The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis

The discovery of Helicobacter pylori overturned the conventional dogma that the stomach was a sterile organ and that pH values < 4 were capable of sterilizing the stomach. H. pylori are an etiological agent associated with gastritis, hypochlorhydria, duodenal ulcers, and gastric cancer. It is now appreciated that the human stomach supports a bacterial community with possibly 100s of bacterial species that influence stomach homeostasis. Other bacteria colonizing the stomach may also influence H. pylori-associated gastric pathogenesis by creating reactive oxygen and nitrogen species and modulating inflammatory responses. In this review, we summarize the available literature concerning the gastric microbiota in humans, mice, and Mongolian gerbils. We also discuss the gastric perturbations, many involving H. pylori, that facilitate the colonization by bacteria from other compartments of the gastrointestinal tract, and identify risk factors known to affect gastric homeostasis that contribute to changes in the microbiota.     

血清IL-10水平及其基因-1082A/G位点单核苷酸多态性与胃窦癌恶病质的关系

目的探讨胃窦癌病人血清细胞因子白细胞介素10（IL-10）水平及-1082A/G位点单核苷酸多态性与恶病质发生的关系。方法采用放射免疫学方法检测150例胃窦癌病人及135例健康人（对照组）血清IL-10水平。用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测胃窦癌病人IL-10基因-1082A/G位点单核苷酸多态性。结果胃窦癌病人血清IL-10水平较对照组显著升高（Z=-11.862,P〈0.001）,胃窦癌Ⅲ、Ⅳ期病人血清IL-10水平较Ⅰ、Ⅱ期显著升高（Z=-10.028,P〈0.001）。胃窦癌恶病质病人血清IL-10水平较非恶病质病人显著升高（Z=-10.369,P〈0.001）。Logistic回归分析显示,IL-10为恶病质发生的高风险性因素（OR=1.559,95%CI=1.299-1.870,P〈0.001）。单核苷酸多态性分析显示,胃窦癌恶病质病人IL-10基因-1082G等位基因频率较非恶病质病人显著升高（χ2=3.953,P〈0.05）。胃窦癌恶病质病人IL-10基因-1082AG基因型频率较非恶病质病人显著升高（χ2=4.511,P〈0.05）。Logistic回归分析显示,校正肿瘤分期后,IL-10基因-1082AG基因型为胃窦癌恶病质的高风险性因素（OR=2.295,95%CI=1.029-5.117,P〈0.05）。结论血清IL-10水平高及IL-10基因-1082AG基因型与胃窦癌病人恶病质的发生具有相关性。     

胃癌组织SDF-1及其受体CXCR4表达和临床意义

目的探讨基质细胞衍生因子1（SDF-1）及其受体CXCR4在胃癌发生和浸润转移中的作用及临床意义。方法应用免疫组织化学SP法检测60例胃癌、30例正常胃黏膜组织中SDF-1和CXCR4的蛋白表达情况。结果胃癌组织中SDF-1和CXCR4蛋白的阳性表达均高于正常胃黏膜组织,差异有显著性（uc=4.013、3.694,P〈0.001）。胃癌组织SDF-1及CXCR4阳性表达与癌组织有无淋巴结转移有关（uc=3.032、2.427,P〈0.05）,而与病人的性别、年龄及癌组织的分化程度、浸润深度无关（uc=0.109~1.673,P〉0.05）。胃癌组织中SDF-1和CXCR4的表达呈正相关（r=0.310,P〈0.05）。结论 SDF-1及其受体CXCR4在胃癌发生和浸润转移中发挥着重要作用。     

抑癌基因LKB1在胃癌组织表达及意义

目的探讨抑癌基因LKB1在胃癌组织表达及意义。方法应用免疫组织化学方法检测60例胃腺癌组织（胃癌组）、16例正常胃黏膜组织（正常组）和21例癌旁胃黏膜组织（癌旁组）标本LKB1的表达,并分析其与肿瘤临床病理特征的关系。结果 LKB1正常组100.0%强阳性表达,癌旁组61.9%强阳性、38.1%弱阳性表达,胃癌组46.7%弱阳性表达,各组间比较差异有显著性（H=60.412,P〈0.001）。胃癌组LKB1阳性表达与pT分期及分化程度有关（χ2=9.386、4.275,P〈0.05）,与病人年龄、性别、大体分型、解剖位置及淋巴结有无转移无关（P〉0.05）。结论 LKB1基因表达与胃癌存在密切关联,检测其在胃癌组织或胃癌细胞中的表达,可为胃癌的诊断提供参考依据。     

Acute upper gastrointestinal bleeding in operated stomach： Outcome of 105 cases

AIM: To compare the causes and clinical outcome of patients with acute upper gastrointestinal bleeding (AUGB) and a history of gastric surgery to those with AUGB but without a history of gastric surgery in the past.METHODS: The causes and clinical outcome were compared between 105 patients with AUGB and a history of gastric surgery, and 608 patients with AUGB but without a history of gastric surgery.RESULTS: Patients who underwent gastric surgery in the past were older (mean age: 68.1±11.7 years vs 62.8±17.8 years, P= 0.001), and the most common cause of bleeding was marginal ulcer in 63 patients (60%). No identifiable source of bleeding could be found in 22 patients (20.9%) compared to 42/608 (6.9%) in patients without a history of gastric surgery (P = 0.003). Endoscopic hemostasis was permanently successful in 26 out of 35 patients (74.3%) with peptic ulcers and active bleeding or non-bleeding visible vessel. Nine patients (8.6%) were operated due to continuing or recurrent bleeding,compared to 23/608 (3.8%) in the group of patients without gastric surgery in the past (P= 0.028). Especially in peptic ulcer bleeding patients, emergency surgery was more common in the group of patients with gastric surgery in the past [9/73 (12.3%) vs 19/360 (5.3%), P = 0.025].Moreover surgically treated patients in the past required more blood transfusion (3.3±4.0 vs 1.5±1.7, P = 0.0001) and longer hospitalization time (8.6±4.0 vs 6.9±4.9 d,P = 0.001) than patients without a history of gastric surgery. Mortality was not different between the two groups [4/105 (3.8%) vs 19/608 (3.1%)].CONCLUSION: Upper gastrointestinal bleeding seems to be more severe in surgically treated patients than in non-operated patients.     

胃幽门螺杆菌感染与抑癌基因失活的关系

目的探讨胃癌及癌前病变组织中幽门螺杆菌(H.pylori)感染与抑癌基因失活间的相互关系.方法运用DNA-PCR技术检测H.Pylori感染,采用PCR-RFLP,PCR-SSCP,RT-PCR及免疫组化技术分析182例胃癌及癌前病变及正常胃粘膜中抑癌基因APC,MCC,DCC,YNZ22及p53基因的杂合缺失、突变、mRNA及蛋白异常表达.结果胃癌及癌前病变组织中H.pylori的感染率(IM61.7%,Dys 63.3%,GC 42.3%)显著高于正常胃粘膜(17.5%,P＜0.05).但胃癌及癌前病变间H.pylori感染率无显著差别(P＞0.05),胃肠两型胃癌中H.pylori感染率分别为47.1%及42.2%,两者无显著差别(P＞0.05).胃癌及癌前病变组织中存在多种抑癌基因失活.H.pylori感染与癌前病变-肠化生中APC基因异常蛋白表达有关(Hp+43.2%vsHp-13.0%,P＜0.05).胃癌组织H.pylori感染阳性组中APC基因突变(50.0%)及蛋白表达(63.6%)、p53基因蛋白表达率(59.1%)显著高于阴性组(vs16.7%,P＜0.05;vs30.0%,P＜0.01;vs20.0%,P＜0.01).结论幽门螺杆菌感染及多种抑癌基因失活可能与胃癌的发生发展相关,H.pylori感染与APC,p53基因失活可能相关.     

The vast majority of gastric T cells are polarized to produce T helper 1 type cytokines upon antigenic stimulation despite the absence of Helicobacter pylori infection

Helicobacter pylori infection is associated with chronic infiltration by various cell types, including T cells, whose cytokine production may regulate the inflammatory reaction as well as local immune response to the bacterium. We prospectively analyzed the constituents of the cellular infiltrates and the cytokines produced by T cells in antral biopsies obtained from 73 subjects with and without H. pylori infection, before and after eradication therapy, and compared them with a histological grade of gastritis. We found that T cells predominated in cell number, followed by granulocytes/monocytes and plasma cells in both H. pylori-infected and H. pylori-uninfected subjects. Despite the absence of H. pylori infection, more than 70% of gastric CD4-positive T cells obtained from uninfected tissue produced interferon-γ (IFN-γ) in the cytosol. Upon receptor cross-linking of a CD3 and a CD28 molecule, T cells in both infected and uninfected tissue continuously secreted a far greater amount of IFN-γ than those in peripheral blood mononuclear cell controls for a period of cell culture, whereas the increase in interleukin-4 (IL-4) was very small, and no increase in IL-2 secretion was seen. In H. pylori-infected patients, IFN-γ secretion was correlated with the grade of mononuclear cell infiltration and decreased to an uninfected control level after eradication therapy. We did not see the effect of eradication on IL-4 secretion. Anti-H. pylori antibody of the IgG2 subclass was remarkably increased in H. pylori-infected subjects. These results together suggest that gastric T cells are already differentiated to produce a large amount of IFN-γ by a mechanism unrelated to H. pylori infection. H. pylori infection appeared to activate T cells to secrete even more IFN-γ, which may contribute to maintaining a perpetual inflammation in H. pylori-infected stomach. Received: January 15, 1999 / Accepted: May 28, 1999     

根治性切除术与扩大根治性切除术对胃癌患者术后生活质量的影响

[目的]探讨根治性切除术与扩大根治性切除术对胃癌患者术后生活质量的影响.[方法]80例胃癌患者随机分为根治性切除术组（A术式组）和扩大根治性切除术组（B术式组）,观察比较两种不同术式的术前术后Karnofsky评分及手术效果比较.[结果]术前两种术式Karnofsky评分差异无显著性,术后A术式Karnofsky评分明显低于B术式组,经统计学分析,差异有显著性（P〈0.05）.两组在平均住院时间、平均手术时间、平均术中术后出血量、平均下地时间、平均术中术后输血量方面比较,经统计学分析,差异有显著性（P〈0.05）.[结论]扩大根治性切除术对胃癌患者术后生活质量的影响较根治性切除术明显,且在住院时间、手术时间、术中术后出血量、下床活动时间、术中术后输血量方面优于根治术.     

参一胶囊联合FOLFOX4方案治疗晚期胃癌的临床研究

目的观察参一胶囊联合FOLFOX4方案化疗治疗晚期胃癌（HI、IVY）的疗效及毒副反应。方法将93例晚期胃癌患者按照治疗方案不同随机分为两组：对照组单纯接受FOLFOX4方案化疗（53例）,治疗组在化疗同时联合应用参一胶囊（40例）。结果对照组、治疗组近期客观疗效（完全缓解＋部分缓解）分别为57．5％和45．3％,差异无统计学意义（P〉0．05）,治疗组血液学毒性发生率低于对照组（P〈0．05）,在生活质量改善方面两组差异有统计学意义（P〈0．05）。结论晚期胃癌患者化疗后联合应用参一胶囊是一种新的安全有效的治疗方法,可减轻化疗毒副反应,改善患者生活质量。