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

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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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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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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Biomarkers for hepatocellular carcinoma: What's new on the horizon?

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World Journal of Gastroenterology 2018年第35期24卷 3974-3979页

作者： Matthias Ocker Department of Translational Medicine Oncology Bayer AGBerlin 13353Germany CharitéUniversity Medicine Berlin Berlin 10117Germany

Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.

关键词： Hepatocellular carcinoma Biomarker Nextgeneration sequencing Liquid Biopsy Functional imaging Molecular imaging Circulating free DNA Circulating tumor cells Immune checkpoint inhibitors

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Influence of solvent mixtures on HPMCAS-celecoxib microparticles prepared by electrospraying

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Asian Journal of Pharmaceutical Sciences 2018年第6期13卷 584-591页

作者： Adam Bohr Yingya Wang Moritz Beck-Broichsitter Mingshi Yang Department of Pharmacy Faculty of Health and Medical SciencesUniversity of Copenhagen Department of Pharmaceutics and Biopharmacy Philipps-Universitat Chemical and Pharmaceutical Development Bayer AG Wuya College of Innovation Shenyang Pharmaceutical University

Hypromellose acetate succinate(HPMCAS) microparticles containing the poorly-water soluble drug celecoxib(CEL) were prepared by electrospraying intended for oral drug delivery. Various solvent mixtures with different solubility for CEL and HPMCAS were used to induce changes in the polymer structural conformation of the microparticles. The performance of the prepared microparticles was evaluated by studying the solid state from, particle size and morphology, radial drug distribution and drug release. CEL was amorphous in all electrosprayed HPMCAS microparticles. The particle size and morphology was dependent on the solubility of HPMCAS in the solvent mixture used with poorer solvents resulting in smaller microparticles with rougher appearance. The CEL distribution on the particles surface was relatively homogeneous and similar for all microparticles. Drug release from the microparticles was observed at a higher rate depending on the solubility of HPMCAS in the solvent used for electrospraying, and in all cases an at least 4-fold higher rate was observed compared with the crystalline drug. Drug precipitation from the supersaturated solution was inhibited by HPMCAS for all microparticles based on its parachute effect while crystalline CEL did not reach supersaturation. This study demonstrated that electrospraying can be used to produce microparticles with tailored properties for pharmaceutical application by adjusting solvent selection.

关键词： Celecoxib Electrospraying Hypromellose acetate succinate Oral drug delivery Polymeric microparticles Solvent mixture

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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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Aspirin plus Pseudoephedrine (Aspirin Complex) for the Treatment of Symptoms of Upper Respiratory Tract Infection

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Open Journal of Respiratory Diseases 2017年第1期7卷 25-40页

作者： Michael Voelker Ronald Eccles Uwe Gessner bayer ag Leverkusen Germany Common Cold Centre Cardiff University Cardiff UK

Upper respiratory tract infections or common colds are a multi-symptom disease which is usually symptomatically treated with fixed dose multi-active ingredient medicinal products which are commonly used as non-prescription and over the counter. However, the active ingredients combined require a particular and clinically sound justification. Analgesics and decongestant can be combined to treat simultaneously the prominent symptoms cold-related pain (e.g. headache, muscle aches and pains), fever, inflammationand nasal/sinus congestion. This overview provides a summary of the evidence supporting the combination of acetylsalicylic acid (aspirin) and pseudoephedrine available in the common cold product Aspirin? Complex.

关键词： Aspirin Acetylsalicylic Acid Pseudoephedrine Dissolution Pharmacokinetic Upper Respiratory Tract Infection Clinical Studies

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Risk factors for major gastrointestinal bleeding in the general population in Finland

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World Journal of Gastroenterology 2022年第18期28卷 2008-2020页

作者： Pareen Vora Ronald Herrera Arto Pietila Ulrich Mansmann Gunnar Brobert Markku Peltonen Veikko Salomaa Integrated Evidence Generation Bayer AGBerlin 13353Germany Institute for Medical Information Processing Biometryand EpidemiologyLudwig Maximilians UniversitätMunich 81337Germany Pettenkofer School of Public Health Ludwig Maximilians UniversitätMunich 81337Germany Department of Public Health and Welfare National Institute for Health and Welfare(THL)Helsinki FI-00271Finland Medical Affairs Bayer ABSolna 17165Sweden

BACKGROUND Data on non-drug related risk-factors for gastrointestinal bleeding(GIB)in the general population are limited,especially for life-style factors,clinical measurements and laboratory *** To identify and investigate non-drug risk factors for major GIB in the general population of *** We performed a retrospective cohort study using data from the FINRISK health examination surveys,which have been conducted every 5 years across Finland from 1987 to *** were adults aged 25 years to 74 years,excluding those with a previous hospitalization for ***-up from enrollment was performed through linkage to national electronic health registers and ended at an event of GIB that led to hospitalization/death,death due to any other cause,or after 10 *** included demographics,socioeconomic and lifestyle factors,clinical measurements,laboratory parameters and *** selection was undertaken using Least Absolute Shrinkage and Selection Operator(LASSO)and factors associated with GIB were identified using Cox *** Among 33,508 participants,403(1.2%)experienced GIB[256 men(63.5%);mean age,56.0 years(standard deviation(SD)±12.1)]and 33105 who did not experience GIB[15768 men(47.6%);mean age,46.8(SD±13)years],within 10 years of *** associated with a significantly increased risk of GIB were baseline age[per 10-year increase;hazard ratio(HR)1.62,95%confidence interval(CI):1.42-1.86],unemployment(HR:1.70,95%CI:1.11-2.59),body mass index(BMI)(HR:1.15,95%CI:1.01-1.32),gamma-glutamyl transferase(GGT)(HR:1.05,95%CI:1.02-1.09),precursors of GIB(HR:1.90,95%CI:1.37-2.63),cancer(HR:1.47,95%CI:1.10-1.97),psychiatric disorders(HR:1.32,95%CI:1.01-1.71),heart failure(HR:1.46,95%CI:1.04-2.05),and liver disorders(HR:3.20,95%CI:2.06-4.97).Factors associated with a significantly decreased risk of GIB were systolic blood pressure(SBP)(HR:0.78,95%CI:0.64-0.96),6-10 cups of coffee a day(HR:0.67,95%CI:0.46-0

关键词： Risk factors Gastrointestinal hemorrhage General population Finland Life style Population health

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The new kid on the block in insect pest management:sprayable RNAi goes commercial

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Science China(Life Sciences) 2024年第8期67卷 1766-1768页

作者： Junjie Yan Ralf Nauen Stuart Reitz Andrei Alyokhin Jiang Zhang David Mota-Sanchez Yonggyun Kim Subba Reddy Palli Silvia I.Rondon Brian A.Nault Juan Luis Jurat-Fuentes Michael S.Crossley William E.Snyder Angharad M.R.Gatehouse Myron P.Zalucki Bruce E.Tabashnik Yulin Gao State Key Laboratory for Biology of Plant Disease and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China bayer ag Crop Science DivisionR&DPest ControlMonheim 40789Germany Department of Crop and Soil Science Oregon State UniversityOntario 97914USA School of Biology and Ecology University of MaineOrono 04469USA Shenzhen Branch Guangdong Laboratory of Lingnan Modern AgricultureKey Laboratory of Synthetic BiologyMinistry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518000China Department of Entomology Michigan State UniversityEast Lansing 48864USA Department of Plant Medicals Andong National UniversityAndong 36729Republic of Korea Department of Entomology University of KentuckyLexington 40503USA Oregon State University Oregon Integrated Pest Management CenterCorvallis 97838USA Department of Entomology Cornell UniversityCornell AgriTechGeneva 14456USA Department of Entomology and Plant Pathology University of TennesseeKnoxville 37996USA Department of Entomology and Wildlife Ecology University of DelawareNewark 19716USA Department of Entomology University of GeorgiaAthensGeorgia 30602USA School of Natural and Environmental Sciences Newcastle UniversityNewcastle upon TyneNE17RUUK School of the Environment University of QueenslandBrisbane 4072Australia Shandong Engineering Research Center for Environment-Friendly agricultural Pest Management College of Plant Health and MedicineQingdao Agricultural UniversityQingdao 266109China Department of Entomology University of ArizonaTucson 85721USA National Center of Excellence for Tuber and Root Crop Research Chinese Academy of Agricultural SciencesBeijing 100081China

Insect pest damage to crops is a threat to global food security(Tilman et al.,2011).Climate change,the evolution of insecticide resistance,and the phasing out of insecticides due to environmental and safety concerns exacerbate this *** urgently need safe and effective crop protection tools to sustainably generate yields that meet ever-increasing global demand.

关键词： crops damage pest

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