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奈妥匹坦帕洛诺司琼预防化疗引起的恶心呕吐:从临床试验到日常临床实践

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中国实用医药 2024年第1期19卷 159-174页

作者： Matti Aapro Karin Jordan florian Scotté Luigi Celio Meinolf Karthaus Eric Roeland Genolier Cancer Centre Clinique de GenolierGenolierSwitzerland Department Haematology Oncology and Palliative CareErnst von Bergmann Klinikum PotsdamPotsdamGermany Department of Medicine V HematologyOncology and RheumatologyUniversity Hospital HeidelbergHeidelbergGermany Interdisciplinary Cancer Course Department Gustave Roussy Cancer InstituteVillejuifFrance Medical Oncology Unit ASST del GardaDesenzano del Garda(BS)Italy Department of Hematology Oncology and Palliative CareKlinikum NeuperlachMunichGermany Department of Hematology Oncology and Palliative CareKlinikum HarlachingMunichGermany Oregon Health and Sciences University Knight Cancer InstitutePortlandORUSA

化疗引起的恶心呕吐(CINV)是众多抗癌药物治疗中常见的不良事件,不仅会对患者生活质量带来负面影响,还有可能影响化疗效果。目前,指南建议的止吐方案可以预防大部分癌症患者的CINV。但临床医师并不能始终遵循指南建议,患者也常常难以坚... 详细信息

化疗引起的恶心呕吐(CINV)是众多抗癌药物治疗中常见的不良事件,不仅会对患者生活质量带来负面影响,还有可能影响化疗效果。目前,指南建议的止吐方案可以预防大部分癌症患者的CINV。但临床医师并不能始终遵循指南建议,患者也常常难以坚持医师处方的治疗。因此需要采取一些提高指南依从性的方法。奈妥匹坦帕洛诺司琼(NEPA)是首个也是唯一一个固定剂量复方止吐药,由奈妥匹坦(口服)/福奈妥匹坦(静脉给药)与帕洛诺司琼(PALO)组成。NEPA可以联合地塞米松组成三联止吐方案,这是用于高致吐性化疗(HEC)患者和部分中致吐性化疗(MEC)患者预防CINV的推荐方案。因此,NEPA止吐治疗操作简单便捷,可能有助于提高指南依从性。本综述对CINV进行了概括,评价了在临床试验和真实实践中积累的NEPA止吐效果及安全性方面的证据,同时也评价了在关键临床试验之外的环境下,即日常临床环境中使用NEPA进行止吐的初步证据。此外,本文还评述了化疗期间使用NEPA控制恶心症状和提高患者生活质量,这是癌症患者管理中面临的两个大挑战。

关键词：奈妥匹坦帕洛诺司琼化疗引起的恶心呕吐 NK1受体拮抗剂 5-羟色胺-3受体拮抗剂生活质量止吐方案

Anemia and long-term outcome in adjuvant and neoadjuvant radiochemotherapy of stage Ⅱ and Ⅲ rectal adenocarcinoma:The Freiburg experience(1989-2002)

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World Journal of Gastroenterology 2006年第12期12卷 1849-1858页

作者： Christian Weissenberger Geissler Michael Otto florian Barke Annette Henne Karl von Plehn Georg Rein Alex Müller Christine Bartelt Susanne Henke Michael Department of Radiotherapy University Hospital of Freiburg79106 FreiburgGermany Department Oncology Gastroenterology and Internal MedicineStidtische Kliniken Esslingen73730 Esslingen a.N.Germany Department of Internal Medicine I Division of OncologyUniversity Hospital of Freiburg79106 FreiburgGermany

AIM： To evaluate the long-term outcome of standard 5-FU based adjuvant or neoadjuvant radiochemotherapy and to identify the predictive factors, especially anemia before and after radiotherapy as well as hemoglobin increase or decrease during radiotherapy. METHODS： Two hundred and eighty-six patients with Union International Contre Cancer （UICC） stage Ⅱ and Ⅲ rectal adenocarcinomas, who underwent resection by conventional surgical techniques （low anterior or abdominoperineal resection）, received either 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 evaluated using Kaplan-Meier, Log-rank test and Cox＇s proportional hazards as statistical methods. Multivariate analysis was used to identify prognostic factors. Median follow-up time was 8 years. RESULTS： Anemia before radiochemotherapy was an independent prognostic factor for improved DFS （risk ratio 0.76, P= 0.04） as well as stage, grading, R status （free radial margins）, type of surgery, carcinoembryonic antigen （CEA） levels, and gender. The univariate analysis revealed that anemia was associated with impaired LRS（better local control） but with improved DFS. In contrast, hemoglobin decrease during radiotherapy was an independent risk factor for DFS （risk ratio 1.97, P= 0.04）. During radiotherapy, only 30.8% of R0-resected patients suffered from hemoglobin decrease compared to 55.6% if R1/2 resection was performed （P= 0.04）. The 5-year OAS, CSS, DFS, LRS and DRS were 47.0%, 60.0%, 41.4%, 67.2%, and 84.3%, respectively. Significant differences between preoperative and postoperative radiochemotherapy were not found. CONCLUSION ： Anemia before radiochemotherapy and hemoglobin decrease during radiotherapy have no predictive value for the outcome of rectal cancer. Stage, grading, R status （free radial margins）, t

关键词： Rectal cancer Adjuvant radiotherapy Adjuvant radiochemotherapy Anemia Procjnostic factor

Changes in ankle work,foot work,and tibialis anterior activation throughout a long run

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Journal of Sport and Health Science 2022年第3期11卷 330-338页

作者： Eric C.Honert florian Ostermair Vinzenzvon Tscharner Benno M.Nigg Human Performance Laboratory Faculty of KinesiologyUniversity of CalgaryCalgaryAlberta T2N 1N4Canada Institute of Sports and Sports Science Karlsruhe Institute of TechnologyKarlsruhe 76131Germany Department of Sports Science and Sports Friedrich Alexander University Erlangen-NurembergErlangen 91058Germany

Background The ankle and foot together contribute to over half of the positive and negative work performed by the lower limbs during ***,little is known about how foot kinetics change throughout a *** amount of negative foot work may decrease as tibialis anterior(TA)electromyography(EMG)changes throughout longer-duration ***,we examined ankle and foot work as well as TA EMG changes throughout a changing-speed *** Fourteen heel-striking subjects ran on a treadmill for 58 *** collected ground reaction forces,motion capture,and *** ran at 110%,100%,and 90%of their 10-km running speed and 2.8 m/s multiple times throughout the *** work was evaluated using the distal rearfoot work,which provides a net estimate of all work contributors within the *** Positive foot work increased and positive ankle work decreased throughout the run at all *** the 110%10-km running speed,negative foot work decreased and TA EMG frequency shifted lower throughout the *** increase in positive foot work may be attributed to increased foot joint work performed by intrinsic foot *** in negative foot work and TA EMG frequency may indicate that the TA plays a role in negative foot work in the early stance of a *** This study is the first to examine how the kinetic contributions of the foot change throughout a *** studies should investigate how increases in foot work affect running performance.

关键词： Electromyography Footwear Running performance

Supportive angiogenic and osteogenic differentiation of mesenchymal stromal cells and endothelial cells in monolayer and co-cultures

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International Journal of Oral Science 2016年第4期8卷 223-230页

作者： florian Bohrnsen Henning Schliephake Clinic of Oral and Maxillofacial Surgery Georg August University Gottingen Germany

Sites of implantation with compromised biology may be unable to achieve the required level of angiogenic and osteogenic regeneration. The specific function and contribution of different cell types to the formation of prevascularized, osteogenic networks in co-culture remains unclear. To determine how bone marrow-derived mesenchymal stromal cells （BMSCs） and endothelial cells （ECs） contribute to cellular proangiogenic differentiation, we analysed the differentiation of BMSCs and ECs in standardized monolayer, Transwell and co-cultures. BMSCs were derived from the iliac bone marrow of five patients, characterized and differentiated in standardized monolayers, permeable Transwells and co-cultures with human umbilical vein ECs （HUVECs）. The expression levels of CD31, von Willebrand factor, osteonectin （ON） and Runx2 were assessed by quantitative reverse transcriptase polymerase chain reaction. The protein expression of alkaline phosphatase, ON and CD31 was demonstrated via histochemical and immunofluorescence analysis. The results showed that BMSCs and HUVECs were able to retain their lineage-specific osteogenic and angiogenic differentiation in direct and indirect co-cultures. In addition, BMSCs demonstrated a supportive expression of angiogenic function in co-culture, while HUVEC was able to improve the expression of osteogenic marker molecules in BMSCs.

关键词： angiogenic co-culture differentiation endothelial cell mesenchymal stromal cell osteogenic

Vitality variation and population structure of a riparian forest in the lower reaches of the Tarim River,NW China

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Journal of Forestry Research 2018年第3期29卷 742-753页

作者： Maierdang Keyimu Umut Halik florian Betz Choimaa Dulamsuren Key Laboratory of Oasis Ecology College of Resources and Environmental ScienceXinjiang UniversityUrumqi 830046China Faculty of Mathematics and Geography Catholic University of Eichstatt-Ingolstadt85072 EichstattGermany Department of Plant Ecology and Ecosystems Research Albrecht von Haller Institute for Plant SciencesGeorg August University of Gottingen37073 GottingenGermany

Since 2000, the Chinese government has implemented emergency water diversion measures to restore the damaged riparian forest ecosystem with dominant tree species Euphrat poplar(Populus euphratica Oliv.)at the lower reaches of the Tarim River. In the present study, comparative analysis of variations in the vitality of P. euphratica trees were made using 2005 and 2010 data to illustrate the revitalization process of riparian forest. Poplar trees within 300 m of the riverbed were positively revitalized, while the vitality of trees farther than 300 m from the river decreased. Population structure was studied to demonstrate the development of poplar community. In the first belt, the class structure for the diameter at breast height(DBH) of P. euphratica fit a logistic model, and the 2nd, 3rd and 4th belt curve fittings were close to a Gaussian model; in other plots they were bimodal. Cluster analysis of the composition of the DBH class of poplar trees demonstrated that those within 16–36 cm DBH were the most abundant(58.49% of total) in study area, under 16 cm of DBH were second(31.36%), and trees >40 cm DBH were the least abundant(10.15%). More than 80% of the trees were young and medium-sized, which means that the poplar forest community in the vicinity of the lower Tarim River is at a stable developmental stage. The abundance of juvenile trees of P. euphratica in the first and second measuring belts was 12.13% in 2005 and increased to 25.52% in 2010, which means that the emergency water transfer had a positive impact on the generation of young P. euphratica trees in the vicinity of the river.

关键词： Lower Tarim River Riparian forest ecosystem Populus euphratica Vitality Population structure Diameter at breast height

Macrophage’s little helper: vitamin A directs alternatively activated monocyte-derived macrophages to tissue-resident macrophages

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Cellular & Molecular Immunology 2017年第10期14卷 805-808页

作者： Dirk Schlüter florian H Heidel Institute of Medical Microbiology and Hospital Hygiene Otto-von-Guericke University MagdeburgMagdeburg 39120Germany Organ-Specific Immune Regulation Helmholtz-Center for Infection ResearchBraunschweig 38124Germany Innere Medizin II Hämatologie und OnkologieUniversitätsklinikum JenaJena 07745Germany Leibniz-Institute on Aging Fritz-Lipmann-InstituteJenaGermany

Tissue-resident macrophages originate from the yolk sac in a Myb-independent manner and populate all organs during *** macrophages are a heterogeneous self-renewing population that adapt to the organ-specific local environment to contribute to tissue *** on the age,organ and inflammatory conditions,macrophages that are derived from hematopoietic stem cells(HSCs)in a Myb-dependent manner may also infiltrate organs and develop into tissueresident macrophages.

关键词： organs vitamin homeostasis

Approximation Algorithms for 3D Orthogonal Knapsack

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Journal of Computer Science & Technology 2008年第5期23卷 749-762页

作者： florian Diedrich Rolf Harren Klaus Jansen Ralf Thle Henning Thomas Institute of Computer Science University of Kiel Max-Planck-Institut für Informatik Campus E1466123 Saarbrücken Germany Department of Computer Science ETH ZurichZurich Switzerland

We study non-overlapping axis-parallel packings of 3D boxes with profits into a dedicated bigger box where rotation is either forbidden or permitted, and we wish to maximize the total profit. Since this optimization problem is NP-hard, we focus on approximation algorithms. We obtain fast and simple algorithms for the non-rotational scenario with approximation ratios 9 ＋ ε and 8 ＋ ε, as well as an algorithm with approximation ratio 7 ＋ ε that uses more sophisticated techniques; these are the smallest approximation ratios known for this problem. Furthermore, we show how the used techniques can be adapted to the case where rotation by 90° either around the z-axis or around all axes is permitted, where we obtain algorithms with approximation ratios 6 ＋ ε and 5 ＋ ε, respectively. Finally our methods yield a 3D generalization of a packability criterion and a strip packing algorithm with absolute approximation ratio 29/4, improving the previously best known result of 45/4.

关键词： approximation algorithm computational and structural complexity geometric configurations

Machine Learning to Detect Alzheimer’s Disease from Circulating Non-coding RNAs

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Genomics, Proteomics & Bioinformatics 2019年第4期17卷 430-440页

作者： Nicole Ludwig Tobias Fehlmann Fabian Kern Manfred Gogol Walter Maetzler Stephanie Deutscher Simone Gurlit Claudia Schulte Anna-Katharina von Thaler Christian Deuschle florian Metzger Daniela Berg Ulrike Suenkel Verena Keller Christina Backes Hans-Peter Lenhof Eckart Meese Andreas Keller Department of Human Genetics Saarland University66421 Homburg/SaarGermany Chair for Clinical Bioinformatics Saarland University66123 Saarbru¨ckenGermany Institut fur Gerontologie Universitat Heidelberg69047 HeidelbergGermany Department of Neurology Christian-Albrechts-University of Kiel24118 KielGermany Center for Neurology and Hertie Institute for Clinical Brain Research Department of NeurodegenerationUniversity of Tuebingen72074 TuebingenGermany German Center for Neurodegenerative Diseases(DZNE) 72076 TuebingenGermany Department of Anesthesiology and Intensive Care St.Franziskus Hospital Muenster48145 MuensterGermany Department of Psychiatry and Psychotherapy University Hospital Tuebingen72016 TuebingenGermany Department of Medicine II Saarland University Medical Center66421 Homburg/SaarGermany Center for Bioinformatics Saarland Informatics Campus66123 SaarbruckenGermany

Blood-borne small non-coding(snc RNAs)are among the prominent candidates for blood-based diagnostic ***,high-throughput approaches are applied to discover biomarker *** have to be validated in larger cohorts and evaluated by adequate statistical learning ***,we published high-throughput sequencing based microRNA(miRNA)signatures in Alzheimer’s disease(AD)patients in the United States(US)and ***,we determined abundance levels of 21 known circulating miRNAs in 465 individuals encompassing AD patients and controls by *** computed models to assess the relation between miRNA expression and phenotypes,gender,age,or disease severity(Mini-Mental State Examination;MMSE).Of the 21 miRNAs,expression levels of 20 miRNAs were consistently de-regulated in the US and German cohorts.18 miRNAs were significantly correlated with neurodegeneration(Benjamini-Hochberg adjusted P<0.05)with highest significance for miR-532-5 p(BenjaminiHochberg adjusted P=4.8×10^-30).Machine learning models reached an area under the curve(AUC)value of 87.6%in differentiating AD patients from ***,ten miRNAs were significantly correlated with MMSE,in particular miR-26a/26b-5p(adjusted P=0.0002).Interestingly,the miRNAs with lower abundance in AD were enriched in monocytes and T-helper cells,while those up-regulated in AD were enriched in serum,exosomes,cytotoxic t-cells,and *** study represents the next important step in translational research for a miRNA-based AD test.

关键词： miRNAs Neurodegeneration Alzheimer’s disease Biomarker Non-coding RNAs Gene regulation

In situ high-pressure nuclear magnetic resonance crystallography in one and two dimensions

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Matter and Radiation at Extremes 2021年第6期6卷 94-103页

作者： Thomas Meier Alena Aslandukova florian Trybel Dominique Laniel Takayuki Ishii Saiana Khandarkhaeva Natalia Dubrovinskaia Leonid Dubrovinsky Center for High Pressure Science and Technology Advanced Research BeijingChina Bayerisches Geoinstitut University of BayreuthBayreuthGermany Department of Physics Chemistry and Biology(IFM)Linkoping UniversitySE-58183 LinkopingSweden Material Physics and Technology at Extreme Conditions Laboratory of CrystallographyUniversity of BayreuthBayreuthGermany

Recent developments in in situ nuclear magnetic resonance(NMR)spectroscopy under extreme conditions have led to the observation of a wide variety of physical phenomena that are not accessible with standard high-pressure experimental ***,inherent di-or quadrupolar line broadening in diamond anvil cell(DAC)-based NMR experiments often limits detailed investigation of local atomic structures,especially if different phases or local environments ***,we describe our progress in the development of high-resolutionNMRexperiments in DACs using one-and two-dimensional homonuclear decoupling experiments at pressures up to the megabar *** this technique,spectral resolutions of the order of 1 ppm and below have been achieved,enabling high-pressure structural *** examples are presented that demonstrate the wide applicability of this method for extreme conditions research.

关键词： NMR extreme dimensions