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| 1 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 2 | The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORCl显示文摘 | Carsten Gram Hansen Yuen Lam Dora Ng Wai-Ling Macrina Lam Steven W Plouffe Kun-Liang Guan | 2015 | Cell Research2015，25，12： | 19 |
| 3 | Gastroenteropancreatic neuroendocrine tumours显示文摘 | Irvin M Modlin Kjell Oberg Daniel C Chung Robert T Jensen Wouter W de Herder Rajesh V Thakker Martyn Caplin Gianfranco Delle Fave Greg A Kaltsas Eric P Krenning Steven F Moss Ola Nilsson Guido Rindi Ramon Salazar Philippe Ruszniewski Anders Sundin | 2008 | Lancet Oncology2008，，1： | 8 |
| 4 | Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-1igase signaling effector DWARF3显示文摘 | Li-Hua Zhao X Edward Zhou Wei Yi Zhongshan Wu Yue Liu Yanyong Kang Li Hou Parker W de Waal Suling Li Yi Jiang Adrian Scaffidi Gavin R Flematti Steven M Smith Vinh Q Lam Patrick R Griffin YonghongWang Jiayang Li Karsten Melcher H Eric Xu | 2015 | Cell Research2015，25，11： | 7 |
| 5 | Non-genetic contributions of the sperm nucleus to embryonic development显示文摘从几个实验室的最近的数据提供了最新使肥沃的卵母细胞从为合适的胚胎的开发被要求的精子染色质继承 epigenetic 信号的证据。为这评论的目的,术语 epigenetic 被用来描述从精子房间被传给胚胎的分子的信息的所有类型。当在哺乳动物或为为哪个有证据,它可以那么做为合适的 embryogenesis 被要求,有已经被建立了的 epigenetic 信息的至少六种不同形式。这些是(i) DNA methylation;(ii ) 精子特定的 histones,(iii ) 另外的联系染色质的蛋白质;(iv ) perinuclear 膜蛋白质;(v) 精子出生的 RNA 并且,这评论的焦点;并且(vi ) 由精子的 DNA 环领域组织原子矩阵。当为有效授精和随后的胚胎开发作为必要部件为帮助繁殖技术为精子的操作和 cryopreservation 设计协议时,这些 epigenetic 信号应该被考虑。 | Yasuhiro Yamauchi Jeffrey A Shaman W Steven Ward | 2011 | Asian Journal of Andrology2011，13，1： | 6 |
| 6 | Magnetic resonance imaging and multi-detector computed tomography assessment of extracellular compartment in ischemic and non-ischemic myocardial pathologies显示文摘Myocardial pathologies are major causes of morbidity and mortality worldwide. Early detection of loss of cellular integrity and expansion in extracellular volume(ECV) in myocardium is critical to initiate effective treatment. The three compartments in healthy myocardium are: intravascular(approximately 10% of tissue volume), interstitium(approximately 15%) and intracellular(approximately 75%). Myocardial cells, fibroblasts and vascular endothelial/smooth muscle cells represent intracellular compartment and the main proteins in the interstitium are types Ⅰ/Ⅲ collagens. Microscopic studies have shown that expansion of ECV is an important feature of diffuse physiologic fibrosis(e.g., aging and obesity) and pathologic fibrosis [heart failure, aortic valve disease, hypertrophic cardiomyopathy, myocarditis, dilated cardiomyopathy, amyloidosis, congenital heart disease, aortic stenosis, restrictive cardiomyopathy(hypereosinophilic and idiopathic types), arrythmogenic right ventricular dysplasia and hypertension]. This review addresses recent advances in measuring of ECV in ischemic and non-ischemic myocardial pathologies. Magnetic resonance imaging(MRI) has the ability to characterize tissue proton relaxation times(T1, T2, and T2*). Proton relaxation times reflect the physical and chemical environments of water protons in myocardium. Delayed contrast enhanced-MRI(DE-MRI) and multi-detector computed tomography(DE-MDCT) demonstrated hyper-enhanced infarct, hypo-enhanced microvascular obstruction zone and moderately enhanced peri-infarct zone, but are limited for visualizing diffuse fibrosis and patchy microinfarct despite the increase in ECV. ECV can be measured on equilibrium contrast enhanced MRI/MDCT and MRI longitudinal relaxation time mapping. Equilibrium contrast enhanced MRI/MDCT and MRI T1 mapping is currently used, but at a lower scale, as an alternative to invasive sub-endomyocardial biopsies to eliminate the need for anesthesia, coronary catheterization and possibility of tissue sampling error. Similar to delayed contrast enhancement, equilibrium contrast enhanced MRI/MDCT and T1 mapping is completely noninvasive and may play a specialized role in diagnosis of subclinical and other myocardial pathologies. DE-MRI and when T1-mapping demonstrated sub-epicardium, sub-endocardial and patchy mid-myocardial enhancement in myocarditis, Behcet's disease and sarcoidosis, respectively. Furthermore, recent studies showed that the combined technique of cine, T2-weighted and DE-MRI technique has high diagnostic accuracy for detecting myocarditis. When the tomographic techniques are coupled with myocardial perfusion and left ventricular function they can provide valuable information on the progression of myocardial pathologies and effectiveness of new therapies. | Maythem Saeed Steven W Hetts Robert Jablonowski Mark W Wilson | 2014 | World Journal of Cardiology2014，6，11： | 4 |
| 7 | 生物素——抗结核药物新研究方向(英文)显示文摘耐药菌的出现对全球公共卫生构成了巨大的挑战,结核分枝杆菌(TB)是结核病的病原菌,是临床上最重要的病原体之一。新抗生素的研发用以治疗耐药性结核病已成为临床及公共卫生管理亟待解决的重要问题。生物素(维生素B7)在结核杆菌的代谢途径如脂肪酸合成和三羧酸循环中发挥重要作用,通过生物素蛋白连接酶连接活性辅助因子而被激活。生物素蛋白连接酶及其相关生物合成通路是微生物合成生物素过程中必不可或缺的关键分子,因而有可能成为新的药物靶点。遗传研究表明,结核杆菌需要由菌体进行生物素的全程合成,因此,生物素合成酶在在结核杆菌代谢过程中起着至关重要的作用,引起了抗结核药物研究者的高度重视。本文论述了结核杆菌生物素合成通路,并重点分析了生物素合成过程中可能成为药物靶点的关键酶,旨在为结核病的治疗提供新思路,具有重要的临床意义。 | THOMPSON Andrew P STERNICKI Louise M WEGENER Kate L 陆伟 竺丽梅 BOOKER Grant W POLYAK Steven W 李燕 | 2016 | 江苏预防医学2016，27，3： | 4 |
| 8 | Cholangiocarcinoma, gone without the Wnt?显示文摘Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy. | Anne T R Noll Thorsten Cramer Steven W M Olde Damink Frank G Schaap | 2016 | World Journal of Hepatology2016，8，26： | 3 |
| 9 | Association of types of diabetes and insulin dependency on birth outcomes显示文摘BACKGROUND Diabetes rates among pregnant women in the United States have been increasing and are associated with adverse pregnancy outcomes.AIM To investigate differences in birth outcomes(preterm birth,macrosomia,and neonatal death)by diabetes status.METHODS Cross-sectional design,using linked Missouri birth and death certificates(singleton births only),2010 to 2012(n=204057).Exposure was diabetes non-diabetic,pre-pregnancy diabetes-insulin dependent(PD-I),pre-pregnancy diabetes-non-insulin dependent(PD-NI),gestational diabetes-insulin dependent(GD-I),and gestational diabetes-non-insulin dependent(GD-NI).Outcomes included preterm birth,macrosomia,and infant mortality.Confounders included demographic characteristics,adequacy of prenatal care,body mass index,smoking,hypertension,and previous preterm birth.Bivariate and multivariate logistic regression assessed differences in outcomes by diabetes status.RESULTS Women with PD-I,PD-NI,and GD-I remained at a significantly increased odds for preterm birth(aOR 2.87,aOR 1.77,and aOR 1.73,respectively)and having a very large baby[macrosomia](aOR 3.01,aOR 2.12,and aOR 1.96,respectively);in reference to non-diabetic women.Women with GDNI were at a significantly increased risk for macrosomia(aOR1.53),decreased risk for their baby to die before their first birthday(aOR 0.41)and no difference in risk for preterm birth in reference to non-diabetic women.CONCLUSION Diabetes is associated with the poor birth outcomes.Clinical management of diabetes during pregnancy and healthy lifestyle behaviors before pregnancy can reduce the risk for diabetes and poor birth outcomes. | Pamela K Xaverius Steven W Howard Deborah Kiel Jerry E Thurman Ethan Wankum Catherine Carter Clairy Fang Romi Carriere | 2022 | World Journal of Clinical Cases2022，10，7： | 2 |
| 10 | 颈部疼痛的诊断和管理进展显示文摘颈部疼痛带来了相当大的个人和社会经济负担——它是患病率和伤残所致生命年损失前五位的慢性疼痛疾病之一——但是仅获得了背部疼痛研究的一小部分经费。尽管大多数颈部疼痛急性发作后自行消退,但有超过三分之一的患者群在一年多以后仍有轻度症状或疼痛复发,遗传和社会心理因素是症状持续存在的危险因素。将近一半的慢性颈部疼痛患者具有神经性一损伤反应性混合症状或主要为神经性症状。很少有临床研究专门针对颈部疼痛,、肌肉松弛剂和非甾体类抗炙药对急性颈部疼痛有效,临床实践主要依据其他慢性疼痛的研究结果。补充和替代疗法中,证据级别最强的就是运动,稍弱证据支持不同状况下进行按摩、针灸、瑜伽和脊椎推拿。对于神经根型颈椎病和小关节病,弱证据分别支持硬膜外类固醇注射和射频去神经支配治疗。对于大部分患者,手术在短期内比保守治疗更有效,但长期效果相似,手术前进行临床观察是一种合理策略. | Steven P Cohen W Michael Hooten 公磊 | 2018 | 英国医学杂志中文版2018，21，3： | 2 |
| 11 | Diabetic Retinopathy显示文摘 | Thomas W Gardner David A Antonetti Alistair J Barber Kathryn F LaNoue Steven W Levison | 2002 | Survey of Ophthalmology2002，，： | 2 |
| 12 | Optimal placement depth for aft-ground heat transfer systems 显示文摘 | James W Stevens | 2004 | Applied Thermal Engineering2004，24，： | 1 |
| 13 | The Impact of High Performance Level Outcomes显示文摘 | STEVEN M SOMMER | 2005 | Journal of Managerial Issues2005，17，3： | 1 |
| 14 | Electric Vehicles as a New Source of Power for Electric Utilities 显示文摘 | Kempton W Steven L | 1997 | Transportation Research1997，2，3： | 1 |
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| 16 | Optimal design of small T thermoelectricgeneration systems显示文摘 | Stevens J W | 2001 | Energy Conversion and Man-agement2001，42，： | 1 |
| 17 | Essentially solvent-independent rates of solvolysis of the 1-adamantyl dimethylsulfonium ion, Implications regarding nucleeophilic assistance in solvolyses of tert-butyl derivatives and the NKL sulvent nucleophilicity scale显示文摘 | Dennis N Kevill Steven W Anderson | 1986 | J Am Chem Soc1986，108，： | 1 |
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| 20 | New Era of Liver Transplantation for Hepatitis B: A 17-Year Single-Center Experience显示文摘 | Dean M. Anselmo Rafik M. Ghobrial Lee Chan Jung Michael Weaver Carlos Cao Sammy Saab Greg Kunder Pauline W. Chen Douglas G. Farmer Hasan Yersiz Angeles Baquerizo Sunil Geevarghese Steven H. Han Leonard Goldstein Curtis D. Holt Jeffrey A. Gornbein Ronald W | 2002 | Annals of Surgery2002，，5： | 1 |
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