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Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients:a multicenter,open-label,phase Ⅲ study

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Hepatobiliary & Pancreatic Diseases International 2013年第6期12卷 607-616页

作者： Meng-Su Zeng Hui-Yi Ye Liang Guo Wei-Jun Peng Jian-Ping Lu Gao-Jun Teng Josy Breuer Yi Huan Ping Li Jian-Rong Xu Chang-Hong Liang Department of Radiology Zhongshan HospitalFudan UniversityNo.180 Fenglin Road Departmentof Radiology General Hospital of PLA Department of Radiology First Affiliated HospitalSoochowUniversity Department of Radiology Cancer HospitalFudan University Department of Radiology Changhai HospitalSecond Military MedicalUniversity Department of Radiology Zhongda HospitalSoutheast University bayer HealthCare bayer schering Pharma AG Department of Radiology Xijing HospitalFourth Military MedicalUniversity bayer HealthCare CompanyLtd Department of Radiology RenjiHospitalShanghai Jiaotong University Department of Radiology Guangdong General Hospital

BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)***,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions and healthy *** study was undertaken to evaluate the efficacy and safety of the liverspecific MR imaging contrast agent gadoxetate disodium(GdEOB-DTPA)in Chinese ***:This was a single-arm,open-label,multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR *** imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA(0.025 mmol/kg body weight).Images were evaluated by clinical study investigators and three independent,blinded *** primary efficacy endpoint was sensitivity in lesion ***:Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46%compared with pre-contrast imaging for the average of the three blinded readers(94.78%vs 85.32%for Gd-EOB-DTPA vs pre-contrast,respectively).Improvements in detection were more pronounced in lesions less than ***-EOB-DTPA improved diagnostic accuracy in lesion ***:This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions,particularly in those smaller than 1 ***-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification,and furthermore,Gd-EOB-DTPA is safe in Chinese patients with liver lesions.

关键词： gadoxetate disodium magnetic resonance imaging liver focal liver lesions

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Wiedendiol-A inhibits cholesteryl ester binding to its transfer protein

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中国药理学报 1998年第5期19卷 408-412页

作者：汪苏克 DepartmentofCNS/CVBiologicalResearch Schering-PloughResearchInstituteKenilworthNJ07033USA.wang@***

Ｅｌｅｖａｔｅｄｈｉｇｈｄｅｎｓｉｔｙｌｉｐｏｐｒｏｔｅｉｎｓ（ＨＤＬ）ａｒｅｐｒｏｔｅｃｔｉｖｅｆｏｒｃｏｒｏｎａｒｙｄｉｓｅａｓｅａｎｄｔｈｅａｃｔｉｖｉｔｉｅｓｏｆｐｌａｓｍａｆａｃｔｏｒｓｔｏｒｅｄｉｓｔｒ... 详细信息

Ｅｌｅｖａｔｅｄｈｉｇｈｄｅｎｓｉｔｙｌｉｐｏｐｒｏｔｅｉｎｓ（ＨＤＬ）ａｒｅｐｒｏｔｅｃｔｉｖｅｆｏｒｃｏｒｏｎａｒｙｄｉｓｅａｓｅａｎｄｔｈｅａｃｔｉｖｉｔｉｅｓｏｆｐｌａｓｍａｆａｃｔｏｒｓｔｏｒｅｄｉｓｔｒｉｂｕｔｅｃｈｏｌｅｓｔｅｒｙｌ...

关键词：维登二醇-A 脂蛋白胆甾醇酯

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特高压设备对高压测试的挑战(英文)

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高电压技术 2011年第11期37卷 2617-2622页

作者： Ernst Gockenbach schering-Institut Leibniz Universitat Hannover Hannover

The increase of voltage level for AC and DC transmission systems requires some changes in the high voltage testing for Ultra High Voltage(UHV) *** a short description of the coordination work in the standardization bodies the requirements for UHV equipment are *** main points concerning high voltage testing of UHV equipment are the impulse shape of standard lightning impulse voltage,the evaluation of the test voltage for impulses with oscillations or overshoot near the peak and the time parameter of switching *** linearity check of the measuring devices,the proximity effect,the wet tests and the atmospheric correction factors are further points to be discussed concerning testing of UHV equipment.

关键词： UHV equipment testing AC lightning impulse voltage switching impulse wet test

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Simultaneous genetic transformation and genome editing of mixed lines in soybean(Glycine max)and maize(Zea mays)

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aBIOTECH 2024年第2期5卷 169-183页

作者： Michelle Valentine David Butruille Frederic Achard Steven Beach Brent Brower-Toland Edward Cargill Megan Hassebrock Jennifer Rinehart Thomas Ream Yurong Chen bayer Crop Science 700 Chesterfield Parkway WChesterfieldMO 63017USA

Robust genome editing technologies are becoming part of the crop breeding ***,genome editing is usually conducted either at a single locus,or multiple loci,in a variety at one *** parallel genomics platforms,multifaceted genome editing capabilities,and flexible transformation systems enable targeted variation at nearly any locus,across the spectrum of genotypes within a *** demonstrate here the simultaneous transformation and editing of many genotypes,by targeting mixed seed embryo explants with genome editing machinery,followed by re-identification through genotyping after plant *** and Editing of Mixed Lines(TREDMIL)produced transformed individuals representing 101 of 104(97%)mixed elite genotypes in soybean;and 22 of 40(55%)and 9 of 36(25%)mixed maize female and male elite inbred genotypes,*** of edited genotypes for the regenerated individuals identified over 800 distinct edits at the Determinate1(Dt1)locus in samples from 101 soybean genotypes and 95 distinct Brown midrib3(Bm3)edits in samples from 17 maize *** results illustrate how TREDMIL can help accelerate the development and deployment of customized crop varieties for future precision breeding.

关键词： Maize Soybean Seed embryo explants TREDMIL Genetic transformation Genome editing

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The global epidemiology of upper and lower gastrointestinal bleeding in general population:A systematic review

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World Journal of Gastrointestinal Surgery 2023年第4期15卷 723-739页

作者： Şiir Su Saydam Megan Molnar Pareen Vora Integrated Evidence Generation Bayer AGBerlin 13353Germany

BACKGROUND Gastrointestinal bleeding(GIB)is a common and potentially life-threatening clinical *** date,the literature on the long-term global epidemiology of GIB has not been systematically *** To systematically review the published literature on the worldwide epidemiology of upper and lower *** EMBASE®and MEDLINE were queried from 01 January 1965 to September 17,2019 to identify population-based studies reporting incidence,mortality,or casefatality rates of upper GIB(UGIB)or lower GIB(LGIB)in the general adult population,*** outcome data were extracted and summarized(including data on rebleeding following initial occurrence of GIB when available).All included studies were assessed for risk of bias based upon reporting *** Of 4203 retrieved database hits,41 studies were included,comprising a total of around 4.1 million patients with GIB worldwide from 1980–***-three studies reported rates for UGIB,four for LGIB,and four presented data on *** rates ranged from 15.0 to 172.0/100000 person-years for UGIB,and from 20.5 to 87.0/100000 person-years for *** studies reported on temporal trends,generally showing an overall decline in UGIB incidence over time,although a slight increase between 2003 and 2005 followed by a decline was shown in 5/13 ***-related mortality data were available from six studies for UGIB,with rates ranging from 0.9 to 9.8/100000 person-years,and from three studies for LGIB,with rates ranging from 0.8 to 3.5/100000 *** rate ranged from 0.7%to 4.8%for UGIB and 0.5%to 8.0%for *** of rebleeding ranged from 7.3%to 32.5%for UGIB and from 6.7%to 13.5%for *** main areas of potential bias were the differences in the operational GIB definition used and inadequate information on how missing data were *** Wide variation was seen in estimates of GIB epidemiology,likely due to high heterogeneity between studies however,UGIB sho

关键词： Gastrointestinal bleeding Gastrointestinal haemorrhage Epidemiology Incidence Mortality Case-fatality

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A transgenic wheat with a stilbene synthase gene resistant to powdery mildew obtained by biolistic method

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Chinese Science Bulletin 2000年第7期45卷 634-638页

作者： R.Hain bayer AG Agrochemicals DivisionDevelopment/BiotechnologyD-51368 LeverkusenGermany

Stilbene, a kind of phytoalexin, plays an important role in resistance to fungal and bacterial infection in plants. It strongly inhibits the growth of fungi and sprout of spore. Stilbene synthase gene (Vst1) obtained from grapevine has been transferred into common spring wheat Jinghong 5 by using the biolistic transformation method. Five transgenic plants (T0) were obtained from the bombarded 2014 immature embryos. One immune plantlet and 3 plantlets with mid-resistance to powdery mildew were identified from the transgenic plants of T3 generation which came from 2 T0 transgenic plants.

关键词： wheat transformation by biolistic method stilbene synthase phytoaiexin powdery mildew.

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Calcitriol analog ZK191784 ameliorates acute and chronic dextran sodium sulfate-induced colitis by modulation of intestinal dendritic cell numbers and phenotype

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World Journal of Gastroenterology 2007年第48期13卷 6529-6537页

作者： Ulrike G Strauch Florian Obermeier Nicole Grunwald Nadja Dunger Heiko C Rath Jürgen Schlmerich A Steinmeyer U Zügel HH Herfarth Department of Internal MedicineⅠ University of Regensburg Medicinal Chemistry Schering AG Berlin Germany Research Business Area Dermatology Schering AG Berlin Germany

AIM: To investigate the effects of ZK1916784, a low calcemic analog of calcitriol on intestinal inflammation. METHODS: Acute and chronic colitis was induced by dextran sodium sulfate (DSS) according to standard procedures. Mice were treated intraperitoneally with ZK1916784 or placebo and colonic inflammation was evaluated. Cytokine production by mesenterial lymph node (MLN) cells was measured by ELISA. Immunohistochemistry was performed to detect intestinal dendritic cells (DCs) within the colonic tissue, and the effect of the calcitriol analog on DCs was investigated. RESULTS: Treatment with ZK191784 resulted in significant amelioration of disease with a reduced histological score in acute and chronic intestinal inflammation. In animals with acute DSS colitis, down- regulation of colonic inflammation was associated with a dramatic reduction in the secretion of the proinflammatory cytokine interferon (IFN)-γ and a significant increase in intereleukin (IL)-10 by MLN cells. Similarly, in chronic colitis, IL-10 expression in colonic tissue increased 1.4-fold when mice were treated with ZK191784, whereas expression of the Th1-specific transcription factor T-beta decreased by 81.6%. Lower numbers of infiltrating activated CD11c+ DCs were found in the colon in ZK191784-treated mice with acute DSScolitis, and secretion of proinflammatory cytokines by primary mucosal DCs was inhibited in the presence of the calcitriol analog. CONCLUSION: The calcitriol analog ZK191784 demonstrated significant anti-inflammatory properties in experimental colitis that were at least partially mediated by the immunosuppressive effects of the derivate on mucosal DCs.

关键词： Dextran sodium sulfate colitis Calcitriol Colonic inflammation Dendritic cells

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Resistance to anti-tubulin agents:From vinca alkaloids to epothilones

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Cancer Drug Resistance 2019年第1期2卷 82-106页

作者： Werner Krause Formerly bayer AG Project ManagementBerlin 13353Germany

This review describes the mechanism of action-inhibition of microtubules-and the most important mechanisms of resistance for vinca alkaloids,taxanes and *** is a major problem in vinca and taxane chemotherapy and arises in most cases from overexpression of efflux pumps that transport the drugs out of the cancer cells and from modifications of the target,the microtubules,by overexpression of tubulin isotypes or by attachment of proteins to the ends of the microtubules so that the target is no longer recognized by the *** some cases,however,this process can have the opposite effect,leading to sensitization,e.g.,for vinca alkaloids in cases where taxanes are not or no longer *** link between resistance due to efflux pumps and the pharmacokinetics and metabolism of the drugs is also *** types of resistance that are addressed include detoxification of drugs within the cancer cell and blockade of apoptosis,post-translational modifications of microtubules and other protein pathways,micro-RNAs,induction of oncogenes,and cancer stem cells,which,taken together,offer particularly multifold possibilities for preventing drug *** use of biomarkers for the prediction of clinical outcome and for the direction of future therapy is also addressed.

关键词： Microtubules tumor heterogeneity mechanisms of resistance cancer stem cells biomarkers pharmacokinetics metabolism

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Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E_2 and cytokines

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World Journal of Gastroenterology 2009年第44期15卷 5549-5557页

作者： Mary Ann Cox James Jackson Michaela Stanton Alberto Rojas-Triana Loretta Bober Maureen Laverty Xiaoxin Yang Feng Zhu Jianjun Liu Suke Wang Frederick Monsma Galya Vassileva Maureen Maguire Eric Gustafson Marvin Bayne Chuan-Chu Chou Daniel Lundell Chung-Her Jenh Department of Tumor Biology Schering-Plough Research Institute Kenilworth NJ 07033 United States Department of Cardiovascular and Metabolic Disease Research Schering-Plough Research Institute Kenilworth NJ 07033 United States Department of Discovery Technologies Schering-Plough Research Institute Kenilworth NJ 07033 United States Department of Discovery Technologies Schering- Plough Research Institute Kenilworth NJ 07033 United States Department of Inflammation Schering-Plough Research Institute Kenilworth NJ 07033 United States

AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human

关键词： Short-chain fatty acids GPR43 GPR41 Human monocytes Prostaglandin E2 Chemokines Cytokines

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Chimeric protein probes for C5a receptors through fusion of the anaphylatoxin C5a core region with a small-molecule antagonist

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Science China Chemistry 2019年第10期62卷 1371-1378页

作者： Chao Zuo Wei-Wei Shi Xiao-Xu Chen Marie Glatz Bernd Riedl Ingo Flamme Elisabeth Pook Jiawei Wang Ge-Min Fang Donald Bierer Lei Liu Tsinghua-Peking Center for Life Sciences Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologyCenter for Synthetic and Systems BiologyDepartment of ChemistryTsinghua UniversityBeijing 100084China School of Life Science Institutes of Physical Science and Information TechnologyAnhui UniversityHefei 230601China bayer AG Department of Medicinal ChemistryAprather Weg 18A42096 WuppertalGermany bayer AG Cardiovascular Research42096 WuppertalGermany bayer AG Lead Discovery42096 WuppertalGermany

Blockade of the interaction of anaphylatoxin C5a with its receptor C5aR1 has been actively studied as a potential treatment for many inflammatory diseases;but current C5a antagonists exhibit inadequate potency and poor species cross-reactivity, and novel biochemical tools are needed to investigate whether the core region of C5a contains important interaction epitopes that can explain these limitations. Herein, we report the development of chimeric protein C5a probes containing both the complete core region of rat or human C5a, and the small-molecule antagonist PMX53-1. These probes were chemically synthesized through hydrazide-based native chemical ligation of a linear peptide hydrazide with the requisite cyclopeptidic antagonist, both of which were made by solid-phase synthesis. Quasi-racemic X-ray crystallography established that attachment of PMX53-1 did not affect the structure of the core region of C5a. Subsequent C5aR1 activity assays demonstrated the probes can provide valuable insights into the development of C5a antagonists;for example, they exhibited significantly better binding affinity and much improved species cross-reactivity than PMX53-1, supporting the notion that the effect of some epitopes outside the C-terminus of C5a should be taken into consideration when designing better C5a antagonists. Surprisingly, the core region of C5a was found to partially agonize C5aR1, suggesting the presence of more than one agonistic interaction in the binding of C5a to C5aR1. This study exemplifies the value of chemical protein synthesis in developing novel receptor probes for drug discovery research.

关键词： anaphylatoxin C5a PMX53 quasi-racemic X-ray crystallography native chemical ligation

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