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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

wjg@wjgnet.com

010-85381901-628

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北京市朝阳区东四环中路62号楼远洋国际中心D座903室

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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    Role of ileostomy in restorative proctocolectomy

    Gianluca PellinoGuido SciaudoneSilvestro CanonicoFrancesco Selvaggi...
    1703-1707页
    查看更多>>摘要：Restorative proctocolectomy (RP) is the treatment of choice in patients affected with refractory ulcerative colitis or familial adenomatous polyposis.Surgery in elective settings is often performed in 2 stages,fashioning an ileostomy which is closed 2-3-mo later.It is still debated whether omitting ileostomy could offer advantages in the management of patients undergoing RP.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Etiology of inflammatory bowel disease: A unified hypothesis

    Xiaofa Qin
    1708-1722页
    查看更多>>摘要：Inflammatory bowel disease (IBD),including both ulcerative colitis (UC) and Crohn's disease (CD),emerged and dramatically increased for about a century.Despite extensive research,its cause remains regarded as unknown.About a decade ago,a series of findings made me suspect that saccharin may be a key causative factor for IBD,through its inhibition on gut bacteria and the resultant impaired inactivation of digestive proteases and over digestion of the mucus layer and gut barrier (the Bacteria-Protease-Mucus-Barrier hypothesis).It explained many puzzles in IBD such as its emergence and temporal changes in last century.Recently I further found evidence suggesting sucralose may be also linked to IBD through a similar mechanism as saccharin and have contributed to the recent worldwide increase of IBD.This new hypothesis suggests that UC and CD are just two symptoms of the same morbidity,rather than two different diseases.They are both caused by a weakening in gut barrier and only differ in that UC is mainly due to increased infiltration of gut bacteria and the resultant recruitment of neutrophils and formation of crypt abscess,while CD is mainly due to increased infiltration of antigens and particles from gut lumen and the resultant recruitment of macrophages and formation of granulomas.It explained the delayed appearance but accelerated increase of CD over UC and many other phenomena.This paper aims to provide a detailed description of a unified hypothesis regarding the etiology of IBD,including the cause and mechanism of IBD,as well as the relationship between UC and CD.
      原文链接:
    • NETL
    • NSTL
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    Epidemiology and clinical course of Crohn's disease: Results from observational studies

    φistein HovdeBjφrn A Moum
    1723-1731页
    查看更多>>摘要：The authors review the clinical outcome in patients with Crohn's disease (CD) based on studies describing the natural course of the disease.Population-based studies have demonstrated that the incidence rates and prevalence rates for CD have increased since the mid-1970s.The authors search for English language articles from 1980 until 2011.Geographical variations,incidence,prevalence,smoking habits,sex,mortality and medications are investigated.An increasing incidence and prevalence of CD have been found over the last three decades.The disease seems to be most common in northern Europe and North America,but is probably increasing also in Asia and Africa.Smoking is associated with an increased risk of developing CD.Age ＜ 40 at diagnosis,penetrating/stricturing complications,need for systemic steroids,and disease location in terminal ileum are factors associated with higher relapse rates.A slight predominance of women diagnosed with CD has been found.Ileocecal resection is the most commonly performed surgical procedure,and within the first five years after the diagnosis about one third of the patients have had intestinal surgery.Smoking is associated with a worse clinical course and with increased risk of flare-ups.In most studies the overall mortality is comparable to the background population.To date,the most effective treatment options in acute flares are glucocorticosteroids and tumor necrosis factor (TNF)-α-blockers.Azathioprine/methotrexate and TNF-α-blockers are effective in maintaining remission.
      原文链接:
    • NETL
    • NSTL
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    Macrophage secretory products induce an inflammatory phenotype in hepatocytes

    Michelle MelinoVictoria L GaddGene V WalkerRichard Skoien...
    1732-1744页
    查看更多>>摘要：AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147patients with hepatitis C virus (HCV) infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin (7.8 ± 2.5-fold,P =0.045) and transforming growth factor (TGF)-β1 (2.6 ± 0.2-fold,P ＜ 0.001) and downregulation of epithelial cadherin (1.7 ± 0.02-fold,P =0.017) mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2 (17-fold,P ＜ 0.001) and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA (F0 1.0± 0.3,F1 2.2 ± 0.2,F2 3.0 ± 9.3,F3/4 4.0 ± 0.8,P =0.003) and protein expression (F1 1.0 ± 0.5,F2 1.3 ±0.4,F3/4 3.6 ± 0.4,P =0.014) with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase (MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9attenuated the change in morphology and mRNA expression of TGF-β1 (2.9 ± 0.2 vs 1.04 ± 0.1,P ＜ 0.001)in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163 (F0 1.0 ± 0.2,F1/2 2.8 ± 0.3,F3/4 5.3 ± 1.0,P =0.001) and MMP-9 (F0 1.0 ± 0.4,F1/2 2.8 ± 0.3,F3/4 4.1 ± 0.8,P =0.011) was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Wnt5a participates in hepatic stellate cell activation observed by gene expression profile and functional assays

    Wu-Jun XiongLi-Juan HuYi-Cheng JianLi-Jing Wang...
    1745-1752页
    查看更多>>摘要：AIM:To identify differentially expressed genes in quiescent and activated hepatic stellate cells (HSCs) and explore their functions.METHODS:HSCs were isolated from the normal Sprague Dawley rats by in suit perfusion of collagenase and pronase and density Nycodenz gradient centrifugation.Total RNA and mRNA of quiescent HSCs,and cultureactivated HSCs were extracted,quantified and reversely transcripted into cDNA.The global gene expression profile was analyzed by microarray with Affymetrix rat genechip.Differentially expressed genes were annotated with Gene Ontology (GO) and analyzed with Kyoto encyclopedia of genes and genomes (KEGG) pathway using the Database for Annotation,Visualization and Integrated Discovery.Microarray data were validated by quantitative real-time polymerase chain reaction (qRTPCR).The function of Wnt5a on human HSCs line LX-2was assessed with lentivirus-mediated Wnt5a RNAi.The expression of Wnt5a in fibrotic liver of a carbon tetrachloride (CCl4)-induced fibrosis rat model was also analyzed with Western blotting.RESULTS:Of the 28 700 genes represented on this chip,2566 genes displayed at least a 2-fold increase or decrease in expression at a P ＜ 0.01 level with a false discovery rate.Of these,1396 genes were upregulated,while 1170 genes were downregulated in culture-activated HSCs.These differentially expressed transcripts were grouped into 545 GO based on biological process GO terms.The most enriched GO terms included response to wounding,wound healing,regulation of cell growth,vasculature development and actin cytoskeleton organization.KEGG pathway analysis revealed that Wnt5a signaling pathway participated in the activation of HSCs.Wnt5a was significantly increased in cultureactivated HSCs as compared with quiescent HSCs.qRTPCR validated the microarray data.Lentivirus-mediated suppression of Wnt5a expression in activated LX-2 resulted in significantly impaired proliferation,downregulated expressions of type I collagen and transforming growth factor-β1.Wnt5a was upregulated in the fibrotic liver of a CCl4-induced fibrosis rat model.CONCLUSION:Wnt5a is involved in the activation of HSCs,and it may serve as a novel therapeutic target in the treatment of liver fibrosis.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Pro-apoptotic effects of tectorigenin on human hepatocellular carcinoma HepG2 cells

    Chun-Ping JiangHui DingDa-Hua ShiYu-Rong Wang...
    1753-1764页
    查看更多>>摘要：AIM:To investigate the effects of tectorigenin on human hepatocellular carcinoma (HCC) HepG2 cells.METHODS::Tectorigenin,one of the main components of rhizome of Iris tectorum,was prepared by simple methods,such as extraction,filtration,concentration,precipitation and recrystallization.HepG2 cells were incubated with tectorigenin at different concentrations,and their viability was assessed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Apoptosis was detected by morphological observation of nuclear change,agarose gel electrophoresis of DNA ladder,and flow cytometry with Hoechst 33342,Annexin V-EGFP and propidium iodide staining.Generation of reactive oxygen species was quantified using DCFH-DA.Intracellular Ca2+ was monitored by Fura 2-AM.Mitochondrial membrane potential was monitored using Rhodamine 123.Release of cytochrome c from mitochondria to cytosol was detected by Western blotting.Activities of caspase-3,-8 and-9 were investigated by Caspase Activity Assay Kit.RESULTS:The viability of HepG2 cells treated by tectorigenin decreased in a concentration-and timedependent manner.The concentration that reduced the number of viable HepG2 cells by 50％ (IC50) after 12,24 and 48 h of incubation was 35.72 mg/L,21.19mg/L and 11.06 mg/L,respectively.However,treatment with tectorigenin at 20 mg/L resulted in a very slight cytotoxicity to L02 cells after incubation for 12,24 or 48 h.Tectorigenin at a concentration of 20 mg/Lgreatly inhibited the viability of HepG2 cells and induced the condensation of chromatin and fragmentation of nuclei.Tectorigenin induced apoptosis of HepG2cells in a time-and dose-dependent manner.Compared with the viability rate,induction of apoptosis was the main mechanism of the anti-proliferation effect of tectorigenin in HepG2 cells.Furthermore,tectorigenininduced apoptosis of HepG2 cells was associated with the generation of reactive oxygen species,increased intracellular [Ca2+]i,loss of mitochondrial membrane potential,translocation of cytochrome c,and activation of caspase-9 and-3.CONCLUSION:Tectorigenin induces apoptosis of HepG2 cells mainly via mitochondrial-mediated pathway,and produces a slight cytotoxicity to L02 cells.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Diazoxide attenuates ischemia/reperfusion injury via upregulation of heme oxygenase-1 after liver transplantation in rats

    Zhong ZengHan-Fei HuangFei HeLin-Xi Wu...
    1765-1772页
    查看更多>>摘要：AIM:To evaluate the effects of diazoxide on ischemia/reperfusion (I/R)-injured hepatocytes and further elucidate its underlying mechanisms.METHODS:Male Sprague-Dawley rats were randomized (8 for donor and recipient per group) into five groups:I/R group (4 h of liver cold ischemia followed by 6 h of reperfusion); heme oxygenase-1 (HO-1) small interfering RNA (siRNA) group (injection of siRNA via donor portal vein 48 h prior to harvest); diazoxide (DZ)group (injection of DZ via donor portal vein 10 min prior to harvest); HO-1 siRNA + DZ group; and siRNA control group.Blood and liver samples were collected at 6 h after reperfusion.The mRNA expressions and protein levels of HO-1 were determined by reverse transcription polymerase chain reaction and Western blotting,and tissue morphology was examined by light and transmission electron microscopy.Serum transaminases level and cytokines concentration were also measured.RESULTS:We observed that a significant reduction of HO-1 mRNA and protein levels in HO-1 siRNA and HO-1siRNA + D7 group when compared with I/R group,while the increases were prominent in the DZ group.Light and transmission electron microscopy indicated severe disruption of tissue with Iobular distortion and mitochondrial cristae damage in the HO-1 siRNA and HO-1 siRNA + DZ groups compared with DZ group.Serum alanine aminotransferase,aspartate transaminase,tumor necrosis factor-α and interleukin-6 levels increased in the HO-1 siRNA and HO-1 siRNA + DZ groups,and decreased in the DZ group.CONCLUSION:The protective effect of DZ may be induced by upregulation of HO-1.By inhibiting expression of HO-1,this protection pretreated with DZ was abolished.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Safety and efficacy of Profermin（R） to induce remission in ulcerative colitis

    Aleksander KragHans IsraelsenBjφrn von RybergKlaus K Andersen...
    1773-1780页
    查看更多>>摘要：AIM:To test the efficacy and safety of Profermin(R) in inducing remission in patients with active ulcerative colitis (UC).METHODS:The study included 39 patients with mild to moderate UC defined as a Simple Clinical Colitis Activity Index (SCCAI) ＞ 4 and ＜ 12 (median:7.5),who were treated open-label with Profermin(R) twice daily for 24 wk.Daily SCCAI was reported observer blinded via the Internet.RESULTS:In an intention to treat (ITT) analysis,the mean reduction in SCCAI score was 56.5％.Of the 39 patients,24 (62％) reached the primary endpoint,which was proportion of patients with ≮ 50％ reduction in SCCAI.Our secondary endpoint,the proportion of patients in remission defined as SCCAI ≤ 2.5,was in ITT analysis reached in 18 of the 39 patients (46％).In a repeated-measure regression analysis,the estimated mean reduction in score was 5.0 points (95％ CI:4.1-5.9,P ＜ 0.001) and the estimated mean time taken to obtain half the reduction in score was 28 d (95％ CI:26-30).There were no serious adverse events (AEs) or withdrawals due to AEs.Profermin(R)was generally well tolerated.CONCLUSION:Profermin(R) is safe and may be effective in inducing remission of active UC.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

    Junichi TakinoShoichi YamagishiMasayoshi Takeuchi
    1781-1788页
    查看更多>>摘要：AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products (Glycer-AGEs)on hepatocellular carcinoma (HCC) cells.METHODS:Two HCC cell lines (Hep3B and HepG2cells) and human umbilical vein endothelial cells (HUVEC) were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs (RAGE) protein was detected in Hep3B and HepG2 cells.HepG2 cells were not affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor (VEGF) mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin (BSA)treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00 ± 0.10 vs 1.92± 0.09 (P ＜ 0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63 ± 0.04ng/mL vs 2.28 ± 0.17 ng/mL for the 24 h treatment and 3.36 ± 0.10 ng/mL vs 4.79 ± 0.31 ng/mL for the 48 h treatment,respectively (P ＜ 0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4％ ± 9.0％ vs 144.5％ ± 11.3％ for cell viability,4.29 ± 1.53 vs 6.78 ± 1.84 for migration indices,and 71.0 ± 7.5 vs 112.4 ± 8.0 for the number of branching points,respectively (P ＜ 0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Prospective controlled study on the effects of polyethylene glycol in capsule endoscopy

    Takafumi ItoKen OhataAkiko OnoHideyuki Chiba...
    1789-1792页
    查看更多>>摘要：AIM:To prospectively confirm whether a small amount of polyethylene glycol (PEG) ingested after swallowing endoscopy capsule improves image quality and completion rate.METHODS:Forty-four consecutive patients referred to us for capsule endoscopy (CE) were randomized to two groups.All patients were restricted to clear fluids for 12 h before the examination.Patients in group A (22cases) received no additional preparation,while those in group B (20 cases) ingested 500 mL of PEG within a 2 h period starting 30 min after swallowing the capsule.Clear fluids and meals were allowed 2 h and 4 h after capsule ingestion,respectively.Image quality was assessed as the percentage of visualized bowel surface area as follows:1:＜ 25％; 2:25％-49％; 3:50％-74％;4:75％-89％; 5:＞ 90％.The small bowel record was divided into five segments by time,and the score for each segment was evaluated.All CE examinations were performed with the Pillcam SB capsule endoscopy system (Given Imaging Co.Ltd.,Yoqnem).RESULTS:This study ended in December 2009,because sample size was considered large enough.A total of 44 patients were enrolled.Two patients in group B were excluded from the analysis because small bowel images could not be obtained from these patients; one had a full stomach,while the other presented with a massive gastric bleed.Thus,22 patients from group A and 20 patients from group B completed the study.There was no significant difference in age (P =0.22),sex (P =0.31),and indication for CE.No significant adverse events occurred in any of the study patients.In group A,image quality deteriorated as the capsule progressed distally.However,in group B,image quality was maintained to the distal small bowel.In each of the five segments,the visibility score was significantly higher in group B than in group A (segment 1:4.3 ±0.7 vs 4.7 ± 0.5,P =0.03; segment 2:4.2 ± 0.9 vs 4.8± 0.4,P =0.01; segment 3:4.0 ± 1.0 vs 4.6 ± 0.7,P=0.04; segment 4:3.6 ± 1.1 vs 4.5 ± 0.6,P =0.003;segment 5:2.7 ± 1.0 vs 4.4 ± 0.8,P =0.00004).Thus,the use of PEG during CE examination significantly improved image quality in all time segments,and this effect was more pronounced in the distal ileum.The completion rate to the cecum was not significantly different between groups A and B (81.8％ vs 85.0％,P=0.89).There was no difference in the gastric transit time between groups (36.2 ± 35.0 min vs 54.0 ± 56.6min,P =0.23),but the small bowel transit time was significantly longer in group A than in group B (246.0 ±107.0 min vs 171.0 ± 104.0 min,P =0.04).CONCLUSION:The ingestion of a small amount of PEG after the swallowing of an endoscopy capsule significantly improved CE image quality,but did not enhance the completion rate to the cecum.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普