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| 1 | 皮质下小血管病诊断的共识声明显示文摘血管性认知损害是用于描述一组涉及大血管和小血管的散发性和遗传性异质性疾病的诊断术语。皮质下小血管病可导致腔隙性梗死和进行性白质损害。被称为宾斯旺格病(Binswanger's disease, BD)的进行性白质损害患者构成了从单纯血管性疾病到合并神经变性病变的疾病谱。BD患者是一个相对同质性的亚组,存在缺氧缺血、腔隙性梗死和炎症,它们协同作用破坏血脑屏障和髓鞘。通过临床、脑脊液、神经心理学和影像学检查获得的多模式疾病标记物能促进该亚组患者的鉴别。本共识声明确定了一系列基于基础病理学改变的潜在生物学标记物,这将有助于诊断以及将来协作性治疗试验的患者选择。 | Gary A Rosenberg Anders Wallin Joanna M Wardlaw Hugh S Markus Joan Montaner Leslie Wolfson Costantino Iadecola Berislav V Zlokovic Anne Joutel Martin Dichgans Marco Duering Reinhold Schmidt Amos D Korczyn Lea T Grinberg Helena C Chui Vladimir Hachinski 王训师 张劼 陈涵丰 俞娅美 徐子奇 罗本燕 | 2016 | 国际脑血管病杂志2016，24，6： | 18 |
| 2 | Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial显示文摘 | Florian Lordick Yoon-Koo Kang Hyun-Cheol Chung Pamela Salman Sang Cheul Oh Gy?rgy Bodoky Galina Kurteva Constantin Volovat Vladimir M Moiseyenko Vera Gorbunova Joon Oh Park Akira Sawaki Ilhan Celik Heiko G?tte Helena Melezínková Markus Moehler | 2013 | Lancet Oncology2013，，6： | 14 |
| 3 | Lrp1 in osteoblasts controls osteoclast activity and protects against osteoporosis by limiting PDGF–RANKL signaling显示文摘Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1(Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass.Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption. Osteoblast Lrp1 limited receptor activator of NF-κB ligand(RANKL) expression in vivo and in vitro through attenuation of platelet-derived growth factor(PDGF-BB) signaling. In co-culture, Lrp1-deficient osteoblasts stimulated osteoclastogenesis in a PDGFRβ-dependent manner and in vivo treatment with the PDGFR tyrosine kinase inhibitor imatinib mesylate limited RANKL production and led to complete remission of the osteoporotic phenotype. These results identify osteoblast Lrp1 as a key regulator of osteoblast-to-osteoclast communication and bone mass through a PDGF–RANKL signaling axis in osteoblasts and open perspectives to further explore the potential of PDGF signaling inhibitors in counteracting bone loss as well as to evaluate the importance of functional LRP1 gene variants in the control of bone mass in humans. | Alexander Bartelt Friederike Behler-Janbeck F.Timo Beil Till Koehne Brigitte Müller Tobias Schmidt Markus Heine Laura Ochs Tayfun Yilmaz Martin Dietrich Jan P.Tuckermann Michael Amling Joachim Herz Thorsten Schinke Joerg Heeren Andreas Niemeier | 2018 | Bone Research2018，6，1： | 5 |
| 4 | A systematic review and meta-analysis of laparoscopic versus open distal pancreatectomy for benign and malignant lesions of the pancreas: It’s time to randomize显示文摘 | Arianeb Mehrabi Mohammadreza Hafezi Jalal Arvin Majid Esmaeilzadeh Camelia Garoussi Golnaz Emami Julia K?ssler-Ebs Beat Peter Müller-Stich Markus W. Büchler Thilo Hackert Markus K. Diener | 2014 | Surgery2014，，： | 4 |
| 5 | Ischemia/Reperfusion Injury in Liver Surgery and Transplantation: Pathophysiology显示文摘 | Kilian Weigand Sylvia Brost Niels Steinebrunner Markus Büchler Peter Schemmer Martina Müller John J. Lemasters | 2012 | HPB Surgery2012，，： | 4 |
| 6 | Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?显示文摘AIM: To define the (co-)expression pattern of target receptor-tyrosine-kinases (RTK) in human gastric adenocarcinoma. METHODS: The (co-)expression pattern of VEGFR1-3,PDGFRα/b and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition,IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS: The majority of samples revealed a VEGFR1 (98%),VEGFR2 (80%),VEGFR3 (67%),PDGFRα (82%) and PDGFRβ(82%) expression,whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells,accompanied by an additional nuclear staining for VEGFR3 ,EGFR1 was almost exclusively detected on the membrane of tumor cells. PDGFRβ was restricted to stromal pericytes,which also depicted a PDGFRα expression.receptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target RTK-inhibitors within a combination therapy. | Daniel Drescher Markus Moehler Ines Gockel Kirsten Frerichs Annett Müller Friedrich Dünschede Thomas Borschitz Stefan Biesterfeld Martin Holtmann Thomas Wehler Andreas Teufel Kerstin Herzer Thomas Fischer Martin R Berger Theodor Junginger Peter R Galle Carl C Schimanski | 2007 | World Journal of Gastroenterology2007，13，26： | 4 |
| 7 | Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound显示文摘AIM To study mucosal addressin cellular adhesion molecule-1(MAd CAM-1) and vascular endothelial growth factor(VEGF)-targeted contrast enhanced ultrasound(CEUS) for the assessment of murine colitis and carcinogenesis. METHODS C57BL/6 mice were challenged with 3% dextran sodium-sulfate(DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAd CAM-1-targeted contrast agent was used to detect and quantify MAd CAM-1 expression. Inflammatory driven colorectal azoxymethane(AOM)/DSS-induced carcinogenesis was examined on day 42 and 84 using VEGF-targeted contrast agent. Highly specific tissue echogenicity was quantified using specialized software. Sonographic findings were correlated to tissue staining, western blot analysis and immunohistochemistry to quantify the degree of inflammation and stage of carcinogenesis. RESULTS Native ultrasound detected increased general bowel wall thickening that correlated with more progressed and more severe DSS-colitis(healthy mice: 0.3 mm ± 0.03 vs six days DSS: 0.5 mm ± 0.2 vs nine days DSS: 0.6 mm ± 0.2, P < 0.05). Moreover, these sonographic findings correlated well with clinical parameters such as weight loss(r2 = 0.74) and histological damage(r2 = 0.86)(P < 0.01). In acute DSS-induced murine colitis, CEUS targeted against MAd CAM-1 detected and differentiated stages of mild, moderate and severe colitis via calculation of mean pixel contrast intensity in decibel(9.6 d B ± 1.6 vs 12.9 d B ± 1.4 vs 18 d B ± 3.33, P < 0.05). Employing the AOM/DSSinduced carcinogenesis model, tumor development was monitored by CEUS targeted against VEGF and detected a significantly increased echogenicity in tumors as compared to adjacent healthy mucosa(healthy mucosa, 1.6 d B ± 1.4 vs 42 d, 18.2 d B ± 3.3 vs 84 d, 18.6 d B ± 4.9, P < 0.01). Tissue echogenicity strongly correlated with histological analysis and immunohistochemistry findings(VEGF-positive cells in 10 high power fields of healthy mucosa: 1 ± 1.2 vs 42 d after DSS start: 2.4 ± 1.6 vs 84 d after DSS start: 3.5 ± 1.3, P < 0.01). CONCLUSION Molecularly targeted CEUS is a highly specific and noninvasive imaging modality, which characterizes murine intestinal inflammation and carcinogenesis in vivo. | Markus Brückner Jan Heidemann Tobias M Nowacki Friederike Cordes Jorg Stypmann Philipp Lenz Faekah Gohar Andreas Lügering Dominik Bettenworth | 2017 | World Journal of Gastroenterology2017，23，16： | 4 |
| 8 | Systematic analysis of the safety and benefits of transvaginal hybrid-NOTES cholecystectomy显示文摘AIM: To evaluate transvaginal hybrid-NOTES cholecystectomy(TVC) during its clinical establishment and compare it with the traditional laparoscopic technique(LC).METHODS: The specific problems and benefits of TVC were reviewed using a registry analysis,a comparative cohort study and a randomized clinical trial. At first,feasibility,safety and specific complications of the TVC were analyzed based on the first 488 data sets of the German NOTES Registry(GNR). Hereafter,we compared the early postoperative results of our first 50 TVC-patients with those of 50 female LCpatients matched by age,BMI and ASA classification. The same cohort was contacted an average of two years later to evaluate long-term results concerning pain and satisfaction with the aesthetic results and the overall postoperative results as well as sexual intercourse by means of two domains of the German version of the Female Sexual Function Index(FSFI-d). Consequently,we performed a randomized clinical trial comparing 20 TVC-patients with 20 needlescopic/3-trocar cholecystectomies(NC) also concerning the early postoperative results as well as pain,satisfaction and quality of life by means of the Eypasch Gastrointestinal Quality of Life Index(GIQLI) in the later course. Finally,we discussed the results in accordance with other published studies.RESULTS: The complication(3.5%) and conversion rates(4.1%) for TVC were low in the GNR and comparable to those of the LC. Access related intraoperative complications included injuries to the bladder(n = 4; 0.8%) and bowel(n = 3; 0.6%). The study cohort revealed less postoperative pain after TVC comparing to the LC-patients on the day of surgery(NRS,1.5/10 vs 3.1/10,P = 0.003),in the morning(NRS,1.9/10 vs 2.8/10,P = 0.047) and in the evening(NRS,1.1/10 vs 1.8/10,P = 0.025) of postoperative day(POD) one. The randomized clinical trial consistently found less cumulative pain until POD 2(NRS,8/40 vs 14/40,P = 0.043),as well as until POD 10(NRS,22/190 vs 41/190,P = 0.010). Furthermore,the TVC-patients had a better quality of life on POD 10 than did the LC-patients(GIQLI,124/144 vs 107/144,P = 0.028). The complication rates were comparable and no specific problems were detected in the long-term follow-up for sexual intercourse for either group. The TVC-patients were more satisfied with the aesthetic result in the long-term course in the matched cohort analysis(1.00 vs 1.88,P < 0.001) as well as in the randomized clinical trial(1.00 vs 1.70,P < 0.001) when compared with the LC-patients.CONCLUSION: TVC is a feasible procedure with a high safety profile and has advantages in regard to postoperative pain and aesthetic results when compared with LC or NC. | Dirk R Bulian Jurgen Knuth Kai S Lehmann Axel Sauerwald Markus M Heiss | 2015 | World Journal of Gastroenterology2015，21，38： | 3 |
| 9 | Influence of experimental soil disturbances on the diversity of plants in agricultural grasslands显示文摘Aims and Methods Disturbance is supposed to play an important role for biodiversity and ecosystem stability as described by the intermediate disturbance hypoth-esis(IDH),which predicts highest species richness at intermediate levels of disturbances.In this study,we tested the effects of artificial soil distur-bances on diversity of annual and perennial vascular plants and bryo-phytes in a field experiment in 86 agricultural grasslands differing in land use in two regions of Germany.On each grassland,we implemented four treatments:three treatments differing in application time of soil dis-turbances and one control.One year after experimental disturbance,we recorded vegetation and measured biomass productivity and bare ground.We analysed the disturbance response taking effects of region and land-use-accompanied disturbance regimes into account.Important Findings Region and land-use type strongly determined plant species rich-ness.Experimental disturbances had small positive effects on the species richness of annuals,but none on perennials or bryophytes.Bare ground was positively related to species richness of bryophytes.However,exceeding the creation of 12%bare ground further distur-bance had a detrimental effect on bryophyte species richness,which corresponds to the IDH.As biomass productivity was unaffected by disturbance our results indicate that the disturbance effect on spe-cies richness of annuals was not due to decreased overall produc-tivity,but rather due to short-term lowered inter-and intraspecific competition at the newly created microsites.Generally,our results highlight the importance of soil disturbances for species richness of annual plants and bryophytes in agricultural grasslands.However,most grasslands were disturbed naturally or by land-use practices and our additional experimental soil dis-turbances only had a small short-term effect.Overall,total plant diversity in grasslands seemed to be more limited by the availabil-ity of propagules rather than by suitable microsites for germination.Thus,nature conservation efforts to increase grassland diversity should focus on overcoming propagule limitation,for instance by additional sowing of seeds,while the creation of additional open patches by disturbance might only be appropriate where natural disturbances are scarce. | Jörg Müller Johannes Heinze Jasmin Joshi Steffen Boch Valentin H.Klaus Markus Fischer Daniel Prati | 2014 | Journal of Plant Ecology2014，7，6： | 3 |
| 10 | Quantification of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) mRNA in testicular tissue of infertile patients显示文摘Aim: To evaluate the quantitative detection of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) mRNA as diagnostic parameters in the workup of testicular tissue specimens from patients presenting with non-obstructive azoospemia. Methods: hTR and hTERT mRNA expression were quantified in 38 cryopreserved testicular tissue specimens by fluorescence real-time reverse transcription- polymerase chain reaction (RT-PCR)in a LightCycler(r). This was paralleled by conventional histological workup in all tissue specimens and additional semithin sectioning preparation in cases with maturation arrest ( n = 12) and Sertoli-cell-only syndrome ( n = 12). Results: The average normalized hTERT expression (NhTERT) Was 131.9 ± 48.0 copies (mean ± SD) in tissue specimens with full spermatogenesis, NhTERT = 51.2 ± 17.2 copies in those with maturation arrest and NhTERT = 2.7 ± 2.4 copies in those with Sertoli-cell-only syndrome (SCOS). The discriminant analysis showed that detection of NhTERT (NhTR) had a predictive value of 86.8 % (55.3 % ) for correct classification in one of the three histological subgroups.Conclusion: Our results demonstrate that quantitative detection of hTERT mRNA expression in testicular tissue enables a molecular-diagnostic classification of gametogenesis. Quantitative detection of hTERT in testicular biopsies is thus well suited for supplementing the histopathological evaluation. | Mark Schrader Markus Müller Rüdiger Heicappell Bernd Straub Kurt Miller | 2001 | Asian Journal of Andrology2001，3，4： | 3 |
| 11 | Distal Pancreatectomy: Risk Factors for Surgical Failure in 302 Consecutive Cases显示文摘 | J?rg Kleeff Markus K. Diener Kaspar Z?graggen Ulf Hinz Markus Wagner Jeannine Bachmann J?rg Zehetner Michael W. Müller Helmut Friess Markus W. Büchler | 2007 | Annals of Surgery2007，，4： | 3 |
| 12 | Hepatocellular Carcinoma: Current Management and Perspectives for the Future显示文摘 | Nuh N. Rahbari Arianeb Mehrabi Nathan M. Mollberg Sascha A. Müller Moritz Koch Markus W. Büchler Jürgen Weitz | 2011 | Annals of Surgery2011，，3： | 3 |
| 13 | Nerve Growth Factor and Artemin Are Paracrine Mediators of Pancreatic Neuropathy in Pancreatic Adenocarcinoma显示文摘 | Güralp O. Ceyhan Karl-Herbert Sch?fer Annika G. Kerscher Ulrich Rauch Ihsan Ekin Demir Mustafa Kadihasanoglu Carolin B?hm Michael W. Müller Markus W. Büchler Nathalia A. Giese Mert Erkan Helmut Friess | 2010 | Annals of Surgery2010，，5： | 2 |
| 14 | National Forest Inventories capture the multifunctionality of managed forests in Germany显示文摘Background:Forests perform various important ecosystem functions that contribute to ecosystem services.In many parts of the world,forest management has shifted from a focus on timber production to multi-purpose forestry,combining timber production with the supply of other forest ecosystem services.However,it is unclear which forest types provide which ecosystem services and to what extent forests primarily managed for timber already supply multiple ecosystem services.Based on a comprehensive dataset collected across 150 forest plots in three regions differing in management intensity and species composition,we develop models to predict the potential supply of 13 ecosystem services.We use those models to assess the level of multifunctionality of managed forests at the national level using national forest inventory data.Results:Looking at the potential supply of ecosystem services,we found trade-offs(e.g.between both bark beetle control or dung decomposition and both productivity or soil carbon stocks)as well as synergies(e.g.for temperature regulation,carbon storage and culturally interesting plants)across the 53 most dominant forest types in Germany.No single forest type provided all ecosystem services equally.Some ecosystem services showed comparable levels across forest types(e.g.decomposition or richness of saprotrophs),while others varied strongly,depending on forest structural attributes(e.g.phosphorous availability or cover of edible plants)or tree species composition(e.g.potential nitrification activity).Variability in potential supply of ecosystem services was only to a lesser extent driven by environmental conditions.However,the geographic variation in ecosystem function supply across Germany was closely linked with the distribution of main tree species.Conclusions:Our results show that forest multifunctionality is limited to subsets of ecosystem services.The importance of tree species composition highlights that a lack of multifunctionality at the stand level can be compensated by managing forests at the landscape level,when stands of complementary forest types are combined.These results imply that multi-purpose forestry should be based on a variety of forest types requiring coordinated planning across larger spatial scales. | Nadja K.Simons María R.Felipe-Lucia Peter Schall Christian Ammer Jürgen Bauhus Nico Blüthgen Steffen Boch François Buscot Markus Fischer Kezia Goldmann Martin M.Gossner Falk Hänsel Kirsten Jung Peter Manning Thomas Nauss Yvonne Oelmann Rodica Pena Andrea Polle Swen C.Renner Michael Schloter Ingo Schöning Ernst-Detlef Schulze Emily F.Solly Elisabeth Sorkau Barbara Stempfhuber Tesfaye Wubet Jörg Müller Sebastian Seibold Wolfgang W.Weisser | 2021 | Forest Ecosystems2021，8，1： | 2 |
| 15 | Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis显示文摘 | Phil A Hart Terumi Kamisawa William R Brugge Jae Bock Chung Emma L Culver László Czakó Luca Frulloni Vay Liang W Go Thomas M Gress Myung-Hwan Kim Shigeyuki Kawa Kyu Taek Lee Markus M Lerch Wei-Chih Liao Matthias L?hr Kazuichi Okazaki Ji Kon Ryu Nicolas Sc | 2013 | Gut2013，，12： | 2 |
| 16 | Combined evaluation of a panel of protein and miRNA serum‐exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity显示文摘 | Bindhu Madhavan Shijing Yue Uwe Galli Sanyukta Rana Wolfgang Gross Miryam Müller Nathalia A. Giese Holger Kalthoff Thomas Becker Markus W Büchler Margot Z?ller | 2015 | Int. J. Cancer2015，，11： | 2 |
| 17 | Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study显示文摘AIM To examine the associations between mental disorders and infectious, atopic, inflammatory diseases while adjusting for other risk factors.METHODS We used data from PsyC oL aus, a large Swiss Population Cohort Study(n = 3720; age range 35-66). Lifetime diagnoses of mental disorders were grouped into the following categories: Neurodevelopmental, anxiety(early and late onset), mood and substance disorders. They were regressed on infectious, atopic and other inflammatory diseases adjusting for sex, educational level, familial aggregation, childhood adversities and traumatic experiences in childhood. A multivariate logistic regression was applied to each group of disorders. In a complementary analysis interactions with sex were introduced via nested effects. RESULTS Associations with infectious, atopic and other chronic inflammatory diseases were observable together with consistent effects of childhood adversities and familial aggregation, and less consistent effects of trauma in each group of mental disorders. Streptococcal infections were associated with neurodevelopmental disorders(men), and measles/mumps/rubella-infections with early and late anxiety disorders(women). Gastric inflammatory diseases took effect in mood disorders(both sexes) and in early disorders(men). Similarly, irritable bowel syndrome was prominent in a sex-specific way in mood disorders in women, and, moreover, was associated with early and late anxiety disorders. Atopic diseases were associated with late anxiety disorders. Acne(associations with mood disorders in men) and psoriasis(associations with early anxiety disorders in men and mood disorders in women) contributed sex-specific results. Urinary tract infections were associated with mood disorders and, in addition, in a sex-specific way with late anxiety disorders(men), and neurodevelopmental and early anxiety disorders(women).CONCLUSION Infectious, atopic and inflammatory diseases areimportant risk factors for all groups of mental disorders. The sexual dimorphism of the associations is pronounced. | Vladeta Ajdacic-Gross Aleksandra Aleksandrowicz Stephanie Rodgers Margot Mutsch Anja Tesic Mario Müller Wolfram Kawohl Wulf R?ssler Erich Seifritz Enrique Castelao Marie-Pierre F Strippoli Caroline Vandeleur Roland von K?nel Rosa Paolicelli Markus A Landolt Cornelia Witthauer Roselind Lieb Martin Preisig | 2016 | World Journal of Psychiatry2016，6，4： | 2 |
| 18 | Gastric Bypass Leads to Improvement of Diabetic Neuropathy Independent of Glucose Normalization—Results of a Prospective Cohort Study (DiaSurg 1 Study)显示文摘 | Beat P. Müller-Stich Lars Fischer Hannes G. Kenngott Matthias Gondan Jonas Senft Gabriella Clemens Felix Nickel Thomas Fleming Peter P. Nawroth Markus W. Büchler | 2013 | Annals of Surgery2013，，5： | 2 |
| 19 | Allogeneic partially HLA-matched dendritic cells pulsed with autologous tumor cell lysate as a vaccine in metastatic renal cell cancer显示文摘 | Anne Fl?rcken Joachim Kopp Antje van Lessen Kamran Movassaghi Anna Takvorian Korinna J?hrens Markus M?bs Constanze Sch?nemann Birgit Sawitzki Karl Egerer Bernd D?rken Antonio Pezzutto J?rg Westermann | 2013 | Human Vaccines & Immunotherapeutics2013，，： | 2 |
| 20 | A vital sugar code for ricin toxicity显示文摘 | Jasmin Taubenschmld Johannes Stadlmann Markus Jost Tove Irene Klok.k Cory D Rillahan Andreas Leibbrandt Karl Mechtler James C Paulson Julian Jude Johannes Zuber Kirsten Sandvig Ulrich Elling Thorsten Marquardt Christian Thiel Christian Koerner Josef M Penninger | 2017 | Cell Research2017，27，11： | 2 |
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