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| 1 | 肌萎缩性侧索硬化蛋白激活小胶质细胞NLRP3炎性小体显示文摘小胶质细胞NLRP3炎性小体激活正在成为神经退行性变过程中神经炎症的关键因素。诸如β-淀粉样蛋白和α-突触核蛋白之类的致病性蛋白质聚集体触发小胶质NLRP3激活,从而导致半胱天冬酶-1激活和IL-1β的分泌。在小鼠肌萎缩性侧索硬化症(ALS)的SOD1G93A模型中,半胱天冬酶-1和IL-1β均促进疾病进展,提示小胶质NLRP3在该进程中发挥作用。然而先前的研究表明,SOD1G93A小鼠小胶质细胞不表达NLRP3,SOD1G93A蛋白在小胶质细胞中产生独立于NLRP3的IL-1β。本研究论证了使用Nlrp3-GFP基因敲入小鼠,在SOD1G93A小鼠中小胶质细胞表达NLRP3。本研究显示聚集和可溶性SOD1G93A均可激活小鼠原代小胶质细胞中的炎性小体,导致半胱天冬酶-1和IL-1β裂解,ASC斑点形成以及呈剂量和时间依赖性的IL-1β分泌。重要的是,SOD1G93A无法从缺乏Nlrp3的小胶质细胞或者用特异性NLRP3抑制剂MCC950预处理的小胶质细胞中诱导IL-1β分泌,从而证实NLRP3是介导SOD1诱导的小胶质细胞IL-1β分泌的关键炎症小体复合物。在TDP-43Q331K ALS小鼠模型中也观察到小胶质NLRP3上调,TDP-43野生型和突变蛋白亦可以NLRP3依赖性的方式激活小胶质炎性小体。从机制上讲,本研究确定了活性氧簇和ATP的生成是SOD1G93A介导的NLRP3激活所需的关键事件。总之,本研究的数据表明ALS小胶质细胞表达NLRP3,而病理ALS蛋白激活小胶质NLRP3炎性小体。因此,NLRP3抑制可能是阻止小胶质细胞神经炎症和ALS疾病进展的潜在治疗方法。 | Vandana Deora John D Lee Eduardo AAlbornoz Luke McAlary Cyril J Jagaraj Avril A B Robertson Julie D Atkin Matthew A Cooper Kate Schroder Justin J Yerbury Richard Gordon Trent MWoodruff 杜一星(编译) | 2020 | 神经损伤与功能重建2020，15，9： | 13 |
| 2 | Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial显示文摘 | Wendy S Atkin Rob Edwards Ines Kralj-Hans Kate Wooldrage Andrew R Hart John MA Northover D Max Parkin Jane Wardle Stephen W Duffy Jack Cuzick | 2010 | The Lancet2010，，9726： | 4 |
| 3 | 拉米夫定/干扰素-α联合治疗围生期感染乙肝的免疫耐受患儿:一项初步研究显示文摘Objective:To investigate whether combining the antiviral effect of lamivudine with the immune-boosting action of interferon-alpha(IFN-α)is effective in treating hepatitis B virus(HBV)“immunotolerant”children.Study design:Twen tythree children(8 boys;mean age,10 years)infected during the first year of life(17 Asian,21 with normal aminotransferase levels,15 with HBV-DNA > 1000 pg/mL by hybridization and all with mild histologic changes)were treated with l amivudine(3 mg/kg)for 8 weeks alone and then lamivudine(3 mg/kg)-and IFN-α(5 MU/m2,3 times weekly)in combination for 10 months.Results:Seventy-eight percent became HBV-DNA negative at the end of treatment,5(22%)seroconverted to anti-HBe,4(17%)of whom achieved complete viral control,becoming persis tently HBsAg negative and anti-HBs positive.None had YMDD mutations.The viral status of the patients has not changed after a median follow-up of 40 months(range,36 to 48).Conclusions:This pilot study suggests that lamivudine pretrea tment followed by a combination of lamivudine and IFN-αcan induce complete vir al control in HBV immunotolerant children,hitherto considered poor responders. | D'Antiga L. Aw M. Atkins M. G.Mieli-Vergani 王一飞 | 2006 | 世界核心医学期刊文摘(儿科学分册)2006，2，8： | 4 |
| 4 | Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial显示文摘 | Wendy S Atkin Rob Edwards Ines Kralj-Hans Kate Wooldrage Andrew R Hart John MA Northover D Max Parkin Jane Wardle Stephen W Duffy Jack Cuzick | 2010 | 2010 (9726)2010，，9726： | 3 |
| 5 | Highaccuracy algorithms for computational aeroacoustics 显示文摘 | Lockard D P Brentner K S Atkins H L | 1995 | J AIAA1995，33，： | 2 |
| 6 | Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial显示文摘 | Wendy S Atkin Rob Edwards Ines Kralj-Hans Kate Wooldrage Andrew R Hart John MA Northover D Max Parkin Jane Wardle Stephen W Duffy Jack Cuzick | 2010 | The Lancet . 2010 (9726)2010，，： | 2 |
| 7 | Reducing Hospital Morbidity and Mortality Following Esophagectomy显示文摘 | B.Zane Atkins Ashish S. Shah Kelley A. Hutcheson Jennifer H. Mangum Theodore N. Pappas David H. Harpole Thomas A. D’Amico | 2004 | The Annals of Thoracic Surgery2004，，4： | 2 |
| 8 | Complete genomes of two clinical Staphylococcus aureus strains:evidence for the rapid evolution of virulence and drug resistance显示文摘 | Holden MT Feil EJ Lindsay JA Peacock SJ Day NP Enright MC Foster TJ Moore CE Hurst L Atkin R Barron A Bason N Bentley SD Chillingworth C Chillingworth T Churcher C Clark L Corton C Cronin A Doggett J Dowd L Feltwell T Hance Z Harris B Hauser H Holroyd S Jagels K James KD Lennard N Line A Mayes R Moule S Mungall K Ormond D Quail MA Rabbinowitsch E Rutherford K Sanders M Sharp S Simmonds M Stevens K Whitehead S Barrell BG Spratt BG Parkhill J | 2004 | Proc Natl Acad Sci USA2004，101，26： | 1 |
| 9 | Treatment selection for patients with metastatic renal cell carcinoma显示文摘 | ATKINS MB CHOUEIR1 TK CHO D | 2009 | Cancer2009，115，10： | 1 |
| 10 | A systemic review of treatments for the painful heel 显示文摘 | Atkins D Crawford F Edwards J | 1999 | Rheumatology (Oxford)1999，，38： | 1 |
| 11 | Joint optimization of ma- intenance and inventory policies for a simple system显示文摘 | ARMSTRONG M ATKINS D | 1996 | lie Transactions1996，28，5： | 1 |
| 12 | Protection in animal models of brain and spinal cord injury with mild to moderate hypothermia 显示文摘 | DIETRICH W D ATKINS C M Bramlett H M | 2009 | J Neurotranma2009，26，3： | 1 |
| 13 | Targeting of tumor associated antigens in renal cell carcinoma using proteome-based analysis and their clinical significance显示文摘 | Kellner R Lichtenfels R Atkins D | 2002 | Proteomics2002，2，12： | 1 |
| 14 | The valid use of utility in adaptive real-time systems 显示文摘 | PRASAD D BURNS A ATKINS M | 2003 | Real-Time System2003，25，23： | 1 |
| 15 | Identification of metabolic enzymes in renal cell carcinoma utilizing PROTEOMEX analyses显示文摘 | Lichtenfels R Kellner R Atkins D | 2003 | Biochim Biophys Acta2003，1646，12： | 1 |
| 16 | Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer显示文摘 | ATKINS M REGAN M MCDERMOTT D | 2005 | Clin Cancer Res2005，11，： | 1 |
| 17 | Automated techniques for qualityassurance of radiological image modalities显示文摘 | Goodenough D Atkins F Dyer S | 1911 | Image Capture For-matting and Display1911，1911，5： | 1 |
| 18 | Periodic versus 'can-order' policies for coordinated muki-item inventory systems显示文摘 | Atkins D R Iyogun P O | 1988 | Management Science1988，34，： | 1 |
| 19 | ()besity and gestational diabetes显示文摘 | Sathyapalan T Mellor D Atkin SL | 2010 | Semin Fetal Neonatal Med2010，15，2： | 1 |
| 20 | A systemic review of the treatment of painful heel显示文摘 | Atkins D Crawford F Edward J | | 0，，： | 1 |
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