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| 1 | 美国临床肿瘤学会IV期非小细胞肺癌化疗的临床实践指南更新显示文摘本文旨在为IV期非小细胞肺癌患者的治疗提供更新版推荐。本文资料检索源自2002年以来公布的相关随机试验文献。此指南范围限于化疗与生物治疗。更新委员会对这些文献进行了总结并提供了推荐更新。162篇文献符合标准被纳入参考。本推荐基于可改善总生存期的治疗方法。仅改善无进展生存期的治疗方法推动了对毒性及生存质量的监测。对于体力状态评分为0分或1分患者的一线治疗,可推荐以铂类为基础的细胞毒性药物的两药联用。对铂类治疗有禁忌的患者,可采用非铂类细胞毒性两药联合。对于体力状态评分为2分的患者,单一细胞毒性药物即可。对于疾病进展或经过4个周期的治疗仍对治疗无反应的患者,应停止一线细胞毒性化疗。即使在6个周期后患者对治疗仍有反应,亦应停止两药细胞毒性化疗。对于伴有明确的表皮生长因子受体(epidermal growth factor receptor,EGFR)突变的患者,可推荐一线采用吉非替尼治疗;对于EGFR突变为阴性或不明确的患者,细胞毒性化疗更佳。除具有特定临床特征的患者外,可推荐贝伐单抗与卡铂-紫杉醇联用。对于通过免疫组化证实EGFR阳性的肿瘤患者,可推荐西妥昔单抗与顺铂-长春瑞滨联用。多西紫杉醇、厄洛替尼、吉非替尼或培美曲塞被推荐作为二线治疗。对于未曾接受过厄洛替尼或吉非替尼治疗的患者,可推荐厄洛替尼作为三线治疗。现有数据不足以推荐常规三线采用细胞毒性药物。已有的证据也不足以推荐常规应用分子标记物选择化疗。 | Christopher G. AZZOLI Sherman Baker JR Sarah TEMIN William PAO Timothy ALIFF Julie BRAHMER David H. JOHNSON Janessa L. LASKIN Gregory MASTERS Daniel MILTON Luke NORDQUIST David G. PFISTER Steven PIANTADOSI Joan H. SCHILLER Reily SMITH Thomas J. SMITH John R. STRAWN David TRENT Giuseppe GIACCONE 丁燕(翻译) 南娟(翻译) 刘谦(翻译) 周清华(校对) 陈军(校对) | 2010 | 中国肺癌杂志2010，13，3： | 43 |
| 2 | 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 |
| 3 | The favorable impact of PIK3CA mutations on survival: an analysis of 2587 patients with breast cancer显示文摘The phosphatidylinositol-3 kinase(PI3K) pathway regulates a number of cellular processes, including cell survival, cell growth, and cell cycle progression. Consequently, this pathway is commonly deregulated in cancer. In particular, mutations in the gene PIK3CA that encodes the p110α catalytic subunit of the PI3K enzymes result in cell proliferation and resistance to apoptosis in vitro and induce breast tumors in transgenic mice. These data underscore the role of this pathway during oncogenesis. Thus, an ongoing, large-scale effort is underway to develop clinically active drugs that target elements of the PI3K pathway. However, conflicting data suggest that gain-of-function PIK3CA mutations may be associated with either a favorable or a poor clinical outcome, compared with the wild-type PIK3CA gene. In the current study, we performed a systematic review of breast cancer clinical studies. Upon evaluation of 2587 breast cancer cases from 12 independent studies, we showed that patients with tumors harboring a PIK3CA mutation have a better clinical outcome than those with a wild-type PIK3CA gene. Importantly, this improved prognosis may pertain only to patients with mutations in the kinase domain of p110α and to postmenopausal women with estrogen receptor-positive breast cancer. We propose three potential explanations for this paradoxical observation. First, PIK3CA mutations may interfere with the metastasis process or may induce senescence, which results in a better outcome for patients with mutated tumors. Secondly, we speculate that PIK3CA mutations may increase early tumor diagnosis by modification of the actin cytoskeleton in tumor cells. Lastly, we propose that PIK3CA mutations may be a favorable predictive factor for response to hormonal therapy, giving a therapeutic advantage to these patients. Ultimately, an improved understanding of the clinical impact of PIK3CA mutations is critical for the development of optimally personalized therapeutics against breast cancer and other solid tumors. This effort will be important to prevent or explain therapeutic failures and select patients who are most likely to respond to new therapies that inhibit the PI3K pathway. | Amaury G. Dumont Sarah N.Dumont Jonathan C. Trent | 2012 | Chinese Journal of Cancer2012，31，7： | 5 |
| 4 | Mesh theory of angle modified dual tori double-enveloping toroidal worm drive显示文摘In this paper, the meshing theory of the angle modified hourglass worm drive is enriched and developed. The ordinary condition of the angle modification is derived and the physical significance of the modification is interpreted. A normal section methodology is proposed for meshing analysis, which can be used to compute the normal distance near a singular meshing point of a conjugate surface couple. By means of the method and after analyzing the normal transversals, it is specified that the worm helicoid, the nominal former contact zone and the new contact zone intersect each other along the locus of singular points of the instantaneous contact lines of an angle-modified worm pair. As a result, it is explained clearly that those three osculate each other but the osculations are different in degree. Moreover, the mechanism of removing the twice-contacted zone from the worm gear tooth surface is clarified and the reason of shortening the worm working length is also elucidated. With the help of the theory described in the present paper and the thorough and systematic research on the relevant meshing characteristics, the angle modified dual tori double-enveloping toroidal worm drive has been shown to be an excellent new-fashioned hourglass worm set. | ZHAO YaPing1, SU DaiZhong2, ZHANG Zhao1, WEI WenJun3 & DONG XueZhu3 1 College of Machinery and Automation, Wuhan University of Science and Technology, Wuhan 430081, China 2 Advanced Design and Manufacturing Engineering Center, Nottingham Trent University, Nottingham NG1 4BU, UK 3 College of Engineering, China Agricultural University, Beijing 100083, China | 2010 | Science China(Technological Sciences)2010，53，7： | 4 |
| 5 | The P132H mutation in the main protease of Omicron SARSCoV-2 decreases thermal stability without compromising catalysis or small-molecule drug inhibition显示文摘Dear Editor,The ongoing SARS-CoV-2 pandemic continues to be a significant threat to global health.First reported in November 2021,the Omicron variant(B.1.1.529)is more transmissible and can evade immunity better than previous SARS-CoV-2 variants,fueling an unprecedented surge in cases.To produce functional proteins from its polyprotein,SARS-CoV-2 relies on the cysteine proteases Nsp3/papain-like protease(PLpro)and Nsp5/main protease(Mpro)/3C-like protease to cleave at three and more than 11 sites,respectively.1 Therefore,Mpro and PLpro inhibitors are considered to be one of the most promising SARS-CoV-2 antivirals.On December 22,2021,the Food and Drug Administration(FDA)issued an Emergency Use Authorization(EUA)for PAXLOVID,a ritonavir-boosted formulation of nirmatrelvir.Nirmatrelvir is a first-in-class orally bioavailable SARSCoV-2 Mpro inhibitor.2 Thus,the scientific community must vigilantly monitor potential mechanisms of drug resistance,especially because SARS-CoV-2 is naïve to Mpro inhibitors.Mutations have been well identified in variants to this point.3 Notably,Omicron Mpro(OMpro)harbors a single mutation—P132H.In this study,we characterized the enzymatic activity,drug inhibition,and structure of OMpro while evaluating the past and future implications of Mpro mutations. | Michael Dominic Sacco Yanmei Hu Maura Verenice Gongora Flora Meilleur Michael Trent Kemp Xiujun Zhang Jun Wang Yu Chen | 2022 | Cell Research2022，32，5： | 3 |
| 6 | An analysis of F-doping in Li-rich cathodes显示文摘Li-rich materials,due to their high capacity(>250 mAh·g^(-1)),have recently been considered as an alternative to the current generation of cathode materials for Li-ion batteries(LIBs).However,their inferior cycling stability limits their practical applicability.Doping is a common technique to solve this problem.However,anion doping remains relatively underexplored.Fluorine(F)is one of the most effective anion dopants owning to the improved capacity,cycling stability,and rate performance in batteries.The explanations and experimental results,however,vary significantly from study to study.Herein,we find that bulk F-doping significantly improves both rate performance and cycling stability,likely driven by charge compensation and greater electronegativity.Additionally,bulk F-doping occasionally improves capacity via enhanced activation and occasionally decreases capacity by preventing activation from occurring.Surface F-doping has similar effects to bulk F-doping on capacity and stability,while significantly hindering the rate performance.Furthermore,the improvements in surface-doped materials do not appear to be a result of specific surface modification,and instead can be ascribed to the effect of fluorine on the near-surface bulk material.Greater understanding of fluo-rine's influence on activation,in particular,is required to unlock the full potential of synergistic cation/anion co-doping. | Trent Seaby Tong-En Lin Yu-Xiang Hu Qing-Hong Yuan Lian-Zhou Wang | 2022 | Rare Metals2022，41，6： | 2 |
| 7 | 平滑肌肉瘤中PRUNE2mRNA的表达及其与非编码RNAPCA3的一致性关系显示文摘目的 探讨平滑肌肉瘤中PRUNE2mRNA的表达及其与非编码RNAPCA3的关系。方法采用安捷伦基凶表达芯片的方法检测31例平滑肌肉瘤和42例胃肠间质瘤中PRUNE2mRNA的表达水平,分析其表达与平滑肌肉瘤患者的预后关系;采用实时荧光定量聚合酶链反应的方法分析13例平滑肌肉瘤中PCA3mRNA和PRUNE2mRNA的表达水平并分析二者间的关系。7例前列腺癌组织作为PCA3mRNA表达的阳性对照。结果在31例平滑肌肉瘤中,PRUNE2mRNA的平均表达水平为368.43±29.67,高于37例胃肠间质瘤(82.56±7.45)和7例前列腺癌(4.76±0.98,均P〈0.05)。PRUNE2mRNA高表达的平滑肌肉瘤患者的生存期与低表达者比较,差异无统计学意义(X2=0.96,P=0.326)。PRUNE2mRNA高表达的胃肠间质瘤患者的生存期与低表达者比较,差异无统计学意义(X2=3.10,P=0.078)。平滑肌肉瘤中PcA3mRNA平均表达水平为26.38±3.04,低于前列腺癌(3272.00±240.87,P=0.004)。在平滑肌肉瘤中,PCA3mRNA与PRUNE2mRNA的表达呈正相关(r=0.901,P〈0.001)。结论PRUNE2的表达与平滑肌肉瘤患者的生存期有关,PCA3的表达与PRUNE2mRNA的表达呈正相关。 | 杨吉龙 David Cogdell James Eddy Jonathan Trent Nathan Price ZHANG Wei | 2012 | 中华肿瘤杂志2012，34，7： | 2 |
| 8 | Cause-related marketing How generation Y responds 显示文摘 | Cui Yanli Trent Elizabeth S Sullivan Pauline M Matiru Grace N | 2003 | International Journal of Retail & Distribution Management2003，31，67： | 1 |
| 9 | Molecular evolution and phylogeny of dengue 4 viruses 显示文摘 | Lanciotti RS Gubler DJ Trent DW | 1997 | J Gen Virol1997，78，： | 1 |
| 10 | Infectious Japanese encephalitis vires RNA can be synthesized from in vitro-ligated cDNA templates显示文摘 | Sumiyoshi H Hoke C Trent D W | 1992 | J Virol1992，66，9： | 1 |
| 11 | Adverse adolescent reproductive health outcomes after pelvic inflammatory disease 显示文摘 | Trent M Haggerty CL Jennings JM | 2011 | Arch Pediatr Adolesc Med2011，165，1： | 1 |
| 12 | Expression profiling using cDNA microarrays显示文摘 | Duggan D J Bittner M Chen Y D Meltzer P Trent J M | 1999 | Nature Genetics1999，21，： | 1 |
| 13 | Infectious Japanese encephalitis virus RNA can be synthesized from in vitro-ligated cDNA templates 显示文摘 | Sumiyoshi H Hoke C Trent D W | 1992 | Journal of Virology1992，66，： | 1 |
| 14 | Diversity of endotoxin and its impact on pathogenesis显示文摘 | Trent MS Stead CM Tran AX | 2006 | J Endotoxin Res2006，12，4： | 1 |
| 15 | LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models显示文摘 | S. Betty Yan Victoria L. Peek Rose Ajamie Sean G. Buchanan Jeremy R. Graff Steven A. Heidler Yu-Hua Hui Karen L. Huss Bruce W. Konicek Jason R. Manro Chuan Shih Julie A. Stewart Trent R. Stewart Stephanie L. Stout Mark T. Uhlik Suzane L. Um Yong Wang Wenj | 2013 | Investigational New Drugs2013，，4： | 1 |
| 16 | Comparative properties of five human ovarian adenocarcinoma cell lines显示文摘 | Buick RN Pullano R Trent JM | 1985 | Cancer Res1985，45，： | 1 |
| 17 | Ultrapulse CO2 used for the successful treatment of basal cell carcinomas found in patients with basal cell nevus syndrome显示文摘 | Nouri K Chang A Trent JT | 2002 | Dermatol Surg2002，28，3： | 1 |
| 18 | Managing GIST in the ima- tinib era: optimization of adjuvant therapy显示文摘 | Trent JC Subramanian MP | 2014 | Exp Rev Ant Ther2014，14，12： | 1 |
| 19 | Evolving sourcing strategies for the 1990s显示文摘 | Monczka R M Trent R J | 1991 | International Journal of Physical Distribution and Logistics Management1991，21，5： | 1 |
| 20 | Traditional and novel approaches to flavivirus vaccines显示文摘 | Pugachev KV Guirakhoo F Trent DW et al | 2003 | Int J Parasitol2003，33，56： | 1 |
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