链霉蛋白酶治疗幽门螺杆菌感染的研究进展

幽门螺杆菌(Helicobacter pylori,H.pylori)是一种可引发多系统病变的致病微生物。根除H.pylori能够改善胃黏膜炎性反应,阻止或延缓胃黏膜萎缩、肠化生的发生和发展,并部分逆转萎缩,也可不同程度地降低胃癌的发生率。以往临床常采用三联疗法作为根除H.pylori的一线治疗方案,但近年由于抗生素的广泛使用,导致H.pylori的抗药性增强,根除率降低。国内外研究均表明,链霉蛋白酶可以通过抑制H.pylori生存和影响抗H.pylori抗菌药起到根治的作用,并且在此方面取得良好疗效,为根除H.pylori开辟出一条崭新的道路。本文就链霉蛋白酶治疗H.pylori的进展作一概述。     

链霉蛋白酶对上消化道内镜检查胃内清晰度的效果观察

目的:评价行胃镜检查的患者使用链霉蛋白酶后胃腔内的清晰度,探讨链霉蛋白酶协助胃镜检查的有效性。方法:收集胃镜检查的100例患者,分为试验组(给药链霉蛋白酶)和对照组(给药Na Cl溶液),分别比较其胃腔内的清晰度评分。结果:试验组使用链霉蛋白酶后胃内清晰度明显较对照组为高。结论:链霉蛋白酶能有效提高胃内清晰度,可作为检查前的辅助手段。     

链霉蛋白酶与二甲硅油对胃镜检查微小病变检出率影响的比较

探讨链霉蛋白酶与二甲硅油对胃镜检查微小病变检出率影响，统计353例接受无痛胃镜检查的患者，分为试验组（予链霉蛋白酶联合碳酸氢钠）176例和对照组（予二甲硅油联合碳酸氢钠）177例。记录两组胃镜检查时视野清晰度、检查时长、冲洗次数、微小病灶检出率、早期癌检出率及不良反应发生率等临床指标。试验组和对照组比较视野清晰度［（1.84±0.51）分比（2.15±0.48）分，t=-5.900］、胃底黏液性状［（1.04±0.43）分比（1.46±0.76）分，t=-6.347］和冲洗次数［（0.76±0.66）次比（1.18±0.72）次，t=-5.628］等方面，差异有统计学意义（P<0.001）。试验组检查时长略高于对照组［（10.01±4.40）min比（8.98±4.22）min，t=2.239，P=0.026］。试验组微小病变检出率显著高于对照组］［97.73%（172/176）比91.53%（162/177），χ2=6.665，P=0.010］。在炎性增生、息肉、癌前病变和癌的检出率方面，试验组与对照组差异均无统计学意义（P>0.05）。两组患者均无术前喝药不适，试验组和对照组各有4例发生术中呛咳，术中呛咳发生率差异无统计学意义（P>0.999），术后均无不良反应。术前服用链霉蛋白酶可显著提高胃镜下视野清晰度并提高微小病变检出率，有助于发现胃内早期病变。     

西甲硅油联合链霉蛋白酶在胃镜检查中的应用

目的探讨西甲硅油联合链霉蛋白酶在胃镜检查中的应用效果。方法选择我院门诊及住院接受胃镜检查的患者200例,随机分成研究组和对照组,每组100例。研究组(西甲硅油联合链霉蛋白酶组)检查前服用西甲硅油及链霉蛋白酶的混合液,并辅以丁卡因口腔喷雾表面麻醉;对照组(盐酸利多卡因胶浆组)检查前常规口服盐酸利多卡因胶浆10 ml。比较两组患者不良反应、胃镜检查时清晰度、检查时间及对微小病灶的观察情况。结果研究组患者检查前恶心程度低于盐酸利多卡因胶浆组(P<0.05),但在检查过程中两组患者的恶心程度比较差异无统计学意义(P>0.05);研究组胃镜检查时视野清晰度明显高于对照组(A+B,89%vs 62%,P<0.05);检查时间缩短(P<0.05);微小病灶(红斑、糜烂、出血点、息肉样增生)的检出率增高(P<0.05),更易于提高早期癌前病变的检出率。结论胃镜检查前应用西甲硅油联合链霉蛋白酶,可有效提高胃镜视野清晰度,并减轻患者的不适感,有利于提高微小病灶,尤其是癌前病变的检出率。     

链霉蛋白酶服用后坐位活动方法对胃镜检查前准备效果的影响

目的探讨链霉蛋白酶服用后坐位活动方法对胃镜检查前准备效果的影响。 方法采用单中心随机对照研究方法,选取2018年8月至2019年5月经北京大学国际医院内镜中心行胃镜检查的202例患者,随机分为服用链霉蛋白酶后坐位活动组99例和传统翻身组103例。比较两组患者胃镜下视野清晰度、胃镜操作时间及检查过程中的清洗水量。 结果两组胃镜下视野清晰度、胃镜检查时间及检查过程中的清洗水量差异无统计学意义。 结论链霉蛋白酶服用后坐位活动方法简便、易行,胃内粘液清除效果满意。     

链霉蛋白酶颗粒用于胃镜检查过程中祛除胃内黏液的多中心随机对照研究

【摘要】目的探讨链霉蛋白酶颗粒提高胃镜检查可见度的有效性及安全性。方法4个中心采用随机、双盲、安慰剂平行对照法,将需要进行胃镜检查的门诊或住院患者240例随机分为试验组与对照组。试验组药物为链霉蛋白酶颗粒剂20000单位／袋,对照组药物为安慰剂（乳糖、羟丙纤维素颗粒剂）0．5g／袋。试验组与对照组均为1袋药物与碳酸氢钠1．0g在50rrIl蒸馏水（20℃一40℃）中振荡溶解后服用。胃镜下观察胃腔各部位的黏液附着量及厚度情况,并进行评分,对比分析两组清洁疗效及不良反应发生情况。结果两组总有效率比较,试验组高于对照组[63．33％（76／120）比45．83％（55／120）,P〈0．05];两组胃体部及胃窦部附着黏液量与厚度合计评分比较,试验组均明显低于对照组（胃体部：1．68±1．51比2．144-1．47,P〈0．05;胃窦部：1．59±1．58比2．054-1．53,P〈0．05）;胃底部合计评分差异无统计学意义（P〉0．05）。在安全性方面,试验组不良事件发生率为5．08％（6／118）,对照组不良事件发生率为6．67％（8／120）,差异无统计学意义（P〉0．05）,且均未发生明确与药物相关的药物不良反应。结论链霉蛋白酶颗粒用于胃镜检查,可明显减少胃黏膜表面附着的黏液,有效提高镜下可见度,从而显著提高胃镜对微小病变的诊断能力,并且安全性较好。     

胃黏液祛除剂——链霉蛋白酶在上消化道内镜诊疗中的应用价值

早期胃癌（earlygastriccancer，EGC）定义为垂直方向的浸润不超过黏膜下层而无论有无转移的胃癌…。在日本，早期胃癌占所有胃癌患者的比例高达40％一60％，然而在我国及欧美还不足15％”0。目前多数学者认为，无论部位、大小及基因类型，EGC是可以治愈的疾病，早期切除病变部位后患者的5年生存率高达90％以上，然而，进展期胃癌患者的5年生存率仅10％一20％”’。     

高效液相色谱法测定直肠癌术中肠腔化疗血液和盆腔液及组织5-Fu浓度

目的:测定直肠癌术中肠腔化疗血液、盆腔液和组织5-Fu浓度。方法:20例直肠癌患者术中行肠腔化疗,注药后不同时相采集门静脉血、周围静脉血、盆腔液和癌旁组织,用高效液相色谱法测定5-Fu浓度。结果:门静脉血、盆腔液和组织2min即测得5-Fu,此后,盆腔液和组织浓度降低,门静脉血药浓度上升,60min达到峰浓度,周围静脉血未测得5-Fu。结论:直肠癌术中肠腔化疗可使5-Fu迅速分布于盆腔液、组织和门静脉血,但组织和盆腔液峰浓度低且下降迅速,对预防术后局部复发和腹腔转移作用有限,含5-Fu的门静脉血对抑制肝脏转移有一定意义。     

链霉蛋白酶与利多卡因胶浆联用提高超声内镜检查清晰度的研究

目的评价检查前联合使用链霉蛋白酶和利多卡因胶浆对缩短超声胃镜操作时间和改善内镜、超声图像方面的效果。方法将超声内镜受检者80例随机分为A、B组,每组40例。A组于检查前15min口服利多卡因胶浆10ml;B组于检查前30rain口服含10000单位链霉蛋白酶和1g碳酸氢钠的温开水50ml,并于检查前15min口服利多卡因胶浆10ml。记录总操作时间,并对超声胃镜下胃内黏液附着量及超声图像的清晰度进行评分。结果A组操作时间长于B组[（15．5±3．0）min比（12．3±2．3）min,P〈0．001],B组内镜和超声内镜图像视野清晰度均优于A组。结论链酶蛋白酶和利多卡因胶浆联用可有效去除胃内黏液艉高超声内镜检查成像质量。     

链霉蛋白酶提高胃镜检查图像可见度的前瞻性、多中心、双盲、随机对照临床研究

目的评价并比较胃镜检查前应用链霉蛋白酶、二甲基硅油及二者联合使用对提高可见度的有效性。方法5个中心选择440例胃镜检查患者随机分为3组，A组170例，口服链霉蛋白酶和碳酸氢钠；B组170例，VIN--甲基硅油和碳酸氢钠；C组100例，口服二甲基硅油、链霉蛋白酶和碳酸氢钠。观察主要疗效指标为胃镜直接观察胃窦、胃体、胃底3个部位黏膜可见度总评分。次要评价指标为胃镜检查喷洒亚甲蓝后观察胃窦、胃体以及胃底部3处的黏膜可见度总评分。结果胃镜检查直接观察可见度总评分在3组间的差异具有统计学意义（P〈0．0001），C组总评分高于A组（P=0．0001），A组总评分高于B组（P=0．0019）；喷亚甲蓝后胃镜检查观察可见度总评分在3组间的差异具有统计学意义（P〈0．0001），C组总评分高于A组（P：0．0054），A组总评分高于B组（P〈0．0001）。结论胃镜检查前联合应用链霉蛋白酶和二甲基硅油可明显提高可见度，具有良好安全性和广泛的应用价值。     

Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue lymphoma

Gastrointestinal lymphoma is the most common type of extranodal lymphoma,and most commonly affects the stomach.Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue(MALT)and diffuse large B-cell lymphoma are the most common histologic types of gastric lymphoma.Despite its increasing incidence,diagnosis of gastric lymphoma is difficult at an earlier stage due to its nonspecific symptoms and endoscopic findings,and,thus,a high index of suspicion,and multiple,deep,repeated biopsies at abnormally and normally appearing sites in the stomach are needed.In addition,testing for Helicobacter pylori(H.pylori)infection and endoscopic ultrasonography to determine the depth of tumor invasion and involvement of regional lymph nodes is essential for predicting response to H.pylori eradication and for assessment of disease progression.In addition,H.pylori infection and MALT lymphoma development are associated,and complete regression of low-grade MALT lymphomas after H.pylori eradication has been demonstrated.Radiotherapy and/or chemotherapy can be used in cases that show poor response to H.pylori eradication,negativity for H.pylori infection,or high-grade lymphoma.     

Effect of non-steroidal anti-inflammatory drugs on gastric and duodenal prostaglandin concentrations in patients with Helicobacter pylori infection.

BACKGROUND/AIMS: Both Helicobacter pylori and non-steroidal anti-inflammatory drugs are reported to affect gastroduodenal prostaglandin synthesis. However, their influence on gastric mucosal prostaglandins remains unclear. The aim of this study was to investigate the influence of nonsteroidal anti-inflammatory drugs on mucosal prostaglandin synthesis in patients with Helicobacter pylori infection. METHODOLOGY: We enrolled 87 Helicobacter pylori-infected patients in this study (gastric ulcer: 33, duodenal ulcer: 41, and non-ulcer dyspepsia: 13). Of them, 27 patients received non-steroidal anti-inflammatory drugs. Endoscopy was performed and biospy specimens from gastric body, antrum and duodenal bulb were assessed for Helicobacter pylori and prostaglandin concentration. RESULTS: A significantly lower mucosal prostaglandin E2 level at gastric body (142.2 +/- 28.1 ng/mg vs. 222.0 +/- 12.4 ng/mg, mean +/- SEM) and antrum (131.3 +/- 26.4 ng/mg vs. 226.0 +/- 19.0 ng/mg) was noted in Helicobacter pylori-infected gastric ulcer patients with non-steroidal anti-inflammatory drugs ingestion than in that of patients without non-steroidal anti-inflammatory drugs ingestion (p < 0.05). Using a multivariate analysis, we found that non-steroidal anti-inflammatory drug was an independent variable affecting gastric and duodenal mucosal prostaglandin E2 synthesis in patients with Helicobacter pylori-infected gastric ulcer. CONCLUSIONS: Non-steroidal anti-inflammatory drugs decrease gastroduodenal mucosal prostaglandin E2 synthesis in gastric ulcer patients with Helicobacter pylori infection.     

口腔幽门螺杆菌感染与胃幽门螺杆菌感染的相关性探讨

目的 分析口腔和胃幽门螺杆菌(Hp)感染的检测结果,探讨口腔Hp感染与胃Hp感染的相关性,及口腔Hp感染对Hp根除治疗的影响.方法 采用唾液测定螺旋杆菌抗原技术(HPS)和13C/14C尿素呼气试验(UBT)同步检测的方法,对114例有上消化道症状的初诊患者(第1组),129例确诊为胃Hp感染经根除治疗后4周复查的患者(第2组)和33例无消化道症状的健康志愿者(第3组),进行口腔和胃Hp检测.结果 第1组、第2组和第3组HPS阳性检出率分别为77.19%、75.97%和81.82%,3组比较差异无统计学意义(χ2=0.47,P值均>0.05);UBT阳性检出率第1组(52.63%)比第2组(34.11%)和第3组(21.21%)高,第1组与第2组和第3组比较,差异有统计学意义(χ2=8.48和10.19,P均<0.05),第2组与第3组之间差异无统计学意义(χ2=2.03,P>0.05);在UBT阳性者中,HPS阳性检出率差异无统计学意义(3组分别为81.67%、88.64%和100%,χ2=2.25,P值均>0.05).结论 唾液中存在高Hp抗原检出现象,口腔可能是Hp在胃以外的"第二定居地".口服药物治疗对口腔Hp感染几乎无效,口腔Hp的存在可能是胃病发病和复发的一个重要和直接的原因.

Abstract：

Objective To explore association between Helicobacter pylori (Hp) infection in oral cavity and gastric Hp infection through oral cavity and gastric Hp infection testing results analysis, and also to study the effect of Hp infection in oral cavity on Hp eradication treatment. Methods Through Hp saliva test (HPS) and 13C/14C urea breath test (UBT) method, the Hp in oral cavity and stomach were tested in 114 first-visit patients with upper gastrointestinal symptoms (group 1), 129 re-visiting patients who were diagnosed gastric Hp infection with eradication treatment for four weeks (group 2) and 33 volunteers without gastrointestinal symptoms. Results The positive rates of Hp infection by HPS method were 77.19%, 75.97% and 81.82% in group 1, group 2 and group 3 respectively. There was no significant difference between these three groups (χ2=0.47, P>0.05). The positive rate of Hp infection by UBT method in group 1 (52.63%) was higher than those of group 2 (34.11%) and group 3 (21.21%). Compared group 1 with group 2 or group 3, there was significant difference (χ2=8.848, 10.19, P<0.05). There was no significant difference between group 2 and 3 (χ2=2.03, P>0.05). In positive individuals of these three groups tested by UBT method, there was no significant difference of positive rate tested by HPS method (81.67%, 88.64% and 100% of three groups respectively, χ2=2.25, P>0.05). Conclusions The High detection of Hp antigen in saliva indicates that the oral cavity may be the "second settlement" of Hp beside stomach. The oral medicine haslittle effect on oral cavity Hp infection. The existence of oral Hp may be an important and direct factor of incidence and recurrent of gastric diseases.     

Elevated concentrations of alpha-defensins in gastric juice of patients with Helicobacter pylori infection

OBJECTIVE: Defensins (alpha- and beta-defensins) are endogenous antimicrobial peptides. Little is known about alpha-defensins during Helicobacter pylori infection. METHODS: The concentrations of human neutrophil peptides (HNP-1, -2, and -3), the major components of neutrophils-derived alpha-defensins, were measured by radioimmunoassay (RIA) in plasma and gastric juice of 61 H. pylori-infected and 33 uninfected subjects, and before and after anti-H. pylori treatment in 12 patients with H. pylori-associated gastritis. Interleukin (IL)-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay. Histological grades of gastritis and neutrophil counts (/mm(2)) infiltrating in the gastric mucosa were determined using two biopsy specimens taken from the antrum and corpus. Immunohistochemistry and reverse-phase high performance liquid chromatography (RP-HPLC) were used to identify HNPs 1-3. RESULTS: HNP 1-3 concentrations in gastric juice were significantly higher in H. pylori-positive than in H. pylori-negative patients and significantly decreased after cure. HNP 1-3 concentrations in gastric juice correlated with IL-8 levels and neutrophil densities in the gastric mucosa and were associated with histological degree of gastritis, especially the grades of activity. Intense immunoreactivity for anti-HNPs 1-3 antiserum was noted in infiltrating neutrophils in H. pylori-infected mucosa. In RP-HPLC analysis, all of the HNP 1-3 molecules were identified as their mature forms. Plasma HNP 1-3 concentrations were similar in H. pylori-infected and non-infected groups and showed no correlations with other parameters. CONCLUSIONS: We demonstrated significantly elevated levels of HNPs 1-3 in gastric juice during H. pylori infection. The elevation of HNPs is presumably secondary to H.pylori-associated gastric inflammation involving neutrophil infiltration.     

Latest insights into the effects of Helicobacter pylori infection on gastric carcinogenesis

There appears to be the strong association between Helicobacter pylori (H pylori) and gastric cancer. We reviewed the latest evidences about the effects of H pylori infection on gastric carcinogenesis, classified into epidemiology, dynamics of gastric mucosal changes, DNA damages, virulence factors, host factors, and source of gastric malignancy. Through the considerable progress made in research into virulence factors resulting from differences between H pylori strains, such as cagA positivity, as well as into host factors, such as gene polymorphisms, a diverse spectrum of H pylori-associated diseases, including gastric cancer, is beginning to lend itself to elucidation. The impact of the novel hypothesis advanced by Houghton et al proposing bone-marrow derived stem cells (BMDC) as a potential source of gastric malignancy on evolving research remains to be seen with interest. Further progress in research into H pylori eradication as a viable prophylaxis of gastric cancer, as well as into the mechanisms of gastric carcinogenesis, is to be eagerly awaited for the current year and beyond.     

幽门螺杆菌菌蜕载体阿霉素对胃癌细胞的杀伤作用

目的 制备幽门螺杆菌(Hp)菌蜕(BG),并装载阿霉素,观察其对胃癌细胞的杀伤作用。方法通过细菌结合作用将裂解质粒导入Hp,42℃诱导细菌裂解制备Hp BG,经悬浮、离心装载阿霉素,分光光度法检测阿霉素装载量,四甲基偶氮唑蓝(MTT)法观察Hp BG-阿霉素对胃癌细胞SGC7901的杀伤作用。结果 成功制备Hp BG并装载阿霉素,阿霉素的装载量为70.4μg/mg。共聚焦显微镜可见HpBG能被胃癌细胞吸附和内化,分布于SGC7901细胞表面或胞质,所携带的阿霉素传递入胃癌细胞,主要积聚于细胞核。MTT法检测显示SGC7901细胞对HpBG-阿霉素的IC50值为0.32±0.15,明显低于游离阿霉素（0.44±0.15,P＜0.05）。结论HpBG-阿霉素能有效抑制胃癌细胞生长,HpBG有望成为理想的抗胃癌药物载体。     

幽门螺杆菌感染治疗现状与展望

随着时间的变迁,幽门螺杆菌(Helicobacter pylori,H.pylori)对常用抗生素的耐药率逐渐增加,其根除率逐渐下降。四联疗法已成为当前治疗H.pylori的主要一线方案,另外欧州MaastrichtIV共识意见中还推荐了序贯疗法和伴同疗法。在H.pylori对常用抗生素耐药的情况下,对于如何提高H.pylori根除率,我国H.pylori学者正在进行H.pylori治疗新路径探索:(1)三联(或四联)联合中药治疗;(2)三联(或四联)联合益生菌治疗;(3)探索口腔H.pylori对H.pylori根除治疗的影响;(4)强调个体化治疗。今天的新思路也许会成为明天治疗H.pylori的新手段。     

High concentrations of human β-defensin 2 in gastric juice of patients with Helicobacter pyloriinfection

AIM: Human beta-defensin (HBD)-1 and HBD-2 are endogenous antimicrobial peptides. Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori (H pylori). We sought to determine HBD-1 and HBD-2 concentrations in gastric juice during H pylori infection. METHODS: HBD-1 and HBD-2 concentrations were measured by radioimmunoassay in plasma and gastric juice of 49 H pylori-infected and 33 uninfected subjects and before and after anti-H pylori treatment in 13 patients with H pylori-associated gastritis. Interleukin (IL)-1beta and IL-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay (ELISA). Histological grades of gastritis were determined using two biopsy specimens taken from the antrum and corpus. Reverse phase high performance liquid chromatography (RP-HPLC) was used to identify HBD-2. RESULTS: HBD-2 concentrations in gastric juice, but not in plasma, were significantly higher in H pylori-positive than -negative subjects, albeit the post-treatment levels were unchanged. Immunoreactivity for HBD-2 was exclusively identified in H pylori-infected mucosa by RP-HPLC. HBD-2 concentrations in gastric juice correlated with histological degree of neutrophil and mononuclear cell infiltration in the corpus. IL-1beta levels correlated with those of IL-8, but not HBD-2. Plasma and gastric juice HBD-1 concentrations were similar in H pylori-infected and uninfected subjects. CONCLUSION: Our results place the beta-defensins, especially HBD-2, in the front line of innate immune defence. Moreover, HBD-2 may be involved in the pathogenesis of H pylori-associated gastritis, possibly through its function as immune and inflammatory mediator.     

Influence of Helicobacter pylori infection and omeprazole treatment on gastric regional CO2

BACKGROUND: Gastric regional CO(2) accumulation indicates gastric mucosal hypoperfusion in critically ill patients. CO(2) is also a reaction product of urea degradation, and we therefore tested the hypothesis if regional pCO(2) is influenced by Helicobacter pylori infection. MATERIAL: Seven H. pylori-positive and 7 H. pylori-negative volunteers (age range 21-30 years) were investigated. During a 6- to 7-hour observation period, we obtained every 30 min arterial blood gases, gastric juice pH from a glass pH electrode and regional pCO2 from a gastric tonometer. The study protocol included subsequent periods of baseline measurements, pentagastrin stimulation (0.6 microg/kg/h/i.v.) and application of omeprazole (40 mg i.v.). RESULTS: Gastric regional pCO(2) was increased in H. pylori-positive versus H. pylori-negative subjects before (64.4 +/- 3.1 vs. 50.0 +/- 2.9 mm Hg, p < 0.005) but not after application of omeprazole. The effect of omeprazole on gastric juice pH was increased in H. pylori-positive subjects (mean pH during 4 h 6.1 +/- 0.3 in H. pylori-positive vs. 2.5 +/- 0.2 in H. pylori-negative subjects; p < 0.0001). There was a difference in arterial pCO(2) between H. pylori-positive and H. pylori- negative subjects (43.1 +/- 0.3 versus 38.9 +/- 0.3 mm Hg; p < 0.0001). CONCLUSION: H. pylori infection has a significant effect on gastric regional CO(2) that is suppressed by application of a proton pump inhibitor.