Objective: To investigate the characteristics of duodenal bulbar microbiota in children with duodenal ulcer and Helicobacter pylori (Hp) infection. Methods: This prospective cohort study enrolled 23 children with duodenal ulcers diagnosed by gastroscopy who were admitted to the Children's Hospital of Zhejiang University School of Medicine due to abdominal pain, abdominal distension, and vomiting from January 2018 to August 2018. They were divided into Hp-positive and Hp-negative groups according to the presence or absence of Hp infection. Duodenal bulbar mucosa was sampled to detect the bacterial DNA by high-throughput sequencing. The statistical difference in α diversity and β diversity, and the relative abundance in taxonomic level between the two groups were compared. Microbial functions were predicted using the software PICRUSt. T-test, Rank sum test or χ² test were used for comparison between the two groups. Results: A total of 23 children diagnosed with duodenal ulcer were enrolled in this study, including 15 cases with Hp infection ((11.2±3.3) years of age, 11 males and 4 females) and 8 cases without Hp infection ((10.1±4.4) years of age, 6 males and 2 females). Compared with Hp-negative group, the Hp-positive group had higher Helicobacter abundance (0.551% (0.258%, 5.368%) vs. 0.143% (0.039%, 0.762%), Z=2.00, P=0.045) and lower abundance of Fusobacterium, Streptococcus and unclassified- Comamonadaceae (0.010% (0.001%, 0.031%) vs. 0.049% (0.011%, 0.310%), Z=-2.24, P=0.025; 0.031% (0.015%, 0.092%) vs. 0.118% (0.046%, 0.410%), Z=-2.10, P=0.036; 0.046% (0.036%, 0.062%) vs. 0.110% (0.045%, 0.176%), Z=-2.01, P=0.045). Linear discriminant analysis (LDA) effect sized showed that at the genus level, only Helicobacter was significantly enriched in Hp-positive group (LDA=4.89, P=0.045), while Streptococcus and Fusobacterium significantly enriched in Hp-negative group (LDA=3.28, 3.11;P=0.036,0.025, respectively). PICRUSt microbial function prediction showed that the expression of oxidative phosphorylation and disease-related pathways (pathways in cancer, renal cell carcinoma, amoebiasis, type 1 diabetes mellitus) in Hp-positive group were significantly higher than that in Hp-negative group (all P<0.05), while the expression of pathways such as energy metabolism and phosphotransferase system pathways were significantly lower than that in Hp-negative group (all P<0.05). Conclusion: In children with Hp-infected duodenal ulcers, the mucosal microbiota of the duodenal bulb is altered, characterized by an increased abundance of Helicobacter and a decreased abundance of Clostridium and Streptococcus, and possibly alters the biological function of the commensal microbiota through specific metabolic pathways.
Male ; Female ; Humans ; Child ; Duodenal Ulcer/diagnosis* ; Helicobacter Infections/complications* ; Helicobacter pylori/genetics* ; Prospective Studies ; Microbiota

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) may be involved in the pathogenesis of peptic ulcers through suppression of fibrinolysis. This study was designed to investigate associations of t-PA and PAI-1 genes with clinical features of the patients with bleeding gastric ulcers. Eighty-four patients with peptic ulcers and 100 controls were studied between January 1998 and April 2000. We used polymerase chain reaction and endonuclease digestion to genotype for 4G/5G polymorphism in the promoter region of the PAI-1 gene and the Alurepeat insertion/deletion (I/D) polymorphism in intron h of the t-PA gene. Various clinical features, including lesion site, bleeding event, recurrence of ulcer, and rebleeding, were assessed using a multiple logistic regression model. The genotype distributions of both the t-PA and PAI-1 genes did not differ between the patient and control groups. The occurrence of the I/D or D/D genotype of t-PA was significantly higher in cases of duodenal ulcer (adjusted OR=4.39, 95% CI=1.12-17.21). When a dominant effect (i.e., 4G/4G or 4G/5G versus 5G/5G) of the 4G allele was assumed, the PAI-1 4G/4G genotype was independently associated with rebleeding after hemostasis (adjusted OR=5.07, 95% CI=1.03-24.87). Our data suggest that t-PA gene polymorphism is associated with duodenal ulcers, and that the PAI-1 gene may be a risk factor leading to recurrent bleeding after initial hemostasis.
Adult ; Aged ; Alu Elements/genetics ; DNA Mutational Analysis ; Duodenal Ulcer/complications ; Duodenal Ulcer/genetics* ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Human ; Male ; Middle Aged ; Mutagenesis, Insertional ; Peptic Ulcer Hemorrhage/etiology ; Peptic Ulcer Hemorrhage/genetics* ; Plasminogen Activator Inhibitor 1/genetics* ; Polymorphism (Genetics)* ; Promoter Regions (Genetics)/genetics ; Recurrence ; Sequence Deletion ; Stomach Ulcer/complications ; Stomach Ulcer/genetics* ; Tissue Plasminogen Activator/genetics*

OBJECTIVEA number of putative virulence factors have been postulated to be relevant to the clinical outcome of Helicobacter pylori infection based on strains identified in the western countries. The aim of this study was to investigate the association between genotypes of vacA, cagA and iceA and duodenal ulcer disease in patients from Hong Kong.

METHODSSeventy-two dyspeptic patients with or without duodenal ulcer disease, with proven H.pylori infection, were studied. Gastric biopsy specimens were analyzed by specific polymerase chain reaction and Southern blot to determine the genotypes of these virulence factors.

RESULTSExcept 6 (8.3%) cases with evidence of multiple infections, all of the remaining 66 cases had vacA signal sequence s1 type strains. Twenty-seven (90%) of the 30 cases with duodenal ulcers were infected with cagA-positive strains, compared with 32 (88.9%) of 36 with non-ulcer dyspepsia (P > 0.05). Similarly, vacA middle region sequences were detected with no significant difference in the two groups, 9 (30.0%) versus 13 (36.1%) for m1b and 21 (70.0%) versus 23 (63.9%) for m2 type. IceA1 subtype was detected in the same frequency in 42 (63.6%) of the 66 cases. Neither cagA nor vacA and iceA were associated with duodenal ulcer disease.

CONCLUSIONNo clear differences were found in the distribution of cagA, vacA and iceA genotypes among patients with duodenal ulcer or non-ulcer dyspepsia. The association of these virulence genes and duodenal ulcer disease needs reappraisal, particularly under geographic considerations.

Antigens, Bacterial ; genetics ; Bacterial Proteins ; genetics ; Duodenal Ulcer ; etiology ; Genotype ; Helicobacter pylori ; pathogenicity ; Humans ; Middle Aged ; Virulence

BACKGROUND: Determination of vacA mosaicism may be important because specific Helicobacter pylori vacA genotype can be used to predict different clinical outcome. The aim of this study was to assess the relationship of vacA genotypes of Helicobacter pylori to cagA status and its development of peptic ulcer diseases in Korean patients. METHODS: Gastric biopsy specimens were obtained from 53 patients with gastric ulcer(GU), 57 with duodenal ulcer (DU) and 26 with chronic gastritis(CG) patients; all patients were infected with Helicobacter pylori. Bacterial mRNAs in the gastric mucosa were amplified by RT-PCR, using synthetic oligonucleotide primers specific for the vacA and the cagA gene. Patients with vacA s1 subtype were further examined to determine whether they had s1a or s1b subtype. RESULTS: There was no correlation in frequency of vacA s1 and/or s1a genotype between CG and either GU or DU, as the vacA s1 and s1a/m1 were present in the majority of strains independent of clinical status(s1 ; 100.0% versus 94.3 % or 93.0 % and s1a/m1 ; 76.9% versus 62.3% or 64.9%, res pectively). Likewise, there was no difference in the prevalence of the cagA gene between CG and either GU or DU patients (92.3% versus 90.6% or 98.2%, respectively). In addition, the cagA-negative status did not predict the presence of vacA s2 genotype. CONCLUSION: These results strongly suggest that either cagA or vacA s1 and/or s1a is not proved to be a useful marker to distinguish disease-specific Helicobacter pylori strains for the development of peptic ulcer diseases in Korean patients.
Adolescence ; Adult ; Aged ; Aged, 80 and over ; Bacterial Proteins/analysis* ; Base Sequence ; Biopsy, Needle ; Chi-Square Distribution ; Chronic Disease ; Duodenal Ulcer/pathology ; Duodenal Ulcer/genetics ; Female ; Gastritis/pathology ; Gastritis/genetics ; Genotype ; Helicobacter Infections/pathology ; Helicobacter Infections/genetics* ; Helicobacter pylori/genetics* ; Human ; Korea ; Male ; Middle Age ; Molecular Sequence Data ; Peptic Ulcer/pathology ; Peptic Ulcer/genetics* ; Polymerase Chain Reaction ; Probability ; Prognosis ; Sensitivity and Specificity ; Stomach Ulcer/pathology ; Stomach Ulcer/genetics ; Support, Non-U.S. Gov't ; Tissue Culture

OBJECTIVETo investigate the relationship of the promoter of matrix metalloproteinase-9 (MMP-9) gene polymorphisms with the susceptibility and clinical features of Helicobacter pylori (H. pylori)-related chronic gastritis and duodenal ulcer in children.

METHODSOne hundred children with chronic gastritis, 32 children with duodenal ulcer and 102 healthy children were enrolled.The promoter of MMP-9-1562C/T gene polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and sequencing. MMP-9 mRNA expression in gastric mucosa was confirmed by reverse transcription polymerase chain reaction.

RESULTSThe genotype distributions and allele frequencies of MMP-9-1562C/T gene polymorphisms were similar in gastric upper gastrointestinal disease and healthy subjects. The relative risk for H.pylori infection in C/C genetype carriers was 3.1 times as high as that in T allele (C/T+T/T) carriers in children with chronic gastritis. MMP-9-1562 C/T gene polymorphisms did not affect MMP-9 mRNA expression level.

CONCLUSIONSThese data suggest that MMP-9-1562 C/T gene polymorphisms are not associated with susceptibility to chronic gastritis and duodenal ulcer in children. The C/C genotype of MMP-9-1562 C/T gene polymorphism might be associated with H.pylori infection.

Adolescent ; Child ; Child, Preschool ; Chronic Disease ; Duodenal Ulcer ; etiology ; genetics ; Female ; Gastritis ; etiology ; genetics ; Genotype ; Helicobacter Infections ; complications ; genetics ; Helicobacter pylori ; Humans ; Male ; Matrix Metalloproteinase 9 ; genetics ; Polymorphism, Genetic

Extranodal NK/T-cell lymphoma is a recently recognized distinct entity within the World Health Organization classification of lymphoid tumors. It is relatively prevalent in Asian and South American populations. It most commonly occurs in the nasal or paranasal areas and less frequently in the skin, the soft tissue, and the gastrointestinal tract. Among these, extranodal NK/T-cell lymphoma of the gastrointestinal tract has shown an aggressive clinical course. We report a case of CD56+ extranodal NK/T-cell lymphoma presenting as a duodenal ulcer bleeding. A 62-year-old male patient presented with melena and abdominal pain. Endoscopic examination of the upper gastrointestinal tract showed the duodenal ulcer covered by blood clot. Pathologic examination revealed the diffuse infiltration of atypical lymphocytes with an angiocentric growth pattern, which was positive for CD3, CD56, and granzyme. The patient showed rapid deteriorating clinical course and died on day 14 after admission. Thus, we report this case with the review of literatures.
Antigens, CD3/metabolism ; Antigens, CD56/*metabolism ; Bone Marrow/pathology ; Duodenal Ulcer/*diagnosis ; Herpesvirus 4, Human/genetics/metabolism ; Humans ; Lymphoma, Extranodal NK-T-Cell/*diagnosis/pathology ; Male ; Middle Aged ; Peptic Ulcer Hemorrhage/*diagnosis ; Tomography, X-Ray Computed

BACKGROUND/AIMS: Genetic polymorphism of cytochrome P450 CYP2C19 influences the efficacy of proton pump inhibitor (PPI) in Helicobacter pylori (H. pylori) eradication therapy. We investigated the difference in the cure rates of H. pylori infection by triple (rabeprazole plus amoxacillin and clarithromycin) therapy in relation to CYP2C19 genotype status. METHODS: One hundred and sixteen H. pylori infected patients with gastric ulcer and duodenal ulcer completed the triple therapy with 10 mg of rabeprazole b.i.d., 1,000 mg amoxacillin b.i.d. and 500 mg of clarithromycin b.i.d. for one week. The genotype of CYP2C19 was determined by a PCR-restriction fragment length polymorphism method. RESULTS: According to the univariate analysis, heterozygous extensive metabolizers (hetero EMs) and poor metabolizers (PMs) showed the highest (87.0%) and the lowest (80.0%) eradication rates, respectively. The difference in the therapeutic efficacy of rabeprazole among the different CYP2C19 genotypes was insignificant. With regard to gender, age and smoking history in relation to eradication rate, a statistical significance was noted only with age with odds ratio of 1.063 and p-value of 0.0202. CONCLUSIONS: In the eradication therapy of H. pylori, no statistically significant difference in therapeutic efficacy of rabeprazole was found among different CYP2C19 genotypes.
2-Pyridinylmethylsulfinylbenzimidazoles ; Adult ; Aged ; Amoxicillin/administration & dosage ; Anti-Bacterial Agents/administration & dosage ; Anti-Ulcer Agents/*administration & dosage ; Aryl Hydrocarbon Hydroxylases/*genetics ; Benzimidazoles/*administration & dosage ; Clarithromycin/administration & dosage ; Drug Therapy, Combination ; Duodenal Ulcer/drug therapy/*genetics/microbiology ; Female ; Genotype ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Mixed Function Oxygenases/*genetics ; Omeprazole/analogs & derivatives ; Proton Pumps/*antagonists & inhibitors ; Stomach Ulcer/drug therapy/*genetics/microbiology

OBJECTIVETo study the genetic susceptibility of HLA-DQB1 alleles to duodenal ulcer in Chinese Hans from Guangdong area around.

METHODSHundred and five patients with duodenal ulcer and hundred and five healthy controls were examined for HLA-DQB1 genotypes. HLA-DQB1 allele typing was carried out by polymerase chain reaction with sequence specific primers (PCR-SSP).

RESULTSThe allele frequency of HLA-DQB1*0602 in patients with duodenal ulcer (64.8%) was significantly higher than that in healthy controls (14.3%).

CONCLUSIONThese findings suggest that HLA-DQB1*0602 is a susceptible gene to duodenal ulcer in Guangdong Hans of China. And at HLA-DQB1 site, there are immunogenetic differences between duodenal ulcer patients and healthy controls.

Adolescent ; Adult ; Aged ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Duodenal Ulcer ; ethnology ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; HLA-DQ Antigens ; genetics ; HLA-DQ beta-Chains ; Humans ; Male ; Membrane Glycoproteins ; genetics ; Middle Aged ; Polymerase Chain Reaction ; Young Adult