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世界胃肠病学杂志（英文版）
世界胃肠病学杂志（英文版）

潘伯荣

周刊

1007-9327

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世界胃肠病学杂志（英文版）/Journal World Journal of GastroenterologyCSCDCSTPCDSCI
查看更多>>主要报道和刊登国内外、特别是我国消化病学者具有创造性的、有较高学术水平的基础和临床研究论文、研究快报等. 对具有中国特色的研究论文, 如食管癌、胃癌、肝癌、大肠癌、病毒性肝炎、幽门螺杆菌、中医中药、中西医结合和基于作者自己研究工作为主的综述性论文, 将优先发表. 读者对象为基础研究或临床研究的消化专业工作者。
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    Pathogenesis of NSAID-induced gastric damage: Importance of cyclooxygenase inhibition and gastric hypermotility

    Koji Takeuchi
    2147-2160页
    查看更多>>摘要：This article reviews the pathogenic mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage,focusing on the relation between cyclooxygenase (COX) inhibition and various functional events.NSAIDs,such as indomethacin,at a dose that inhibits prostaglandin (PG) production,enhance gastric motility,resulting in an increase in mucosal permeability,neutrophil infiltration and oxyradical production,and eventually producing gastric lesions.These lesions are prevented by pretreatment with PGE2 and antisecretory drugs,and also via an atropine-sensitive mechanism,not related to antisecretory action.Although neither rofecoxib (a selective COX-2 inhibitor) nor SC-560 (a selective COX-1 inhibitor) alone damages the stomach,the combined administration of these drugs provokes gastric lesions.SC-560,but not rofecoxib,decreases prostaglandin E2 (PGE2) production and causes gastric hypermotility and an increase in mucosal permeability.COX-2 mRNA is expressed in the stomach after administration of indomethacin and SC-560 but not rofecoxib.The up-regulation of indomethacin-induced COX-2 expression is prevented by atropine at a dose that inhibits gastric hypermotility.In addition,selective COX-2 inhibitors have deleterious influences on the stomach when COX-2 is overexpressed under various conditions,including adrenalectomy,arthritis,and Helicobacter pylori-infection.In summary,gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage,and the response,causally related with PG deficiency due to COX-1 inhibition,occurs prior to other pathogenic events such as increased mucosal permeability; and the ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2,the inhibition of COX-1 upregulates COX-2 expression in association with gastric hypermotility,and PGs produced by COX-2 counteract the deleterious effect of COX-1 inhibition.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Clopidogrel and proton pump inhibitors-where do we stand in 2012?

    Michael D DrepperLaurent SpahrJean Louis Frossard
    2161-2171页
    查看更多>>摘要：Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Enhanced apoptosis in post-liver transplant hepatitis C:Effects of virus and immunosuppressants

    Eu Jin LimRuth ChinPeter W AngusJoseph Torresi...
    2172-2179页
    查看更多>>摘要：Hepatitis C (HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive course.There is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote apoptosis.Recent studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis.Although the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important role.It is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral replication.However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication.Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis.These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Side-stream smoking reduces intestinal inflammation and increases expression of tight junction proteins

    Hui WangJun-Xing ZhaoNan HuJun Ren...
    2180-2187页
    查看更多>>摘要：AIM:To investigate the effect of side-stream smoking on gut microflora composition,intestinal inflammation and expression of tight junction proteins.METHODS:C57BL/6 mice were exposed to side-stream cigarette smoking for one hour daily over eight weeks.Cecal contents were collected for microbial composition analysis.Large intestine was collected for immunoblotting and quantitative reverse transcriptase polymerase chain reaction analyses of the inflammatory pathway and tight junction proteins.RESULTS:Side-stream smoking induced significant changes in the gut microbiota with increased mouse intestinal bacteria,Clostridium but decreased Fermicutes (Lactoccoci and Ruminococcus),Enterobacteriaceae family and Segmented filamentous baceteria compared to the control mice.Meanwhile,side-stream smoking inhibited the nuclear factor-κB pathway with reduced phosphorylation of p65 and IκBα,accompanied with unchanged mRNA expression of tumor necrosis factor-α or interleukin-6.The contents of tight junction proteins,claudin3 and ZO2 were up-regulated in the large intestine of mice exposed side-stream smoking.In addition,side-stream smoking increased c-Jun N-terminal kinase and p38 MAPK kinase signaling,while inhibiting AMP-activated protein kinase in the large intestine.CONCLUSION:Side-stream smoking altered gut microflora composition and reduced the inflammatory response,which was associated with increased expression of tight junction proteins.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Agmatine induces gastric protection against ischemic injury by reducing vascular permeability in rats

    Abeer A Al MasriEman El Eter
    2188-2196页
    查看更多>>摘要：AIM:To investigate the effect of administration of agmarine (AGM) on gastric protection against ischemia reperfusion (I/R)injury.METHODS:Three groups of rats (6/group); sham,gastric I/R injury,and gastric I/R + AGM (100 mg/kg,i.p.given 15 min prior to gastric ischemia) were recruited.Gastric injury was conducted by ligating celiac artery for 30 rmin and reperfusion for another 30 min.Gastric tissues were histologically studied and immunostained with angiopoietin 1 (Ang-1) and Ang-2.Vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) were measured in gastric tissue homogenate.To assess whether AKt/phosphatidyl inositol-3-kinase (PI3K) mediated the effect of AGM,an additional group was pretreated with Wortmannin (WM) (inhibitor of Akt/PI3K,15 μg/kg,i.p.),prior to ischemic injury and AGM treatment,and examined histologically and immunostained.Another set of experiments was run to study vascular permeability of the stomach using Evan's blue dye.RESULTS:AGM markedly reduced Evan's blue dye extravasation (3.58 ± 0.975 μg/stomach vs 1.175 ±0.374 μg/stomach,P ＜ 0.05),and VEGF (36.87 ± 2.71 pg/100 mg protein vs 48.4 ± 6.53 pg/100 mg protein,P ＜ 0.05) and MCP-1 tissue level (29.5 ± 7 pg/100 mg protein vs 41.17 ± 10.4 pg/100 mg protein,P ＜ 0.01).It preserved gastric histology and reduced congestion.Ang-1 and Ang-2 immunostaining were reduced in stomach sections of AGM-treated animals.The administration of WM abolished the protective effects of AGM and extensive hemorrhage and ulcerations were seen.CONCLUSION:AGM protects the stomach against I/R injury by reducing vascular permeability and inflammation.This protection is possibly mediated by Akt/PI3K.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice

    Wei-Xia LiuFeng-Lan JiaYue-Ying HeBao-Xu Zhang...
    2197-2202页
    查看更多>>摘要：AIM:To investigate the hepatic protective effects of 5-methoxypsoralen (5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS:C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5,25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen (APAP) subcutaneously at a dose of 500 mg/kg.The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP.Twenty-four hours after APAP administration,blood samples of mice were analyzed for serum enzyme alanine transaminase (ALT),aspartate transaminase (AST),lactate dehydrogenase (LDH) levels,and malondialdehyde (MDA),reduced glutathione (GSH) and oxidized glutathione (GSSG) of liver tissues were measured and histopathologic changes of the liver were observed.RESULTS:Compared with the vehicle control group,the serum levels (IU/L) of ALT,AST and LDH were all increased significantly in APAP group (8355 ± 3940vs 30 ± 21,P ＜ 0.05; 6482 ± 4018 vs 146 ± 58,P ＜0.05; 24627 ± 10975 vs 1504 ± 410,P ＜ 0.05).Compared with APAP group,the serum ALT levels (IU/L) (1674 ± 1810 vs 8355 ± 3940,P ＜ 0.05; 54 ± 39 vs 8355 ± 3940,P ＜ 0.05; 19 ± 9 vs 8355 ± 3940,P ＜0.05),AST levels (IU/L) (729 ± 685 vs 6482 ± 4108,P ＜ 0.05; 187 ± 149 vs 6482 ± 4108,P ＜ 0.05; 141 ± 12 vs 6482 ± 4108,P ＜ 0.05) and LDH levels (IU/L) (7220 ± 6317 vs 24 627 ± 10 975,P ＜ 0.05; 1618± 719 vs 24 627 ± 10 975,P ＜ 0.05; 1394 ± 469 vs 24 627 ± 10 975,P ＜ 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups.Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP,including hepatocellular necrosis and infiltration of inflammatory cells,and the effect was dose-dependent.MDA levels (nmol/mg)were decreased by 5-MOP in a dose-dependent manner (0.98 ± 0.45 vs 2.15 ± 1.07,P ＞ 0.05; 0.59 ± 0.07 vs 2.15 ± 1.07,P ＜ 0.05; 0.47 ± 0.06 vs 2.15 ± 1.07,P ＜0.05).The pretreatment of 5-MOP could also increase the GSH/GSSG ratio (3.834 ± 0.340 vs 3.306 ± 0.282,P ＞ 0.05; 5.330 ± 0.421 vs 3.306 ± 0.282,P ＜ 0.05;6.180 ± 0.212 vs 3.306 ± 0.282,P ＜ 0.05).In the group treated with 5-MOP but without APAP,the serum enzyme levels,the liver histopathologic manifestation,and the values of MDA and GSH/GSSG ratio were all normal.CONCLUSION:5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity,and does not cause liver injury at the protective doses.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Effect of soy protein supplementation in patients with chronic hepatitis C: A randomized clinical trial

    Lucivalda PM OliveiraRosangela P de JesusRamona SSB BoulhosaCarlos Mauricio C Mendes...
    2203-2211页
    查看更多>>摘要：AIM:To evaluate the effects of soy supplementation on insulin resistance,fatty liver and alanine aminotransferase (ALT) levels in non-diabetic patients with chronic hepatitis C (CHC).METHODS:In a prospective,randomized and singleblinded clinical trial,we compared patients with CHC who had casein as a supplement (n =80) (control group),with patients who consumed a soy supplement diet (n =80) [intervention group (IG)].Both groups received 32 g/d of protein for 12 wk.RESULTS:Patients' baseline features showed that 48.1％ were overweight,43.7％ had abdominal fat accumulation,34.7％ had hepatic steatosis and 36.3％ had an homeostasis model assessment index of insulin resistance (HOMA-IR) ≥ 3.0.Descriptive analysis showed that protein supplementation diet reduced hepatic steatosis in both groups; however,significant reductions in ALT levels occurred in the soy group.Multiple regression modeling indicated that in the presence of severe fibrosis (F3/F4),y glutamyl transferase elevation and high density lipoprotein (HDL) reduction,the intervention group had 75％ less chance of developing hepatic steatosis (OR=0.25; 95％ CI:0.06-0.82) and 55％ less chance of presenting with an ALT level ≥ 1.5× the upper limit of normal (ULN) (OR =0.45,95％CI:0.22-0.89).Soy treatment did not have any effect on insulin resistance (OR =1.92; 95％ CI:0.80-4.83),which might be attributed to the fact that the HOMAIR values at baseline in most of our patients were in the normal range.Advanced hepatic fibrosis,an ALT level ＞ 1.5 × ULN and visceral fat were predictors of an HOMA-IR ≥ 3.The IG group had a reduced risk of an ALT level ＞ 1.5 × ULN.An HOMA-IR ≥ 3.0 and HDL ＜35 mg/dL were also risk factors for increased ALT.CONCLUSION:Soy supplementation decreased ALT levels and thus may improve liver inflammation in hepatitis C virus (HCV) patients; it also reduced hepatic steatosis in a subgroup of patients but did not change insulin resistance.It should be considered in the nutritional care of HCV patients.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Satisfaction with patient-doctor relationships in inflammatory bowel diseases: Examining patient-initiated change of specialist

    Daniel R van LangenbergJane M Andrews
    2212-2218页
    查看更多>>摘要：AIM:To assess the reasons for,and factors associated with,patient-initiated changes in treating specialist in inflammatory bowel diseases (IBD).METHODS:Prospectively identified IBD patients (n =256) with ≥ 1 encounter at a metropolitan hospital were surveyed,including whether they had changed treating specialist and why.Negative reasons included loss of confidence,disagreement,and/or personality clash with the specialist.RESULTS:Of 162 respondents,70 (43％) had ever changed specialists; 30/70 (43％) for negative reasons,52/70 (74％) in the preceding year.Patients with negative reasons for changing (n =30) were younger (median,35.2 years vs 45.3 years),had higher IBD knowledge (median,5.0 years vs 4.0 years),yet had lower medication adherence and satisfaction scores (median,19.0 years vs 22.0 years,14.0 years vs 16.0 years respectively,Mann-Whitney tests,all P ＜ 0.05),compared to all other responders (n =132).Patients with a recent change (for any reason) were more likely to have Crohn's disease,currently active disease,previous bowel resection and recent hospitalization [OR 2.6,95％ CI (1.3-5.4),2.2 (1.0-4.7),5.56 (1.92-16.67),2.0(1.3-3.0),each P ＜ 0.05].CONCLUSION:Changing specialist appears associated with patient-related (age,nonadherence) and contemporaneous disease-related factors (recent relapse) which,where modifiable,may enhance patient-doctor relationships and therefore quality of care.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Endoclips vs large or small-volume epinephrine in peptic ulcer recurrent bleeding

    Neven LjubicicIvan BudimirAlen BiscaninMarko Nikolic...
    2219-2224页
    查看更多>>摘要：AIM:To compare the recurrent bleeding after endoscopic injection of different epinephrine volumes with hemoclips in patients with bleeding peptic ulcer.METHODS:Between January 2005 and December 2009,150 patients with gastric or duodenal bleeding ulcer with major stigmata of hemorrhage and nonbleeding visible vessel in an ulcer bed (Forrest Ⅱa) were included in the study.Patients were randomized to receive a small-volume epinephrine group (15 to 25 mL injection group; Group 1,n =50),a large-volume epinephrine group (30 to 40 mL injection group; Group 2,n =50) and a hemoclip group (Group 3,n =50).The rate of recurrent bleeding,as the primary outcome,was compared between the groups of patients included in the study.Secondary outcomes compared between the groups were primary hemostasis rate,permanent hemostasis,need for emergency surgery,30 d mortal-ity,bleeding-related deaths,length of hospital stay and transfusion requirements.RESULTS:Initial hemostasis was obtained in all patients.The rate of early recurrent bleeding was 30％ (15/50) in the small-volume epinephrine group (Group 1) and 16％ (8/50) in the large-volume epinephrine group (Group 2) (P =0.09).The rate of recurrent bleeding was 4％ (2/50) in the hemoclip group (Group 3); the difference was statistically significant with regard to patients treated with either small-volume or large-volume epinephrine solution (P =0.0005 and P =0.045,respectively).Duration of hospital stay was significantly shorter among patients treated with hemoclips than among patients treated with epinephrine whereas there were no differences in transfusion requirement or even 30 d mortality between the groups.CONCLUSION:Endoclip is superior to both small and large volume injection of epinephrine in the prevention of recurrent bleeding in patients with peptic ulcer.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Beneficial effects of fucoidan in patients with chronic hepatitis C virus infection

    Naoki MoriKazunori NakasoneKoh TomimoriChie Ishikawa...
    2225-2230页
    查看更多>>摘要：AIM:To evaluate the effects of fucoidan,a complex sulfated polysaccharide extract from marine seaweed,on hepatitis C virus (HCV) RNA load both in vitro and in vivo.METHODS:HCV-1b replicon-expressing cells were cultured in the presence of fucoidan obtained from Cladosiphon okamuranus Tokida cultivated in Okinawa,Japan,and quantified the level of HCV replication.In an open-label uncontrolled study,15 patients with chronic hepatitis C,and HCV-related cirrhosis and hepatocellular carcinoma were treated with fucoidan (0.83 g/d) for 12 mo.The clinical symptoms,biochemical tests,and HCV RNA levels were assessed before,during,and after treatment.RESULTS:Fucoidan dose-dependently inhibited the expression of HCV replicon.At 8-10 mo of treatment with fucoidan,HCV RNA levels were significantly lower relative to the baseline.The same treatment also tended to lower serum alanine aminotransferase levels,and the latter correlated with HCV RNA levels.However,the improved laboratory tests did not translate into significant clinical improvement.Fucoidan had no serious adverse effects.CONCLUSION:Our findings suggest that fucoidan is safe and useful in the treatment of patients with HCV-related chronic liver diseases.Further controlled clinical trials are needed to confirm the present findings.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普