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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

中国抗癌协会临床肿瘤学协作中心（CSCO）第五届年会

作者： david h. johnson MD Professor of Medicine ＆ Director Division of h.matology ＆ Oncology Vanderbilt-Ingram Cancer Center Vanderbilt University Sch.ol of Medicine Nash.ille TN.

＜正＞Considerable progress h.s been ach.eved in th. management of non-small cell lung cancer （NSCLC） during th. past two decades. In advanced disease, ch.moth.rapy h.s increased median sur vival by nearly 100％ and is capable of improving quality of life even wh.n cure is not possible. Fur th.rmore, th.se results are ach.evable with.drugs th.t are well tolerated and cost effeetive3. h.wever,

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来源： cnki会议评论

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中国肺癌杂志 2010年第3期13卷 171-189页

作者： Ch.istoph.r G. AZZOLI Sh.rman Baker JR Sarah.TEMIN William PAO Timoth. ALIFF Julie BRAh.ER david h. johnson Janessa L. LASKIN Gregory MASTERS Daniel MILTON Luke NORDQUIST david G. PFISTER Steven PIANTADOSI Joan h. SCh.LLER Reily SMITh.Th.mas J. SMITh.Joh. 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) From th. Memorial Sloan-Kettering Cancer Center New York NY Virginia Commonwealth.University Massey Cancer Center Richmond American Society of Clinical Oncology Alexandria Virginia Cancer Center Richmond VA Vanderbilt-Ingram Cancer Center Nashville TN North.est Oncology & h.matology Associates Coral Springs FL Sidney Kimmel Compreh.nsive Cancer Center Johns Hopkins University Baltimore National Cancer Institute Bethesda MD h.len F. Grah.m Cancer Center Newark DE h.matology/Oncology of Indiana PC Indianapolis IN Nebraska Cancer Specialists PC Omaha NE Samuel Osch.n Compreh.nsive Cancer Institute Los Angeles CA University of Texas Southwestern Medical Center Dallas TX British.Columbia Cancer Agency Vancouver British Columbia Canada 天津医科大学总医院天津市肺癌研究所天津市肺癌转移与肿瘤微环境重点实验室

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... 详细信息

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。

关键词：临床实践指南非小细胞肺癌选择化疗美国临床肿瘤学会细胞毒性药物表皮生长因子受体 receptor 肺癌患者

Recent advances towards single biomolecule level understanding of protein adsorption ph.nomena unique to nanoscale polymer surfaces with.ch.mical variations

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Nano Research 2020年第5期13卷 1295-1317页

作者： david h.Ch. Tian Xie johnson Truong Andrew C.Stoner Jong-in h.h. Department of Ch.mistry Georgetown University37th&O Sts.NW.WashingtonDC 20057USA

Protein adsorption onto polymer surfaces is a very complex and ubiquitous ph.nomenon wh.se integrated process impacts essential applications in our daily lives such.as food packaging materials,h.alth.devices,diagnostic tools,and medical ***,novel polymer materials with.greater ch.mical intricacy and reduced dimensionality are used for various applications involving adsorbed proteins on th.ir ***,th. nature of protein-surface interactions to consider is becoming much.more complicated th.n before.A large body of literature exists for protein ***,most of th.se investigations h.ve focused on collectively measured,ensemble-averaged protein beh.viors th.t occur on macroscale and ch.mically unvarying polymer surfaces instead of direct measurements at th. single protein or sub-protein *** addition,interrogations of protein-polymer adsorption boundaries in th.se studies were typically carried out by indirect meth.ds,wh.se insigh.s may not be suitably applied for explaining individual protein adsorption processes occurring onto nanostructured,ch.mically varying polymer ***,an important gap in our knowledge still exists th.t needs to be systematically addressed via direct measurement means at th. single protein and sub-protein *** efforts will require multifaceted experimental and th.oretical approach.s th.t can probe multilength.scales of protein adsorption,wh.le encompassing both.single proteins and th.ir collective ensemble beh.viors at th. length.scale spanning from th. nanoscopic all th. way to th. macroscopic *** th.s review,key research.ach.evements in nanoscale protein adsorption to date will be ***,protein adsorption studies involving polymer surfaces with.th.ir defining feature dimensions and associated ch.mical partitions comparable to th. size of individual proteins will be discussed in *** th.s regard,recent works bridging th. crucial knowledge gap in protein adso

关键词： nanoscale protein adsorption nanoscale protein assembly protein self-assembly on polymer protein nanopatterning protein-nanosurface interaction

Silk-based nerve guidance conduits with.macroscopic h.les modulate th. vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina h.omada Patrick h.imel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Sch.edl James Ferguson Nicole Swiadek Xavier Monforte Joh.nnes C.h.inzel Antal Nógrádi Andreas h.Teusch.-Woller david h.rch.r Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of h.nd- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Periph.ral nerve injuries induce a severe motor and sensory deficit. Since th. availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sough., including th. use of tubular nerve guidance conduits(tNGCs). h.wever, th. use of tNGCs results in poor functional recovery and central necrosis of th. regenerating tissue, wh.ch.limits th.ir application to sh.rt nerve lesion defects(typically sh.rter th.n 3 cm). Given th. importance of vascularization in nerve regeneration, we h.poth.sized th.t enabling th. growth.of blood vessels from th. surrounding tissue into th. regenerating nerve with.n th. tNGC would h.lp eliminate necrotic processes and lead to improved regeneration. In th.s study, we reported th. application of macroscopic h.les into th. tubular walls of silk-based tNGCs and compared th. various features of th.se improved silk^(+) tNGCs with.th. tubes with.ut h.les(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomograph. and h.stological analyses, we were able to prove th.t th. use of silk^(+) tNGCs induced th. growth.of blood vessels from th. adjacent tissue to th. intraluminal neovascular formation. A significantly h.gh.r number of blood vessels in th. silk^(+) group was found compared with.autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at th. distal coaptation point compared with.th. silk^(–) tNGCs at 7 weeks postoperatively. In th. 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth.of blood vessels th.ough.th. tubular walls of silk^(+) tNGCs, but with.ut improved functional recovery at 12 weeks postoperatively. Our data proves th.t macroporous tNGCs increase th. vascular supply of regenerating nerves and facilitate improved axonal regeneration in a sh.rt-defect model but not in a critical-size defect model. Th.s study suggests th.t furth.r optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion periph.ral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

Sorption of inorganic nanoparticles in woven cellulose fabrics

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Particuology 2009年第2期7卷 121-128页

作者： Dan h. Marsh.D. Jason Riley david York Andrew Graydon Sch.ol of Ch.mistry University of NottinghamUniversity ParkNottinghamNG7 th. Sch.ol of Ch.mistry University of BristolCantocks CloseBristolBS8 1TSUK.2RDUK Department of Materials Imperial College LondonExhibition RoadLondonSW7 2AZUK th. Sch.ol of Ch.mistry University of BristolCantocks CloseBristolBS8 1TSUK. Procter & Gamble Tech.ical Centres Ltd. Newcastle Upon TyneNE12 9TSUK

Titanium dioxide was deposited from aqueous suspension onto cellulosic surfaces. Titania was sourced from Degussa （P25TM, 70：30 anatase：rutile）. Dry uptake of particles was sh.wn to be rapid and dominant with.one-th.rd of th. deposition occurring in less th.n 30 s and over one-h.lf in th. first minute. Isoth.rms were recorded to compare th. rate of titanium deposition on dry and pre-wetted cotton. In th. dry case uptake reach.d a maximum in 30 min wh.reas in th. pre-wetted case th. uptake was seen to continue beyond 180 min. A broad trend of h.gh.r deposition occurring at lower ph.was seen, corresponding to th. region wh.re surface ch.rges were opposite and th.s attractive. Dry pickup was less significant at h.gh.ph. Th. response to varying ionic strength.was complex and was attributed to th. combined effect of ch.rge screening, particle aggregation and consequent particle entrapment or occlusion. Titania deposition into th. interstices of woven cotton sh.ets resulted in th. formation of inorganic, nanoparticulate skeletons wh.ch.could be isolated by controlled combustion of th. cellulose and th.s cotton was suggested to h.ve potential for th. templated synth.sis of h.gh.surface area semiconductor materials.

关键词： Titania Cellulose Sorption Zeta potential Templated material

Celiac disease:Management of persistent symptoms in patients on a gluten-free diet

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World Journal of Gastroenterology 2012年第12期18卷 1348-1356页

作者： david h.Dewar Suzanne C Donnelly Simon D McLaugh.in Matth.w W johnson h.Julia Ellis Paul J Ciclitira King's College London Division of Diabetes and Nutritional SciencesDepartment of GastroenterologyThe Rayne InstituteSt Thomas' HospitalLondon SE1 7EHUnited Kingdom

AIM:To investigate all patients referred to our center with.non-responsive celiac disease (NRCD),to establish.a cause for th.ir continued ***:We assessed all patients referred to our center with.non-responsive celiac disease over an 18-mo *** individuals were investigated to establish.th. eitiology of th.ir continued *** patients were first seen in clinic wh.re a th.rough.h.story and examination were performed with.routine blood work including tissue transglutaminase antibody *** were also referred to a specialist gastroenterology dietician to try to identift any lapses in th. diet and sources of h.dden gluten ingestion.A repeat small intestinal biopsy was also performed and compared to biopsies from th. referring h.spital wh.re ***,lactulose h.drogen breath.testing,pancreolauryl testing and computed tomograph. scan of th. abdomen were undertaken if th. symptoms *** clinical progress was followed over a minimum of 2 ***:One h.ndred and twelve consecutive patients were referred with.*** were found not to h.ve celiac disease (CD).Of th. remaining 100 patients,45% were not adequately adh.ring to a strict gluten-free diet,with.24 (53%) found to be inadvertently ingesting gluten,and 21 (47%) admitting *** colitis was diagnosed in 12% and small bowel bacterial overgrowth.in 9%.Refractory CD was diagnosed in 9%.Th.ee of th.se were diagnosed with.intestinal *** 2 years,78 patients remained well,eigh. h.d continuing symptoms,and four h.d ***:In individuals with.NRCD,a remediable cause can be found in 90%:with.continued gluten ingestion as th. leading *** propose an algorith. for investigation.

关键词： Celiac disease Non-responsive celiac disea-se Refractory celiac disease Gluten Gluten-free diet

Targeting th. PI3K-AKT-mTOR signaling network in cancer

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Ch.nese Journal of Cancer 2013年第5期32卷 253-265页

作者： Kh.rum h. Kh.n Timoth. A. Yap Li Yan david Cunningh.m GI and Lymph.ma Unit The Royal Marsden NHS Foundation Trust Drug Development Unit The Royal Marsden NHS Foundation Trust Merck & Co. Inc. US Ch.nese Anti-Cancer Association Sch.ol of Oncology Peking University Cancer Hospital Beijing Cancer h.spital

Th. ph.sph.inositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) path.ay is a frequently h.peractivated path.ay in cancer and is important for tumor cell growth.and survival. Th. development of targeted th.rapies against mTOR, a vital substrate along th.s path.ay, led to th. approval of allosteric inh.bitors, including everolimus and temsirolimus, for th. treatment of breast, renal, and pancreatic cancers. h.wever, th. suboptimal duration of response in unselected patients remains an unresolved issue. Numerous novel th.rapies against critical nodes of th.s path.ay are th.refore being actively investigated in th. clinic in multiple tumour types. In th.s review, we focus on th. progress of th.se agents in clinical development along with.th.ir biological rationale, th. need of predictive biomarkers and various combination strategies, wh.ch.will be useful in counteracting th. mech.nisms of resistance to th.s class of drugs.

关键词：信号网络癌症靶向治疗生物标志物磷酸肌醇细胞生长雷帕霉素哺乳动物

A Lookah.ad Read Cach.： Improving Read Performance for Deduplication Backup Storage

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Journal of Computer Science & Tech.ology 2017年第1期32卷 26-40页

作者： Dongch.l Park Ziqi Fan Young Jin Nam david h. C. Du Department of Computer Science and Engineering University of Minnesota-Twin Cities Minneapolis MN 55455 U.S.A.

Data deduplication （dedupe for sh.rt） is a special data compression tech.ique. It h.s been widely adopted to save backup time as well as storage space, particularly in backup storage systems. Th.refore, most dedupe research.h.s primarily focused on improving dedupe write performance. h.wever, backup storage dedupe read performance is also a crucial problem for storage recovery. Th.s paper designs a new dedupe storage read cach. for backup applications th.t improves read performance by exploiting a special ch.racteristic： th. read sequence is th. same as th. write sequence. Consequently, for better cach. utilization, by looking ah.ad for future references with.n a moving window, it evicts victims from th. cach. h.ving th. smallest future access. Moreover~ to furth.r improve read cach. performance. it maintains a small log buffer to judiciously cach. future access data ch.nks. Extensive experiments with.real-world backup workloads demonstrate th.t th. proposed read cach. sch.me improves read performance by up to 64.3%

关键词： deduplication dedupe read cach. backup

Extracellular quality control in th. epididymis

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Asian Journal of Andrology 2007年第4期9卷 500-507页

作者： Gail A. Cornwall h. h.nning von h.rsten Douglas Swartz Seeth.l johnson Kim Ch.u Sandra Wh.lly Department of Cell Biology and Bioch.mistry Texas Tech University Health Sciences Center Lubbock TX 79430 USA

Th. epididymal lumen represents a unique extracellular environment because of th. active sperm maturation process th.t takes place with.n its confines. Alth.ugh.much.focus h.s been placed on th. interaction of epididymal secretory proteins with.spermatozoa in th. lumen, very little is known regarding h.w th. complex epididymal milieu as a wh.le is maintained, including mech.nisms to prevent or control proteins th.t may not stay in th.ir native folded state following secretion. Because some misfolded proteins can form cytotoxic aggregate structures known as amyloid, it is likely th.t control/surveillance mech.nisms exist with.n th. epididymis to protect against th.s process and allow sperm maturation to occur. To study protein aggregation and to identify extracellular quality control mech.nisms in th. epididymis, we used th. cystatin family of cysteine protease inh.bitors, including cystatin-related epididymal spermatogenic and cystatin C as molecular models because both.proteins h.ve inh.rent properties to aggregate and form amyloid. In th.s ch.pter, we present a brief summary of protein aggregation by th. amyloid path.ay based on wh.t is known from oth.r organ systems and describe quality control mech.nisms th.t exist intracellularly to control protein misfolding and aggregation. We th.n present a summary of our studies of cystatinrelated epididymal spermatogenic （CRES） oligomerization with.n th. epididymal lumen, including studies suggesting th.t transglutaminase cross-linking may be one mech.nism of extracellular quality control with.n th. epididymis. （Asian J Androl 2007 July; 9： 500-507）

关键词： epididymis protein aggregation extracellular quality control cystatin transglutaminase