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Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第20期12卷 3275-3282页

作者： Lars A Ormandy Anatol frber Tobias Cantz Susanne Petrykowska Heiner Wedemeyer Monique Hrning frank Lehner Michael P manns firouzeh Korangy Tim f Greten Department of Gastroenterology Hepatology and Endocrinology Hannover Medical SchoolGermany Departments of Visceral and Transplantation Surgery Hannover Medical School Germany

瞄准：与肝细胞癌(HCC ) 从病人分析树枝状的房间(DC ) 的显型和功能以便在这疾病理解他们的角色。方法：骨髓的的树枝状的房间在 HCC 病人的外部血被枚举。从外部血的天真、刺激的骨髓的的树枝状的房间上的 CD80， CD83， CD86 和 HLA... 详细信息

瞄准：与肝细胞癌(HCC ) 从病人分析树枝状的房间(DC ) 的显型和功能以便在这疾病理解他们的角色。方法：骨髓的的树枝状的房间在 HCC 病人的外部血被枚举。从外部血的天真、刺激的骨髓的的树枝状的房间上的 CD80， CD83， CD86 和 HLA 医生表示被分析。骨髓的的树枝状的房间从外部血被孤立，他们的功能被测试。吞噬作用用 fITC 葡聚糖祷告被分析，肽特殊刺激，在多形核白细胞 dI:dC 之上刺激 allogeneic T 房间和 cytokines 的分泌物的能力被测试。结果：骨髓的的树枝状的房间与 HCC 在病人被减少。在 CD80， CD83， CD86 和 HLA 医生表示的差别都没从 HCC 病人和健康控制在天真、刺激的骨髓的的树枝状的房间上被发现。肽 specific T 房间的正常吞噬作用或刺激与一个损害 allo-stimulatory 能力和减少的 IL-12 分泌物相对照被观察。结论：在病人的 mDCs 的损害 IL-12 生产能导致建议指导治疗可以提高的那 IL-12 的天真的 T 房间的一个损害 stimulatory 能力在 HCC 病人的肿瘤 specific 免疫者回答。

关键词：树状细胞肝细胞癌骨髓细胞外周血

Comparison of Granules for Prescription and Classical Decoctions by High-performance Thin-layer Chromatography-fingerprint Analysis

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World Journal of Traditional Chinese Medicine 2018年第1期4卷 1-7页

作者： Katharina Schiller Jorg Heilmann Detlef.manns Gerhard franz Department of Pharmaceutical Biology Institute of PharmacyUniversity of Regensburg federal Institute for Drugs and Medicinal Devices(BfArM)

Objective: The so?called granules for prescription have been developed about 20 years ago as a new form of modernizing and simplification of the classical decoction common in Traditional Chinese Medicine (TCM) practice. Due to actual problems in Germany/Europe, which are caused by the lack of quality monographs and judicial classification of granules for prescription, the aim of the study was a comparison of the chemical composition of commercial granules versus decoctions. Taking an example, decoctions, commercial granules, and organic extracts of two well?established TCM herbal drugs, Scrophulariae Radix and Xanthii fructus, were examined in their specific composition. Methods: Using high?performance thin?layer chromatography (HPTLC) for fingerprint analysis of different batches of herbal drugs and samples from various suppliers of Xanthii fructus and Scrophulariae Radix were critically examined. The decoctions were prepared according to traditional rules, while the granules were dissolved in water in accordance with actual regulations. furthermore, organic extracts of the plant material were examined and compared with aqueous extracts. Results: It could be demonstrated, that in some cases, there are remarkable differences in the specific composition between granules from different suppliers, the classical aqueous decoction and the organic extract used for the HPTLC fingerprinting. On the other hand, few examples exist for good comparability of decoctions and commercial granules. Conclusion: After critical evaluation of the above results, it can be questioned, if there is a so?called phytoequivalence between decoctions and commercial granules for prescription used in TCM practice.

关键词： Granules for prescription phytoequivalence quality control quality monographs Scrophulariae Radix Xanthii fructus

Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival

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Hepatobiliary & Pancreatic Diseases International 2007年第3期6卷 259-266页

作者： Timm D Kirchhoff Joerg S Bleck Arne Dettmer Ajay Chavan Herbert Rosenthal Sonja Merkesdal Bernd frericks Lars Zender Nisar P Malek Tim f Greten Stefan Kubicka Michael P manns Michael Galanski Department of Diagnostic Radiology Hannover Medical School Germany Department of Gastroenterology Hepatology and Endocrinology Hannover Medical School Germany Department of Diagnostic and Interventional Radiology Klinikum Oldenburg Germany Division of Rheumatology Hannover Medical School Germany Department of Radiology and Nuclear Medicine Campus B.F-Charité-University Medicine Berlin Germany

BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics,toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4±1.5 courses per patient). Mean maximum tumor size was 75 (± 43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size ≤75 mm, tumor number ≤5, and tumor hypervascularization as predictors for PR. The overall 1-, 2-, and 3-year-survival rates were 75%, 59%, and 41%, respectively, and the median survival was 26 months. Low α-fetoprotein levels (ficantly associated with long term survival (>30 months, R2=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major

关键词： carcinoma, hepatocellular transarterial chemoembolization degradable starch microspheres Lipiodol tumor response survival

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从1到100，用心求变

Regulation of plasma erythropoietin in chronic liver disease

作者： Mary Lynn manns Linda Rising

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World Journal of Gastroenterology 2004年第19期10卷 2922-2923页

作者： frank Tacke Tom Luedde Michael P.manns Christian Trautwein Department of Gastroenterology Hepatology and EndocrinologyHannover Medical School 30625 HannoverGermany Department of Gastroenterology Hepatology and EndocrinologyHannover Medical School 30625 HannoverGermany M.D.Professor of Medicine

In a May-issue of the World Journal of Gastroenterology, there is a very interesting study by Bruno et al. on erythropoietin (EPO) levels in patients with chronic liver disease. We have very recently reported a similar, but much larger study by Tacke et al. on the role of EPO in chronic liver disease. By comparing Bruno's results with our patient cohort and applying their

关键词：调节作用血浆红细胞生成素肝脏疾病肠胃病学

Homologous recombination mediates stable fah gene integration and phenotypic correction in tyrosinaemia mouse-model

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World Journal of Hepatology 2018年第2期10卷 277-286页

作者： Norman Junge Qinggong Yuan Thu Huong Vu Simon Krooss Christien Bednarski Asha Balakrishnan Toni Cathomen Michael P manns Ulrich Baumann Amar Deep Sharma Michael Ott Department of Pediatric Gastroenterology and Hepatology Hannover Medical School Department of Gastroenterology Hepatology and Endocrinology Hannover Medical School TWINCORE Centre for Experimental and Clinical Infection Research Medical Center University of Freiburg Institute for Cell and Gene Therapy Research Group Micro RNA in Liver Regeneration Cluster of Excellence REBIRTH Hannover Medical School

AIM To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout(fah-/-) mice by homologous-recombination-mediated targeted addition of the fah *** C57 BL/6 fah?exon5 mice served as an animal model for human tyrosinaemia type 1 in our study. The vector was created by amplifying human fah c DNA including the TTR promoter from a lentivirus plasmid as described. The fah expression cassette was flanked by homologous arms(620 bp and 749 bp long) of the Rosa26 gene locus. Mice were injected with 2.1 × 108 VP of this vector(r ***) via the tail vein. Mice in the control group were injected with 2.1 × 108 VP of a similar vector but missing the homologous arms(r ***). Primary hepatocytes from fah-/-recipient mice, treated with our vectors, were isolated and 1 × 106 hepatocytes were transplanted into secondary fah-/-recipient mice by injection into the spleen. Upon either vector application or hepatocyte transplantation NTBC treatment was stopped in recipient mice. RESULTS Here, we report successful HR-mediated genome editing by integration of a fah gene expression cassette into the "safe harbour locus" Rosa26 by recombinant AAV8. Both groups of mice showed long-term survival, weight gain and fAH positive clusters as determined by immunohistochemistry analysis of liver sections in the absence of NTBC treatment. In the group of C57 BL/6 fah?exon5 mice, which have been transplanted with hepatocytes from a mouse injected with r *** 156 d before, 6 out of 6 mice showed long-term survival, weight gain and fAH positive clusters without need for NTBC treatment. In contrast only 1 out 5 mice, who received hepatocytes from r *** treated mice, survived and showed few and smaller fAH positive clusters. These results demonstrate that homologous recombinationmediated fah gene transfer corrects the phenotype in a mouse model of human tyrosinaemia type 1(fah-/-mice) and

关键词： Gene therapy AAV8 Liver based metabolic disease Targeted integration ROSA26 Paediatric liver disease

fibroSURE^(TM) and fibroScan~ in relation to treatment response in chronic hepatitis C virus

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World Journal of Gastroenterology 2011年第41期17卷 4581-4589页

作者： Keyur Patel Mireen friedrich-Rust Yoav Lurie Mircea Grigorescu Carol Stanciu Chuan-Mo Lee Eugene R Schiff Dieter Hussinger Michael P manns Guido Gerken Isabelle Colle Michael Torbenson Erik Pulkstenis G Mani Subramanian John G McHutchison Stefan Zeuzem Department of Gastroenterology and Hepatology Duke Clinical Research Institute Department of Gastroenterology and Hepatology J.W.Goethe University Hospital Department of Gastroenterology and Hepatology Tel Aviv Sourasky Medical Center Department of Clinical Infectious Disease Spitalul Clinic de Urgenta Department of Gastroenterology and Hepatology Institutul de Gastroenterologie si Hepatologie Department of Gastroenterology Chang Gung Memorial Hospital-Kaohsiung Medical CenterChang Gung University College of Medicine Departments of Gastroenterology and Internal Medicine University of Miami Department of Gastroenterology and Hepatology Universittsklinik Department of Gastroenterology and Hepatology Department of Gastroenterology and Hepatology Ghent University Hospital Department of Pathology Johns Hopkins University School of Medicine Department of Biostatistics Human Genome Sciences Department of Clinical Research Human Genome Sciences

AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)***:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)***～TM(fS)was assessed at baseline and at week-12 post-treatment *** biopsy for METAVIR was assessed by a single ***～ transient elastogra-phy(TE)was performed during treatment in a patient ***:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR f0-1(n = 1682)or f2-4(n = 378).for f2-4,fS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined fS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and *** fS/TE agreement for f2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;P fS/TE had 97% accuracy in Asians(n = 33).Baseline fS(0.38 vs 0.51,P fS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV.

关键词：丙型肝炎病毒治疗慢性 TM 评估基准亚洲人工作曲线 TE

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四极技术在CIP系统中的电导率测量

酒．饮料技术装备 2010年第5期 62-63页

作者： Oeznur Alp Reinhard manns 久茂自动化大连有限公司

四极式电导率电极是专门针对CIP系统研发的新式电极，不仅覆盖了清洁杀菌溶液的电导率范同，也覆盖了清洗过程的电导率范围。对控制清洁和杀菌溶液储备罐内溶液的浓度和清洗杀菌液的分离回收具有重要的意义。

关键词：电导率测量 CIP系统四极技术清洗过程分离回收溶液电极

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拉米夫定：副作用小的乙肝病毒抑制剂

德国临床用药 2000年第3期3卷 32-36页

作者： Till.,H manns,MP

乙肝病毒感染是最常见的病毒病,在全世界受感染者约达3亿.迄今被批准用于治疗乙肝的药物只有a-干扰素,但是它通常会引起流感样副作用,而且只使一部份病人的活动性肝炎症状减轻.拉米夫定是被批准用于治疗乙肝的首个核苷类似物.本品治疗... 详细信息

乙肝病毒感染是最常见的病毒病,在全世界受感染者约达3亿.迄今被批准用于治疗乙肝的药物只有a-干扰素,但是它通常会引起流感样副作用,而且只使一部份病人的活动性肝炎症状减轻.拉米夫定是被批准用于治疗乙肝的首个核苷类似物.本品治疗组的副作用发生率与安慰剂组相似.但是,这个副作用少的药物在治疗中出现的问题与HIV治疗中已知的一样,即耐药性的发生率相当高.在HIV感染中,病情基本上无变化,仍向前发展;而感染耐拉米夫定的乙肝突变种的免疫活性病人,经拉米夫定治疗,乙肝病程似乎受到抑制.但是,停止治疗后,似乎只有部份病人的乙肝病毒受到持续抑制.与其它药物的相互作用极为罕见,而且目前这种相互作用似乎无临床重要性.

关键词：乙型肝炎药物疗法拉米夫定副作用