. pylori) has been classified as class I carcinogen, key virulence factor(s) generated by H. pylori that causes gastric cancer remains to be fully determined. Here, we show that deletion of peptidyl-prolyl cis-trans isomerase (PPIase) prevented H. pylori from stimulating human gastric epithelial cell (AGS) proliferation. Consistent with this observation, ectopic expression of H. pylori PPIase promoted AGS cell proliferation and anchorage-independent growth. To gain insight into the biochemical mechanism of PPIase-induced effect, early signal events involved in mitogenic signaling pathways were evaluated. Expression of H. pylori PPIase caused an increase in basal as well as EGF-stimulated phosphorylation of ERK and EGF receptor at Tyr1086. Treatment with MEK inhibitor completely blocked PPIase-induced cell proliferation. Our results suggest that H. pylori PPIase has the potential to activate mitogenic signaling pathway and to promote transformation of gastric epithelial cells. H. pylori PPIase may represent a novel target for therapeutic management of gastric cancer patients.

Host genetic factors respond to pathogenic step-specific virulence factors of Helicobacter pylori in gastric carcinogenesis.

The interindividual differences in risk of Helicobacter pylori (H. pylori)-associated gastric cancer involve significant heterogeneities of both host genetics and H. pylori strains. Several recent studies proposed a distinct sequence for H. pylori exerting its virulence in the host stomach: (i) adhering to and colonizing the surface of gastric epithelial cells, (ii) evading and attenuating the host defense, and (iii) invading and damaging the gastric mucosa. This review focuses on several key issues that still need to be clarified, such as which virulence factors of H. pylori are involved in the three pathogenic steps, which host genes respond to the step-specific virulence factors, and whether and/or how the corresponding host genetic variations influence the risk of gastric carcinogenesis. Urease, BabA and SabA in the adhesion-step, PGN and LPS in the immune evasion-step, and CagA, VacA and Tipα in the mucosal damage-step were documented to play an important role in step-specific pathogenicity of H. pylori infection. There is evidence further supporting a role of potentially functional polymorphisms of host genes directly responding to these pathogenic step-specific virulence factors in the susceptibility of gastric carcinogenesis, especially for urease-interacting HLA class II genes, BabA-interacting MUC1, PGN-interacting NOD1, LPS-interacting TLR4, and CagA-interacting PTPN11 and CDH1. With the continuous improvement of understanding the genetic profile of H. pylori-associated gastric carcinogenesis, a person at increased risk for gastric cancer may benefit from several aspects of efforts: (i) prevent H. pylori infection with a vaccine targeting certain step-specific virulence factor; (ii) eradicate H. pylori infection by blocking step-specific psychopathological characteristics of virulence factors; and (iii) adjust host physiological function to resist the carcinogenic role of step-specific virulence factors or interrupt the cellular signal transduction of the interplay between H. pylori and host in each pathogenic step, especially for the subjects with precancerous lesions in the stomach.

Association of presence/absence and on/off patterns of Helicobacter pylori oipA gene with peptic ulcer disease and gastric cancer risks: a meta-analysis.

BACKGROUND: There are increasing studies examining the relationship between the status of H. pylori oipA gene and peptic ulcer disease (PUD) and gastric cancer (GC) but the results turn out to be controversial. We attempted to clarify whether oipA gene status is linked with PUD and/or GC risks. METHODS: A systematically literature search was performed through four electronic databases. According to the specific inclusion and exclusion criteria, seven articles were ultimately available for the meta-analysis of oipA presence/absence with PUD and GC, and eleven articles were included for the meta-analysis of oipA on/off status with PUD and GC. RESULTS: For the on/off functional status analysis of oipA gene, the "on" status showed significant associations with increased risks of PUD (OR = 3.97, 95% CI: 2.89, 5.45; P < 0.001) and GC (OR = 2.43, 95% CI: 1.45, 4.07; P = 0.001) compared with gastritis and functional dyspepsia controls. Results of the homogeneity test indicated different effects of oipA "on" status on PUD risk between children and adult subgroups and on GC risk between PCR-sequencing and immunoblot subgroups. For the presence/absence analysis of oipA gene, we found null association of the presence of oipA gene with the risks of PUD (OR = 1.93, 95% CI: 0.60, 6.25; P = 0.278) and GC (OR = 2.09, 95% CI: 0.51, 8.66; P = 0.308) compared with gastritis and functional dyspepsia controls. CONCLUSIONS: To be concluded, when oipA exists, the functional "on" status of this gene showed association with increased risks for PUD and GC compared with gastritis and FD controls. However, merely investigating the presence/absence of oipA would overlook the importance of its functional on/off status and would not be reliable to predict risks of PUD and GC. Further large-scale and well-designed studies concerning on/off status of oipA are required to confirm our meta-analysis results.

[DNA repair gene polymorphisms in ERCC4 rs6498486 and ERCC5 rs751402 and risk of salivary gland tumors].

PURPOSE: To investigate the association between ERCC4 and ERCC5 polymorphisms and risk of salivary gland tumors. METHODS: Case-control study was carried out in 133 cases of histologically confirmed salivary gland tumors and 142 age and gender matched healthy control cases. Polymorphisms of ERCC4 rs6498486 and ERCC5 rs751402 were detected by PCR-RFLP. Multiple factors logistic regression analysis was conducted to investigate the association between gene polymorphisms and risk of salivary gland tumors using SPSS 18.0 software package. RESULTS: The genotype distribution of each polymorphism was found to be of Hardy-Weinberg equilibrium in the study. ERCC5 rs751402 TT genotype was associated with risk of salivary gland tumors (TT vs. CC+CT: OR=0.45, 95% CI: 0.21-0.98, P=0.046). No significant association was found in ERCC4 rs6498486. CONCLUSIONS: The results suggest that ERCC5 rs751402 polymorphism may be associated with risk of salivary gland tumors.

Promoter polymorphisms in trefoil factor 2 and trefoil factor 3 genes and susceptibility to gastric cancer and atrophic gastritis among Chinese population.

The polymorphisms in trefoil factor (TFF) gene family that protect gastrointestinal epithelium might influence individual vulnerability to gastric cancer (GC) and atrophic gastritis. We used the Sequenom MassARRAY platform to identify the genotypes of TFF2 rs3814896 and TFF3 rs9981660 polymorphisms in 478 GC patients, 652 atrophic gastritis patients, and 724 controls. For the TFF2 rs3814896 polymorphism, in the subgroup aged ≤ 50 years, we found that AG+GG genotypes were associated with a 0.746-fold decreased risk of atrophic gastritis [p=0.023, 95% confidence interval (CI)=0.580-0.960], a 0.626-fold decreased risk of GC (p=0.005, 95% CI=0.451-0.868), and a 0.663-fold decreased risk of diffuse-type GC (p=0.034, 95% CI=0.452-0.970) compared with the common AA genotype. For the TFF3 rs9981660 polymorphism, in the male subgroup, individuals with variant AG+AA genotype were associated with a 0.761-fold decreased risk of diffuse-type GC compared with the common GG genotype (p=0.043, 95% CI=0.584-0.992). Additionally, we found that in subjects aged ≤ 50 years compared with common AA genotype, TFF2 rs3814896 AG+GG genotypes were associated with increased TFF2 mRNA levels in the total gastric cancer specimens and in the diffuse-type gastric cancer specimens; and in males aged ≤ 50 years compared with common GG genotype, TFF3 rs9981660 AA+AG genotypes were associated with TFF3 mRNA levels in diffuse-type gastric cancer tissues and their corresponding non-cancerous tissues. To our knowledge, this is the first report of an association between the TFF2 rs3814896 AG+GG genotypes and decreased risks of GC, diffuse-type GC, and atrophic gastritis in younger people aged ≤ 50 years, and an association between TFF3 rs9981660 AG+AA genotype and decreased risk of diffuse-type GC in men. Moreover, we found that TFF2 rs3814896 AG+GG genotypes in people aged ≤ 50 years and TFF3 rs9981660 AG+AA genotypes in younger males with diffuse-type GC were associated with higher levels of TFF2 and TFF3 mRNA respectively.

Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric cancer.

AIM: To investigate the association between babA2 gene and peptic ulcer disease (PUD) and gastric cancer (GC) in Helicobacter pylori-infected populations. METHODS: We evaluated the relationship between babA2 and clinical outcomes (PUD and GC) using a meta-analysis. A literature search was performed using the PubMed and Web of Science databases for relevant case-control studies that met the defined inclusion criteria. The ORs and 95%CIs were calculated to estimate the association between babA2 genotype and clinical outcomes. A fixed-effect or random-effect model was performed depending on the absence or presence of significant heterogeneity. RESULTS: A total of 25 articles with 38 studies met the inclusion criteria and were finally included in this meta-analysis. The results showed that the babA2 genotype was significantly associated with an increased risk of PUD (OR = 2.069, 95%CI: 1.530-2.794, P < 0.001) and especially in the subgroup of duodenal ulcer (OR = 1.588, 95%CI: 1.141-2.209, P = 0.006). Moreover, a significant association between babA2 gene and PUD and duodenal ulcer (OR = 2.739, 95%CI: 1.860-4.032, P < 0.001; OR = 2.239, 95%CI: 1.468-3.415, P < 0.001, respectively) was observed in western countries but not in Asian countries. CONCLUSION: We demonstrated that the presence of babA2 may be associated with increased risks for PUD, especially duodenal ulcer, in western countries.

Subtractive hybridization analysis of gastric diseases-associated Helicobacter pylori identifies peptidyl-prolyl isomerase as a potential marker for gastric cancer.

Helicobacter pylori, a microaerophilic Gram-negative bacterium, is known to cause chronic gastritis, peptic ulcer and gastric cancer. Genes that are present in certain isolates may determine strain-specific traits such as disease association and drug resistance. In order to understand the pathogenic mechanisms of gastric diseases, identify molecular markers of the diseases associated with H. pylori strains and provide clues for target treatment of H. pylori-related diseases, a subtracted DNA library was constructed from a gastric cancer-associated H. pylori strain and a superficial gastritis-associated H. pylori strain by suppression subtractive hybridization. The presence of gastric cancer-specific genes was identified by dot blot hybridization, DNA sequencing and PCR-based screening. Twelve gastric cancer-specific high-copy genes and nine low-copy genes were found in gastric cancer compared with the superficial gastritis strain. These genes were confirmed by PCR analysis of H. pylori isolates. Notably, peptidyl-prolyl cis-trans isomerase (PPIase) was detected positively in 11 out of 22 (50%) gastric cancer-associated H. pylori strains. In contrast, <24% of the H. pylori strains from superficial gastritis showed positive results. Given the potential role of PPIases in cell growth, apoptosis and oncogenic transformation, our results suggest that PPIase may represent a novel marker and potential therapeutic target for gastric cancer.

[Relationship between the immunohistopathological changes of hepatitis B virus carrier mothers' placentas and fetal hepatitis B virus infection].

OBJECTIVE: To investigate the role of placenta in intrauterine transmission of hepatitis B virus (HBV), and the relationship between the fetal HBV infection and the placental infection. METHODS: Cord blood or peripheral blood was obtained from 61 newborn infants of HBsAg positive mothers. Neonates (28 of 61) infected by HBV were assigned to fetal infected group, and 33 infants without infection were assigned to control group. Histopathological changes of placentas from 61 HBsAg positive mothers were observed by pathological examination and classification. RESULTS: (1) The positive rate of HBsAg/HBcAg detected in the placentas of fetal infected group was 82% (23/28), which was significant higher than that of control group (55%), P < 0.05. (2) Among various types of cells in placental tissue, the amnionic cell showed higher HBsAg/HBcAg positive rate in fetal infection group, which was 36% (10/28), than that of control group (6%) (P < 0.01). (3) The syncitial cell was the cell with the higher detecting HBsAg/HBcAg positive rate (49%) comparing with other types of cells in placental barrier (P < 0.05). (4) The incidence of fibrinoid necrosis and chorionic hyperemia in fetal infection group were 29% and 50%, respectively, which were higher than those in control group (9%, 15%). The detecting rate of Hofbauer cell in fetal infection group was 46%, significantly lower than that in control group (79%) (P < 0.05). CONCLUSIONS: HBV infection of fetus is associated with placental infection. HBV infection of amnionic cell is an important factor of intrauterine infection. Placental barrier can protect the fetuses from infection to some extent. Some histopathological changes of placental tissue, for example fibrinoid necrosis, chorionic hyperemia and decreasing number of Hofbauer cells, may play a role in fetal HBV infection.