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中国药理学与毒理学杂志 2018年第11期32卷 839-840页

作者：斯图尔特.阿拉斯泰尔澳大利亚墨尔本大学亚太药理学家联合会

【超过10%的人口受哮喘影响。严重的类固醇依赖性哮喘患者大约有5%,却消耗了估计50%的费用。在过去30年中,哮喘治疗新方法仅有针对由Ⅱ型T辅助细胞因子驱动的所谓T2型哮喘,以及具有针对白细胞介素4、白细胞介素5或其受体的抗体。

关键词：信号转导抑制剂 CK TGF 哮喘患者

Altered energy metabolism and metabolic gene expression associated with increased metastatic capacity identified in MDA -MB-231 cell line variants

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 678-693页

作者： Yan Tu Cameron N.Johnstone James G.Ryall Guillermo H.Lopez-Campos Christine R.Keenan alastair G.stewart Department of Pharmacology and Therapeutics the University of MelbourneParkvilleVictoria 3010Australia Cancer Research Division Peter MacCallum Cancer CentreEast MelbourneVictoria 3000Australia Olivia Newton-John Cancer Research Institute HeidelbergVictoria 3084Australia School of Cancer Medicine La Trobe UniversityBundooraVictoria 3086Australia Department of Biochemistry&Molecular Biology Monash UniversityClaytonVictoria 3800Australia Department of Pathology the University of MelbourneParkvilleVictoria 3010Australia Department of Physiology the University of MelbourneParkvilleVictoria 3010Australia Health and Biomedical Informatics Centre Melbourne Medical Schoolthe University of MelbourneVictoria 3010Australia The Wellcome-Wolfson Institute for Experimental Medicine Queen's UniversityBelfast BT97BLUK The Walter and Eliza Hall Institute of Medical Research ParkvilleVictoria 3010Australia Department of Medical Biology The University of MelbourneParkvilleVictoria 3010Australia

Aim:Despite current advances in therapies and the gradual decline in breast cancer-related mortality,metastasis remains a major therapeutic challenge for *** reprogramming is now recognized to be an important part of tumorigenic processes,but its relevance in metastatic dissemination has yet to be ***:Using the ***5 cell line,a novel,highly metastatic variant line derived from TN hu-man breast adenocarcinoma MDA-MB-231 line,alteration in growth and energy metabolisms associated with en-hanced metastatic potential were *** and oxidative phosphorylation(OXPHOS)was character-ized using the seahorse XF *** transcriptome sequencing(RNA-seq)and quantitative real-time PCR was used to ascertain expression differences in metabolic ***:We observed reduced proliferation,and an elevation of both glycolytic and OXPHOS metabolism in the highly metastatic daughter *** elevated metabolic rate is only partially reflected by transcript levels of rel-evant metabolic *** mitochondrial respiration is potentially underpinned by increased expres-sion mitochondrial electron transport chain ***,increased glycolysis was not underpinned by up-regulation of metabolic genes encoding enzymes participating in ***:Our results indicate breast tumour cells with elevated metastatic propensity are more metabolic *** also identified differentially expressed metabolic genes,such as IDH2,that may play a part in the meta-static process beyond energy reprogramming.

关键词： Breast cancer energy reprogramming cancer metabolism metastasis RNA-seq

新形势·新策略--网络药理学与中药新药研发

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中国药理学与毒理学杂志 2018年第11期32卷 827-828页

作者：韩露程肖蕊伯晓晨曹亮陈纯陈洛南陈禹保段大跃方坚松高丽高莉高耀李美娜李学军刘艾林刘骏秦雪梅 Bauer RUDOLF 宋文婷 alastair stewart 孙蓉孙妩弋田俊生王永华王忠魏伟肖伟徐峰徐筱杰张文娟张媛媛赵静周文霞张永祥北京药理毒理研究所北京100850 北京辐射医学研究所北京100850 江苏康缘药业股份有限公司江苏连云港222001 福建医科大学福建福州350122 中国科学院上海生命科学研究院上海200031 北京市计算中心北京100094 美国内华达州立大学医学院药理系美国内华达广州中医药大学临床药理研究所广州广东510006 山西大学中医药现代研究中心山西太原030006 新疆维吾尔医药研究所新疆乌鲁木齐830001 墨尔本大学澳大利亚墨尔本北京大学基础医学院北京100191 中国医学科学院北京协和医学院北京100730 中国中医科学院中医临床基础医学研究所北京100700 格拉茨卡尔弗朗森大学奥地利格拉茨中国中医科学院西苑医院北京100091 墨尔本大学ARC个性化治疗技术转换中心澳大利亚墨尔本山东大学高等医学研究院山东济南250012 安徽医科大学临床药理研究所安徽合肥230032 西北大学生命科学学院陕西西安710127 上海交通大学附属第六人民医院南院上海200030 北京大学化学与分子工程学院北京100871 四川大学华西基础医学与法医学院四川成都610041 上海中医药大学交叉科学研究院上海200032

"网络药理学与生物医药发展国际论坛"于2018年8月23-25日在江苏省连云港市召开。本次论坛由中国科协海智办、国际药理学联合会天然药物药理学分会、中国药理学会、中国药学会、江苏省科学技术协会、江苏省食品药品监督管理局和连云港市... 详细信息

"网络药理学与生物医药发展国际论坛"于2018年8月23-25日在江苏省连云港市召开。本次论坛由中国科协海智办、国际药理学联合会天然药物药理学分会、中国药理学会、中国药学会、江苏省科学技术协会、江苏省食品药品监督管理局和连云港市人民政府共同主办,中国药理学会网络药理学专业委员会承办,江苏康缘药业股份有限公司协办,中国药理学会网络药理学专业委员会主任委员周文霞教授和常务委员、江苏康缘药业股份有限公司董事长肖伟教授共同担任论坛主席。有来自美国、澳大利亚、奥地利、中国大陆和中国澳门等多个国家和地区的97名代表出席本次论坛。国家卫生健康委员会科技教育司监察刘登峰专员应邀参会。论坛针对国际、国内网络药理学研究的现状、最新进展和发展前沿等有关问题进行了综合讨论,展示了该研究领域的新技术、新进展和新应用。为促进国内外学术交流,本文对部分专家的观点和意见进行了整理,以期为促进我国网络药理学和生物医药研究与发展起到积极的推动作用。

关键词：网络药理学生物医药中药

Arbitrary Lagrangian–Eulerian simulations of highly electrically charged micro-droplet Coulomb explosion deformation pathways

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International Journal of Modeling, Simulation, and Scientific Computing 2016年第3期7卷 136-149页

作者： alastair Radcliffe CIMAP unit´e mixte CEA-CNRS-ENSICAEN-UCBN 6252 BP 5133F-14070 CaenCedex 05France University of Warwick Coventry CV47ALUK.

Numerical simulation results of the Coulomb explosion pathways of cooled water and heated glycol droplets electrically charged to the critical Rayleigh limit are presented,calculated using an axi-symmetric finite element scheme previously used for the same problem[Radcliffe A.J.,Non-conforming finite elements for axisymmetric charged droplet deformation dynamics and Coulomb explosions,*** 71:249–268,(2013),doi:10.1002/fld.3667.]which has been adapted to use arbitrary Lagrangian–Eulerian(ALE)methods and a novel tip reconstruction technique in order to greatly improve its accuracy in matching available experimental data.

关键词： Electrohydrodynamics finite elements droplet deformations.

Omics Approaches to Identify PotentialBiomarkers of Inflammatory Diseases in the FocalAdhesion Complex

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Genomics, Proteomics & Bioinformatics 2017年第2期15卷 101-109页

作者： Johanne Brooks alastair Watson Tamas Korcsmaros Gut Health and Food Safety Institute Strategic Programme Institute of Food Research Norwich Research Park Norwich NR4 7UA United Kingdom Norwich Medical School University of East Anglia Norwich Research Park Norwich NR4 7T J United Kingdom Gastroenterology Department Norfolk and Norwich University Hospital Norwich NR4 7UY United Kingdom Earlham Institute Norwich Research Park Norwich NR4 7UZ United Kingdom

Inflammatory diseases such as inflammatory bowel disease(IBD) require recurrent invasive tests, including blood tests, radiology, and endoscopic evaluation both to diagnose and assess disease activity, and to determine optimal therapeutic strategies. Simple ‘bedside’ biomarkers could be used in all phases of patient management to avoid unnecessary investigation and guide further management. The focal adhesion complex(FAC) has been implicated in the pathogenesis of multiple inflammatory diseases, including IBD, rheumatoid arthritis, and multiple sclerosis. Utilizing omics technologies has proven to be an efficient approach to identify biomarkers from within the FAC in the field of cancer medicine. Predictive biomarkers are paving the way for the success of precision medicine for cancer patients, but inflammatory diseases have lagged behind in this respect. This review explores the current status of biomarker prediction for inflammatory diseases from within the FAC using omics technologies and highlights the benefits of future potential biomarker identification approaches.

关键词： Focal adhesion complex Biomarkers Inflammation Omics Systems biology

In search of a roadmap towards improving care of patients with cirrhosis and ascites, could a platform trial design transform clinical research?

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Hepatobiliary Surgery and Nutrition 2022年第6期11卷 889-892页

作者： alastair O’Brien University College London(UCL)Institute for Liver and Digestive Health Division of MedicineRoyal Free CampusLondonUK

The authors of“Diagnosis,Evaluation,and Management of Ascites,Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome:2021 Practice Guidance by the American Association for the Study of Liver Diseases”are to be congratulated on their exhaustive assessment of the data published on patients with cirrhosis and ascites and their guidelines represent a pragmatic,evidence-based,common-sense approach(1).

关键词： patients ascites cirrhosis

Interaction of Waves, Surface Currents, and Turbulence: the Application of Surface-Following Coordinate Systems

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Journal of Ocean University of China 2007年第4期6卷 319-331页

作者： Jenkins alastair D Bjerknes Centre for Climate Research Geophysical Institute Allegaten 70 N-5007 Bergen Norway

Surface waves comprise an important aspect of the interaction between the atmosphere and the ocean, so a dynamically consistent framework for modelling atmosphere-ocean interaction must take account of surface waves, either implicitly or explicitly. In order to calculate the effect of wind forcing on waves and currents, and vice versa, it is necessary to employ a consistent formula- tion of the energy and momentum balance within the airflow, wave field, and water column. It is very advantageous to apply sur- face-following coordinate systems, whereby the steep gradients in mean flow properties near the air-water interface in the cross-interface direction may be resolved over distances which are much smaller than the height of the waves themselves. We may account for the waves explicitly by employing a numerical spectral wave model, and applying a suitable theory of wave–mean flow interaction. If the mean flow is small compared with the wave phase speed, perturbation expansions of the hydrodynamic equations in a Lagrangian or generalized Lagrangian mean framework are useful: for stronger flows, such as for wind blowing over waves, the presence of critical levels where the mean flow velocity is equal to the wave phase speed necessitates the application of more general types of surface-following coordinate system. The interaction of the flow of air and water and associated differences in temperature and the concentration of various substances (such as gas species) gives rise to a complex boundary-layer structure at a wide range of vertical scales, from the sub-millimetre scales of gaseous diffusion, to several tens of metres for the turbulent Ekman layer. The bal- ance of momentum, heat, and mass is also affected significantly by breaking waves, which act to increase the effective area of the surface for mass transfer, and increase turbulent diffusive fluxes via the conversion of wave energy to turbulent kinetic energy.

关键词： wind-wave-current interaction coordinate systems upper-ocean turbulence air-sea exchange of momentum, heat, andmass

Acupuncture for irritable bowel syndrome: A blinded placebo-controlled trial

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World Journal of Gastroenterology 2005年第26期11卷 4040-4044页

作者： alastair Forbes Sue Jackson Clare Walter Shafi Quraishi Meron Jacyna Max Pitcher St Mark's Hospital Watford Road Harrow HA1 3UJ United Kingdom

AIM:Irritable bowel syndrome (IBS) is a common disorder and many patients fail to find adequate relief from conventional therapies for their symptoms. This study tests the claim that acupuncture is effective for a majority of these patients. METHODS: A prospective, blinded, sham acupuncture-controlled trial of traditional Chinese acupuncture was performed at a single postgraduate teaching hospital in Europe. Sixty patients with well-established IBS were recruited. The blinded comparator was sham acupuncture administered by the second of two acupuncturists who alone was aware of the randomization, and who otherwise followed the prescription of the first. The primary end-point was a defined fall in the symptom score at 13 wk (by intention to treat). The prior expectation was a 30% placebo response, and a response rate of 70% from acupuncture, for which the study was adequately powered. RESULTS: Patients in treated and sham groups improved significantly during the study-mean improvement in scores being equal (minus 1.9) and significant for both (P<0.05; one-tailed t test). There was a small numeric but nonsignificant difference between the response rate in patients receiving acupuncture (40.7%) and sham treatment (31.2%). Several secondary end-points marginally favored active treatment, but an improved symptom score of any degree of magnitude occurred more often with sham therapy (65.6% vs 59.2%). For no criterion was statistical significance approached. CONCLUSION: Traditional Chinese acupuncture is relatively ineffective in IBS in the European hospital setting, and the magnitude of any effect appears insufficient to warrant investment in acupuncture services.

关键词： Acupuncture Complementary therapy Irritable bowel syndrome Traditional medicine

Sessile serrated adenoma/polyps: Where are we at in 2016?

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World Journal of Gastroenterology 2016年第34期22卷 7754-7759页

作者： Rajvinder Singh Leonardo Zorrón Cheng Tao Pu Doreen Koay alastair Burt Gastroenterology Department Lyell Mc Ewin and Modbury HospitalNALHN School of MedicineUniversity of Adelaide Gastrointestinal Endoscopy Division Department of GastroenterologyHospital das Clínicas da Faculdade de Medicina da Universidade de S?o Paulo Gastroenterology Department Lyell Mc Ewin and Modbury HospitalUniversity of Adelaide Executive Dean Faculty of Health SciencesUniversity of Adelaide

It is currently known that colorectal cancers(CRC) arise from 3 different pathways: the adenoma to carcinoma chromosomal instability pathway(50%-70%); the mutator "Lynch syndrome" route(3%-5%); and the serrated pathway(30%-35%). The World Health Organization has classified serrated polyps into three types of lesions: hyperplastic polyps(HP),sessile serrated adenomas/polyps(SSA/P) and traditional serrated adenomas(TSA),the latter two strongly associated with development of CRCs. HPs do not cause cancer and TSAs are rare. SSA/P appear to be the responsible precursor lesion for the development of cancers through the serrated pathway. Both HPs and SSA/Ps appear morphologically similar. SSA/P are difficult to detect. The margins are normally inconspicuous. En bloc resection of these polyps can hence be troublesome. A careful examination of borders,submucosal injection of a dye solution(for larger lesions) and resection of a rim of normal tissue around the lesion may ensure total eradication of these lesions.

关键词： Colonoscopy Sessile serrated adenoma/ polyp Serrated lesion Colorectal polyps Colorectal cancer Polypectomy Image enhancing endoscopy Narrow band imaging Endocytoscopy

A Rare Case of Non-small Cell Lung Carcinoma Squamous Phenotype with Epstein-Barr Virus Positivity with Prolonged Response to both Chemotherapy and Radiotherapy

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中国肺癌杂志 2021年第7期24卷 526-528页

作者： Carolina Navarro RODRIGUEZ Muhammad Shahid IQBAL Max ROBINSON Graham BURNS alastair GREYSTOKE Department of Clinical Oncology Freeman Hospital Department of Pathology Freeman Hospital Department of Respiratory Medicine Royal Victoria Infirmary Department of Medical Oncology Northern Centre for Cancer CareThe Newcastle-upon-Tyne Hospitals NHS Foundation TrustNewcastle-upon-TyneUK

We present a rare challenging case of metastatic non-small cell lung cancer with Epstein-Barr virus positivity that was also diagnosed with pulmonary tuberculosis at the same time. Palliative chemotherapy gemcitabine and carboplatin was started after two weeks of anti-tuberculosis treatment with the hopes that this period would be sufficient to keep acid fast bacilli non-viable to minimise risk of tuberculosis re-activation due to chemotherapy induced immunosuppression. She completed four cycles of chemotherapy and six months of anti-tuberculosis treatment with good results and minimal side effects. Two years later, there was disease recurrence in cervical and mediastinal lymph nodes which was treated with local treatment i.e. surgery and palliative radiotherapy. It has been two years since last radiotherapy and overall more than five years since diagnosis with no active disease at present. Given the complexity and rarity of this case, significant multidisciplinary team involvement, including oncologists and radiation oncologists, pulmonologists with special interest in tuberculosis and pathologists was necessary throughout.

关键词： Lung neoplasms Epstein-Barr Virus Tuberculosis Chemotherapy Radiotherapy