1. 幽门螺杆菌通过直接定植在胃腺激活和放大Lgr5(+)干细胞
本研究在人和小鼠幽门螺杆菌感染模型中探讨了幽门螺杆菌与胃上皮干细胞间交互作用在胃上皮病理改变中的作用。定植于胃腺的幽门螺杆菌刺激干细胞增殖和表达Lgr，并且上调干细胞相关基因表达。在小鼠中，伴有趋化因子基因突变的菌株和不能分泌幽门螺杆菌相关毒力因子CagA的菌株不能激活干细胞进而导致胃黏膜病理改变。
Sigal M(1), Rothenberg ME(2), Logan CY(3), Lee JY(4), Honaker RW(5), Cooper
RL(5), Passarelli B(6), Camorlinga M(7), Bouley DM(8), Alvarez G(9), Nusse R(3),
Torres J(7), Amieva MR(10).
Gastroenterology. 2015 Feb 25. pii: S0016-5085(15)00271-1. doi: 10.1053/j.gastro.2015.02.049. [Epub ahead of print]
BACKGROUND & AIMS: Helicobacter pylori infection is the main risk factor for gastric cancer. We characterized
the interactions of H pylori with gastric epithelial progenitor and stem cells in humans and mice and investigated how
these interactions contribute to H pylori-induced pathology.
METHODS: We used quantitative confocal microscopy and 3-dimensional reconstruction of entire gastric glands to determine the localizations of H pylori in stomach tissues from
humans and infected mice. Using lineage tracing to mark cells derived from Lgr5+ stem cells (Lgr5-eGFP-IRES-CreERT2/Rosa26-TdTomato mice) and in situ hybridization, we analyzed gastric stem cell responses to infection. Isogenic H pylori
mutants were used to determine the role of specific virulence factors in stem cell activation and pathology.
RESULTS: H pylori grow as distinct bacterial microcolonies deep in the stomach glands and interact directly with
gastric progenitor and stem cells in tissues from mice and humans. These gland-associated bacteria activate stem cells, increasing the number of stem cells, accelerating Lgr5(+) stem cell proliferation, and upregulating expression of stem cell-related genes. Mutant bacteria with defects in chemotaxis that are able to colonize the stomach surface but not the
antral glands in mice do not activate stem cells. Moreover, bacteria that are unable to inject the contact-dependent virulence factor CagA into the epithelium colonized stomach glands in mice, but did not activate stem
cells or produce hyperplasia to the same extent as wild-type H pylori.
CONCLUSIONS: H pylori colonize and manipulate the progenitor and stem cell compartments, which alters turnover
kinetics and glandular hyperplasia. Bacterial ability to alter the stem cells has important implications for
gastrointestinal stem cell biology and H pylori-induced gastric pathology.
2. 炎症和增生：宿主对幽门螺杆菌感染的应答反应
本文详细阐述了当前有关幽门螺杆菌感染导致机体多条调控信号通路激活并导致癌症发生发展的相关研究。
Inflammation and proliferation- A causal event of host response to H. pylori infection.
Subhash VV(1), Ho B(1).
Microbiology. 2015 Feb 26. pii: mic.0.000066. doi: 10.1099/mic.0.000066. [Epub ahead of print]
H. pylori is a major etiological agent in the development of various gastro-duodenal diseases. Its persistence in gastric mucosa is determined by the interaction between various host, microbial
and environmental factors. The bacteria colonizes the gastric epithelium and induces activation of various chemokine
mediators, including NFKB, the master regulator of inflammation. H.pylori infection is also associated with an
increase in expression of cell cycle regulators thereby leading to mucosal cell hyper proliferation. Thus, H.pylori-associated infections manifest activation of key host response events, which inadvertently could lead to the
establishment of chronic infection and neoplastic progression. This article reviews and elaborates the current
knowledge in H. pylori induced activation of various host signaling pathways that could promote cancer development.
Special focus is placed on the inflammatory and proliferative responses that could serve as suitable biomarkers of
infection, since a sustained cell proliferation in an environment rich in inflammatory cells is characteristic in
H. pylori-associated gastric malignancies. Here, the role of ERK and WNT signaling in H. pylori-induced activation of inflammatory and proliferative responses respectively is discussed in detail. An in depth analysis
of the underlying signaling pathways and interacting partners causing alterations in these crucial host responses could
contribute to the development of successful therapeutic strategies for the prevention, management and treatment of
H. pylori infection.
3.含环丙沙星与含克拉霉素的序贯疗法对幽门螺杆菌根除治疗疗效的随机对照研究
这项在印度进行的研究将212例患者随机分为2组，旨在评价含环丙沙星和含克拉霉素14天序贯疗法的幽门螺杆菌根除治疗疗效。结果显示，含环丙沙星序贯疗法的根除率高于含克拉霉素序贯疗法（根除率分别为87.6% vs 76%），且两者在患者依从性和副作用方面无显著差异。
Ciprofloxacin-containing versus clarithromycin-containing sequential therapy for
Helicobacter pylori eradication: A randomized trial.
Chaabane NB(1), Al-Adhba HS.
Indian J Gastroenterol. 2015 Feb 28. [Epub ahead of print]
BACKGROUND AND STUDY AIMS: Helicobacter pylori eradication rates with standard triple therapy have declined
to unacceptable levels. This randomized trial aimed at evaluating the efficacy of a ciprofloxacin containing sequential
regimen in the eradication of H. pylori-infected patients vs. a clarithromycin containing sequential therapy.
METHODS: A total of 212 patients were randomized into 14-day therapeutic schemes (106 patients per group): (1) clarithromycin-containing sequential therapy rabeprazole plus amoxicillin for 7 days, followed by rabeprazole plus clarithromycin
plus metronidazole for 7 days, and (2) ciprofloxacin-containing sequential therapy using ciprofloxacin instead of clarithromycin. Eradication was confirmed by stool
H. pylori antigen. Adverse effects and compliance were assessed by a questionnaire.
RESULTS: Per protocol cure rates were as follows: 87.6 % in the ciprofloxacin-containing sequential therapy and 76 % in the clarithromycin group. Intention-to-treat cure rates were as follows: 73.5 % for the ciprofloxacin group and 66 % for the clarithromycin group. No
differences in compliance or adverse effects were demonstrated among treatments.
CONCLUSION: Ciprofloxacin-containing sequential therapy is more effective and equally safe compared to a clarithromycin-containing sequential therapy.
4. 幽门螺杆菌在喉鳞状细胞癌中的作用
本研究为病例对照研究，通过实时定量PCR方法对74例土耳其喉鳞状细胞癌患者的组织样本进行HP检测，发现1例患者组织中存在HP。然而，进一步采用组织病理学评价和HP免疫组织化学检查均未得到证实，表明HP与上呼吸道病患之间的关联尚不能得到肯定结论。
The presence of Helicobacter pylori in laryngeal squamous cell carcinoma.
Yilmaz I(1), Erkul E, Berber U, Kucukodaci Z, Narli G, Haholu A, Demirel D.
Eur Arch Otorhinolaryngol. 2015 Feb 27. [Epub ahead of print]
A definitive relationship between Helicobacter pylori (HP) and upper respiratory tract disorders has not been
established. In this case-control study, we investigated the relationship between HP and laryngeal carcinoma by real-time PCR method in Turkey. 74 subjects were enrolled from patients who were admitted to the Otolaryngology
Department. Formalin-fixed-paraffin-embedded tissue samples with laryngeal cancer were used and all samples were evaluated by real-time PCR method. Our study population included 72 males and 2 females with a mean age range of 62.7 years.
Helicobacter Pylori was detected in only one case. The positive case was also investigated with histopathologic
evaluation and HP immunohistochemistry. However, we could not detect HP in this case with both methods.
This study revealed that HP might not contribute to the pathogenesis of laryngeal carcinoma. A definitive relationship
between HP and upper respiratory tract disorders has not been established.
5.骨髓中HIF-1在幽门螺杆菌相关胃炎中的保护作用
低氧诱导因子（HIFs）是细胞适应低氧环境的核心调控分子，近期被发现在免疫和炎症中起重要的转录调控作用。本研究检测了幽门螺杆菌相关胃炎组织，幽门螺杆菌感染野生型和骨髓HIF-1α敲除小鼠的HIF1和HIF2的表达，提示骨髓中HIF-1在幽门螺杆菌相关胃炎中的保护作用。
Myeloid HIF-1 Is Protective in Helicobacter pylori-Mediated Gastritis.
Matak P(1), Heinis M(1), Mathieu JR(1), Corriden R(2), Cuvellier S(1), Delga
S(1), Mounier R(3), Rouquette A(4), Raymond J(4), Lamarque D(5), Emile JF(5),
Nizet V(2), Touati E(6), Peyssonnaux C(7).
J Immunol. 2015 Feb 20. pii: 1401260. [Epub ahead of print]
Helicobacter pylori infection triggers chronic inflammation of the gastric mucosa that may progress to gastric cancer.
The hypoxia-inducible factors (HIFs) are the central mediators of cellular adaptation to low oxygen levels (hypoxia), but they have
emerged recently as major transcriptional regulators of immunity and inflammation. No studies have investigated
whether H. pylori affects HIF signaling in immune cells and a potential role for HIF in H. pylori-mediated gastritis. HIF-1 and HIF-2 expression was examined in human H. pylori-positive gastritis biopsies. Subsequent experiments were performed in naive and polarized bone marrow-derived macrophages from wild-type (WT) and myeloid HIF-1α-null mice (HIF-1(Δmyel)). WT and HIF-1(Δmyel) mice were inoculated with H. pylori by oral gavage and sacrificed 6 mo postinfection. HIF-1 was specifically expressed in macrophages of human H. pylori-positive gastritis biopsies. Macrophage HIF-1 strongly contributed to the induction of proinflammatory genes (IL-6, IL-1β) and inducible NO synthase in response to H. pylori. HIF-2 expression and markers of M2 macrophage differentiation were decreased in response to H. Pylori. HIF-1(Δmyel) mice inoculated with H. pylori for 6 mo presented with a similar bacterial colonization than WT mice but,
surprisingly, a global increase of inflammation, leading to a worsening of the gastritis, measured by an increased
epithelial cell proliferation. In conclusion, myeloid HIF-1 is protective in H.pylori-mediated gastritis, pointing to the complex counterbalancing roles of innate immune and inflammatory phenotypes
in driving this pathology.
6. 幽门螺杆菌毒力因子CagA 在细菌微转运系统（ibNOTs）内的转运路径
本研究采用免疫电子显微镜技术发现幽门螺杆菌内CagA定位于MreB细丝附近，并且MreB阻断剂A22能够影响细菌对CagA的转运，而此种效应未在尿素酶转运中发现。提示MreB细丝参与了CagA在幽门螺杆菌菌体内的转运。
Route of intrabacterial nanotransportation system for CagA in Helicobacter pylori.
Wu H(1), Iwai N, Nakano T, Ooi Y, Ishihara S, Sano K.
Med Mol Morphol. 2015 Feb 24. [Epub ahead of print]
Helicobacter pylori (H. pylori) possesses an intrabacterial nanotransportation system (ibNoTS) for transporting CagA
and urease within the bacterial cytoplasm; this system is controlled by the extrabacterial environment.
The transportation routes of the system have not yet been studied in detail. In this study, we demonstrated by
immunoelectron microscopy that CagA localizes closely with the MreB filament in the bacterium, and MreB
polymerization inhibitor A22 obstructs ibNoTS for CagA. These findings indicate that the route of ibNoTS for
CagA is closely associated with the MreB filament. Because these phenomena were not observed in ibNoTS for
urease, the route of ibNoTS for CagA is different from that of ibNoTS for urease as previously suggested.
We propose that the route of ibNoTS for CagA is associated with the MreB filament in H. pylori.
7. 幽门螺杆菌根除后胃腺瘤的形态学和组织学改变：一项长期前瞻性研究
通过对27例成功根除幽门螺杆菌的胃腺瘤患者进行平均长达91.9个月的随访研究发现12例患者出现了肉眼可见的逆转，其中7例患者出现了组织学逆转，其平均好转时间为19.9个月；另15例患者的腺瘤在肉眼和组织学上保持稳定，其中6例患者在随访期间进展为恶性肿瘤。提示根除幽门螺杆菌可能逆转部分胃腺瘤患者组织学改变。
Morphologic and Histologic Changes in Gastric Adenomas After Helicobacter pylori
Eradication: A Long-Term Prospective Analysis.
Suzuki S(1), Gotoda T, Suzuki H, Kono S, Iwatsuka K, Kusano C, Oda I, Sekine S,
Moriyasu F.
Helicobacter. 2015 Feb 23. doi: 10.1111/hel.12218. [Epub ahead of print]
BACKGROUND: Helicobacter pylori infection causes gastric neoplasia via development of chronic atrophic gastritis
and intestinal metaplasia. The effect of H. pylori eradication on pre-existing gastric neoplasias is still controversial. The aim of this study was to use long-term observation to clarify morphologic and histologic changes in gastric adenomas following H. Pylori eradication.
MATERIALS AND METHODS: Twenty-seven patients with gastric adenomas (revised Vienna classification category 3 or 4.1) who underwent successful
H. Pylori eradication between April 1996 and December 1997 were followed up at regular intervals with endoscopic
and histologic examination. The association between macroscopic and histologic regressions of the lesions and the
following patient and lesion characteristics was assessed with univariate analysis: follow-up period, age, sex, serum pepsinogen level, lesion size, lesion location, and histologic gastritis.
RESULTS: The mean follow-up period was 91.9 months (range 44-181 months). Twelve lesions (44.4%) showed macroscopic regression, of which 7 (25.9% of the total) also showed
histologic regression, with the mean duration from H. Pylori eradication to complete macroscopic and histologic
regression being 19.9 months. The other 15 lesions (55.6%) remained stable macroscopically and histologically,
of which 6 (22.2% of the total) progressed to malignancy during the follow-up period. Univariate analysis revealed that female sex (p = .005), smaller lesion size (p = .025), higher baseline
serum pepsinogen II level (p = .041), and absence of intestinal metaplasia in the greater curvature of the corpus
(p = .026) were significantly associated with complete regression.
CONCLUSIONS: Helicobacter pylori eradication may induce regression in some gastric adenomas.
8.幽门螺杆菌通过新的非HB-EGF依赖的TAK1-p38活化途径导致EGFR丝氨酸磷酸化
感染野生型和cagA（-）幽门螺杆菌菌株的胃上皮细胞中可观察到EGFR 丝氨酸残端的快速和瞬态磷酸化。其磷酸化可被针对TAK1和p38的siRNA阻断，进一步流式细胞术和免疫荧光显示，EGFR以依赖p38磷酸化的方式进入幽门螺杆菌感染的细胞内。而EGFR的磷酸化及入胞不能被提前的药物和抗HB-EGF处理所阻断。
Zaidi SF(1), Refaat A, Zhou Y, Sualeh Muhammad J, Shin MS, Saiki I, Sakurai H,
Sugiyama T.
Helicobacter. 2015 Feb 23. doi: 10.1111/hel.12215. [Epub ahead of print]
BACKGROUND: The interaction of Helicobacter pylori with gastric epithelial cells can result in the activation of
transcription factor NF-κB via TGF-β-activated kinase 1 (TAK1). In this study, we have demonstrated the role of H. pylori in the activation of EGFR via
TAK1-mediated phosphorylation of p38.
MATERIALS AND METHODS: Gastric epithelial AGS or MKN-45 cells were co-cultured with wild-type or cagA(-) H. pylori strains. H. pylori was added to the cells, and the activation of EGFR, p65 (NF-κB) subunit, p38, ERK, and TAK1 was examined by Western blotting. Infected cells were pretreated with or without
ligands, chemical inhibitors, anti-HB-EGF antibody, and siRNAs to evaluate the effects on phosphorylation of various EGFR residues. Fluorescence
microscopy and flow cytometry were performed to detect the internalization of EGFR.
RESULTS: Incubating cells with wild-type and CagA(-) H. pylori strains resulted in the rapid and transient phosphorylation of serine residues of EGFR. RNAi experiments
using siRNA against TAK1 and p38 pathways blocked the phosphorylation of serine residue. Immunofluorescence
and flow cytometry revealed that EGFR was internalized in H. pylori-infected cells after EGFR phosphorylation in a p38-dependent manner. In contrast, pretreatment with gefitinib and anti-HB-EGF antibody did not block both the phosphorylation and internalization of EGFR.
CONCLUSION: Helicobacter pylori induces internalization of EGFR via novel TAK1-p38-serine activation pathway which is independent of HB-EGF. The interaction between TAK1 and EGFR in
H. pylori-infected cells might open new dimensions in understanding H. pylori-associated gastric carcinogenesis.
9.MUC2, MUC5AC和MUC6在儿童和青少年正常、幽门螺杆菌感染和肠化生胃黏膜的表达
本文探讨了胃黏蛋白表达与年龄和幽门螺杆菌感染状况的关系。根据年龄、幽门螺杆菌感染和肠化生情况将样本分为9组：是否小于5岁感染幽门螺杆菌、是否在5岁至9岁之间感染、是否在10至14岁之间感染、是否在21岁至29岁之间感染和21-35岁发生肠化生。结果显示与在21岁至29岁之间感染幽门螺杆菌患者相比，肠上皮化生患者MUC2, MUC5AC和MUC6表达增加；MUC5AC在大于5岁感染患者中与非感染患者中表达明显下降；MUC2和MUC6表达水平与幽门螺杆菌感染状态不相关。
Park JS , Yeom JS, Seo JH, Lim JY, Park CH, Woo HO, Youn HS, Jun JS, Park JH,Ko GH, Baik SC, Lee WK, Cho MJ,
Rhee KH.
Helicobacter. 2015 Feb 23. doi: 10.1111/hel.12198. [Epub ahead of print]
OBJECTIVES: The aim of this study was to investigate expression of gastric mucins in children and adolescents and
to assess their relations with age and Helicobacter pylori (H. pylori) infection.
METHODS: Gastric biopsies were collected from 259 pediatric and adulthood patients with gastrointestinal
symptoms among all of patients undergone gastroduodenoscopy from 1990 to 2004 at Gyeongsang National
University hospital and assorted based on H. pylori infection, age, and intestinal metaplasia as follows; H. pylori
infection before 5 years of age or not, H. pylori infection between 5 and 9 years of age or not, H. pylori infection
between 10 and 14 years of age or not, H. pylori infection between 20 and 29 years of age or not and intestinal
metaplasia between 21 and 35 years of age. Total 810 tissue slides from the subjects were examined regarding
expressions of Mucin2 (MUC2), Mucin5AC (MUC5AC), and Mucin6 (MUC6) in nine groups using immunohistochemical
stains. A semiquantitative approach was used to score the staining extent of tissue slide.
RESULTS: Increased expressions of MUC2, MUC5AC, and MUC6 were noted in intestinal metaplasia compared with
subjects infected with H. pylori between 20 and 29 years. Gastric expressions of MUC5AC were decreased in older
than 5 years with H. pylori compared with in older than 5 years without H. pylori (p < .001). Expressions of MUC2
and MUC6 did not change significantly by H. pylori status. Some nuclear expressions of MUC2 and MUC6 were noted
in children without intestinal metaplasia.
CONCLUSIONS: MUC5AC might be affected by chronic H. pylori infection. In addition to biomarkers for intestinal
metaplasia or prognostic factors for gastric cancer in adults, MUC2 and MUC6 in children might have an another role,
based on ectopic gastric nuclear expressions of MUC2 and MUC6 in children without intestinal metaplasia.
10.由高剪切熔体造粒技术制备的高载量克拉霉素胃悬浮颗粒能增强幽门螺杆菌根除率。
本文对由高剪切熔体造粒工艺制备的75%克拉霉素（CAM）与三种不同的疏水性粘合剂组成的细颗粒性能进行了评价，并且在体内实验证明该种新型药物与单纯克拉霉素相比能更有效根除幽门螺杆菌。
Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear
melt granulation can enhance the efficacy of Helicobacter pylori eradication.
Aoki H(1), Iwao Y(1), Mizoguchi M(1), Noguchi S(1), Itai S(2).
Eur J Pharm Biopharm. 2015 Feb 19. pii: S0939-6411(15)00094-6. doi:10.1016/j.ejpb.2015.02.012. [Epub ahead of print]
In an effort to develop a new gastro-retentive drug delivery system (GRDDS) without a large amount of additives, 75% clarithromycin (CAM) loaded fine
granules were prepared with three different hydrophobic binders by high-shear melt granulation and their properties were evaluated. Granules containing the higher hydrophobic binder showed
sustained drug release and were able to float over 24h. The synchrotron X-ray CT measurement indicated that both the high hydrophobicity of the binder and the void space inside the granules
might be involved in their buoyancy. In an in vivo experiment, the floating granules more effectively eradicated
Helicobacterpylori than a CAM suspension by remaining in the stomach for a longer period. In short, CAM highly-loaded gastro-floating fine granules can enhance the eradication efficiency of H. pylori compared with CAM alone.
11.含左氧氟沙星铋剂四联14 天疗法在标准三联或不含铋剂四联疗法根除幽门螺杆菌失败后的二线补救治疗
最常用的二线治疗方案有含铋四联疗法和含左氧氟沙星三联疗法，然而其疗效欠佳，这项纳入了200例患者的前瞻性多中心研究结果显示含左氧氟沙星铋剂四联14天疗法是一种简单、有效、安全的补救治疗方案，其根除率PP和ITT分别为91.1%和90%。
Gisbert JP(1), Romano M, Gravina AG, Solís-Muñoz P, Bermejo F, Molina-Infante J,
Castro-Fernández M, Ortuño J, Lucendo AJ, Herranz M, Modolell I, Del Castillo F,
Gómez J, Barrio J, Velayos B, Gómez B, Domínguez JL, Miranda A, Martorano M,
Algaba A, Pabón M, Angueira T, Fernández-Salazar L, Federico A, Marín AC,
McNicholl AG.
Aliment Pharmacol Ther. 2015 Feb 23. doi: 10.1111/apt.13128. [Epub ahead of print]
BACKGROUND: The most commonly used second-line Helicobacter pylori eradication regimens are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the
efficacy of rescue eradication regimens.
AIMS: To evaluate the efficacy and tolerability of a second-line quadruple regimen containing levofloxacin and bismuth in patients whose previous H. pylori eradication treatment
failed.
METHODS: This was a prospective multicenter study including patients in whom a standard triple therapy (PPI-clarithromycin-amoxicillin) or a non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-metronidazole, either sequential or concomitant) had failed. Esomeprazole (40 mg b.d.), amoxicillin (1 g b.d.),
levofloxacin (500 mg o.d.) and bismuth (240 mg b.d.) was prescribed for 14 days. Eradication was confirmed by
(13) C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes.
Incidence of adverse effects was evaluated by questionnaires.
RESULTS: 200 patients were included consecutively (mean age 47 years, 67% women, 13% ulcer). Previous failed
therapy included: standard clarithromycin triple therapy (131 patients), sequential (32) and concomitant (37).
A total of 96% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 91.1% (95%CI = 87-95%) and 90% (95%CI = 86-94%). Cure rates were similar regardless of previous (failed) treatment or country of origin. Adverse effects were
reported in 46% of patients, most commonly nausea (17%) and diarrhoea (16%); 3% were intense but none was
serious.
CONCLUSIONS: Fourteen-day bismuth- and levofloxacin-containing quadruple therapy is an effective (≥90% cure rate), simple and safe second-line strategy in patients whose previous standard triple or non-bismuth quadruple (sequential or concomitant) therapies have failed.
12.幽门螺杆菌菌株Hp238的全基因组测序和结果注释：分离自一名台湾MALT淋巴瘤患者
Hp238菌株能够通过诱导自噬小体形成内化至THP-1细胞内进行繁殖，本研究通过对该菌株进行全基因组测序，以期了解其繁殖相关基因和机制。
Genome Sequence and Annotation of Helicobacter pylori Strain Hp238, Isolated from
a Taiwanese Patient with Mucosa-Associated Lymphoid Tissue Lymphoma.
Kao CY(1), Chen JW(2), Huang YT(1), Sheu SM(3), Sheu BS(3), Wu JJ(4).
Genome Announc. 2015 Feb 19;3(1). pii: e00006-15. doi: 10.1128/genomeA.00006-15.
We present the complete genome sequence of Helicobacter pylori strain Hp238, isolated from a Taiwanese patient
with gastric mucosa-associated lymphoid tissue lymphoma. Importantly, H. pylori strain Hp238 can multiply in THP-1 cells after internalization through the induction of autophagosome formation. These genome data will help to identify
genes associated with H. pylori intracellular multiplication and pathogenesis.
13. 幽门螺杆菌通过c-Jun/miR-203/SOCS3信号途径造成肝脏胰岛素抵抗
合并幽门螺杆菌感染的患者和小鼠模型体内快速血糖水平明显升高。在幽门螺杆菌感染的糖尿病小鼠模型中，幽门螺杆菌通过诱导转录因子c-Jun来下调miR-203的表达进而上调胰岛素信号转导抑制蛋白SOCS3导致肝脏细胞的胰岛素抵抗。
Zhou X(1), Liu W, Gu M, Zhou H, Zhang G.
J Gastroenterol. 2015 Feb 19. [Epub ahead of print]
BACKGROUND: Epidemiological studies have indicated that patients with chronic Helicobacter pylori infection have
an increased risk of developing type 2 diabetes mellitus, but the underlying mechanisms remain largely unknown.
This study aimed to investigate whether H. pylori infection contributes to the development of insulin resistance,
as well as the underlying mechanisms both in vivo and in vitro.
METHODS: The effect of H. pylori infection on glucose metabolism was evaluated in humans and mouse models.
The role of the c-Jun/miR-203/suppressor of cytokine signaling 3 (SOCS3) pathway in H. pylori-induced insulin resistance was determined in vitro and was validated in vivo.
RESULTS: Average fasting glucose levels were increased in patients (P = 0.012) and mice (P = 0.004) with H. pylori
infection. Diabetic mice with H. Pylori infection showed impaired glucose metabolism and insulin tolerance and
hyperinsulinemia. Furthermore, H. pylori infection impaired insulin signaling in primary hepatocytes. H. pylori
infection could upregulate SOCS3, a well-known insulin signaling inhibitor, by downregulating miR-203. SOCS3 overexpression interfered with insulin signaling proteins, and knockdown of SOCS3 alleviated H. pylori-induced impairment of insulin signaling. The transcription factor c-Jun, which affects gene expression, was induced by H. pylori infection and suppressed miR-203 expression.
CONCLUSIONS: Our results demonstrated that H. pylori infection induced hepatic insulin resistance by the c-Jun/miR-203/SOCS3 signaling pathway and provide possible implications with regard to resolving insulin resistance.
14. 幽门螺杆菌在非裔美国人和拉非裔退伍军人中流行率仍很高
本研究采用横断面调查研究观察了随着社会经济水平提高不同种族人群幽门螺杆菌感染差别是否有所改变。结果显示退伍军人中幽门螺杆菌现症感染率仍很高，达28.9%，而在具有更低教育水平的非裔和拉非裔人群中甚至更高。
The Prevalence of Helicobacter pylori Remains High in African American and Hispanic Veterans.
Nguyen T(1), Ramsey D, Graham D, Shaib Y, Shiota S, Velez M, Cole R, Anand B,
Vela M, El-Serag HB.
Helicobacter. 2015 Feb 17. doi: 10.1111/hel.12199. [Epub ahead of print]
BACKGROUND: Helicobacter pylori in the United States has been declining in the 1990s albeit less so among blacks
and Hispanics. As the socioeconomic status of racial groups has evolved, it remains unclear whether the prevalence or
the racial and ethnic disparities in the prevalence of H. pylori have changed.
METHODS: This is a cross-sectional study from a Veteran Affairs center among patients aged 40-80 years old who underwent a study esophagogastroduodenoscopy with gastric biopsies, which were cultured for
H. pylori irrespective of findings on histopathology. Positive H. pylori was defined as positive culture or
histopathology (stained organism combined with active gastritis). We calculated age-, race-, and birth cohort-specific H. pylori prevalence rates and examined predictors of H. pylori infection in logistic regression models.
RESULTS: We analyzed data on 1200 patients; most (92.8%) were men and non-Hispanic white (59.9%) or black (28.9%). H. pylori was positive in 347 (28.9%) and was highest among black males
aged 50-59 (53.3%; 44.0-62.4%), followed by Hispanic males aged 60-69 (48.1%; 34.2-62.2%), and lowest in non-Hispanic white males aged 40-49 (8.2%; 2.7-20.5%). In multivariate analysis, age group 50-59 was significantly associated with H. pylori (adjusted odds ratio (OR), 2.32; 95% confidence interval (CI), 1.21-4.45) compared with those aged 40-49, and with black race (adjusted OR, 2.57; 95% CI, 1.83-3.60) and Hispanic ethnicity (adjusted OR, 3.01; 95% CI, 1.70-5.34) compared with non-Hispanic white. Irrespective of age group, patients born during 1960-1969 had a lower risk of H. pylori (adjusted OR, 0.45; 95% CI, 0.22-0.96) compared to those born in 1930-1939. Those with some college education were less likely to have H. Pylori compared to those with no college
education (adjusted OR 0.51; 95% CI, 0.37-0.69).
CONCLUSION: Among veterans, the prevalence of active H. pylori remains high (28.9%) with even higher rates in
blacks and Hispanics with lower education levels.
15.幽门螺杆菌FK506结合蛋白家族肽基脯氨酰顺反异构酶通过激活ERK介导的促有丝分裂信号通路促进胃上皮细胞增殖和非锚定式增长
去除幽门螺杆菌肽基脯氨酰顺反异构酶能够抑制胃上皮细胞增殖。进一步研究显示幽门螺杆菌肽基脯氨酰顺反异构酶能够增加ERK和EGF受体在Tyr1086的磷酸化，而用MEK抑制剂能够完全阻断肽基脯氨酰顺反异构酶导致的上皮细胞增殖效应。
Zhu Y(1), Chen M(2), Gong Y(2), Liu Z(3), Li A(2), Kang D(2), Han F(2), Liu J(2),
Liu J(4), Yuan Y(2).
FEMS Microbiol Lett. 2015 Feb 16. pii: fnv023. [Epub ahead of print]
ThoSugh Helicobacter pylori (H. pylori) has been classified as class I carcinogen, key virulence factorabs(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.
16.在高危中国人群中探索Toll样受体1和10基因多态性与幽门螺杆菌易感性和胃黏膜病变之间的相关性
本研究探讨了TLR1 rs4833095, TLR10 rs10004195和TLR10 rs4129009基因多态性与幽门螺杆菌易感性和胃黏膜病变之间的相关性，关联分析结果表明TLR1 rs4833095 T等位基因或CT 基因型与幽门螺杆菌低感染率、慢性萎缩性胃炎和肠上皮化生低风险相关。TLR10 rs10004195 T 等位基因亦和慢性萎缩性胃炎低风险相关。单倍型分析显示rs4833095和rs10004195TT基因型在幽门螺杆菌易感性和胃部癌前病变中起保护性作用。
Toll-like receptor 1 and 10 polymorphisms, Helicobacter pylori susceptibility and
risk of gastric lesions in a high-risk Chinese population.
Tang FB(1), Li ZX(1), Wang YM(1), Zhang L(1), Ma JL(1), Zhou T(1), Zhang Y(1),
Gao JJ(1), Wu S(1), Yang T(1), You WC(2), Pan KF(3).
Infect Genet Evol. 2015 Feb 14;31C:263-269. doi: 10.1016/j.meegid.2015.02.005.
[Epub ahead of print]
Genetic polymorphisms of Toll-like receptor (TLR) 1 and 10 may influence Helicobacter pylori (H. pylori) susceptibility. To evaluate associations
between TLR1 and 10 polymorphisms, H. pylori infection, and precancerous gastric lesions, a population-based study was conducted in a high-risk Chinese population. Three single-nucleotide polymorphisms, TLR1 rs4833095, TLR10 rs10004195, and TLR10 rs4129009 were genotyped by TaqMan
SNP genotyping assay in 2553 participants with diverse gastric lesions. The status of H. pylori infection was
determined by (13)C-urea breath test. TLR1 rs4833095 T and TLR10 rs10004195 T alleles were the minor alleles and showed in linkage
disequilibrium (D'=0.98, r(2)=0.73) in the Chinese population. A decreased risk of H. pylori infection was observed in subjects with TLR1
rs4833095 CT genotype [adjusted odds ratio (OR)=0.80; 95% confidence interval (CI): 0.66-0.96] or T allele (OR=0.82; 95%CI: 0.69-0.99). Moreover, subjects carrying TLR1 rs4833095 TT genotype were associated with reduced risks of chronic
atrophic gastritis (CAG, OR=0.66; 95%CI: 0.45-0.97) and intestinal metaplasia (IM, OR=0.57; 95%CI: 0.36-0.90). The risk of CAG was also decreased in subjects carrying TLR10 rs10004195 T allele (OR=0.75; 95%CI:0.57-0.99). Furthermore, haplotype analysis indicated that haplotype TT of rs4833095 and rs10004195 had a protective
effect on H. pylori infection (OR=0.83; 95%CI: 0.72-0.96) or precancerous gastric lesions (OR=0.78; 95%CI: 0.64-0.96 for CAG, and OR=0.74; 95%CI: 0.57-0.96 for IM). These findings suggest that TLR1 rs4833095 and TLR10 rs10004195 may play crucial roles in H. pylori
susceptibility and gastric pathogenesis.
17.美国男性退伍军人中幽门螺杆菌的抗生素耐药情况调查
本文通过横断面调查研究发现美国男性退伍军人中幽门螺杆菌对甲硝唑耐药率仍较高（20.3%），而对克拉霉素的耐药率自2009年至2013年有所增加（9.1%到24.2%），对左氧氟沙星的高耐药率（31.3%）是新出现和需要关注的情况。
Antibiotic Resistance of Helicobacter pylori Among Male US Veterans.
Shiota S(1), Reddy R(2), Alsarraj A(3), El-Serag HB(4), Graham DY(1).
Clin Gastroenterol Hepatol. 2015 Feb 11. pii: S1542-3565(15)00122-6. doi: 10.1016/j.cgh.2015.02.005. [Epub ahead of print]
BACKGROUND & AIMS: The most recent information published on resistance of Helicobacter pylori to antibiotics
in a large population in the United States is more than 10 y old. We assessed the susceptibility of H pylori to
antibiotics among patients in a large metropolitan hospital, as well as demographic, clinical, and life-style factors associated with antimicrobial resistance.
METHODS: We performed a cross-sectional study at the Houston Veterans Affairs Medical Center of a random sample of 656 patients (90.2% men) from
a cohort of 1559 undergoing esophagastroduodenoscopy with collection of gastric biopsies from 2009 through 2013.
We performed culture analyses of gastric tissues to detect H.pylori. The minimum inhibitory concentrations of
amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were determined by the Epsilometer test.
Logistic regression analysis was performed to estimate the association between risk factors and antimicrobial
resistance.
RESULTS: Biopsies from 135 subjects (20.6%) tested positive for H pylori; 128 of these were from men (94.8%).
Only 65 strains were susceptible to all 5 antibiotics. The prevalence of resistance to levofloxacin was 31.3%
(95% confidence interval [CI], 23.1-39.4), to metronidazole was 20.3% (95% CI, 13.2-27.4), to clarithromycin was 16.4% (95% CI, 9.9-22.9), and to tetracycline was 0.8% (95% CI, 0.0-2.3). No isolate was resistant to amoxicillin. Clarithromycin resistance increased from 9.1% in 2009-2010 to&nbs