Relationship between different types of helicobacter pylori infection and metabolic syndrome in healthy people / 中国综合临床

Objective:To explore the relationship between different types of helicobacter pylori (Hp) infection and metabolic Syndrome (MS) in healthy population.Methods:The data of 4 602 adults who underwent physical examination in the Space Center Hospital from January to December 2019 were collected for research, the serum Hp antibody typing was detected by immunoblotting, and the results of liver ultrasound and blood biochemical examination were collected for statistical analysis.Results:Among the physical examination population,there were 2 018 cases with positive serum Hp antibody and 2 584 cases with negative serum Hp antibody.According to the expression of cytotoxin-associated gene A protein (CagA) and vacuolar toxin, 2 018 patients with positive serum Hp antibody were divided into 1 088 cases in type Ⅰ group (53.9%(1 088/2 018)) and 930 cases in type Ⅱ Group (46.1%(930/2 018)). There were significant differences in age, systolic blood pressure and prevalence of nonalcoholic fatty liver disease (NAFLD) between type Ⅰ group and type Ⅱ Group ( P<0.05). There was no significant difference in gender, fasting blood glucose, triglyceride,high-density lipoprotein cholesterol (HDL-C), diastolic blood pressure, body mass index (BMI) and waist circumference between the two groups ( P>0.05). There was no significant difference in the prevalence of ms between the two groups (18.3% (199/1 088)) and 19.0%(177/930), P=0.670). Multivariate logistic regression analysis showed that there was no correlation. between different serum Hp antibody typing and MS ( OR=1.194,95% CI 0.842-1.693, P=0.319). Conclusion:Different subtypes of type Ⅰ and type Ⅱ Hp infection are not distinctly associated with metabolic syndrome.

Correlation between the severity of peptic ulcer bleeding and Helicobacter pylori type / 中华消化杂志

Objective To investigate the correlation between the severity of peptic ulcer bleeding (PUB) and the serum antibody typing of Helicobacter pylori (H.pylori).Methods From January 1, 2009 to December 31, 2018, at Guangzhou First People's Hospital, 1 444 patients diagnosed with PUB and received H.pylori serum antibody test at the same time were enrolled and divided into high-risk group (324 cases) and low-risk group ( 1 120 cases ) according to Forrest classification , and according to recurrent bleeding , the patients were divided into recurrent bleeding group (32 cases) and non-rebleeding group (1 412 cases).Serum H.pylori specific antibodies cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA) and urease were detected by protein array .The correlation between H.pylori positive rate, H.pylori type, PUB and rebleeding were analyzed .Chi-square test and logistic regression analysis were used for statistical analysis . Results Among 1 444 PUB patients, there were 709 patients with gastric ulcer bleeding ( GUB) and 735 patients with duodenal ulcer bleeding ( DUB).Previous history of peptic ulcer disease ( odds ratio (OR)＝ 1.501, P＝0.006), the maximum diameter of ulcer over 2 cm (OR＝2.484, P?0.01) and H.pylori infection (OR＝1.508, P＝0.005) were independent risk factors of the severity of PUB .The total H.pylori positive rate was 68.49%(989/1 444), H.pylori type Ⅰwas the main type.Of which, 61.34%(549/895) were CagA and VacA double positive strains , 31.73%(284/895) were VacA single positive bacteria and CagA single positive bacteria was only 6.93%(62/895).The positive rate of H.pylori of high-risk group was higher than that of low-risk group (75.31%, 244/324 vs.66.52%, 745/1 120), and the difference was statistically significant (χ2 ＝8.999, P ＝0.004).In addition, the more serious Forrest classification , the higher the detection rate of H.pylori, and the difference was statistically significant (χ2 ＝11.840, P＝0.037).There was no significant difference in the positive rate of H.pylori between recurrent bleeding group and non-rebleeding group (81.25%, 26/32 vs.68.20%, 963/1 412; χ2 ＝2.469, P＞0.05).According to H.pylori antibody type, H.pylori typeⅠinfection was mainly in both high-risk group and low-risk group.The positive rate of H.pylori typeⅠstrain of high-risk group was higher than that of low-risk group (67.28%, 218/324 vs.60.45%, 677/1 120), and the difference was statistically significant ( χ2 ＝4.986, P ＝0.026).There was no statistically significant difference in the positive rate of H.pylori between GUB group and DUB group (68.41%, 485/709 vs. 68.57%, 504/735; χ2 ＝0.005, P＞0.05).Conclusions The infection of H.pylori is positively correlated with the severity of PUB, but not correlated with early ulcer rebleeding .H.pylori typeⅠis the main pathogenic strain of GUB and DUB, and CagA and VacA double positive strain is the most common strain .

Correlation between the severity of peptic ulcer bleeding and Helicobacter pylori type / 中华消化杂志

Objective@#To investigate the correlation between the severity of peptic ulcer bleeding (PUB) and the serum antibody typing of Helicobacter pylori (H.pylori).@*Methods@#From January 1, 2009 to December 31, 2018, at Guangzhou First People′s Hospital, 1 444 patients diagnosed with PUB and received H. pylori serum antibody test at the same time were enrolled and divided into high-risk group (324 cases) and low-risk group (1 120 cases) according to Forrest classification, and according to recurrent bleeding, the patients were divided into recurrent bleeding group (32 cases) and non-rebleeding group (1 412 cases). Serum H. pylori specific antibodies cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA) and urease were detected by protein array. The correlation between H. pylori positive rate, H. pylori type, PUB and rebleeding were analyzed. Chi-square test and logistic regression analysis were used for statistical analysis.@*Results@#Among 1 444 PUB patients, there were 709 patients with gastric ulcer bleeding (GUB) and 735 patients with duodenal ulcer bleeding (DUB). Previous history of peptic ulcer disease (odds ratio (OR)=1.501, P=0.006), the maximum diameter of ulcer over 2 cm (OR=2.484, P<0.01) and H. pylori infection (OR=1.508, P=0.005) were independent risk factors of the severity of PUB. The total H. pylori positive rate was 68.49% (989/1 444), H. pylori type Ⅰ was the main type. Of which, 61.34% (549/895) were CagA and VacA double positive strains, 31.73% (284/895) were VacA single positive bacteria and CagA single positive bacteria was only 6.93% (62/895). The positive rate of H. pylori of high-risk group was higher than that of low-risk group (75.31%, 244/324 vs. 66.52%, 745/1 120), and the difference was statistically significant (χ2=8.999, P=0.004). In addition, the more serious Forrest classification, the higher the detection rate of H. pylori, and the difference was statistically significant (χ2=11.840, P=0.037). There was no significant difference in the positive rate of H. pylori between recurrent bleeding group and non-rebleeding group (81.25%, 26/32 vs. 68.20%, 963/1 412; χ2=2.469, P>0.05). According to H. pylori antibody type, H. pylori type Ⅰ infection was mainly in both high-risk group and low-risk group. The positive rate of H. pylori type Ⅰ strain of high-risk group was higher than that of low-risk group (67.28%, 218/324 vs. 60.45%, 677/1 120), and the difference was statistically significant (χ2=4.986, P=0.026). There was no statistically significant difference in the positive rate of H. pylori between GUB group and DUB group (68.41%, 485/709 vs. 68.57%, 504/735; χ2=0.005, P>0.05).@*Conclusions@#The infection of H. pylori is positively correlated with the severity of PUB, but not correlated with early ulcer rebleeding. H. pylori type Ⅰ is the main pathogenic strain of GUB and DUB, and CagA and VacA double positive strain is the most common strain.

Anti-bacterial effects of enzymatically-isolated sialic acid from glycomacropeptide in a Helicobacter pylori-infected murine model

BACKGROUND/OBJECTIVES: Helicobacter pylori (H. pylori) colonization of the stomach mucosa and duodenum is the major cause of acute and chronic gastroduodenal pathology in humans. Efforts to find effective anti-bacterial strategies against H. pylori for the non-antibiotic control of H. pylori infection are urgently required. In this study, we used whey to prepare glycomacropeptide (GMP), from which sialic acid (G-SA) was enzymatically isolated. We investigated the anti-bacterial effects of G-SA against H. pylori in vitro and in an H. pylori-infected murine model. MATERIALS/METHODS: The anti-bacterial activity of G-SA was measured in vitro using the macrodilution method, and interleukin-8 (IL-8) production was measured in H. pylori and AGS cell co-cultures by ELISA. For in vivo study, G-SA 5 g/kg body weight (bw)/day and H. pylori were administered to mice three times over one week. After one week, G-SA 5 g/kg bw/day alone was administered every day for one week. Tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and IL-10 levels were measured by ELISA to determine the anti-inflammatory effects of G-SA. In addition, real-time PCR was performed to measure the genetic expression of cytotoxin-associated gene A (cagA). RESULTS: G-SA inhibited the growth of H. pylori and suppressed IL-8 production in H. pylori and in AGS cell co-cultures in vitro. In the in vivo assay, administration of G-SA reduced levels of IL-1β and IL-6 pro-inflammatory cytokines whereas IL-10 level increased. Also, G-SA suppressed the expression of cagA in the stomach of H. pylori-infected mice. CONCLUSION: G-SA possesses anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect in an experimental H. pylori-infected murine model. G-SA has potential as an alternative to antibiotics for the prevention of H. pylori infection and H. pylori-induced gastric disease prevention.

Experimental study on bacteriostatic effect of recombinant human lactoferrin on Helicobacter pylori / 重庆医学

Objective To evaluate the bacteriostatic effect of recombinant human lactoferrin(rhLF) on Helicobacter(H .) py‐lori and its influence on CagA ,Ure and gastric mucosal IL‐8 .Methods The minimum inhibitory concentration(MIC)and the influ‐ence of different drug concentrations on the proliferation of H .pylori were detected .The effects of rhLF on the mRNA and protein expressions of CagA and Ure in H .pylori were detected by RT‐PCR and Western blot ,respectively .The animal study :Balb/c mice were adopted and assigned randomly into four groups ,including the standard triple+rhLF(group A) ,rhLF(group B) ,standard tri‐ple(group C) and normal saline(group D) .The histopathological HE staining was used to observe the gastric inflammation and ELISA was used to detect the IL‐8 level of gastric tissue in each group .Results MIC was 0 .5 mg/mL ,moreover rhLF inhibited the bacterial growth and proliferation with a concentration‐dependent manner .rhLF could reduce the expression of H .pylori major viru‐lence factor CagA ,mRNA and protein of Ure .Comparing the group A with the group B ,C and D ,the gastric mucosal inflammation score and the IL‐8 levels of gastric tissue homogenates had statistically significant differences(P<0 .05) .Conclusion rhLF inhibits the growth and proliferation of H .pylori ,moreover inhibit the expression of major virulence factor CagA in H .pylori ,mRNA and protein of Ure in different degrees ,weakens its pathogenicity ,meanwhile reduces the IL‐8 level in mice gastric mucosa ,and allevi‐ates H .pylori related gastric mucosal inflammatory response .

Meta-analysis on the relationship between virulent strains of Helicobacter pylori and risk of atherosclerotic cerebral infarction / 中国感染控制杂志

Objective To evaluate the relationship between cytotoxin-associated gene-A (CagA)seropositive of Helicobacter pylori (H .pylori )infection and risk of atherosclerotic cerebral infarction(ACI).Methods Related literatures were researched through literature retrieval ,literatures were obtained by uniformed criteria of inclusion and exclusion,and Meta analysis was performed with RevMan 4.2 software.Results A total of 10 literatures which met the inclusion criteria were retrieved,all were case-control study,case group included 907 studied subjects,and control group included 966 subjects;the included population were divided into Chinese subgroup and European Caucasian sub-group.Meta analysis of CagA seropositive of H .pylori infection and risk of ACI revealed that OR of the overall popula-tion,Chinese subgroup,and European Caucasian subgroup was 2.66(2.17-3.26),2.60(1.93-3.49),and 2.71(2.05-3.59)respectively;Meta analysis of CagA seronegative of H .pylori infection and risk of ACI revealed that OR of the overall population,Chinese subgroup,and European Caucasian subgroup was 0.74(0.49-1.10),0.81(0.45-1.48),and 0.64(0.37-1.09)respectively.The funnel plot and fail-safe number showed that there was no significant publication bias, the result was stable and reliable.Conclusion Chronic infection caused by CagA seropositive strains of H .pylori may be one of the risk factors of CAI,whether the eradication treatment of seropositive strains of H .pylori influences the process of atherosclerotic diseases like CAI needs to be further studied.

In silico experiment with an-antigen-toll like receptor-5 agonist fusion construct for immunogenic application to Helicobacter pylori.

BACKGROUNDS: Helicobacter pylori colonize the gastric mucosa of half of the world's population. Although it is classified as a definitive type I carcinogen by World Health Organization, there is no effective vaccine against this bacterium. H. pylori evade the host immune response by avoiding toll-like detection, such as detection via toll-like receptor-5 (TLR-5). Thus, a chimeric construct consisting of selected epitopes from virulence factors that is incorporated into a TLR-5 ligand (Pseudomonas flagellin) could result in more potent innate and adaptive immune responses. MATERIALS AND METHODS: Based on the histocompatibility antigens of BALB/c mice, in silico techniques were used to select several fragments from H. pylori virulence factors with a high density of B- and T-cell epitopes. RESULTS: These segments consist of cytotoxin-associated geneA (residue 162-283), neutrophil activating protein (residue 30-135) and outer inflammatory protein A (residue 155-268). The secondary and tertiary structure of the chimeric constructs and other bioinformatics analyses such as stability, solubility, and antigenicity were performed. The chimeric construct containing antigenic segments of H. pylori proteins was fused with the D3 domain of Pseudomonas flagellin. This recombinant chimeric gene was optimized for expression in Escherichia coli. The in silico results showed that the conserved C- and N-terminal domains of flagellin and the antigenicity of selected fragments were retained. DISCUSSION: In silico analysis showed that Pseudomonas flagellin is a suitable platform for incorporation of an antigenic construct from H. pylori. This strategy may be an effective tool for the control of H. pylori and other persistent infections.

The association between cytotoxin-associated gene A of Helicobacter pylori and the expressions of mtp53 and c-myc protein in different subtypes of intestinal metaplasia / 中国医师进修杂志

Objective To study the association between cytotoxin-associated gene A of Helicobacter pylori (Hp-CagA) and the expressions of mtp53 and c-myc protein in different subtypes of intestinal metaplasia.Methods One hundred and sixty-five patients with gastroscopy included 125 cases with chronic atrophic gastritis with intestinal metaplasia,40 cases with non-atrophic gastritis.Intestinal metaplasia included complete intestinal metaplasia,incompletetype intestinal metaplasia,complete colonic epithelial metaplasia and incomplete colonic epithelial metaplasia.The carbon-14-urea breath test was used to determine Helicobacter pylori (Hp);AB-PAS and HID-AB mucinous staining was used to distinguish intestinal metaplasia subtypes; the immunohistochemical Elivision method was used to determine the expressions ofmtp53 and c-myc protein;indirect ELISA was used to determine Hp-CagA.Results Forty-five cases with incomplete colonic epithelial metaplasia,47 cases with incomplete type intestinal metaplasta,17 cases with complete colonic epithelial metaplasia,16 cases with complete intestinal metaplasia.The positive rate of Hp-CagA in all intestinal metaplasia subtypes was higher than that in non-atrophic gastritis,but there was no significant difference (P ＞ 0.05).The expression of mtp53 protein in incomplete colonic type of intestinal metaplasia with Hp-CagA positive was higher than that in incomplete colonic type of intestinal metaplasia with Hp-CagA negative (x2 =5.494,P ＜ 0.05).The expression of c-myc protein in incomplete colonic type of intestinal metaplasia with Hp-CagA positive was higher than that in incomplete colonic type of intestinal metaplasia with Hp-CagA negative (x2 =13.950,P ＜ 0.01).Conclusion Hp-CagA is a sort of highly virulent strain,and Hp-CagA may do a strong role in the promotion of gastric atrophy and intestinal metaplasia.

Prevalence of Helicobacter pylori and cytotoxin-associated gene A in Iranian patients with non-erosive and erosive reflux disease.

Background: The prevalence of Helicobacter pylori (H. pylori) infection and its virulent strain (cytotoxin-associated gene A: CagA) has not been evaluated in patients with gastroesophageal reflux disease (GERD) subgroups (erosive and non-erosive) in Iran. AIMS: This study was conducted to evaluate H. pylori infection and anti-CagA status in GERD. Setting and Design: One hundred fifty-four patients (71 male and 83 female; mean age, 42.6± 15.5 years) were evaluated for symptoms - heartburn and acid regurgitation - compatible with GERD. Materials and Methods: The esophagus was diagnosed endoscopically whether it was with erosion (erosive reflux disease, ERD) or without erosion (non-erosive reflux disease, NERD). Rates of anti-H. pylori and anti-CagA-IgG (immunoglobulin G) antibodies were determined for each subject by ELISA. H. pylori was considered by ELISA if the rapid urease test proved positive. Statistical Analysis: anti-H. pylori and anti-CagA statuses were compared in ERD and NERD patients with and without related IgG antibodies. Mean values and P values were calculated using SPSS (version 12). Results: The overall prevalence of H. pylori infection was 75.3% (116/154). Anti-CagA antibody was found in 60.3% (70/116) of infected patients. The prevalence of H. pylori infection in patients with NERD and ERD was 81.2% (56/69) and 70.6% (60/85), respectively (OR= 0.56; 95% CI [confidence interval]= 0.26-1.20; P= .14). The prevalence of anti-CagA antibody in infected NERD and ERD patients was 58.9% (33/56) and 61.7% (37/60), respectively (OR= 1.16; 95% CI= 0.49-1.70; P= 0.83). Conclusion: The results showed that more than 70% of the patients, either NERD or ERD, acquire H. pylori infection. Anti-CagA antibody is also common in patients with reflux disorders in our community.

Length polymorphism of cagA genotype in Helicobacter pylori isolates and its clinical significance / 解放军医学杂志

Objective To investigate the relationship of the distribution and heterogeneity of cagA gene of Chinese H. pylori isolates with Hp-associated gastroduodenal!diseases in China. Methods Pairs of oligonucleotide primers flanking a conservative 297bp segment and the variable segment of 3' region of cagA gene were designed according to the conserved cagA sequences, and the distribution of cagA gene in 82 Chinese H. pylori isolates and the heterogeneity of variable segment of cagA gene 3' region of 77 H. pylori strains were determined with PCR. Results 77(93.9%) of 82 Chinese Hp isolates were found to be cagA-positive by PCR amplification of the 297bp segment. The variable segment of 3' region of cagA genes was detected in 71(93.9%) of 77 Chinese H. pylori strains, including two without 297bp amplicon, with predominance of PCR products of about 825bp which were designated as type Ⅰ in China. Conclusion The prevalence of cagA is high in Chinese Hp isolates, and the cagA of type Ⅰ with the shortest variable 3' region predominates in China. Neither cagA nor the length of cagA 3' region is associated with the clinical outcome of Hp infection.