2014年10月Pubmed幽门螺杆菌相关文献汇总
1. LOTUS 试验的事后分析：每日维持20mg埃索美拉唑治疗量对患者的症状和生活质量的长期影响
对参与LOTUS trial (ClinicalTrials.gov identifier: NCT00251927)的256例GRED患者进行包括胃镜、24小时试管PH监测在内的检测来评估消化道的症状。结果证明每日20mg埃索美拉唑能够为慢性GRED患者提供长期有效的治疗效果。研究结果提到无HP感染的患者有可能埃索美拉唑的每日量应该加到40mg。
Long-term effect on symptoms and quality of life of maintenance therapy with esomeprazole 20 mg daily: a post hoc analysis of the LOTUS trial.
Lundell L1, Hatlebakk J, Galmiche JP, Attwood SE, Ell C, Fiocca R, Persson T, Nagy P, Eklund S, Lind T.
Abstract
Objective:To assess the long-term effect on symptoms and quality of life of esomeprazole 20 mg once daily, a recommended dose for maintenance therapy of gastroesophageal reflux disease (GERD).
Research design and methods: This is a post hoc analysis of 5 year data from patients in the LOTUS trial (ClinicalTrials.gov identifier: NCT00251927) who were randomized to esomeprazole 20 mg once daily. All participants had chronic, symptomatic GERD responsive to treatment. Gastrointestinal symptoms were assessed by physicians and by using patient-reported outcome instruments. Investigations included gastrointestinal endoscopy (with biopsy sampling), 24 hour esophageal pH monitoring and laboratory measurements.
Results: In total, 157 of 256 patients randomized to esomeprazole 20 mg once daily remained on this dose until the end of follow-up or study discontinuation, whereas 99 patients had their dose increased because of inadequate symptom control (of these, 29 subsequently returned to the allocated dose). On logistic regression, a long objectively defined GERD history, smoking, female sex, absence of Helicobacter pylori infection and high supine baseline acid reflux into the esophagus were associated with an increased likelihood of requiring dose escalation to esomeprazole 40 mg daily (all p < 0.05). Symptoms were fairly stable and quality of life was normal throughout follow-up in patients remaining on esomeprazole 20 mg once daily, with no more than mild symptom severity, and mean (standard deviation) percentage time with intraesophageal pH <4 was reduced from 10.7 (10.7) pre-randomization to 6.3 (10.2) at 6 months and 4.9 (7.3) at 5 years. The number of serious adverse events was low (0.079 per patient per year).
Conclusions:Esomeprazole at a maintenance dose of 20 mg once daily offers effective long-term treatment for chronic GERD in patients initially responsive to the medication, with durable symptom control and sustained reductions in intraesophageal acid exposure.
2.一项长达17年的前瞻性队列研究：HP根除对消化性溃疡患者预防胃癌的影响
研究对象总数1222例。研究者分析后认为HP的根除对消化性溃疡患者胃癌发生风险降低的效果可能超过10年之久，但即便根除了Hp患者也有发生胃癌的风险。
J Gastroenterol. 2014 Oct 29.
Seventeen-year effects of eradicating Helicobacter pylori on the prevention of gastric cancer in patients with peptic ulcer; a prospective cohort study.
Take S1, Mizuno M, Ishiki K, Hamada F, Yoshida T, Yokota K, Okada H, Yamamoto K.
Abstract
BACKGROUND:
We previously reported that eradication of Helicobacter pylori in our cohort of patients with peptic ulcer disease reduced their risk of developing gastric cancer to approximately one-third after a mean follow-up period of 3.4 years (up to 8.6 years). We have now followed these patients for a longer period.
METHODS:
A total of 1,222 consecutive patients with peptic ulcer diseases who completed more than 1-year follow-up after receiving H. pylori eradication therapy were followed with annual endoscopic surveillance for a mean of 9.9 years (as long as 17.4 years).
RESULTS:
H. pylori infection was judged cured in 1,030 patients (eradication-success group) but persisted in 192 (eradication-failure group) after initial eradication therapy. In the eradication-failure group, 114 patients received re-treatment at a mean of 4.4 years after the start of follow-up, and 105 of these were cured of infection. Gastric cancer developed in 21 of the 1,030 patients in the eradication-success group and in nine of the 192 in the failure group (p = 0.04). The risk of developing gastric cancer in the eradication-success group (0.21 %/year) was significantly lower than that in the failure group (0.45 %, p = 0.049). The longest interval between the initial H. pylori eradication and the occurrence of gastric cancer was 14.5 years in the eradication-success group and 13.7 years in the eradication-failure group.
CONCLUSIONS:
A prophylactic effect for gastric cancer persists for more than 10 years after H. pylori eradication therapy, but we should be aware that cancer can develop even after that interval.
3. 枯草芽孢杆菌表面幽门螺杆菌尿素酶B的表达研究
文章提到近年来HP的耐药性越来越高。因此，研发幽门螺杆菌疫苗重新被人们所重视。研究显示，枯草芽孢杆菌表面表达的尿素酶B具有免疫原的特点，通过口服可能可以预防HP的感染。
J Med Microbiol. 2014 Oct 29. pii: jmm.0.076430-0. doi: 10.1099/jmm.0.076430-0.
Expression of Helicobacter pylori urease B on the surface of Bacillus subtilis spores.
Zhou Z1, Gong S2, Li X3, Yang Y2, Guan R2, Zhou S2, Yao S2, Xie Y2, Ou Z2, Zhao J2, Liu Z4.
Abstract
Helicobacter pylori infection is a major risk factor for chronic gastritis, digestive ulcers, gastric adenocarcinoma and lymphoma. Due to the decreasing efficacy of anti-Helicobacter pylori antibiotic therapy in clinical practice, there is renewed interest in the development of anti-Helicobacter pylori vaccines. Bacillus subtilis is nonpathogenic and can produce endospores, which can survive under extreme conditions. These features make the Bacillus subtilis spore an ideal vehicle for delivery of heterologous antigens to extreme environments such as the gastrointestinal tract. In this study, we displayed Helicobacter pylori urease B protein on the Bacillus subtilis spore coat using spore coat protein CotC as a fusion partner. Western blotting analyses were used to verify urease B surface expression on spores. Recombinant spores displaying the urease B antigen were used for oral immunization and were shown to generate humoral response in mice. Urease B-specific secretory IgA in feces and IgG in serum reached significant levels 2 weeks after oral dosing. In addition, oral immunization of recombinant urease B spores induced a significant reduction (84%) in the stomach bacterial load (0.25±0.13 x 106CFU) compared to that in non-recombinant spores treated group (1.56±0.3 x 106CFU, P < 0.01). This report shows that urease B expressed on Bacillus subtilis spores was immunogenic and oral administration of urease B spores can provide protection against Helicobacter pylori infection.
Copyright © 2014, the Society for General Microbiology.
4. 应用多能干细胞衍生的类胃组织建模研究人类相关器官的发育及其相关疾病
在应用干细胞的产生人胃组织体(hGOs)后，该研究模拟了人类器官的发育和相关疾病发病机制。研究过程中发现，幽门螺旋杆菌感染后，致病因子CagA与c-Met受体的快速结合，进而激活信号通路和诱导上皮细胞增生。
Nature. 2014 Oct 29. doi: 10.1038/nature13863. [Epub ahead of print]
Modelling human development and disease in pluripotent stem-cell-derived gastric organoids.
McCracken KW1, Catá EM1, Crawford CM1, Sinagoga KL1, Schumacher M2, Rockich BE3, Tsai YH4, Mayhew CN1,Spence JR5, Zavros Y2, Wells JM6.
Author information
Abstract
Gastric diseases, including peptic ulcer disease and gastric cancer, affect 10% of the world's population and are largely due to chronic Helicobacter pylori infection. Species differences in embryonic development and architecture of the adult stomach make animal models suboptimal for studying human stomach organogenesis and pathogenesis, and there is no experimental model of normal human gastric mucosa. Here we report the de novo generation of three-dimensional human gastric tissue in vitro through the directed differentiation of human pluripotent stem cells. We show that temporal manipulation of the FGF, WNT, BMP, retinoic acid and EGF signalling pathways and three-dimensional growth are sufficient to generate human gastric organoids (hGOs). Developing hGOs progressed through molecular and morphogenetic stages that were nearly identical to the developing antrum of the mouse stomach. Organoids formed primitive gastric gland- and pit-like domains, proliferative zones containing LGR5-expressing cells, surface and antral mucous cells, and a diversity of gastric endocrine cells. We used hGO cultures to identify novel signalling mechanisms that regulate early endoderm patterning and gastric endocrine cell differentiation upstream of the transcription factor NEUROG3. Using hGOs to model pathogenesis of human disease, we found that H. pylori infection resulted in rapid association of the virulence factor CagA with the c-Met receptor, activation of signalling and induction of epithelial proliferation. Together, these studies describe a new and robust in vitro system for elucidating the mechanisms underlying human stomach development and disease.
5. KIR基因型与幽门螺杆菌感染之间的关系
对101例研究对象的杀伤免疫球蛋白样受体（KIR）基因型和HP感染进行了分析，发现在无HP感染的患者中A单倍型相对HP阳性的患者减少。
J Clin Pathol. 2014 Oct 28. pii: jclinpath-2014-202638. doi: 10.1136/jclinpath-2014-202638. [Epub ahead of print]
KIR genotype distribution among symptomatic patients with and without Helicobacter pylori infection: is there any role for the B haplotype?
Mahfouz R1, Hoteit R1, El Hajj N1, Shammaa D1, Sharara AI2.
Abstract
Contact of peripheral blood lymphocytes with Helicobacter pylori was proved to induce non- major histocompatibility complex-restricted cytotoxicity and natural killer cells are thought to play an important role in the immunity against H. pylori.
AIMS:
In this research, we investigated any possible association between killer immunoglobulin-likereceptors (KIR) genotypes and H. pylori infection.
METHODS:
KIR genotype was analysed in 101 Lebanese symptomatic patients (51 H. pylori positive and 50 H. pylori-negative) using the KIR Genotyping SSP kit.
RESULTS:
Among the H. pylori-positive patients, the AA, AB and BB genotypical frequencies were, respectively, 43.14%, 41.18% and 15.68% with an A:B ratio of 1.76:1. The AA, AB and BB genotypes frequencies for H. pylori-negative individuals were 18%, 62% and 20%, respectively, with an A:B ratio of 0.96:1. No significant difference between patients and controls was detected.
CONCLUSIONS:
We noticed a reduced distribution of A haplotype among the 'H. pylori-negative' patients as compared with the "H. pylori-positive" group. This is the first study in the international literature that targets the correlation between KIR genotypes and H. pylori.
6. 幽门螺杆菌在日本家庭家庭内传播的分析
对从5个家庭分离出的19株Hp菌株分析结果显示，在5个家庭中母子传播占4/5；父子传播占2/5；同胞传播占4/5。
J Med Microbiol. 2014 Oct 28. pii: jmm.0.080507-0. doi: 10.1099/jmm.0.080507-0. [Epub ahead of print]
Analysis of intra-familial transmission of Helicobacter pylori in Japanese families.
Osaki T1, Konno M2, Yonezawa H3, Hojo F3, Zaman C3, Takahashi M2, Fujiwara S2, Kamiya S3.
Author information
Abstract
Intra-familial infection is considered to be one of the main routes of transmission for Helicobacter pylori in Japan. We assessed the genomic profiles of H. pylori isolates from family members by multi-locus sequence typing (MLST) and identified the original strain infecting the index child. A total of 19 isolates from 5 families were analyzed by MLST using 7 housekeeping genes and by random amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR). The phylogenetic analysis was performed using nucleotide sequences of the 7 loci. Two or more different types of H. pylori strains were indicated in 3 (K-1, K-2 and K-5) out of 5 families. Independent genotypes of H. pylori strains were detected from all members of the other two families suggesting that these strains (K26-28 and K29-33) may be dominant. Mother to child transmission of H. pylori was demonstrated in 4 out of 5 families, whilst transmission from father to child and sibling to sibling were demonstrated in 2 families and 1 family, respectively.
7. 荟萃分析：中国标准三联疗法治疗幽门螺旋杆菌感染。
49项随机对照研究共纳入了8332例患者，结论：含PPI、阿莫西林和克拉霉素的标准三联疗法不能获得理想的根除率。
World J Gastroenterol. 2014 Oct 28;20(40):14973-85. doi: 10.3748/wjg.v20.i40.14973.
Standard triple therapy for Helicobacter pylori infection in China: A meta-analysis.
Wang B, Lv ZF, Wang YH, Wang H, Liu XQ, Xie Y, Zhou XJ.
Abstract
AIM:
To assess the efficacy and safety of standard triple therapy compared with other pre-existing and new therapies in China.
METHODS:
Literature searches were conducted in the following databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the VIP database, the China National Knowledge Infrastructure database, and the Chinese Biomedical Database. A meta-analysis of all randomized controlled trials (RCTs) comparing standard triple therapy for the eradication of Helicobacter pylori with pre-existing and new therapies in China was performed using Comprehensive Meta-Analysis 2.0. There were 49 studies that met our criteria and the qualities of these studies were assessed using the Jadad scale. The Mantel-Haenszel method was used for pooling dichotomous data. We also conducted subgroup analyses according to age, duration of treatment and drug type. Sensitivity analyses and a cumulative meta-analysis were also performed with CMA 2.0. Publication bias was evaluated using Egger's test, Begg's test or a funnel plot.
RESULTS:
A total of 49 RCTs including 8332 patients were assessed. This meta-analysis showed that standard triple therapy with proton pump inhibitors (PPIs), amoxicillin (AMO) and clarithromycin (CLA) was inferior to sequential therapy [relative risk (RR) = 0.863; 95% confidence interval (CI): 0.824-0.904], but was not superior to quadruple therapy (RR = 1.073; 95%CI: 0.849-1.357) or other triple therapies (RR = 1.01; 95%CI: 0.936-1.089). The meta-analysis also suggested that standard triple therapy is slightly more effective than dual therapy (RR = 1.14; 95%CI: 0.99-1.31). However, the differences were not statistically significant. We removed the only trial with a regimen lasting 14 d by sensitivity analysis and found that 7-d standard triple therapy was superior to 7-d dual therapy (RR = 1.222; 95%CI: 1.021-1.461). Moreover, a sub-analysis based on the duration of quadruple therapy indicated that the 7-d and 10-d standard triple therapies were inferior to sequential therapy (RR = 0.790; 95%CI: 0.718-0.868; RR = 0.917; 95%CI: 0.839-1.002, respectively). Additionally, there were no significant differences in cure rate or adverse events among standard triple therapy, quadruple therapy, and other triple therapies (RR = 0.940; 95%CI: 0.825-1.072; RR = 1.081; 95%CI: 0.848-1.378, respectively). Standard triple therapy had a higher occurrence of side effects than sequential therapy (RR = 1.283; 95%CI: 1.066-1.544).
CONCLUSION:
The eradication rates with a standard triple therapy consisting of PPI, AMO, and CLA are suboptimal in China, and new treatment agents need to be developed.
8. Meta分析：幽门螺杆菌感染与偏头痛的关系。
5项病例对照研究纳入了903例患者，Hp总感染率39.31%。亚组分析显示亚洲患者Hp感染率与偏头痛具有明显相关性，而欧洲患者无明显相关性。
World J Gastroenterol. 2014 Oct 28;20(40):14965-72. doi: 10.3748/wjg.v20.i40.14965.
Association between Helicobacter pylori infection and migraine: A meta-analysis.
Abstract
AIM:
To quantify the association between Helicobacter pylori (H. pylori) infection and migraine.
METHODS:
A systematic literature search of PubMed and EMBASE was conducted from inception to December 2013. Studies that provided data dealing with H. pylori infection in patients with migraine, as well as healthy controls, were selected. Meta-analysis was carried out using the odds ratio (OR) with a fixed or random effects model, and a 95%CI for the OR was calculated. An unconditional logistic regression model was used to analyze potential parameters related to H. pylori prevalence. Subgroup analyses were conducted as methods of detection and evidence grade.
RESULTS:
Five case-control studies published between 2000 and 2013 were finally identified, involving 903 patients, with a total H. pylori infection rate of 39.31%. The prevalence of H. pylori infection was significantly greater in migraineurs than in controls (44.97% vs 33.26%, OR = 1.92, 95%CI: 1.05-3.51, P = 0.001). A sensitivity test indicated that no single study dominated the combined results. Univariate regression analysis found that publication year, geographical distribution and evidence grade were relevant to the results and were the main reason for the heterogeneity. Subgroup analysis found a significantly greater infection rate of H. pyloriin Asian patients with migraine, but no statistically significant infection rate in European patients. The ORs were 3.48 (95%CI: 2.09-5.81, P = 0.000) and 1.19 (95%CI: 0.86-1.65, P = 0.288), respectively.
CONCLUSION:
The pooled data suggest a trend of more frequent H. pylori infections in patients with migraine.
9. 膜结合粘蛋白和终端粘蛋白聚糖在特发性、HP相关性、或NSAID相关性消化性溃疡中的表达
研究认为，不同酸化模式的黏蛋白可能对抵抗胃酸和胃蛋白酶的损害具有不同的保护作用。
World J Gastroenterol. 2014 Oct 28;20(40):14913-20. doi: 10.3748/wjg.v20.i40.14913.
Membrane-bound mucins and mucin terminal glycans expression in idiopathic orHelicobacter pylori, associated peptic ulcers.
Niv Y, Boltin D, Halpern M, Cohen M, Levi Z, Vilkin A, Morgenstern S, Manugian V, St Lawrence E, Gagneux P, Kaur S,Sharma P, Batra SK, Ho SB.
Author information
Abstract
AIM:
To determine the expression of membrane-bound mucins and glycan side chain sialic acids inHelicobacter pylori (H. pylori)-associated, non-steroidal inflammatory drug (NSAID)-associated and idiopathic-gastric ulcers.
METHODS:
We studied a cohort of randomly selected patients with H. pylori (group 1, n = 30), NSAID (group 2, n = 18), combined H. pylori and NSAID associated gastric ulcers (group 3, n = 24), and patients with idiopathic gastric ulcers (group 4, n = 20). Immunohistochemistry for MUC1, MUC4, MUC17, and staining for Erythrina cristagalli agglutinin and Sambucus nigra agglutinin (SNA) lectins was performed on sections from the ulcer margins.
RESULTS:
Staining intensity of MUC17 was higher in H. pylori ulcers (group 1) than in idiopathic ulcers (group 4), 11.05 ± 3.67 vs 6.93 ± 4.00 for foveola cells, and 10.29 ± 4.67 vs 8.00 ± 3.48 for gland cells, respectively (P < 0.0001). In contrast, MUC1 expression was higher in group 4 compared group 1, 9.89 ± 4.17 vs 2.93 ± 5.13 in foveola cells and 7.63 ± 4.60 vs 2.57± 4.50 for glands, respectively (P < 0.0001). SNA lectin staining was increased in group 4, in parallel to elevated MUC1 expression, indicating more abundant α2-6 sialylation in that group.
CONCLUSION:
Cytoplasmic MUC17 staining was significantly decreased in the cases with idiopathic ulcer. The opposite was observed for both MUC1 and SNA lectin. This observation may reflect important pathogenic mechanisms, since different mucins with altered sialylation patterns may differ in their protection efficiency against acid and pepsin.
10. 综述：评价不同类型、不同剂量、不同疗程质子泵抑制剂在根除HP中的作用，细菌对克拉霉素和甲硝唑的耐药性是根除失败最主要的的原因。
World J Gastroenterol. 2014 Oct 28;20(40):14527-14536.
Evidence-based assessment of proton-pump inhibitors in Helicobacter pylorieradication: A systematic review.
Author information
Abstract
Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori (H. pylori) infection associated duodenal ulcers should undergo eradication therapy. There are many regimens offered for H. pylori eradication which include triple, quadruple, or sequential therapy regimens. The central aim of this systematic review is to evaluate the evidence for H. pylori therapy from a meta-analytical outlook. The consequence of the dose, type of proton-pump inhibitor, and the length of the treatment will be debated. The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.
11. 乙醇脱氢酶同工酶--乙醇脱氢酶IV作为幽门螺杆菌感染的潜在标记物
幽门螺杆菌感染与胃黏膜中乙醇脱氢酶(ADH)活性的降低相关。胃黏膜ADH活性的降低程度取决于炎症和黏膜损伤的严重程度。这种损伤可能导致胃黏膜乙醇脱氢酶进一步释放,最终导致幽门螺旋杆菌感染患者血清中ADH活性增加。对140幽门螺旋杆菌感染病例进行分析。研究结果显示幽门螺旋杆菌感染患者血清中总ADH以及ADH IV活性显著增加，提示ADH IV可以作为幽门螺杆菌感染的潜在标记物。
Arch Med Sci. 2014 Oct 27;10(5):951-5. doi: 10.5114/aoms.2014.46215. Epub 2014 Oct 23.
The alcohol dehydrogenase isoenzyme alcohol dehydrogenase IV as a candidate marker of Helicobacter pylori infection.
Jelski W, Laniewska-Dunaj M, Strumnik A, Szmitkowski M.
Abstract
INTRODUCTION:
Helicobacter pylori infection is associated with decreased alcohol dehydrogenase (ADH) activity in the gastric mucosa. The decrease in gastric ADH activity depends on the severity of inflammation and mucosal injury. This damage can be a reason of the release of enzyme from gastric mucosa and leads to the increase of the ADH activity in the sera of patients with H. pylori infection.
MATERIAL AND METHODS:
Serum samples were taken from 140 patients with H. pylori infection. Total ADH activity was measured by photometric method with p-nitrosodimethylaniline as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde. For the measurement of the activity of class I and II isoenzymes we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as a substrate.
RESULTS:
The activity of ADH IV in the serum of patients with H. pylori infection increased about 42% (7.86 mU/l) in the comparison to the control level (4.52 mU/l). Total activity of ADH was 1105 mU/l in patients group and 682 mU/l in control. The diagnostic sensitivity for ADH IV was 88%, specificity 90%, positive and negative predictive values were 91% and 84% respectively. Area under ROC curve for ADH IV was 0.84.
CONCLUSIONS:
Helicobacter pylori infection of gastric mucosa is reflected in the serum by significant increase of class IV and total ADH activity. The results suggest a potential role for ADH IV as a marker of H.pylori infection.
12利用MicroRNA网络分析法识别在胃癌癌前病变中的关键微小RNAs及基因
为了寻找胃癌的早期治疗及预防的潜在靶点,利用microRNA 基因表达谱对10例幽门螺杆菌相关胃炎标本及10例胃肠上皮化生样本进行筛查。实验结果提示RAB22A, SOX4, IKZF2, PLAG1, and BTBD7这5个基因可能可作为调节胃癌进展的靶向基因。
Genet Mol Res. 2014 Oct 27;13(4):8695-703. doi: 10.4238/2014.October.27.10.
MicroRNA network analysis identifies key associated with precancerous lesions of gastric cancer.
Wang XW1, Wu Y2, Wang D1, Qin ZF3.
Author information
Abstract
To identify potential targets for the early treatment and prevention of gastric cancer, microRNA (miRNA) expression profiles of precancerous lesions of gastric cancer were investigated.The miRNA microarray dataset GSE24839 was downloaded from Gene Expression Omnibus (GEO) and included 10 Helicobacter pylori-related gastritis samples and 10 gastric intestinal metaplasia samples. Differentially expressed miRNAs (DEMs) were screened using the Student t-test; P < 0.05 was considered to be statistically significant. Co-expression networks of total miRNAs and DEMs were constructed based on the Pearson correlation coefficient for the two diseases. Target genes of the DEMs were retrieved using miRecords and pathway-enrichment analysis was performed using a hypergeometric test. A total of 20 DEMs were obtained for H.pylori-related gastritis and gastric intestinal metaplasia samples, including 12 up-regulated and 8 down-regulated miRNAs. The identified DEMs appear to play key roles in gastric cancer, as the average degree of the DEM sub-network was higher than that of the total miRNA co-expression network. Furthermore, target genes for 6 DEMs (hsa-miR-106b, hsa-miR-193a-3p, hsa-miR-204, hsa-miR-30e, hsa-miR-519d, and hsa-miR-524-5p) are in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including signal transduction, cell growth and death, and transport and catabolism. Among the target genes, 5 (RAB22A, SOX4, IKZF2, PLAG1, and BTBD7) were of interest because they can be simultaneously regulated by several DEMs. These findings suggest that these genes may be targets for modulating gastric cancer progression.
13幽门螺杆菌是动脉粥样硬化的感染性危险因素?
大量研究表明，幽门螺旋杆菌感染与某些发病机制以持续、低度系统性炎症为特征的胃外疾病有关。近期，幽门螺旋杆菌感染与动脉粥样硬化及其并发症临床之间的关系备受关注。动脉粥样硬化是一种多因素的疾病,传统的风险因素只能解释50%的病因。因此,寻找动脉粥样硬化的危险因素是十分重要的。本文从流行病学与病原学的角度寻找幽门螺旋杆菌的感染与动脉粥样硬化发生发展间的关系。
J Atheroscler Thromb. 2014 Oct 24. [Epub ahead of print]
Helicobacter pylori-An Infectious Risk Factor for Atherosclerosis?
Author information
Abstract
Accumulating evidence implicates Helicobacter pylori (H. pylori) infection in the pathogenesis of certain diseases localized outside the stomach, particularly those characterized by persistent and low-grade systematic inflammation. Recently, the role of H. pylori infection in the development of atherosclerosis and its clinical complications has received attention. Atherosclerosis is a high-cost disease, and acute events resulting from this condition rank first among morbidity and mortality statistics in most industrialized countries. Atherosclerosis is a multifactorial disorder, and traditional risk factors explain only 50% of its etiology. Therefore, identifying new risk factors for atherosclerosis is necessary. Serological studies indicate that chronic H. pylori infection, especially that with more virulent strains, may predispose patients to the onset of atherosclerosis and related adverse clinical events, and PCR studies have detected H. pylori DNA in atherosclerotic plaques, although this finding remains controversial. If this association were to be confirmed, its importance to public health would be substantial, as the eradication of H. pylori is more straightforward and less costly than the long-term treatment of other risk factors. This review investigates the potential relationship between H. pylori infection and atherosclerosis from both epidemiological and pathogenic perspectives and characterizes the potential mechanisms underlying this correlation.
14病例对照研究：幽门螺杆菌感染、非甾体类抗炎药、小剂量阿司匹林、抗高血压药物引起消化性溃疡出血的风险
截至目前，在幽门螺杆菌感染率高的亚洲地区，仍不明确抗凝或抗高血压药物等是否为消化性溃疡出血的危险因素。本研究旨在评估抗血栓形成的药物、血管紧张素II受体拮抗剂、血管紧张素转换酶(ACE)抑制剂、钙通道阻滞剂、α受体阻断剂、β受体阻断剂消化性溃疡出血引起风险。研究结果显示饮酒、消化性溃疡病史、幽门螺旋杆菌感染、非甾体类抗炎药的使用以及小剂量阿司匹林均为消化性溃疡出血的独立危险因素，但是一旦幽门螺旋杆菌得到根除或使用PPIs、H2RA可降低出血的风险
J Gastroenterol Hepatol. 2014 Oct 22. doi: 10.1111/jgh.12805. [Epub ahead of print]
Risk of peptic ulcer bleeding associated with Helicobacter pylori infection, NSAIDs, low-dose aspirin, and antihypertensive drugs: A case-control study.
Nagata N1, Niikura R, Sekine K, Sakurai T, Shimbo T, Kishida Y, Tanaka S, Aoki T, Okubo H, Watanabe K, Yokoi C,Akiyama J, Yanase M, Mizokami M, Uemura N.
Author information
Abstract
BACKGROUND:
The associations between antithrombotic or antihypertensive drugs and peptic ulcer bleeding (PUB) remain unknown, particularly in Asia, where Helicobacter pylori infection is prevalent. This study aims to evaluate the risks of PUB from antithrombotic drugs, angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, α-blockers, and β-blockers.
METHODS:
This prospective hospital-based case-control study included 230 patients with endoscopically verified PUB and 920 age- and sex-matched controls (1:4) without bleeding on screening endoscopy. Adjusted odds ratios (AOR) for the risk of PUB were determined by conditional logistic regression analysis.
RESULTS:
In multivariate analysis, alcohol consumption (AOR, 2.2; p<0.001), history of peptic ulcer (AOR, 4.8; p<0.001), H. pylori infection (AOR, 2.1; P<0.001), comorbidity index (AOR, 1.1; p=0.089), non-steroidal anti-inflammatory drugs (NSAIDs) (AOR, 2.0; P=0.025) and low-dose aspirin (AOR, 2.8; P=0.003) increased the risk of PUB, whereas H. pylori-eradication (AOR, 0.03; P<0.001), proton pump inhibitors (PPIs) (AOR, 0.1; P<0.001) and histamine 2-receptor antagonists (H2RA) (AOR, 0.1; P<0.001) reduced it. No significant interactions were observed between H. pylori infection and NSAIDs use for PUB (P=0.913). ARBs (P=0.564), ACE inhibitors (P=0.213), calcium channel blockers (P=0.215), α-blockers (P=0.810), and β-blockers (P=0.864) were not associated with PUB.
CONCLUSIONS:
We found that alcohol consumption, history of peptic ulcer, H. pylori infection, NSAIDs use, and low-dose aspirin use were independent risk factors for PUB, whereas H. pylori-eradication, PPIs use, and H2RA use reduced its risk. Interactions between H. pylori and NSAIDs use in PUB were not observed. No antihypertensive drug was associated with PUB.
This article is protected by copyright. All rights reserved.
15巨噬细胞释放的细胞因子BAFF在幽门螺旋杆菌感染性慢性胃炎中引发Th17 响应
BAFF是一种重要的细胞因子，可影响固有免疫细胞及适应性免疫细胞的活性。它促进Th17细胞在自身免疫性疾病的进展。本研究旨在探索在幽门螺旋杆菌感染性慢性胃炎中BAFF对Th17的影响。
研究结果显示，确实存在幽门螺旋杆菌感染患者体内确实存在依赖幽门螺旋杆菌的BAFF/Th17反应链。此外，本研究还发现，BAFF既可通过影响固有免疫细胞分泌Th17前体来间接诱导Th17反应活动，还可通过影响变异T细胞直接接到Th17反应活动。
J Immunol. 2014 Oct 22. pii: 1302865. [Epub ahead of print]
Cytokine BAFF Released by Helicobacter pylori-Infected Macrophages Triggers the Th17 Response in Human Chronic Gastritis.
Munari F1, Fassan M2, Capitani N3, Codolo G1, Vila-Caballer M1, Pizzi M4, Rugge M4, Della Bella C5, Troilo A5,D'Elios S5, Baldari CT6, D'Elios MM7, de Bernard M8.
Author information
Abstract
BAFF is a crucial cytokine that affects the activity of both innate and adaptive immune cells. It promotes the expansion of Th17 cells in autoimmune disorders. With this study, we investigated the BAFF/Th17 responses in Helicobacter pylori-induced gastritis in humans. Our results show that the mucosa from Helicobacter+patients with chronic gastritis is enriched in IL-17 and BAFF, whereas the two cytokines are weakly expressed in Helicobacter- patients with chronic gastritis; moreover, the expression of both BAFF and IL-17 decreases after bacteria eradication. We demonstrate that BAFF accumulates in macrophages in vivo and that it is produced by monocyte-derived macrophages in vitro, after Helicobacter stimulation. Application of BAFF on monocytes triggers the accumulation of reactive oxygen species that are crucial for the release of pro-Th17 cytokines, such as IL-23, IL-1β, and TGF-β. Moreover, BAFF directly promotes the differentiation of Th17 cells. In conclusion, our results support the notion that an axis BAFF/Th17 exists in chronic gastritis of Helicobacter+ patients and that its presence strictly depends on the bacterium. Moreover, we demonstrated that BAFF is able to drive Th17 responses both indirectly, by creating a pro-Th17 cytokine milieu through the involvement of innate immune cells, and directly, via the differentiation of T cells toward the specific profile. The results obtained in this study are of great interest for Helicobacter-related diseases and the development of novel therapeutic strategies based on the inhibition of the BAFF/IL-17 response.
16 幽门螺杆菌外炎性蛋白的核酸菌蜕疫苗能够提高C57BL/6小鼠的免疫保护力
该项研究探索了新的研发抗HP感染疫苗的方法。并在小鼠中做了评估实验。
Vaccine. 2014 Oct 21;32(46):6054-60. doi: 10.1016/j.vaccine.2014.09.014. Epub 2014 Sep 16.
Helicobacter pylori outer inflammatory protein DNA vaccine-loaded bacterial ghost enhances immune protective efficacy in C57BL/6 mice.
Author information
Abstract
Helicobacter pylori (H. pylori) infection is associated with incidents of gastrointestinal diseases in half of the human population. However, management of its infection remains a challenge. Hence, it is necessary to develop an efficient vaccine to fight against this pathogen. In the present study, a novel vaccine based on the production of attenuated Salmonella typhimurium bacterial ghost (SL7207-BG), delivering H. pylori outer inflammatory protein gene (oipA) encoded DNA vaccine was developed, and the efficiency was evaluated in C57BL/6 mice. Significant higher levels of IgG2a/IgG1 antibodies and IFN-γ/IL-4 cytokines were detected after mice were oral administered with oipA DNA vaccine loaded SL7207-BG, indicating that a mixed Th1/Th2 immune response was elicited. When challenged with infective doses H. pylori strain SS1, the ghost based vaccine was capable of reducing bacterium colonization in the vaccinated mice. In addition, codon-optimized oipA plasmid loaded SL7207-BG significantly eliminates H. pylori colonization density in mice model. Thus, it has been demonstrated that this novel bacterial ghost based DNA vaccine could be used as a promising vaccine candidate for the control of H. pylori infection.
Copyright © 2014 Elsevier Ltd. All rights reserved.
17. 对日本儿童和青少年的发炎牙髓标本进行幽门螺杆菌DNA的检测
口腔感染被人为是儿童期HP感染的一个传播途径。已有很多研究报道利用不同PCR方法检测口腔标本中HP的DNA，其检出率亦不同。在该研究中，研究者构建了一个新的PCR幽门螺杆菌检测系统，并用它来分析口腔标本。结果显示在牙髓标本中可以检测到HP，而在唾液中为阴性。提示牙髓的根管可能是HP贮存的场所。
J Med Microbiol. 2014 Oct 20. pii: jmm.0.079491-0. doi: 10.1099/jmm.0.079491-0. [Epub ahead of print]
Detection of Helicobacter pylori DNA in inflamed dental pulp specimens from Japanese children and adolescents.
Ogaya Y1, Nomura R2, Watanabe Y3, Nakano K1.
Author information
Abstract
The oral cavity has been implicated as a source of Helicobacter pylori infection in childhood. Various PCR methods have been used to detect H. pylori DNA in oral specimens with various detection rates reported. Such disparity in detection rates complicates the estimation of the true infectious rate of H. pylori in the oral cavity. In the present study, we constructed a novel PCR system for H. pylori detection and used it to analyze oral specimens. Firstly, the nucleotide alignments of genes commonly used for H. pylori detection were compared using complete genome information for 48 strains registered in the GenBank database. Candidate primer sets with an estimated amplification size of approximately 300-400 bp were selected, and the specificity and sensitivity of the detection system using each primer set evaluated. Five sets of primers targeting urea were considered appropriate, of which a single primer set was chosen for inclusion in the PCR system. The sensitivity of the system was considered appropriate and its detection limit established as 1-10 cells per reaction. The novel PCR system was used to examine H. pylori distribution in oral specimens (40 inflamed pulp tissues, 40 saliva samples) collected from Japanese children, adolescents, and young adults. PCR analysis revealed that the detection rate of H. pylori in inflamed pulp was 15%, whereas no positive reaction was found in any of the saliva specimens. Taken together, our novel PCR system was found to be reliable for detecting H. pylori. The results obtained showed that H. pylori was detected in inflamed pulp but not saliva specimens, indicating that an infected root canal may be a reservoir for H. pylori.
Copyright © 2014, the Society for General Microbiology.
18. 对使用过氧化氢酶单克隆抗体来检测粪便标本中幽门螺杆菌方法在儿童和成人人群中应用的评价
找到无创检测HP的合适方法意义重大。该研究对151例粪便样本应用过氧化氢酶单克隆抗体法进行了HP的检测。结果证明非常有效，而且特异性较高。
J Med Microbiol. 2014 Oct 20. pii: jmm.0.077370-0. doi: 10.1099/jmm.0.077370-0. [Epub ahead of print]