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| 1 | Long-term outcome and prognostic factors of patients with hilar cholangiocarcinoma显示文摘AIM: To evaluate the long-term outcome and prognostic factors of patients with hilar cholangiocarinoma. METHODS: Ninety-six consecutive patients underwent treatment for malignant hilar bile duct tumors during 1995–2005. Of the 96 patients, 20 were initially treated with surgery (n = 2 R0 / n = 18 R1). In non-operated patients, data analysis was performed retrospectively. RESULTS: Among the 96 patients, 76 were treated with endoscopic transpapillary (ERC, n = 45) and/or percutaneous transhepatic biliary drainage (PTBD, n = 31). The mean survival time of these 76 patients undergoing palliative endoscopic and/or percutaneous drainage was 359 ± 296 d. The mean survival time of patients with initial bilirubin levels > 10 mg/dL was significantly lower (P < 0.001) than patients with bilirubin levels < 10 mg/dL. The mean survival time of patients with Bismuth stage Ⅱ (n = 8), Ⅲ (n = 28) and Ⅳ (n = 40) was 496 ± 300 d, 441 ± 385 d and 274 ± 218 d, respectively. Thus, patients with advanced Bismuth stage showed a reduced mean survival time, but the difference was not significant. The type of biliary drainage had no significant beneficial effect on the mean survival time (ERC vs PTBD, P = 0.806). CONCLUSION: Initial bilirubin level is a significant prognostic factor for survival of patients. In contrast, age, tumor stage according to the Bismuth-Corlette classification, and types of intervention are not significant prognostic parameters for survival. Palliative treatment with endoscopic or percutaneous biliary drainage is still suboptimal, new diagnostic and therapeutic tools need to be evaluated. | Andreas Weber Sonja Landrock Jochen Schneider Manfred Stangl Bruno Neu Peter Born Meinhard Classen Thomas Rsch Roland M Schmid Christian Prinz | 2007 | World Journal of Gastroenterology2007，13，9： | 23 |
| 2 | Diagnostic approaches for cholangiocarcinoma显示文摘Cholangiocarcinomas arise from the epithelial cells of the bile ducts and are associated with poor prognosis. Despite new diagnostic approaches, the definite diagnosis of this malignancy continues to be challenging. Cholangiocarcinomas often grow longitudinally along the bile duct rather than in a radial direction. Thus, large tumor masses are frequently absent and imaging techniques, including ultrasound, CT, and MRI have only limited sensitivity. Tissue collection during endoscopic (ERCP) and/or percutaneous transhepatic (PTC) procedures are usually used to confirm a definitive diagnosis of cholangiocarcinoma. However, forceps biopsy and brush cytology provide positive results for malignancy in about only 50% of patients. Percutaneous and peroral cholangioscopy using fiber-optic techniques were therefore developed for direct visualization of the biliary tree, yielding additional information about endoscopic appearance and tumor extension, as well as a guided biopsy acquistion. Finally, endoscopic ultrasonography (EUS) complements endoscopic and percutaneous approaches and may provide a tissue diagnosis of tumors in the biliary region through fine-needle aspiration. In the future, new techniques allowing for early detection, including molecular markers, should be developed to improve the diagnostic sensitivity in this increasing tumor entity. | Andreas Weber Roland M Schmid Christian Prinz | 2008 | World Journal of Gastroenterology2008，14，26： | 21 |
| 3 | In vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens of acute cholangitis显示文摘AIM: To analyze the in vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens isolated from patients with acute cholangitis. METHODS: In this prospective study a total of 65 patients with acute cholangitis due to biliary stone obstruction (n = 7), benign biliary stricture (n = 16), and malignant biliary stricture (n = 42) were investigated with regard to spectrum of bacterial infection and antibiotic resistance. Pathogens were isolated from bile cultures in all study patients. In 22 febrile patients, blood cultures were also obtained. In vitro activity of moxifloxacin and piperacillin/ sulbactam was determined by agar diffusion. RESULTS: Thirty-one out of 65 patients had positive bile and/or blood cultures. In 31 patients, 63 isolates with 17 different species were identified. The predominant strains were Enterococcus species (26/63), E.coli (13/63) and Klebsiella species (8/63). A comparable in vitro activity of moxifloxacin and piperacillin/sulbactam was observed for E.coli and Klebsiella species. In contrast, Enterococcus species had higher resistances towards moxifloxacin. Overall bacteria showed antibiotic resistances in vitro of 34.9% for piperacillin/sulbactam and 36.5% for moxifloxacin.CONCLUSION: Enterococcus species , E.coli and Klebsiella species were the most common bacteria isolated from bile and/or blood from patients with acute cholangitis. Overall, a mixed infection with several species was observed, and bacteria showed a comparable in vitro activity for piperacillin/sulbactam and moxifloxacin. | Andreas Weber Wolfgang Huber Klaus Kamereck Philipp Winkle Petra Voland Hans Weidenbach Roland M Schmid Christian Prinz | 2008 | World Journal of Gastroenterology2008，14，20： | 18 |
| 4 | Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma显示文摘AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings. | Andreas Weber Claus von Weyhern Falko Fend Jochen Schneider Bruno Neu Alexander Meining Hans Weidenbach Roland M Schmid Christian Prinz | 2008 | World Journal of Gastroenterology2008，14，7： | 17 |
| 5 | Nat Biotechnol:将人星形胶质细胞重编程为多巴胺能神经元,有助治疗帕金森病显示文摘帕金森病是一种主要影响运动系统的神经退行性疾病。它的特征在于大脑中的多巴胺能神经元(dopaminergic neuron)渐进性丧失。尽管当前的疗法旨在补充多巴胺水平,但是没有一种疗法能够恢复这些丢失的细胞。如今。在一项新的研究中,来自瑞典、奥地利、西班牙和美国的研究人员开发出一种方法:将神经胶质细胞(glialcell)转化为活性的多巴胺能神经元,并且所产生的多巴胺能神经元能够部分恢复帕金森病模式小鼠的运动功能。这项概念验证研究可能为开发出一种治疗这种疾病的新方法铺平道路。 | Pia Rivetti di Val Cervo, Elisa Martín-Montañez, Enrique M Toledo, Gioele La Manno, Sara Padrell Sánchez, Sten Linnarsson Ernest Arenas Roman A Romanov, Christian Pifl Tibor Harkany Roman A Romanov, Giada Spigolon, Débora Masini, Michael Feyder, Tibor Harkany Gilberto Fisone Elisa Martín-Montañez Yi-Han Ng Marius Wernig | 2017 | 现代生物医学进展2017，17，17： | 11 |
| 6 | Comparison of high-resolution ultrasound and MR-enterography in patients with inflammatory bowel disease显示文摘AIM:To compare the results of high-resolution ultrasound(HR-US) and magnetic resonance enterography(MRE) examinations in patients with inflammatory bowel disease(IBD).METHODS:The reports of 250 consecutive cases with known IBD,who had an MRE and HR-US examination,were retrospectively analyzed.Using a patient-based approach we evaluated morphological disease features such as affected bowel wall,stenosis,abscess and fistula.The comparison between the two modalities was based on the hypothesis,that any pathological change described in any imaging modality was a true finding,as no further standard of reference was available for complete assessment.RESULTS:Two hundred and fifty examinations representing 207 different patients were evaluated.Both modalities assessed similar bowel wall changes in 65% of the examinations,with more US findings in 11% and more MRE findings in 15%.When the reports were analyzed with regard to 'bowel wall inflammation',US reported more findings in 2%,while MRE reported more findings in 53%.Stenoses were assessed to be identical in 8%,while US found more in 3% and MRE in 29%(P < 0.01).For abscess detection,US showed more findings in 2%(n = 4) while MRE detected more in 6%(n = 16).US detected more fistulas in 1%(n = 2),while MRE detected more in 13%(n = 32)(P < 0.001).The most common reason for no detected pathology by US was a difficult to assess anatomical region(lesser pelvis,n = 72).CONCLUSION:US can miss clinically relevant pathological changes in patients with IBD mostly due to difficulty in assessing certain anatomical regions. | Andreas G Schreyer Cynthia Menzel Chris Friedrich Florian Poschenrieder Lukas Egger Christian Dornia Gabriela Schill Lena M Dendl Doris Schacherer Christl Girlich Ernst-Michael Jung | 2011 | World Journal of Gastroenterology2011，17，8： | 7 |
| 7 | Dynamic magnetic resonance defecography in 10 asymptomatic volunteers显示文摘AIM: Evaluation of the wide range of normal findings in asymptomatic women undergoing dynamic magnetic resonance (MR) defecography. METHODS: MR defecography of 10 healthy female volunteers (median age: 31 years) without previous pregnancies or history of surgery were evaluated. The rectum was filled with 180 mL gadolinium ultrasound gel mixture. MR defecography was performed in the supine position. The pelvic floor was visualized with a dynamic T2-weighted sagittal plane where all relevant pelvic floor organs were acquired during defecation. The volunteers were instructed to relax and then to perform straining maneuvers to empty the rectum. The pubococcygeal line (PCGL) was used as the line of reference. The movement of pelvic floor organs was measured as the vertical distance to this reference line. Data were recorded in the resting position as well as during the defecation process with maximal straining. Examinations were performed and evaluated by two experienced abdominal radiologists without knowledge of patient history. RESULTS: Average position of the anorectal junction was located at -5.3 mm at rest and -29.9 mm during straining. The anorectal angle widened significantly from 93° at rest to 109° during defecation. A rectocele was diagnosed in eight out of 10 volunteers showing an average diameter of 25.9 mm. The bladder base was located at a position of +23 mm at rest and descended to -8.1 mm during defecation in relation to the PCGL. The bladder base moved below the PCGL in six out of 10 volunteers, which was formally defined as a cystocele. The uterocervical junction was located at an average level of +43.1 mm at rest and at +7.9 mm during straining. The uterocervical junction of three volunteers fell below the PCGL; described formally as uterocervical prolapse. CONCLUSION: Based on the range of standard values in asymptomatic volunteers, MR defecography values for pathological changes have to be re-evaluated. | Andreas G Schreyer Christian Paetzel Alois Fürst Lena M Dendl Elisabeth Hutzel René Müller-Wille Philipp Wiggermann Stephan Schleder Christian Stroszczynski Patrick Hoffstetter | 2012 | World Journal of Gastroenterology2012，18，46： | 7 |
| 8 | 术中二维相干光断层扫描作为前节手术的一个新工具显示文摘我们测试了1310nm相干光断层扫描仪与手术显微镜前部镜头的分光镜连接后对前节手术过程中术中的非接触性成像。这项对相干光断层成像技术的新改进可完成前节手术术中角膜、巩膜的高分辨率横断面的成像与厚度测量。其在板层切开技术如深层前板层角膜移植术和小梁切除术中尤为有用。 | Gerd Geerling Maya Müller Christian Winter Hans Hoerauf Stefan Oelckers Horst Laqua Reginald Birngruber 李晓宁(译) 任泽钦(校) | 2005 | 美国医学会眼科杂志(中文版)2005，17，4： | 7 |
| 9 | Isolation and characterisation of human gingival margin-derived STRO-1/MACS^+ and MACS^-cell populations显示文摘Recently,gingival margin-derived stem/progenitor cells isolated via STRO-1/magnetic activated cell sorting(MACS) showed remarkable periodontal regenerative potential in vivo.As a second-stage investigation,the present study's aim was to perform in vitro characterisation and comparison of the stem/progenitor cell characteristics of sorted STRO-1-positive(MACS^+) and STRO-1-negative(MACS^-) cell populations from the human free gingival margin.Cells were isolated from the free gingiva using a minimally invasive technique and were magnetically sorted using anti-STRO-1 antibodies.Subsequently,the MACS^+ and MACS^- cell fractions were characterized by flow cytometry for expression of CD14,CD34,CD45,CD73,CD90,CD105,CD146/MUC18 and STRO-1.Colony-forming unit(CFU) and multilineage differentiation potential were assayed for both cell fractions.Mineralisation marker expression was examined using real-time polymerase chain reaction(PCR).MACS^+ and MACS- cell fractions showed plastic adherence.MACS^+ cells,in contrast to MACS- cells,showed all of the predefined mesenchymal stem/progenitor cell characteristics and a significantly higher number of CFUs(P<0.01).More than 95%of MACS^+ cells expressed CD105,CD90 and CD73;lacked the haematopoietic markers CD45,CD34 and CD14,and expressed STRO-1 and CD146/MUC18.MACS- cells showed a different surface marker expression profile,with almost no expression of CD14 or STRO-1,and more than 95%of these cells expressed CD73,CD90 and CD146/MUC18,as well as the haematopoietic markers CD34 and CD45 and CD105.MACS^+ cells could be differentiated along osteoblastic,adipocytic and chondroblastic lineages.In contrast,MACS- cells demonstrated slight osteogenic potential.Unstimulated MACS^+ cells showed significantly higher expression of collagen I(P<0.05) and collagen III(P<0.01),whereas MACS^- cells demonstrated higher expression of osteonectin(P<0.05;MannWhitney).The present study is the first to compare gingival MACS^+ and MACS- cell populations demonstrating that MACS^+ cells,in contrast to MACS- cells,harbour stem/progenitor cell characteristics.This study also validates the effectiveness of the STRO-l/MACS^+technique for the isolation of gingival stem/progenitor cells.Human free gingival margin-derived STRO-1/MACS^+ cells are a unique renewable source of multipotent stem/progenitor cells. | Karim M Fawzy El-Sayed Sebastian Paris Christian Graetz Neemat Kassem Mohamed Mekhemar Hendrick Ungefroren Fred Fndrich Christof Drfer | 2015 | International Journal of Oral Science2015，7，2： | 6 |
| 10 | 猪微卫星标记多重PCR扩增组合显示文摘采用多重PCR的方法,以快速扩增微卫星标记和节约试剂为目标,对其反应条件进行优化后,获得了46个扩增效果理想的微卫星标记多重PCR组合,其中30个为二重PCR,16个为三重PCR。实验结果表明,这些多重PCP反应的引物浓度为0.06~0.3μmol/L,Mg2+的浓度变化范围为1.5~3.0mmol/L,采用的PCR缓冲液的倍数为1.0、1.2、1.4或1.6,每个PCR反应聚合酶的用量在0.2和0.4U之间,退火温度及反应循环数分别为52~60℃和32~50℃。所有多重PCR进一步合并为17个可在ABI337测序仪上进行电泳的组合。 | 郭晓令 徐宁迎 LOOFT Christian REINSCH Norbert KAL M Ernst | 2004 | 遗传2004，26，1： | 6 |
| 11 | Limb symmetry index in competitive alpine ski racers:Reference values and injury risk identification according to age-related performance levels显示文摘Purpose: The aims of this study were to assess differences of limb symmetry index(LSI) in strength-and coordination-related tasks between high-level, competitive, noninjured ski racers of different age-related performance levels and to prospectively assess limb differences as a possible risk factor for traumatic and overuse injury in youth ski racers.Methods: The study(Study 1) included 285 high-level competitive ski racers(125 females, 160 males) of 3 age-related performance levels and based on the school system: 95 youth(10à14 years, secondary modern school), 107 adolescent(15à19 years, grammar school), and 83 elite athletes(20à34 years). To investigate the second aim(Study 2), 67 of the 95 youth athletes were included and any traumatic or overuse injuries were prospectively recorded over 2 seasons. All athletes performed 4 unilateral tests(strength related: one-leg counter movement jump(OL-CMJ) and one-leg isometric/isokinetic press strength test(OL-ILS); coordination related: one-leg stability test(OL-ST) and one-leg speedy jump test(OL-SJ)). The LSI was calculated by dividing the dominant leg by the nondominant leg and multiplying by 100. Kruskal-Wallis H tests and binary logistic regression analyses were conducted.Results: There were significant differences between the LSI of the 3 age-related performance-level groups only in the strength-related tests: the OL-CMJ(x2(2, 285) = 9.09; p = 0.01) and the OL-ILS(x2(2, 285) = 14.79; p < 0.01). The LSI for OL-ILS was found to be a significant risk factor for traumatic injury in youth ski racers(Wald = 7.08; p < 0.01). No significant risk factors were found for overuse injuries.Conclusion: Younger athletes display slightly greater LSI values only in the strength-related tests. The cut-off value of limb differences of <10%for return to sport decisions seems to be appropriate for elite athletes, but for youth and adolescent athletes it has to be critically discussed. It seems to be necessary to define thresholds based on specific performance tasks(strength vs. coordination related) rather than on generalizations,and age-related performance levels must be considered. Limb differences in unilateral leg extension strength represent a significant injury risk factor in youth ski racers. | Lisa Steidl-Müller Carolin Hildebrandt Erich Müiller Christian Fink Christian Raschner | 2018 | Journal of Sport and Health Science2018，7，4： | 6 |
| 12 | DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori-specific immune tolerance, and asthma protection显示文摘 | Oertli Mathias Sundquist Malin Hitzler Iris Engler Daniela B Arnold Isabelle C Reuter Sebastian Maxeiner Joachim Hansson Malin Taube Christian Quiding-J?rbrink Marianne Müller Anne | 2012 | EN2012，，3： | 5 |
| 13 | Safety of gastrointestinal endoscopy with conscious sedation in obstructive sleep apnea显示文摘AIM To perform a systematic review and meta-analysis to assess the safety of conscious sedation in patients with obstructive sleep apnea(OSA).METHODS A comprehensive electronic search of MEDLINE and EMBASE was performed from inception until March 1, 2015. In an effort to include unpublished data, abstracts from prior gastroenterological society meetings as well as other reference sources were interrogated. After study selection, two authors utilizing a standardized data extraction form collected the data independently. Any disagreements between authors were resolved by consensus among four authors. The methodological quality was assessed using the Newcastle Ottawa tool for observational studies. The primary variables of interest included incidence of hypoxia, hypotension, tachycardia, and bradycardia. Continuous data were summarized as odds ratio(OR) and 95%CI and pooled using generic inverse variance under the random-effects model. Heterogeneity between pooled studies was assessed using the I2 statistic.RESULTS Initial search of MEDLINE and EMBASE identified 357 citations. A search of meeting abstracts did not yield any relevant citations. After systematic review and exclusion consensus meetings, seven studies met the a priori determined inclusion criteria. The overall methodological quality of included studies ranged from moderate to low. No significant differences between OSA patients and controls were identified among any of the study variables: Incidence of hypoxia(7 studies, 3005 patients; OR = 1.11; 95%CI: 0.73-1.11; P = 0.47; I2 = 0%), incidence of hypotension(4 studies, 2125 patients; OR = 1.10; 95%CI: 0.75-1.60; P = 0.63; I2 = 0%), incidence of tachycardia(3 studies, 2030 patients; OR = 0.94; 95%CI: 0.53-1.65; P = 0.28; I2 = 21%), and incidence of bradycardia(3 studies, 2030 patients; OR = 0.88; 95%CI: 0.63-1.22; P = 0.59; I2 = 0%).CONCLUSION OSA is not a significant risk factor for cardiopulmonary complications in patients undergoing endoscopic procedures with conscious sedation. | Christian M Andrade Brijesh Patel Meghana Vellanki Ambuj Kumar Gitanjali Vidyarthi | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，11： | 4 |
| 14 | Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells显示文摘 | Arnold Isabelle C Dehzad Nina Reuter Sebastian Martin Helen Becher Burkhard Taube Christian Müller Anne | 2011 | Journal of Clinical Investigation2011，，8： | 4 |
| 15 | 软启动——降低三相异步电动机的启动电流与启动转矩的峰值显示文摘此实验是在德国汉诺威应用科学技术大学完成的,考虑到我国现有的电网在供电稳定性与供电质量上与发达国家尚存在差距,因此将此文翻译发表,希望能够起到一定的参考作用。 | Peter F.Brosch Chen Min Christian Mnnink | 2003 | 现代制造2003，，27： | 4 |
| 16 | Acoustic radiation force impulse imaging (ARFI) for non-invasive detection of liver fibrosis: examination standards and evaluation of interlobe differences in healthy subjects and chronic liver disease显示文摘 | Thomas Karlas Cornelia Pfrepper Johannes Wiegand Christian Wittekind Marie Neuschulz Joachim M?ssner Thomas Berg Michael Tr?ltzsch Volker Keim | 2011 | Scandinavian Journal of Gastroenterology2011，，12： | 4 |
| 17 | Anemia and long-term outcome in adjuvant and neoadjuvant radiochemotherapy of stage Ⅱ and Ⅲ rectal adenocarcinoma:The Freiburg experience(1989-2002)显示文摘AIM:To evaluate the long-term outcome of standard5-FU based adjuvant or neoadjuvant radiochemotherapyand to identify the predictive factors,especially anemiabefore and after radiotherapy as well as hemoglobinincrease or decrease during radiotherapy.METHODS:Two hundred and eighty-six patientswith Union International Contre Cancer(UICC)stageⅡ and Ⅲ rectal adenocarcinomas,who underwentresection by conventional surgical techniques(lowanterior or abdominoperineal resection),receivedeither postoperative(n=233)or preoperative(n=53)radiochemotherapy from January 1989 until July 2002.Overall survival(OAS),cancer-specific survival(CSS),disease-free survival(DFS),local-relapse-free(LRS)and distant-relapse-free survival(DRS)were evaluatedusing Kaplan-Meier,Log-rank test and Cox's proportionalhazards as statistical methods.Multivariate analysis wasused to identify prognostic factors.Median follow-uptime was 8 years.RESULTS:Anemia before radiochemotherapy was anindependent prognostic factor for improved DFS(riskratio 0.76,P=0.04)as well as stage,grading,R status(free radial margins),type of surgery,carcinoembryonicantigen(CEA)levels,and gender.The univariate analysisrevealed that anemia was associated with impaired LRS (better local control)but with improved DFS.In contrast,hemoglobin decrease during radiotherapy was anindependent risk factor for DFS(risk ratio 1.97,P=0.04).During radiotherapy,only 30.8% of RO-resected patientssuffered from hemoglobin decrease compared to 55.6%if R1/2 resection was performed(P=0.04).The 5-yearOAS,CSS,DFS,LRS and DRS were 47.0%,60.0%,41.4%,67.2%,and 84.3%,respectively.Significantdifferences between preoperative and postoperativeradiochemotherapy were not found.CONCLUSION:Anemia before radiochemotherapyand hemoglobin decrease during radiotherapy have nopredictive value for the outcome of rectal cancer.Stage,grading,R status(free radial margins),type of surgery,CEA levels,and gender have predictive value for theoutcome of rectal cancer. | Christian Weissenberger Geissler Michael Otto Florian Barke Annette Henne Karl von Plehn Georg Rein Alex Müller Christine Bartelt Susanne Henke Michael | 2006 | World Journal of Gastroenterology2006，12，12： | 4 |
| 18 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 19 | RANKL/RANK control Brca1 mutation-driven mammary tumors显示文摘 | Verena Sig Kwadwo Owusu-Boaitey Puma A Joshi Anoop Kavirayani Gerald Wimsberger Maria Novatchkova Ivona Kozieradzki Daniel Schramek Nnamdi Edokobi Jerome Hersl Aishia Sampson Ashley Odai-Afotey Conxi Lazaro Eva Gonzalez-Suarez Miguel A Pujaaa for CIMBA Holger Heyn Enrique Vidal Jennifer Cru. ickshank Hal Berman Renu Sarao Melita Tieevic Iris Uribesalgo Luigi Tortola Shuan Rao Yen Tan Georg Pfeiler Eva YHP Lee Zsuzsanna Bago-Horvath Lukas Kenner Helmuth Popper Christian Singer Rama Khokha LaundeRe P Jones Josef M Penninger | 2016 | Cell Research2016，26，7： | 3 |
| 20 | Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis:A global survey of physicians'practice显示文摘AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients. | Shomron Ben-Horin Jane M Andrews Konstantinos H Katsanos Florian Rieder Flavio Steinwurz Konstantinos Karmiris Jae Hee Cheon Gordon William Moran Monica Cesarini Christian D Stone Doron Schwartz Marijana Protic Xavier Roblin Giulia Roda Min-Hu Chen Ofir Har-Noy Charles N Bernstein | 2017 | World Journal of Gastroenterology2017，23，16： | 3 |
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