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Liver stiffness in pregnant women with intrahepatic cholestasis of pregnancy:A case control study

World Journal of Hepatology 2023年第7期15卷 904-913页

作者： Juliane Nees Franziska J Ammon johannes mueller Herbert Fluhr Sebastian mueller Department of Gynecology and Obstetrics University Hospital HeidelbergHeidelberg 69120Germany Center for Alcohol Research University Hospital HeidelbergHeidelberg 69120Germany Division of Obstetrics Department of Obstetrics and GynecologyMedical University of GrazGraz 8036Austria

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a rare but severe complication for both the mother and the unborn *** diagnosis is primarily based on elevated serum levels of bile *** a large ICP cohort,we here study in detail liver stiffness(LS)using transient elastography(TE),now widely used to noninvasively screen for liver cirrhosis within *** To specifically explore LS in a large cohort of women with ICP compared to a control group with uncomplicated *** LS and hepatic steatosis marker controlled attenuation parameter(CAP)were measured in 100 pregnant women with ICP using TE(Fibroscan,Echosens,Paris,France)between 2010 and *** 17 cases,LS could be measured postpartum.450 women before and 38 women after delivery with uncomplicated pregnancy served as control *** laboratory,levels of bile acids and apoptosis marker caspase-cleaved cytokeratin 18 fragment(M30)were also *** Women with ICP had significantly elevated transaminases but normal gammaglutamyl transferase(GGT).Mean LS was significantly increased at 7.3±3.0 kPa compared to the control group at 6.2±2.3 kPa(P<0.0001).Postpartum LS decreased significantly in both groups but was still higher in ICP(5.8±1.7 kPa vs 4.2±0.9 kPa,P<0.0001),*** ICP,LS was highly significantly correlated with levels of bile acids and M30 but not *** correlation was seen with GGT that even increased significantly after delivery in the ICP *** acids were mostly correlated with the liver apoptosis marker M30,LS and levels of alanine aminotransferase,aspartate aminotransferase,and *** multivariate analysis,LS remained the sole parameter that was independently associated with elevated bile *** In conclusion,LS is significantly elevated in ICP which is most likely due to toxic bile acid accumulation and hepatocyte *** association with conventional laboratory markers,LS provides additional non-invasive informati

关键词： Intrahepatic cholestasis of pregnancy Transient elastography Bile acids Liver stiffness High risk pregnancy

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Liver stiffness reversibly increases during pregnancy and independently predicts preeclampsia

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World Journal of Gastroenterology 2018年第38期24卷 4393-4402页

作者： Franziska J Ammon Anna Kohlhaas Omar Elshaarawy johannes mueller Thomas Bruckner Christof Sohn Gabriele Fluhr Herbert Fluhr Sebastian mueller Department of Obstetrics and Gynecology University of Heidelberg Department of Medicine and Center for Alcohol Research Liver Disease and NutritionSalem Medical CenterUniversity of Heidelberg Institute of Medical Biometry und Informatics University of Heidelberg

AIM To study liver stiffness(LS) during pregnancy and its association with complications during *** In this observational, diagnostic study, 537 pregnant women were prospectively enrolled at the Department of Obstetrics and Gynecology, University hospital Heidelberg and Salem Medical Center. LS was measured using the Fibroscan device(Echosens, Paris) in all women and in 41 cases 24 h after delivery. Clinical and morphological data were recorded and abdominal ultrasound and standard laboratory tests were performed. No complications were observed in 475 women(controls) while preeclampsia and intrahepatic cholestasis of pregnancy(ICP) developed in 22 and 40 women, *** In controls, LS increased significantly from initially 4.5 ± 1.2 kPa in the second trimester to 6.0 ± 2.3 kPa(P < 0.001) in the third trimester. In the third trimester, 41% of women had a LS higher than 6 kPa. Elevated LS in controls was significantly correlated with alkaline phosphatase, leukocytes, gestational age and an increase in body weight and body mass index(BMI). In women with pregnancy complications, LS was significantly higher as compared to controls(P < 0.0001). Moreover, in multivariate analysis, LS was an independent predictor for preeclampsia with an odds ratio of 2.05(1.27-3.31) and a cut-off value of 7.6 kPa. In contrast, ICP could not be predicted by LS. Finally, LS rapidly decreased in all women within 24 h after delivery from 7.2 ± 3.3 kPa down to 4.9 ± 2.2 kPa(P < 0.001).CONCLUSION During pregnancy, LS significantly and reversibly increases in the final trimester of pregnant women without complications. In women with preeclampsia, LS is significantly elevated and an independent noninvasive predictor.

关键词： Pregnancy Transient elastography Liver stiffness Pregnancy complications Hemolysis,elevated liver enzymes and low platelets syndrome Intrahepatic cholestasis of pregnancy Preeclampsia

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Meta-Analysis to Determine the Diagnostic Value of 2-<sup>18</sup>Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography in Assessing Residual Tumors after Systemic Therapy for Metastatic Seminoma

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Open Journal of Urology 2011年第3期1卷 50-55页

作者： johannes mueller Thomas Schnoeller Friedemann Zengerling Sandra Waalkes Andreas Al Ghazal Florian Jentzmik Mark Schrader Andres Jan Schrader 不详

Background: A meta-analysis was performed to determine the value of 2-18fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for assessing viable tumor residuals after chemotherapy in patients with pure seminoma. Materials and methods: This review included five studies published between 1999 and 2010 with a total of 130 patients who underwent both computed tomography (CT) and FDG-PET scanning for residual tumor detection after systemic therapy. We compared the sensitivity and specificity of FDG-PET and CT (tumor size ≤ or > 3 cm) in identifying vital tumor tissue. Results: On the average, FDG-PET had higher specificity (92% vs. 59%) and sensitivity (72% vs. 63%) as well as a higher positive predictive value (PPV) than the solely size-based CT assessment of residual tumors (70% vs. 28%). PEt also tended to have a higher negative predictive value (93% vs. 86%). Conclusion: The present evaluation of currently available data indicates that FDG-PET is superior to CT in detecting viable tumor residuals after chemotherapy in patients with metastatic seminoma. Its application can thus be recommended.

关键词： FDG-PET Seminoma Testicular Cancer Diagnosis Residual Disease

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Evaluation of joint awareness after acetabular fracture:Validation of the Forgotten Joint Score according to the COSMIN checklist protocol

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World Journal of Orthopedics 2021年第2期12卷 69-81页

作者： Viola Freigang johannes Weber Karolina mueller Christian Pfeifer Michael Worlicek Volker Alt Florian Michael Baumann Department of Trauma Surgery Regensburg University Medical CenterRegensburg 93042Germany Center for Clinical Studies Regensburg University Medical CenterRegensburg 93042Germany

BACKGROUND A fracture of the acetabulum is an uncommon,but serious *** outcome tools do not reflect the patient’s perspective after fracture of the hip *** designed for post-arthroplasty patients,the Forgotten Joint Score(FJS)is a patient-reported outcome measurement(PROM)tool evaluating the diseasespecific health-related quality of life(HR-QoL).AIM To validate the FJS in patients after acetabular *** In a prospective mono-centric cohort study,we evaluated 100 patients at mean 5.2±3.6 years after a fracture of the *** validation study followed the complete COSMIN checklist *** calculation of convergent validity,we used the Tegner-Activity Scale,the Western Ontario and McMaster Universities Osteoarthritis Index,the EuroQol-5D,and a subjective rating of change as an anchor *** We confirmed good internal consistency with a Cronbach‘s alpha of *** an intraclass correlation coefficient of 0.99(95%CI:0.97,0.99),test-retest reliability of the FJS was *** coefficients between the questionnaires were moderate to high ranging from|0.56|to|0.83|(absolute value).No relevant floor or ceiling effects *** error of measurement was 3.2 and smallest detectable change(SDC)was ***,changes greater than 8.8 points between two assessments denote a real change in *** The FJS is a valid and reliable tool for evaluation of patient-reported outcome in posttraumatic condition after acetabular *** SDC indicating a real clinical improvement was 8.8 points in the *** could confirm responsiveness of the FJS and found no relevant floor-or ceiling effects.

关键词： Patient reported outcome measurement Validation study Hip joint Forgotten Joint Score Acetabulum fracture COSMIN checklist

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VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab

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World Journal of Gastroenterology 2008年第26期14卷 4156-4167页

作者： Markus Moehler Christian Frings Annett mueller Ines Gockel Carl C Schimanski Stefan Biesterfeld Institute of Pathology johannes Gutenberg University Mainz 55101 Germany Peter R Galle Martin H Holtmann 1st Department of Medicine Johannes Gutenberg University Mainz 55101 Germany Department of General and Abdominal Surgery johannes Gutenberg University Mainz 55101 Germany

AIM:To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS:The impact of high-level expression of the growth factor receptors EGFR and VEGF receptor (VEGFR)3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in human CRC was investigated in 108 patients using immunohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse xenograft model. RESULTS: Human CRC specimens and cell lines displayed EGFR, VEGF-C and VEGF-D expression with varying intensities. VEGF-C expression was associated with histological grade. Strong expression of VEGF-D was significantly associated with lymph node metastases and linked to a trend for decreased survival in lymph node-positive patients. EGFR blockade with cetuximab resulted in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION:In conclusion, the expression of VEGF-D in colorectal tumours is significantly associated with lymphatic involvement in CRC patients and such expression might be blocked effectively by cetuximab.

关键词： Human colorectal cancer Lymphangiogenesis Vascular endothelial growth factor-C Vascular endothelial growth factor-D Epidermal growth factor receptor

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Gonadal damage and options for fertility preservation in female and male cancer survivors

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Asian Journal of Andrology 2006年第5期8卷 515-533页

作者： Theodoros Maltaris Heinz Koelbl Rudolf Seufert Franklin Kiesewetter Matthias W. Beckmann Andreas mueller Ralf Dittrich Department of Obstetrics and Gynecology Johannes Gutenberg University Mainz D-55124 Germany Division of Andrology Erlangen University Hospital University of Erlangen-Nuremberg Erlangen Germany Department of Obstetrics and Gynecology Erlangen University Hospital University of Erlangen-Nuremberg Erlangen Germany

It is estimated that in 2010, 1 in every 250 adults will be a childhood cancer survivor. Today, oncological surgery, radiotherapy and chemotherapy achieve relatively high rates of remission and long-term survival, yet are often detrimental to fertility. Quality of life is increasingly important to long-term survivors of cancer, and one of the major quality-of-life issues is the ability to produce and raise normal children. Developments in the near future in the emerging field of fertility preservation in cancer survivors promise to be very exciting. This article reviews the published literature, discusses the effects of cancer treatment on fertility and presents the options available today thanks to advances in assisted-reproduction technology for maintaining fertility in male and female patients undergoing this type of treatment. The various diagnostic methods of assessing the fertility potential and the efficacy of in vitro fertilization （IVF） after cancer treatment are also presented.

关键词： reproduction cryopreservation male infertility semen preservation fertility preservation cancer treatment ovarian tissue

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难治性类风湿关节炎的临床特点:一项国际问卷调查研究

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英国医学杂志中文版 2019年第2期22卷 122-122页

作者： Nadia MT Roodenrijs Maria J H de Hair Marlies C van der Goes johannes WG Jacobs Paco MJ Welsing Désirée van der Heijde Daniel Aletaha Maxime Dougados Kimme L Hyrich Iain B McInnes Ulf mueller-Ladner Ladislav Senolt Zoltan Szekanecz Jacob Mvan Laar Nagy Gyorgy 黄艳荣(译) 张卓莉(审校) 不详北京大学第一医院风湿免疫科

目的尽管按照目前欧洲抗风湿联盟(EULAR)的推荐对类风湿关节炎(rheumatoid arthritis,RA)患者进行治疗,难治性RA患者的临床症状却仍然没有得到完全控制,目前EULAR指南主要关注的是RA的早期治疗和药物治疗。本研究的目的在于分析难治性R... 详细信息

目的尽管按照目前欧洲抗风湿联盟(EULAR)的推荐对类风湿关节炎(rheumatoid arthritis,RA)患者进行治疗,难治性RA患者的临床症状却仍然没有得到完全控制,目前EULAR指南主要关注的是RA的早期治疗和药物治疗。本研究的目的在于分析难治性RA患者的临床特点,以及在患者管理中需要探索然而现有EULAR指南并未涉及的问题。方法对多个国家的风湿科医生进行问卷调查,分析难治性RA的临床特点。问卷包括多选题以及开放性问题,从开放性问题的回答中发现需要进一步阐明的问题以及现有EULAR指南需要增加的内容。结果410名受访者完成了调查问卷,关于难治性RA的特点:50%受访者认为基于28个关节评估的疾病活动评分(disease activity score assessing 28 joints,DAS28)>3.2或存在疾病活动的征象;42%受访者认为疲劳是其特点;48%认为至少两种传统合成改变病情抗风湿药(DMARDs)以及使用至少两种生物制剂或靶向合成DMARDs治疗失败;89%认为糖皮质激素不能减量到5 mg/天或泼尼松不能减量到10 mg/天或同等剂量的其他激素。另外,现有EULAR指南中应增加合并症和关节外表现的干预以及多种药物联合治疗等重要内容。结论目前风湿科医生对难治性RA的定义有很大争议。难治性RA患者的很多重要问题目前EULAR指南中均没有涉及。

关键词：难治性类风湿关节炎临床特点问卷调查改变病情抗风湿药 DMARDs 患者管理糖皮质激素国际

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Measurement of the integrated luminosity of the Phase 2 data of the Belle Ⅱ experiment

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Chinese Physics C 2020年第2期44卷 1-12页

作者： F.Abudinén I.Adachi P.Ahlburg H.Aihara N.Akopov A.Aloisio F.Ameli L.Andricek N.Anh Ky D.M.Asner H.Atmacan T.Aushev V.Aushev T.Aziz K.Azmi V.Babu S.Baehr S.Bahinipati A.M.Bakich P.Bambade Sw.Banerjee S.Bansal V.Bansal M.Barrett J.Baudot A.Beaulieu J.Becker P.K.Behera J.V.Bennett E.Bernieri F.U.Bernlochner M.Bertemes M.Bessner S.Bettarini V.Bhardwaj F.Bianchi T.Bilka S.Bilokin D.Biswas G.Bonvicini A.Bozek M.Bračko P.Branchini N.Braun T.E.Browder A.Budano S.Bussino M.Campajola L.Cao G.Casarosa C.Cecchi D.Červenkov M.-C.Chang P.Chang R.Cheaib V.Chekelian Y.Q.Chen Y.-T.Chen B.G.Cheon K.Chilikin H.-E.Cho K.Cho S.Cho S.-K.Choi S.Choudhury D.Cinabro L.Corona L.M.Cremaldi S.Cunliffe T.Czank F.Dattola E.De La Cruz-Burelo G.De Nardo M.De Nuccio G.De Pietro R.de Sangro M.Destefanis S.Dey A.De Yta-Hernandez F.Di Capua S.Di Carlo J.Dingfelder Z.Doležal I.Domínguez Jiménez T.V.Dong K.Dort S.Dubey S.Duell S.Eidelman M.Eliachevitch T.Ferber D.Ferlewicz G.Finocchiaro S.Fiore A.Fodor F.Forti A.Frey B.G.Fulsom M.Gabriel E.Ganiev M.Garcia-Hernandez R.Garg A.Garmash V.Gaur A.Gaz U.Gebauer A.Gellrich J.Gemmler T.Geßler R.Giordano A.Giri B.Gobbo R.Godang P.Goldenzweig B.Golob P.Gomis P.Grace W.Gradl E.Graziani D.Greenwald C.Hadjivasiliou S.Halder K.Hara T.Hara O.Hartbrich K.Hayasaka H.Hayashii C.Hearty M.T.Hedges I.Heredia de la Cruz M.Hernández Villanueva A.Hershenhorn T.Higuchi E.C.Hill H.Hirata M.Hoek S.Hollitt T.Hotta C.-L.Hsu Y.Hu K.Huang T.Iijima K.Inami G.Inguglia J.Irakkathil Jabbar A.Ishikawa R.Itoh M.Iwasaki Y.Iwasaki S.Iwata P.Jackson W.W.Jacobs D.E.Jaffe E.-J.Jang H.B.Jeon S.Jia Y.Jin C.Joo J.Kahn H.Kakuno A.B.Kaliyar G.Karyan Y.Kato T.Kawasaki H.Kichimi C.Kiesling B.H.Kim C.-H.Kim D.Y.Kim S.-H.Kim Y.K.Kim Y.Kim T.D.Kimmel K.Kinoshita C.Kleinwort B.Knysh P.Kodyš T.Koga I.Komarov T.Konno S.Korpar D.Kotchetkov N.Kovalchuk T.M.G.Kraetzschmar P.Križan R.Kroeger J.F.Krohn P.Krokovny W.Kuehn T.Kuhr M.Kumar R.Kumar K.Kumara S.Kurz A.Kuzmin Y.-J.Kwon S.Lacaprara Y.-T.Lai C.La Licata K.Lalwani L.Lanceri J.S.Lange K.Lautenbach I.-S.Le Beihang University Beijing 100191 Brookhaven National Laboratory UptonNew York 11973 Budker Institute of Nuclear Physics SB RAS Novosibirsk 630090 Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional Mexico City 07360 Faculty of Mathematics and Physics Charles University12116 Prague Chiba University Chiba 263-8522 Consejo Nacional de Ciencia y Tecnología Mexico City 03940 Deutsches Elektronen–Synchrotron 22607 Hamburg Duke University DurhamNorth Carolina 27708 Earthquake Research Institute University of TokyoTokyo 113-0032 Forschungszentrum Jülich 52425 Jülich Department of Physics Fu Jen Catholic UniversityTaipei 24205 Key Laboratory of Nuclear Physics and Ion-beam Application(MOE)and Institute of Modern Physics Fudan UniversityShanghai 200443 II.Physikalisches Institut Georg-August-Universität Göttingen37073 Göttingen Gifu University Gifu 501-1193 The Graduate University for Advanced Studies(SOKENDAI) Hayama 240-0193 Gyeongsang National University Jinju 52828 Department of Physics and Institute of Natural Sciences Hanyang UniversitySeoul 04763 High Energy Accelerator Research Organization(KEK) Tsukuba 305-0801 J-PARC Branch KEK Theory CenterHigh Energy Accelerator Research Organization(KEK)Tsukuba 305-0801 Indian Institute of Science Education and Research Mohali SAS Nagar140306 Indian Institute of Technology Bhubaneswar Satya Nagar 751007 Indian Institute of Technology Hyderabad Telangana 502285 Indian Institute of Technology Madras Chennai 600036 Indiana University BloomingtonIndiana 47408 Institute for High Energy Physics Protvino 142281 Institute of High Energy Physics Vienna 1050 Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049 Institute of Particle Physics(Canada) VictoriaBritish Columbia V8W 2Y2 Institute of Physics Hanoi Instituto de Fisica Corpuscular Paterna 46980 INFN Laboratori Nazionali di Frascati I-00044 Frascati INFN Sezione di Napoli I-80126 Napoli INFN Sezione di Padova I-35131 Padova INFN Sezione di Perugia I-06123 Perugia

From April to July 2018,a data sample at the peak energy of the T(4 S) resonance was collected with the Belle Ⅱ detector at the SuperKEKB electron-positron *** is the first data sample of the Belle Ⅱ *** Bhabha and digamma events,we measure the integrated luminosity of the data sample to be(496.3±0.3±3.0) pb-1,where the first uncertainty is statistical and the second is *** work provides a basis for future luminosity measurements at Belle Ⅱ.

关键词： luminosity Bhabha digamma Belle II

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