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| 1 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 2 | 东南极拉斯曼丘陵泥质麻粒岩的变质作用演化显示文摘普里兹湾拉斯曼丘陵代表了东南极一条重要的早古生代的~530Ma泛非期(Pan-African)高级构造活动带。然而,该区早期的晚元古代的~1000Ma格林维尔期(Grenvellian)高级变质作用的演化历史至今仍有争论。该区呈透镜状产出的泥质麻粒岩峰期矿物组合(M1)为石榴石+堇青石+斜方辉石+钾长石+石英,峰期石榴石变斑晶发育堇青石或堇青石+斜方辉石反应边(M2)。利用Thermocalc程序在KFMASH模式体系对该泥质麻粒岩进行的定量模拟表明,其峰期矿物组合是由反应石榴石+黑云母+石英=堇青石+斜方辉石+钾长石+熔体形成的。利用Themocalc平均P-T计算方法获得峰期M1变质P-T条件为~0.9GPa和~900℃,而叠加的M2组合反映了一个减压冷却的过程,其变质P-T条件为~0.7GPa和800~850℃。结合已有的年代学数据,认为该区泥质麻粒岩的峰期M1矿物组合反映晚元古代(~1000Ma)格林维尔期挤压D1构造事件,而叠加的M2矿物组合与M3蠕虫状结构则形成于早古生代泛非期(~530Ma)D2~D3高级扭压剪切构造期间。该扭压事件导致了面状高低应变带的发育以及进步花岗岩和伟晶岩的侵入。 | 仝来喜 刘小汉 王彦斌 Chris J L Wilson | 2012 | 地质学报2012，86，8： | 12 |
| 3 | Hematopoietic stem cell-derived adipocytes and fibroblasts in the tumor microenvironment显示文摘The tumor microenvironment(TME) is complex and constantly evolving. This is due, in part, to the crosstalk between tumor cells and the multiple cell types that comprise the TME, which results in a heterogeneous population of tumor cells and TME cells. This review will focus on two stromal cell types, the cancerassociated adipocyte(CAA) and the cancer-associated fibroblast(CAF). In the clinic, the presence of CAAs and CAFs in the TME translates to poor prognosis in multiple tumor types. CAAs and CAFs have an activated phenotype and produce growth factors, inflammatory factors, cytokines, chemokines, extracellular matrix components, and proteases in an accelerated and aberrant fashion. Through this activated state, CAAs and CAFs remodel the TME, thereby driving all aspects of tumor progression, including tumor growth and survival, chemoresistance, tumor vascularization, tumor invasion, and tumor cell metastasis. Similarities in the tumorpromoting functions of CAAs and CAFs suggest that a multipronged therapeutic approach may be necessary to achieve maximal impact on disease. While CAAs and CAFs are thought to arise from tissues adjacent to the tumor, multiple alternative origins for CAAs and CAFs have recently been identified. Recent studies from our lab and others suggest that the hematopoietic stem cell, through the myeloid lineage, may serve as a progenitor for CAAs and CAFs. We hypothesize that the multiple origins of CAAs and CAFs may contribute to the heterogeneity seen in the TME. Thus, a better understanding of the origin of CAAs and CAFs, how this origin impacts their functions in the TME, and thetemporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics. | Ying Xiong Lindsay T Mc Donald Dayvia L Russell Ryan R Kelly Katie R Wilson Meenal Mehrotra Adam C Soloff Amanda C LaRue | 2015 | World Journal of Stem Cells2015，7，2： | 6 |
| 4 | Aging:A mitochondrial DNA perspective,critical analysis and an update显示文摘The mitochondrial theory of aging, a mainstream theory of aging which once included accumulation of mitochondrial DNA(mt DNA) damage by reactive oxygen species(ROS) as its cornerstone, has been increasingly losing ground and is undergoing extensive revision due to its inability to explain a growing body of emerging data. Concurrently, the notion of the central role for mtDNA in the aging process is being met with increased skepticism. Our progress in understanding the processes of mtDNA maintenance, repair, damage, and degradation in response to damage has largely refuted the view of mt DNA as being particularly susceptible to ROS-mediated mutagenesis due to its lack of 'protective' histones and reduced complement of available DNA repair pathways. Recent research on mitochondrial ROS production has led to the appreciation that mitochondria, even in vitro, produce much less ROS than previously thought, automatically leading to a decreased expectation of physiologically achievable levels of mtDNA damage. New evidence suggests that both experimentally induced oxidative stress and radiation therapy result in very low levels of mtDNA mutagenesis. Recent advances provide evidence against the existence of the 'vicious' cycle of mtDNA damage and ROS production. Meta-studies reveal no longevity benefit of increased antioxidant defenses. Simultaneously, exciting new observations from both comparative biology and experimental systems indicate that increased ROS production and oxidative damage to cellular macromolecules, including mtDNA, can be associated with extended longevity. A novel paradigm suggests that increased ROS production in aging may be the result of adaptive signaling rather than a detrimental byproduct of normal respiration that drives aging. Here, we review issues pertaining to the role of mtDNA in aging. | Inna N Shokolenko Glenn L Wilson Mikhail F Alexeyev | 2014 | World Journal of Experimental Medicine2014，4，4： | 6 |
| 5 | Mapping QTL associated with Verticillium dahliae resistance in the cultivated strawberry(Fragaria×ananassa)显示文摘A biparental cross of octoploid strawberry segregating for resistance to Verticillium dahliae,the causative agent of Verticillium wilt,was screened under field conditions for three seasons.Average wilt scores were significantly associated with multiple QTL,which were mostly significant across all years.Markers significantly associated with the traits were used to screen material with known wilt resistance and susceptibility phenotypes.A clear and statistically significant relationship was observed between resistant,tolerant and susceptible material and the total number of markers present in the different resistance classes.In field situations resistance QTL appear to behave in an additive manner.These markers are abundant in the cultivated strawberry germplasm indicating that,despite the large number of markers,clear genetic gain is possible through marker-assisted breeding. | L Antanaviciute NŠurbanovski N Harrison K J McLeary D W Simpson F Wilson D J Sargent R J Harrison | 2015 | Horticulture Research2015，2，1： | 5 |
| 6 | 健康领域的文化能力显示文摘1背景
尽管人类对其他社会的兴趣纵贯历史的各个阶段,但是检验不同文化概念对人类健康实践的影响从20世纪才开始,当时是伴随着长期的人类学田野调查产生的,这些田野调查揭露了不同文化之间相关卫生实践的多样性、复杂性和连续性。 | Napier A D Ancarno C Butler B Calabrese j Chater A Chatterjee H Guesnet F Home R Jacyna S Jadhav S Macdonald A Neuendorf U Parkhurst A Reynolds R Scambler G Shamdasani S Smith S Z Stougaard-Nielsen J Thomson L Tyler N Volkmann A M Walker T Watson J Williams AC Willott C Wilson J Woolf K | 2016 | 中国卫生政策研究2016，9，2： | 5 |
| 7 | Estimation and inference in two-stage, semi-parametric models of production processes显示文摘 | Léopold Simar Paul W. Wilson | 2005 | Journal of Econometrics2005，，1： | 3 |
| 8 | Changes in the colon microbiota and intestinal cytokine gene expression following minimal intestinal surgery显示文摘AIM: To investigate the impact of minor abdominal surgery on the caecal microbial population and on markers of gut inflammation.METHODS: Four week old piglets were randomly allocated to a no-surgery 'control' group(n = 6) or a 'transection surgery' group(n = 5).During the transection surgery procedure, a conventional midline incision of the lower abdominal wall was made and the small intestine was transected at a site 225 cm proximal to the ileocaecal valve, a 2 cm segment was removed and the intestine was re-anastomosed.Piglets received a polymeric infant formula diet throughout the study period and were sacrificed at two weeks post-surgery.Clinical outcomes including weight, stool consistency and presence of stool fat globules were monitored.High throughput DNA sequencing of colonic content was used to detect surgery-relateddisturbances in microbial composition at phylum, family and genus level.Diversity and richness estimates were calculated for the control and minor surgery groups.As disturbances in the gut microbial community are linked to inflammation we compared the gene expression of key inflammatory cytokines(TNF, IL1 B, IL18, IL12, IL8, IL6 and IL10) in ileum, terminal ileum and colon mucosal extracts obtained from control and abdominal surgery groups at two weeks post-surgery.RESULTS: Changes in the relative abundance of bacterial species at family and genus level were confined to bacterial members of the Proteobacteria and Bacteroidetes phyla.Family level compositional shifts included a reduction in the relative abundance of Enterobacteriaceae(22.95 ± 5.27 vs 2.07 ± 0.72, P < 0.01), Bacteroidaceae(2.54 ± 0.56 vs 0.86 ± 0.43, P < 0.05) and Rhodospirillaceae(0.40 ± 0.14 vs 0.00 ± 0.00, P < 0.05) following transection surgery.Similarly, at the genus level, changes associated with transection surgery were restricted to members of the Proteobacteria and Bacteroidetes phyla and included decreased relative abundance of Enterobacteriaceae(29.20 ± 6.74 vs 2.88 ± 1.08, P < 0.01), Alistipes(4.82 ± 1.73 vs 0.18 ± 0.13, P < 0.05) and Thalassospira(0.53 ± 0.19 vs 0.00 ± 0.00, P < 0.05).Surgeryassociated microbial dysbiosis was accompanied by increased gene expression of markers of inflammation.Within the ileum IL6 expression was decreased(4.46 ± 1.60 vs 0.24 ± 0.06, P < 0.05) following transection surgery.In the terminal ileum, gene expression of TNF was decreased(1.51 ± 0.13 vs 0.80 ± 0.16, P < 0.01) and IL18(1.21 ± 0.18 vs 2.13 ± 0.24, P < 0.01), IL12(1.04 ± 0.16 vs 1.82 ± 0.32, P < 0.05) and IL10(1.04 ± 0.06 vs 1.43 ± 0.09, P < 0.01) gene expression increased following transection surgery.Within the colon, IL12(0.72 ± 0.13 vs 1.78 ± 0.28, P < 0.01) and IL10(0.98 ± 0.02 vs 1.95 ± 0.14, P < 0.01) gene expression were increased following transection surgery.CONCLUSION: This study suggests that minor abdominal surgery in infants, results in long-term alteration of the colonic microbial composition and persistent gastrointestinal inflammation. | Susan Lapthorne Julie E Bines Fiona Fouhy Nicole L Dellios Guineva Wilson Sarah L Thomas Michelle Scurr Catherine Stanton Paul D Cotter Prue M Pereira-Fantini | 2015 | World Journal of Gastroenterology2015，21，14： | 3 |
| 9 | 生活方式和饮食因素:预防致死性前列腺癌显示文摘预防致死性前列腺癌是一个重要的公共卫生难题。解决该难题可以改善人们的健康状况,减少罹患该疾病的痛苦。本综述围绕某些与致命性前列腺癌预防有关的生活方式和饮食因素研究进行讨论。我们还对以下行为风险因素的研究进行总结:肥胖和体重变化、体育活动、吸烟状况、抗氧化剂摄入量、维生素D和钙、以及咖啡摄入量。 | Kathryn M Wilson Edward L Giovannucci Lorelei A Mucci | 2012 | Asian Journal of Andrology2012，14，3： | 3 |
| 10 | 显示文摘 | Hench L L Wilson J | 1984 | Science1984，226，： | 2 |
| 11 | 文化、不平等性与卫生服务提供显示文摘1动态不平等性对基层医疗卫生人力的影响
政治、社会、文化、专业群体皆建立在一致且常规的人类行为之上。当遭受巨大变革和内外压力时,这些群体会变得十分脆弱。尤其在动荡时期,这些群体往往更关注社会和文化的差异性,而非二者的一致性。尽管社会中的个体思维和行为会呈现较大的差异,但对健康的感知具有统一性,并在更广范围人群内尤为突出,这主要归因于文化价值观的作用。广义的文化心态会随着时间和地理位置的不同而不同,就像健康的社会决定因素也会因文化类型的不同而产生差异。 | Napier A D Ancarno C Butler B Calabrese J Chater A Chatterjee H Guesnet F Horne R Jacyna S Jadhav S Macdonald A Neuendorf U Parkhurst A Reynolds R Scambler G Shamdasani S Smith S Z Stougaard-Nielsen J Thomson L Tyler N Volkmann A M Walker T Watson J Williams A C Willott C Wilson J Woolf K | 2016 | 中国卫生政策研究2016，9，3： | 2 |
| 12 | A nonconforming element for stress analysis显示文摘 | Toylor R L Beresford P J Wilson E L | 1976 | International Journal for Numerical Methods in Engineering1976，，10： | 2 |
| 13 | A robust quadrilateral membrane finite element with drilling degrees of freedom显示文摘 | Ibrahimbegovic A Taylor R L Wilson E L | 1990 | International Journal for Numerical Methods in Engineering1990，30，： | 2 |
| 14 | Polymorphic sites and the mechanism of evolution in human mitochondrial DNA 显示文摘 | Cano R L Brown W M Wilson A C | 1984 | Genetics1984，106，： | 2 |
| 15 | Overweight and obesity as determinants of eardiovascular risk:The Framingham experience显示文摘 | Wilson PW D' Agostino RB Sullivan L | 2002 | Arch Intern Med2002，162，16： | 1 |
| 16 | Human and machine recognition of faces : a survey 显示文摘 | RAMA CHELLAPPA WILSON C L SIROHEY S | 1995 | Proceedings of the IEEE1995，83，5： | 1 |
| 17 | Optimal Entry Time for a Product Line Extension显示文摘 | Wilson L O Norton J A | 1989 | Marketing Science1989，8，： | 1 |
| 18 | Construction of the affine Lie algebra A1(1) 显示文摘 | Lepowsky J Wilson R L | 1978 | Commun Math Phys1978，62，： | 1 |
| 19 | Spatial Sensitivity of the Gravity Recovery and Climate Experiment (GRACE) Time-variable Gravity Observations显示文摘 | Chen J L Wilson C R Famiglictti J S | 2005 | Journal of Geophysical Research2005，110，： | 1 |
| 20 | Radar detection in multipath显示文摘 | Wilson S L and Carlson B D | 1999 | IEE Proceedings of Radar Sonar and Navigation1999，146，1： | 1 |
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