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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

100025

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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    Physiological and pathological role of local and immigrating colonic stem cells

    Ferenc SiposGábor ValczBéla Molnár
    295-301页
    查看更多>>摘要:The latest avenue of research is revealing the existence of and role for the colonic stem cells in the physiological renewal of the mucosa and in pathological circumstances where they have both positive and negative effects. In the case of human colon, different levels of stem cell compartments exist. First, the crypt epithelial stem cells, which have a role in the normal crypt epithelial cell dynamics and in colorectal carcinogenesis. Close to the crypts, the second layer of stem cells can be found; the local subepithelial stem cell niche, including the pericryptic subepithelial myofibroblasts that regulate the epithelial cell differentiation and have a crucial role in cancer progression and chronic inflammation-related fibrosis. The third level of stem cell compartment is the immigrating bone-marrow-derived stem cells, which have an important role in wound healing after severe mucosal inflammation, but are also involved in cancer invasion. This paper focuses on stem cell biology in the context of physiological and pathological processes in the human colon.

    8-Hydroxydeoxyguanosine: Not mere biomarker for oxidative stress, but remedy for oxidative stress-implicated gastrointestinal diseases

    Chan-Young OckEun-Hee KimDuck Joo ChoiHo Jae Lee...
    302-308页
    查看更多>>摘要:Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine (8-OHdG), which can bind to thymidine rather than cytosine, based on which, the level of 8-OHdG is generally regarded as a biomarker of mutagenesis consequent to oxidative stress. For example, higher levels of 8-OHdG are noted in Helicobacter pylori -associated chronic atrophic gastritis as well as gastric cancer. However, we have found that exogenous 8-OHdG can paradoxically reduce ROS production, attenuate the nuclear factor-κB signaling pathway, and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1, IL-6, cyclo-oxygenase-2, and inducible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1, NOX organizer-1 and NOX activator-1 in various conditions of inflammation-based gastrointestinal (GI) diseases including gastritis, inflammatory bowel disease, pancreatitis, and even colitis-associated carcinogenesis. Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases, as well as the prevention of inflammation-associated GI cancer. In this editorial review, the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidativestress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.

    Embryonic hepatocyte transplantation for hepatic cirrhosis:Efficacy and mechanism of action

    Wen-Ting BinLi-Mei MaQing XuXiao-Lin Shi...
    309-322页
    查看更多>>摘要:AIM: To investigate the efficacy and mechanism of action of allogeneic embryonic hepatocyte transplantation for the treatment of hepatic cirrhosis. METHODS: Rat embryonic hepatocytes were characterized by examining cell markers. Wistar rats with CCl4-induced cirrhosis were randomly divided into two groups: a model group receiving continuous CCl4, and a cell transplantation group receiving continuous CCl4 and transplanted with embryonic fluorescent-labeled hepatocytes. In addition, a normal control group was composed of healthy rats. All rats were sacrificed after 2 wk following the initiation of the cell transplant. Ultrasound, pathological analyses and serum biochemical tests were used to evaluate the efficacy of embryonic hepatocyte transplantation. To analyze the recovery status of cirrhotic hepatocytes and the signaling pathways influenced by embryonic hepatocyte transplantation, real-time polymerase chain reaction was performed to examine the mRNA expression of stellate activation-associated protein (STAP), c-myb, α smooth muscle actin (α-SMA) and endothelin-1 (ET-1). Western blotting and immunohistochemistry were employed to detect α-SMA and ET-1 protein expression in hepatic tissues. RESULTS: Gross morphological, ultrasound and histopathological examinations, serum biochemical tests and radioimmunoassays demonstrated that hepatic cirrhosis was successfully established in the Wistar rats. Stem cell factor receptor (c-kit), hepatocyte growth factor receptor (c-Met), Nestin, α fetal protein, albumin and cytokeratin19 markers were observed in the rat embryonic hepatocytes. Following embryonic hepatocyte transplantation, there was a significant reversal in the gross appearance, ultrasound findings, histopathological properties, and serum biochemical parameters of the rat liver. In addition, after the activation of hepatic stellate cells and STAP signaling, α-SMA, c-myb and ET-1 mRNA levels became significantly lower than in the untreated cirrhotic group (P < 0.05). These levels, however, were not statistically different from those of the normal healthy group. Immunohistochemical staining and Western blot analyses revealed that α-SMA and ET-1 protein expression levels in the transplantation group were significantly lower than in the untreated cirrhotic group, but being not statistically different from the normal group. CONCLUSION: Transplantation of embryonic hepatocytes in rats has therapeutic effects on cirrhosis. The described treatment may significantly reduce the expression of STAP and ET-1.

    Liver cold preservation induce lung surfactant changes and acute lung injury in rat liver transplantation

    An JiangChang LiuFeng LiuYu-Long Song...
    323-330页
    查看更多>>摘要:AIM: To investigate the relationship between donor liver cold preservation, lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation. METHODS: Liver transplantation models were established using male Wistar rats. Donor livers were preserved in University of Wisconsin solution at 4 ℃ for different lengths of time. The effect of ammonium pyrrolidinedithiocarbamate (PDTC) on ALI was also detected. All samples were harvested after 3 h reperfusion.The severity of ALI was evaluated by lung weight/body weight ratio, lung histopathological score, serum nitric oxide (NO) and endothelin (ET)-1 levels, lung tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels. Lung surfactants (LSs) were determined by micellar electrokinetic capillary chromatography. RESULTS: With extended donor liver cold preservation time (CPT), lung histopathological scores, serum ET-1 levels, lung weight/body weight ratio and the level of TNF-α and IL-1β in lung were increased significantly in the 180-min group compared with the sham group (3.16 ± 0.28 vs 1.12 ± 0.21, P < 0.001; 343.59 ± 53.97 vs 141.53 ± 48.48, P < 0.001; 0.00687 ± 0.00037 vs 0.00557 ± 0.00056, P < 0.001; 17.5 ± 3.0 vs 1.3 ± 0.3, P < 0.001; 10.8 ± 2.3 vs 1.8 ± 0.4, P < 0.001), but serum NO levels decreased remarkably (74.67 ± 10.01 vs 24.97 ± 3.18, P < 0.001). The expression of lung phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS) increased when CPT was < 120 min, and decreased when CPT was > 180 min (PC: 1318.89 ± 54.79 vs 1011.18 ± 59.99, P < 0.001; PE: 1504.45 ± 119.96 vs 1340.80 ± 76.39, P = 0.0019; PI: 201.23 ± 34.82 vs 185.88 ± 17.04, P = 0.2265; PS: 300.43 ± 32.95 vs 286.55 ± 55.55, P = 0.5054). All these ALI-associated indexes could be partially reversed by PDTC treatment. CONCLUSION: Prolonged CPT could induce or inhibit the expression of LSs at the compensation or decompensation stage, and some antioxidants (e.g., PDTC) may reverse the pathological process partially.

    Nitroglycerine effects on portal vein mechanics and oxidative stress in portal hypertension

    Andreja VujanacVladimir JakovljevicDusica DjordjevicVladimir Zivkovic...
    331-339页
    查看更多>>摘要:vein haemodynamics and oxidative stress in patients with portal hypertension. METHODS: Thirty healthy controls and 39 patients with clinically verified portal hypertension and increasedvascular resistance participated in the study. Liver diameters, portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection. Cross-section area, portal flow and index of vascular resistance were calculated. In collected blood samples, superoxide anion radical (O2 -), hydrogen peroxide (H2O2), index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO2 -) were determined. Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration. RESULTS: Oxidative stress parameters changed significantly during the study. H2O2 decreased at the end of study, probably via O2 -mediated disassembling in Haber Weiss and Fenton reaction; O2 -increased significantly probably due to increased diameter and tension and decreased shear rate level. Consequently O2 -and H2O2 degradation products, like hydroxyl radical, initiated lipid peroxidation. Increased blood flow was to some extent lower in patients than in controls due to double paradoxes, flow velocity decreased, shear rate decreased significantly indicating non Newtonian characteristics of portal blood flow. CONCLUSION: This pilot study could be a starting point for further investigation and possible implementation of some antioxidants in the treatment of portal hypertension.

    α-fetoprotein, vascular endothelial growth factor receptor-1 and early recurrence of hepatoma

    Toshiya KamiyamaMasato TakahashiKazuaki NakanishiHideki Yokoo...
    340-348页
    查看更多>>摘要:AIM: To investigate whether α-fetoprotein (AFP) and vascular endothelial growth factor receptor (VEGFR)-1 correlate with early recurrence of hepatoma/hepatocellular carcinoma (HCC). METHODS: From 2000 to 2005, 114 consecutive patients with HCC underwent primary curative hepatectomy. The mean age was 60.7 (8.7) years and 94 patients were male. The median follow-up period was 71.2 mo (range: 43-100 mo). Immediately prior to commencing laparotomy, 5 mL bone marrow was aspirated from thesternum and collected in citrate-coated test tubes. The initial 2 mL of bone marrow aspirate was discarded in each case. AFP mRNA and VEGFR-1 mRNA in the bone marrow and peripheral blood (BM-and PH-AFP mRNA and BM-and PH-VEGFR-1 mRNA, respectively) were measured by real-time quantitative reverse transcription polymerase chain reaction. As normal controls, VEGFR-1 mRNA in the bone marrow and peripheral blood was also measured in 11 living liver donors. These data were evaluated for any correlation with early recurrence, comparing clinical and pathological outcomes. RESULTS: The cut-off value of the BM-AFP mRNA and PH-AFP mRNA level in patients with HCC was set at 1.92 × 10-7 and zero, respectively, based on data from the controls. A total of 34 (29.8%) and six (5.4%) patients were positive for BM-AFP mRNA and PH-AFP mRNA, respectively. The BM-VEGFR-1 mRNA levels in all HCC patients were higher than those in the normal controls, and this was the case also for PH-VEGFR-1mRNA. The 25-percentile values for the BM-and PH-VEGFR-1 mRNA in HCC patients were used as the cut-off values for assigning the patients into two groups based on these transcript levels. The High group for BM-VEGFR-1 mRNA contained 81 (71.1%) HCC cases and the Low group was assigned 33 (28.9%) patients. These numbers for PH-VEGFR-1mRNA were 78 (75.0%) and 26 (25.0%), respectively. HCC recurred in 80 patients; in the remnant liver in 48 cases, in the remnant liver and remote tissue in 20, and in the remote tissue alone in 12. BM-AFP mRNA-positive cases showed a significantly higher rate of early recurrence (within 1 year of surgical treatment) compared with BM-AFP mRNAnegative patients (P = 0.0091). Patients were classified into four groups according to the level/status of their BM-VEGFR-1 and BM-AFP mRNA as follows: group A (n = 23), BM-VEGFR-1/BM-AFP mRNA = low/negative; group B (n = 57) high/negative; group C (n = 10) low/ positive; group D (n = 24), high/positive. This classification was found to correlate with a recurrence of thisdisease within 1 year (P = 0.0228). The disease-free survival curve of group A was significantly better than that of groups B, C or D (P = 0.0437, P = 0.0325, P = 0.0225). No other classification (i.e., PH-VEGF-R1/BMAFP, BM-VEGF-R1/PH-AFP, and PH-VEGF-R1/PH-AFP mRNA) showed such a correlation. CONCLUSION: The evaluation of BM-AFP and BM-VEGFR-1 mRNA in patients with HCC may be a valuable predictor of disease recurrence following curative resection.

    Adenovirus-expressed preS2 antibody inhibits hepatitis B virus infection and hepatic carcinogenesis

    Qian ZhangZhi-Qing LiHu LiuJia-He Yang...
    349-355页
    查看更多>>摘要:AIM: To investigate the inhibitory effect of hepatitis B virus (HBV) preS2 antibody (preS2Ab) against HBV infection and HBV-associated hepatic carcinogenesis. METHODS: An adenoviral vector carrying the fulllength light and heavy chains of the HBV preS2Ab gene, Ad315-preS2Ab, was constructed. Enzyme linked immunosorbent assay (ELISA) and Western blotting analyses were used to determine the preS2Ab expression levels in vitro . Immunofluorescent techniques were used to examine the binding affinity between the expressed HBV preS2Ab and HBV-positive liver cells. ELISAs were also used to determine hepatitis B surface antigen (HBsAg) levels to assess the inhibitory effect of the preS2Ab against HBV infection in L02 cells. The inhibitory effect of preS2Ab against hepatic carcinogenesiswas studied with diethylnitrosamine (DEN)-induced hepatocellular carcinomas (HCCs) in HBV transgenic mice. RESULTS: The expression of HBV preS2Ab increased with increases in the multiplicity of infection (MOI) of Ad315-preS2Ab in L02 cells, with 350.87 ± 17.37 μg/L of preS2Ab when the MOI was 100 plaque forming units (pfu)/cell. The expressed preS2Abs could recognize liver cells from HBV transgenic mice. ELISA results showed that L02 cells expressing preS2Ab produced less HBsAg after treatment with the serum of HBV patients than parental L02 cells expressing no preS2Ab. HBV transgenic mice treated with Ad315-preS2Ab had fewer and smaller cancerous nodes after induction with DEN than mice treated with a blank Ad315 vector or untreated mice. Additionally, the administration of Ad315-preS2Ab could alleviate hepatic cirrhosis and decrease the serum levels of alanine transaminase and aspartate transaminase. CONCLUSION: Adenovirus-mediated HBV preS2Ab expression could inhibit HBV infection in L02 cells, and then inhibit DEN-induced hepatocellular carcinogenesis and protect hepatic function in HBV transgenic mice.

    Effects and mechanisms of store-operated calcium channel blockade on hepatic ischemia-reperfusion injury in rats

    Li-Jie PanZi-Chao ZhangZhen-Ya ZhangWen-Jun Wang...
    356-367页
    查看更多>>摘要:AIM: To further investigate the important role of storeoperated calcium channels (SOCs) in rat hepatocytes and to explore the effects of SOC blockers on hepatic ischemia-reperfusion injury (HIRI). METHODS: Using freshly isolated hepatocytes from a rat model of HIRI (and controls), we measured cytosolic free Ca2+ concentration (by calcium imaging), net Ca2+ fluxes (by a non-invasive micro-test technique), the SOC current (ISOC; by whole-cell patch-clamp recording), and taurocholate secretion [by high-performance liquid chromatography and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays]. RESULTS: Ca2+ oscillations and net Ca2+ fluxes mediated by Ca2+ entry via SOCs were observed in rat hepatocytes. ISOC was significantly higher in HIRI groups than in controls (57.0 ± 7.5 pA vs 31.6 ± 2.7 pA, P <0.05) and was inhibited by La3+. Taurocholate secretion by hepatocytes into culture supernatant was distinctly lower in HIRI hepatocytes than in controls, an effect reversed by SOC blockers. CONCLUSION: SOCs are pivotal in HIRI. SOC blockers protected against HIRI and assisted the recovery of secretory function in hepatocytes. Thus, they are likely to become a novel class of effective drugs for prevention or therapy of HIRI patients in the future.

    Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis

    Meng-Meng TianYu SunZhong-Wu LiYing Wu...
    368-374页
    查看更多>>摘要:AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 (ICAM-1) and the risk, biological behavior and prognosis of gastric cancer (GC) in Chinese population. METHODS: The study group consisted of 332 GC patients and 380 healthy controls. Genotyping was performed using polymerase chain reaction and the results were confirmed by sequencing. The association of ICAM-1 K469E polymorphisms and the risk of GC were studied, and the correlation of ICAM-1 K469E polymorphisms with the clinicopathological parameters and prognosis of the patients with complete clinical and follow-up data was analyzed.RESULTS: Carriers of AA genotype had a significantly increased risk of GC compared with carriers of AG and GG genotypes [odds ratios: 1.36; 95% confidence interval (CI): 1.01-1.84; P = 0.041]. GC patients with AA genotype were more prone to distant metastasis than those carrying AG and GG genotypes (18.9% vs 7.0%, respectively; P = 0.002). In addition, patients at stage Ⅳ had significantly more carriers of AA genotype than those of AG and GG genotype (27.4% vs 16.9%, respectively; P = 0.046). Follow-up study showed that the overall cumulative survival rate was 23.7% in AA genotype group and 42.9% in AG and GG genotypes group. In univariate analysis, AA genotype was correlated with the overall cumulative survival (P = 0.034). But in multivariate analysis, ICAM-1 polymorphism was not an independent prognostic factor for the overall survival (relative risk, 1.145; 95% CI: 0.851-1.540; P = 0.370). CONCLUSION: Polymorphisms of ICAM-1 K469E can be a useful biomarker for identifying individuals with higher risk of GC, predicting disease progression, and guiding individualized treatment.

    Population-based study of DNA image cytometry as screening method for esophageal cancer

    Lin ZhaoWen-Qiang WeiDe-Li ZhaoChang-Qing Hao...
    375-382页
    查看更多>>摘要:AIM: To explore the DNA image cytometry (DNA-ICM) technique as a primary screening method for esophageal squamous precancerous lesions.METHODS: This study was designed as a populationbased screening study. A total of 582 local residents aged 40 years-69 years were recruited from Linzhou in Henan and Feicheng in Shandong. However, only 452 subjects had results of liquid-based cytology, DNA-ICM and pathology. The sensitivity and specificity of DNAICM were calculated and compared with liquid-based cytology in moderate dysplasia or worse. RESULTS: Sensitivities of DNA-ICM ranging from at least 1 to 4 aneuploid cells were 90.91%, 86.36%, 79.55% and 77.27%, respectively, which were better than that of liquid-based cytology (75%). Specificities of DNA-ICM were 70.83%, 84.07%, 92.65% and 96.81%, but the specificity of liquid-based cytology was 91.91%. The sensitivity and specificity of a combination of liquid-based cytology and DNA-ICM were 84.09% and 85.78%, respectively. CONCLUSION: It is possible to use DNA-ICM technique as a primary screening method for esophageal squamous precancerous lesions.