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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 | Biomonitoring for traditional herbal medicinal products using DNA metabarcoding and single molecule, real-time sequencing显示文摘Global concerns have been paid to the potential hazard of traditional herbal medicinal products(THMPs). Substandard and counterfeit THMPs, including traditional Chinese patent medicine, health foods, dietary supplements, etc. are potential threats to public health. Recent marketplace studies using DNA barcoding have determined that the current quality control methods are not sufficient for ensuring the presence of authentic herbal ingredients and detection of contaminants/adulterants. An efficient biomonitoring method for THMPs is of great needed. Herein, metabarcoding and single-molecule, realtime(SMRT) sequencing were used to detect the multiple ingredients in Jiuwei Qianghuo Wan(JWQHW), a classical herbal prescription widely used in China for the last 800 years. Reference experimental mixtures and commercial JWQHW products from the marketplace were used to confirm the method. Successful SMRT sequencing results recovered 5416 and 4342 circular-consensus sequencing(CCS) reads belonging to the ITS2 and psb A-trn H regions. The results suggest that with the combination of metabarcoding and SMRT sequencing, it is repeatable, reliable, and sensitive enough to detect species in the THMPs, and the error in SMRT sequencing did not affect the ability to identify multiple prescribed species and several adulterants/contaminants. It has the potential for becoming a valuable tool for the biomonitoring of multi-ingredient THMPs. | Tianyi Xin Zhichao Xu Jing Jia Christine Leon Songnian Hu Yulin Lin Subramanyam Ragupathy Jingyuan Song Steven G.Newmaster | 2018 | Acta Pharmaceutica Sinica B2018，8，3： | 22 |
| 3 | Encapsulating peritoneal sclerosis显示文摘Encapsulating peritoneal sclerosis(EPS) is a debilitating condition characterized by a fibrocollagenous membrane encasing the small intestine, resulting in recurrent small bowel obstructions. EPS is most commonly associated with long-term peritoneal dialysis, though medications, peritoneal infection, and systemic inflammatory disorders have been implicated. Many cases remain idiopathic. Diagnosis is often delayed given the rarity of the disorder combined with non-specific symptoms and laboratory findings. Although cross-sectional imaging with computed tomography of the abdomen can be suggestive of the disorder, many patients undergo exploratory laparotomy for diagnosis. Mortality approaches 50% one year after diagnosis. Treatment for EPS involves treating the underlying condition or eliminating possible inciting agents(i.e. peritoneal dialysis, medications, infections) and nutritional support, frequently with total parenteral nutrition. EPSspecific treatment depends on the disease stage. In the inflammatory stage, corticosteroids are the treatment of choice, while in the fibrotic stage, tamoxifen may be beneficial. In practice, distinguishing between stages may be difficult and both may be used. Surgical intervention, consisting of peritonectomy and enterolysis, is timeconsuming and high-risk and is reserved for situations in which conservative medical therapy fails in institutions with surgical expertise in this area. Herein we review the available literature of the etiology, pathogenesis, diagnosis, and treatment of this rare, but potentially devastating disease. | Christopher J Danford Steven C Lin Martin P Smith Jacqueline L Wolf | 2018 | World Journal of Gastroenterology2018，24，28： | 13 |
| 4 | The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function: a systematic review显示文摘使随机化的控制试用和队研究的系统的评论被进行在男性功能上为征兆的良性的 prostatic 增生(BPH ) 的处理为最低限度地侵略的过程的效果评估数据。寻找的研究是与征兆的 BPH 注册了人的试用与激光手术,经尿道的微波治疗( TUMT ),前列腺(金枪鱼)的经尿道的针脱离,前列腺( TEAP )的经尿道的乙醇脱离和高紧张的频率超声( HIFU )被对待,与前列腺( TURP )或假冒的操作的传统的经尿道的切除术比较。72 研究的一个总数被识别,哪个 33 满足了包括标准。33 研究, 21 涉及了激光手术,六与 TUMT,四与金枪鱼并且二与包含信息考虑的 TEAP 男性功能。没有学习关于为男性功能上的 BPH 的 HIFU 的效果是可得到的。我们的分析证明为 BPH 的最低限度地侵略的手术在男可勃起的功能上 TURP 有可比较的效果到那些。一起,分别地,不到 15.4% 病人或 15.2% 将在激光过程, TUMT 和金枪鱼以后可勃起的功能有减少或增加。是与 TURP 观察了,射精的机能障碍(EjD ) 的高发生在有钬, potassium-titanyl-phosphate 和铥激光治疗的 BPH 的治疗以后是普通的(>33.6%) 。TUMT,金枪鱼和 neodymium:yttrium 铝石榴石为 BPH 的视觉激光脱离或空隙的激光凝结有更少的发生 EjD,而是这些过程为 BPH 治疗被认为更少有效什么时候与 TURP 相比。 | Ryan W. Frieben Hao-Cheng Lin Peter E Hinh Francesco Berardinelli Steven E. Canfield Run Wang | 2010 | Asian Journal of Andrology2010，12，4： | 13 |
| 5 | A functional C-terminal TRAF3-binding site in MAVS participates in positive and negative regulation of the IFN antiviral response显示文摘病毒的 RNA 的识别由 cytosolic 传感器 retinoic 组织酸可诱导的基因 --(RIG-I ) 我导致表明与类型的产生达到顶点的串联的激活我干扰素(IFN ) 抗病毒的反应。对病毒的病原体的抗病毒、煽动性的回答的发作要求表明改编者, kinases 和 transcriptional 蛋白质到 mitochondrial 的调整空间与时间的招募抗病毒的发信号蛋白质(MAVS ) 。我们以前示威了 serine/threonine kinase IKKε被招募到 MAVS 后面的仙台或小囊的口炎病毒(VSV ) 感染的 C 终端区域,在 Lys500 由 MAVS 的连接 Lys63 的 polyubiquitination 调停了,导致下游的 IFN 发信号的抑制(Paz 等,摩尔房间 Biol, 2009 ) 。在这研究,我们证明 MAVS 的 C 终点在 MAVS 的 aa450-468 区域怀有一个新奇 TRAF3 有约束力的地点。一个一致交往 TRAF 主题(提姆) , 455-PEENEY-460,在这以内,地点为 TRAF3 绑定和 IFN 抗病毒的反应基因的激活被要求,而 TIM 的变化消除 TRAF3 绑定和下游的 IFN 反应。有表示 MAVS 的一个变异提姆的版本的构造的 MAVS −/− 老鼠胚胎成纤维细胞的宪法没能恢复抗病毒的反应或块 VSV 复制,而野类型的 MAVS 重新组成 VSV 复制的抗病毒的抑制。而且, IKKε 的招募;到在经由 Lys500 的 MAVS 的一个邻近的 C 终端地点(aa 468-540 ) , ubiquitination 减少了 TRAF3 绑定和蛋白质稳定性,因此贡献 IKKε调停 IFN 反应关机。这研究证明 MAVS 怀有功能的 C 终端参予 IFN 抗病毒的反应的积极、否定的规定的 TRAF3 有约束力的地点。 | Suzanne Paz Myriam Vilasco Steven J Werden Meztli Arguello Deshanthe Joseph-Pillai Tiejun Zhao Thi Lien-Anh Nguyen Qiang Sun Eliane F Meurs Rongtuan Lin John Hiscott | 2011 | Cell Research2011，21，6： | 12 |
| 6 | 勃起功能障碍(ED)的联合疗法显示文摘二十世纪九十年代末二十一世纪初,口服PDE5抑制剂(PDE5Is)的引入在很大程度上革新了性医学领域。目前PDE5I已经成为勃起功能障碍(ED)的首选单一疗法。然而,对一些复杂型ED患者来说,PDE5I单一疗法的疗效还不尽人意。目前越来越多不易治疗的ED病例开始采用联合疗法治疗,但还缺少对当前使用的联合疗法的严格评估。基于此,本综述在Pubmed和Cochrane Library数据库中进行了全面的文献检索.主要检索对象是1990年1月到2010年12月间研究PDE5I单一治疗失败后接受联合疗法的所有相关综述、随机对照试验、队列研究和回顾性研究。同时还对检索所得文献的参考文献进行了人工筛选,获得了其它一些相关的文献资料。目前发表的联合疗法主要包括PDE5I加真空吸引器(VED)、尿道给药、阴茎注射(ICI)、雄激素补充疗法、α-阻断剂,还有其它一些联合疗法。本综述发现,有些联合疗法的初步试验结果是有效的。然而,进行治疗时还是要谨慎,因为近十年来发表的大部分联合疗法相关文章的研究方法有很多问题,比如研究偏见和样本量小等。尽管如此,目前的研究结果还是在为将来复杂型ED的治疗研究方面奠定了坚实的基础。 | Rohit R Dhir Hao-Cheng Lin Steven E Canfield Run Wang | 2011 | Asian Journal of Andrology2011，13，3： | 7 |
| 7 | 帕博利珠单抗联合以铂类为基础的化疗治疗非小细胞肺癌合并稳定性脑转移患者的结局:KEYNOTE-021、-189和-407研究的汇总分析显示文摘背景与目的此项探索性分析回顾评价了晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的结局,旨在确定基线时合并脑转移是否会影响一线应用帕博利珠单抗联合化疗(pembrolizumab plus chemotherapy,PC)比对单用化疗的疗效。患者和方法对KEYNOTE-021队列G(非鳞癌)、KEYNOTE-189(非鳞癌)和KEYNOTE-407(鳞癌)三项研究晚期NSCLC患者的数据进行汇总分析。患者接受含铂两药化疗和/或35个周期帕博利珠单抗治疗(每3周200 mg)。所有研究均纳入了经治或初治的稳定性脑转移患者(KEYNOTE-189与KEYNOTE-407研究纳入初治脑转移患者)。经治的脑转移患者已处于病情稳定的状态≥2周(KEYNOTE-021队列G患者≥4周),无新发或脑转移病灶扩大的证据且入组前至少3天以上未使用激素。初治的无症状脑转移患者需定期接受脑部影像学检查。结果共纳入1298例患者,其中171例有基线脑转移,1127例无脑转移。两组的中位随访时间(范围)在数据截止时分别为10.9(0.1-35.1)个月和11.0(0.1-34.9)个月。合并脑转移和无脑转移患者的总生存期[0.48(95%CI:0.32-0.70)和0.63(95%CI:0.53-0.75)]和无进展生存期[0.44(95%CI:0.31-0.62)和0.55(95%CI:0.48-0.63)]的风险比(PC/化疗)相似。合并脑转移的患者中,PC组和单用化疗组患者的中位总生存期分别为18.8个月和7.6个月,中位无进展生存期分别为6.9个月和4.1个月。无论是否合并脑转移,PC组患者的客观缓解率都高于单用化疗组,且缓解持续时间有显著延长。合并脑转移的患者中,PC组与单用化疗组的治疗相关不良事件发生率分别为88.2%和82.8%;而无脑转移的患者中,两组治疗相关不良事件的发生率分别为94.5%和90.6%。结论无论是否合并脑转移,与单用化疗相比,帕博利珠单抗联合以铂类为基础的组织学特异性化疗可改善所有PD-L1亚组的临床结局,其中包括PD-L1肿瘤比例评分<1%的患者,并且在晚期NSCLC患者中安全性良好。该方案是晚期NSCLC初治患者的标准方案,并可用于合并稳定性脑转移的患者。 | 周清(翻译校对) Steven F Powell Delvys Rodríguez-Abreu Corey J Langer Ali Tafreshi Luis Paz-Ares Hans-Georg Kopp Jeronimo Rodríguez-Cid Dariusz M Kowalski Ying Cheng Takayasu Kurata Mark M Awad Jinaxin Lin Bin Zhao M Catherine Pietanza Bilal Piperdi Marina C Garassino | 2022 | 中国肺癌杂志2022，25，1： | 6 |
| 8 | National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants显示文摘 | Goodarz Danaei Mariel M Finucane Yuan Lu Gitanjali M Singh Melanie J Cowan Christopher J Paciorek John K Lin Farshad Farzadfar Young-Ho Khang Gretchen A Stevens Mayuree Rao Mohammed K Ali Leanne M Riley Carolyn A Robinson Majid Ezzati | 2011 | The Lancet2011，，9785： | 6 |
| 9 | Inhibition of CDK9 by voruciclib synergistically enhances cell death induced by the Bcl-2 selective inhibitor venetoclax in preclinical models of acute myeloid leukemia显示文摘Venetoclax,an FDA-approved Bcl-2 selective inhibitor for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia(AML),is tolerated well in elderly patients with AML and has good overall response rates;however,resistance remains a concern.In this study,we show that targeting CDK9 with voruciclib in combination with venetoclax results in synergistic antileukemic activity against AML cell lines and primary patient samples.CDK9 inhibition enhances venetoclax activity through downregulation of Mcl-1 and c-Myc.However,downregulation of Mcl-1 is transient,which necessitates an intermittent treatment schedule to allow for repeated downregulation of Mcl-1.Accordingly,an every other day schedule of the CDK9 inhibitor is effective in vitro and in vivo in enhancing the efficacy of venetoclax.Our preclinical data provide a rationale for an intermittent drug administration schedule for the clinical evaluation of the combination treatment for AML. | Daniel A.Luedtke Yongwei Su Jun Ma Xinyu Li Steven ABuck Holly Edwards Lisa Polin Juiwanna Kushner Sijana HDzinic Kathryn White Hai Lin Jeffrey WTaub Yubin Ge | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 3 |
| 10 | Management of Newly Diagnosed Symptomatic Multiple Myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013显示文摘 | Joseph R. Mikhael David Dingli Vivek Roy Craig B. Reeder Francis K. Buadi Suzanne R. Hayman Angela Dispenzieri Rafael Fonseca Taimur Sher Robert A. Kyle Yi Lin Stephen J. Russell Shaji Kumar P. Leif Bergsagel Steven R. Zeldenrust Nelson Leung Matthew T. D | 2013 | Mayo Clinic Proceedings2013，，4： | 2 |
| 11 | National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants显示文摘 | Goodarz Danaei Mariel M Finucane Yuan Lu Gitanjali M Singh Melanie J Cowan Christopher J Paciorek John K Lin Farshad Farzadfar Young-Ho Khang Gretchen A Stevens Mayuree Rao Mohammed K Ali Leanne M Riley Carolyn A Robinson Majid Ezzati | 2011 | The Lancet2011，，9785： | 2 |
| 12 | National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants显示文摘 | Goodarz Danaei Mariel M Finucane Yuan Lu Gitanjali M Singh Melanie J Cowan Christopher J Paciorek John K Lin Farshad Farzadfar Young-Ho Khang Gretchen A Stevens Mayuree Rao Mohammed K Ali Leanne M Riley Carolyn A Robinson Majid Ezzati | 2011 | 2011 (9785)2011，，9785： | 2 |
| 13 | Growth inhibition of selected food-borne bacteria by tannic acid,propyl gallate and related compounds显示文摘 | Stevens JR Lin WF | 1993 | Letters in Applied Microbiology1993，17，： | 1 |
| 14 | Government spending and economic growth显示文摘 | Steven A. Y. Lin | 1994 | Applied Economics1994，，1： | 1 |
| 15 | Peptide combinatorial libraries identify TSC2 as a death - associated protein kinase (DAPK) death domain - binding protein and reveal a stimulatory role for DAPK in mTORC1 signaling 显示文摘 | Stevens C Lin Y Harrison B | 2009 | JBiolChem2009，284，1： | 1 |
| 16 | Cell-free Formation of RNA Granules: Low Complexity Sequence Domains Form Dynamic Fibers within Hydrogels显示文摘 | Masato Kato Tina W. Han Shanhai Xie Kevin Shi Xinlin Du Leeju C. Wu Hamid Mirzaei Elizabeth J. Goldsmith Jamie Longgood Jimin Pei Nick V. Grishin Douglas E. Frantz Jay W. Schneider She Chen Lin Li Michael R. Sawaya David Eisenberg Robert Tycko Steven L. M | 2012 | Cell2012，，： | 1 |
| 17 | An MDP-based vertical handoff decision algorithm for heterogeneous wireless net- works 显示文摘 | Stevens Navarro E Lin Y X Vincent Wong W S | 2008 | IEEE Transactions on Vehicular Technology2008，57，2： | 1 |
| 18 | The Appendix May Protect Against Clostridium difficile Recurrence显示文摘 | Gene Y. Im Rani J. Modayil Cheng T. Lin Steven J. Geier Douglas S. Katz Martin Feuerman James H. Grendell | 2011 | Clinical Gastroenterology and Hepatology2011，，12： | 1 |
| 19 | The Appendix May Protect Against Clostridium difficile Recurrence显示文摘 | Gene Y. Im Rani J. Modayil Cheng T. Lin Steven J. Geier Douglas S. Katz Martin Feuerman James H. Grendell | 2011 | Clinical Gastroenterology and Hepatology2011，，12： | 1 |
| 20 | Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum (Reishi)polysaccharides显示文摘 | Tsai Yow-Fu Lin Steven | 2004 | Bioorganic & Medicinal Chemistry2004，，12： | 1 |
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