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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 | Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function显示文摘在肿瘤和免疫系统之间的相互作用仍然糟糕被理解。重要临床的回答在对 CTLA4 和 PD-1/PD-L1 检查点与抗体对待的癌症病人被完成了;然而,仅仅病人的小部分对治疗作出回应,显示需要探索为癌症治疗的另外的 co 禁止的分子。B7-H3, B7 总科的一个成员,被我们以前显示出禁止 T 房间激活和 autoimmunity。在这研究,我们在肿瘤免疫分析了 B7-H3 的功能。B7-H3 的表示在多重肿瘤线,渗入肿瘤的树枝状的房间,和巨噬细胞被发现。与对抗抗体对待到 B7-H3 的 B7-H3-deficient 老鼠或老鼠显示出多重肿瘤的减少的生长,它取决于 NK 和 CD8 + T 房间。与细胞毒素的淋巴细胞表示的通常认为的受体, B7-H3 禁止了他们的激活,并且它的缺乏在忍受肿瘤的鼠标导致了增加的细胞毒素的淋巴细胞功能。B7-H3 和 PD-1 的联合封锁导致了迟了阶段的肿瘤的进一步提高的治疗学的控制。一起拿,我们的结果显示 B7-H3 检查点可以对癌症为免疫疗法用作一个新奇目标。 | Young-hee Lee Natalia Martin-Orozco Peilin Zheng Jing Li Peng Zhang Haidong Tan Hyun Jung Park Mira Jeong Seon Hee Chang Byung-Seok Kim Wei Xiong Wenjuan Zang Li Guo Yang Liu Zhong-jun Dong Willem W Overwijk Patrick Hwu Qing Yi Larry Kwak Zhiying Yang Tak W Mak Wei-Li Laszlo G Radvanyi Ling Ni Dongfang Liu Chen Dong | 2017 | Cell Research2017，27，8： | 29 |
| 3 | Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine显示文摘AIM: To investigate the reduction in hepatitis B virus(HBV) covalently closed-circular DNA(ccc DNA) with entecavir(ETV) or lamivudine(LAM). METHODS: This analysis included patients who had participated in the randomized Phase Ⅲ study ETV-022 comparing ETV vs LAM in nucleos(t)ide-naive, HBe Agpositive patients. Patients received ETV(0.5 mg daily) or LAM(100 mg daily) for a minimum of 52 wk. Patients were eligible to participate in this sub-study if they had paired biopsies at baseline and week 48 with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA. The main objective was to compare changes in hepatic HBV ccc DNA and total hepatic HBV DNA at week 48 of ETV or LAM treatment, which was a secondary endpoint of study ETV-022. Additional post hoc analyses included linear regression analyses to assess associations of baseline levels and on-treatment changes of ccc DNA with other baseline factors [sex,age, serum HBV DNA, alanine aminotransferase(ALT), Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBV genotype], or ontreatment factors(changes from baseline at week 48 in serum HBV DNA, ALT, Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBe Ag loss at week 48).RESULTS: Overall, 305 patients(ETV = 159; LAM = 146) of ETV-022 had paired baseline and week 48 liver biopsies with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA, and were included in this analysis. Baseline demographics and disease characteristics were comparable between the two arms. After 48 wk, ETV resulted in significantly greater reductions in hepatic HBV ccc DNA [-0.9 log10 copies/human genome equivalent(HGEq) vs-0.7 log10 copies/HGEq; P = 0.0033] and total hepatic DNA levels(-2.1 log10 copies/HGEq vs-1.6 log10 copies/HGEq; P < 0.0001) than LAM. Virologic, biochemical, and histologic response rates at week 48 were also greater with ETV than with LAM. Baseline HBV ccc DNA levels were positively associated with baseline levels of serum HBV DNA and total hepatic HBV DNA, and negatively associated with HBV genotype F. On-treatment changes in HBV ccc DNA levels were negatively associated with baseline levels of serum HBV DNA and baseline ALT, and were positively associated with on-treatment changes in the levels of serum HBV DNA, total hepatic HBV DNA levels, and ALT, change in Knodell necroinflammatory score, and HBe Ag loss.CONCLUSION: Forty-eight weeks of ETV resulted in greater reductions in ccc DNA and total hepatic HBV DNA than LAM, but long-term therapy may be needed for ccc DNA elimination. | Scott Bowden Stephen Locarnini Ting-Tsung Chang You-Chen Chao Kwang-Hyub Han Robert G Gish Robert A de Man Miao Yu Cyril Llamoso Hong Tang | 2015 | World Journal of Gastroenterology2015，21，15： | 11 |
| 4 | Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density显示文摘 | W.S Simonet D.L Lacey C.R Dunstan M Kelley M.-S Chang R Lüthy H.Q Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero H.-L Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg T.M Hughes D Hill W Pattison P Campbell S Sander G Van | 1997 | Cell1997，，2： | 6 |
| 5 | Engineering osteoarthritic cartilage model through differentiating senescent human mesenchymal stem cells for testing disease-modifying drugs显示文摘Significant cellular senescence has been observed in cartilage harvested from patients with osteoarthritis(OA).In this study,we aim to develop a senescence-relevant OA-like cartilage model for developing disease-modifying OA drugs(DMOADs).Spe-cifically,human bone marrow-derived mesenchymal stromal cells(MSCs)were expanded in vitro up to passage 10(P10-MSCs).Following their senescent phenotype formation,P10-MSCs were subjected to pellet culture in chondrogenic medium.Results from qRT-PCR,histology,and immunostaining indicated that cartilage generated from P10-MSCs displayed both senescent and OA-like phenotypes without using other OA-inducing agents,when compared to that from normal passage 4(P4)-MSCs.Interestingly,the same gene expression differences observed between P4-MSCs and P10-MSC-derived cartilage tissues were also observed between the preserved and damaged OA cartilage regions taken from human samples,as demonstrated by RNA sequencing data and other analysis methods.Lastly,the utility of this senescence-initiated OA-like cartilage model in drug development was assessed by testing several potential DMOADs and senolytics.The results suggest that pre-existing cellular senescence can induce the generation of OA-like changes in cartilage.The P4-and P10-MSCs derived cartilage models also represent a novel platform for predicting the efficacy and toxicity of potential DMOADs on both preserved and damaged cartilage in humans. | Ning Wang Yuchen He Silvia Liu Meagan J.Makarcyzk Guanghua Lei Alexander Chang Peter G Alexander Tingjun Hao Anne-Marie Padget Nuria de Pedro Tsapekos Menelaos Hang Lin | 2022 | Science China(Life Sciences)2022，65，2： | 5 |
| 6 | Second-look endoscopy with prophylactic hemostasis is still effective after endoscopic submucosal dissection for gastric neoplasm显示文摘AIM: The clinical value of second-look endoscopy(SLE) after endoscopic submucosal dissection(ESD) has been doubted continuously. The aim of this study was to assess the effectiveness of SLE based on the risk of delayed bleeding after ESD. METHODS: A total of 310 lesions of gastric epithelial neoplasms treated by ESD were reviewed. The lesions were divided into two groups based on the risk of postprocedural bleeding estimated by Forrest classification. The high risk of rebleeding group(Forrest?Ⅰa,?Ⅰb and Ⅱa) required endoscopic treatment, while the low risk of rebleeding group(Forrest Ⅱb, Ⅱc and Ⅲ) did not. Delayed bleeding after ESD was investigated. RESULTS: Sixty-six lesions were included in the high risk of rebleeding group and 244 lesions in the low risk of rebleeding group. There were no significant differences in delayed bleeding between the high risk group(1/66) and the low risk group(1/244)(P = 0.38). The high risk of rebleeding group tended to be located more often in the mid-third and had higher appearance of flat or depressed shape than the low risk group(P = 0.004 and P = 0.006, respectively). CONCLUSION: SLE with pre-emptive prophylactic endoscopic treatment is still effective in preventing delayed bleeding after ESD. | Ji Hye Jung Beom Jin Kim Chang Hwan Choi Jae G Kim | 2015 | World Journal of Gastroenterology2015，21，48： | 3 |
| 7 | 基于工作地点的分组干预对高血压控制的影响:一项随机临床研究显示文摘基于工作地点的干预可能为一种管理高血压的有效方法。但是目前缺少针对中国工作人群高血压控制情况的研究。本研究旨在评估基于工作地点的多组分别干预策略对改善血压控制的影响。研究设计及受试者:研究者在2013年1月至2014年12月于中国20个城区的60个工作地点进行了一系列高血压管理的随机临床试验。工作地点随机分为干预组(n=40)和对照组(n=20)。每个工作地点的受试者都需要完成一项横断面调查。 | 袁源(摘译) 叶鹏(审校) Wang Z Wang X Shen Y Li S Chen Z Zheng C Kang Y Jiang L Hao G Chang C Gao R | 2020 | 中华高血压杂志2020，28，6： | 3 |
| 8 | The acute effects of exercise on prolactin and growth hormone secretion: Comparison between sedentary women and women runners with normal and abnormal menstrual cycles 显示文摘 | CHANG F E DODDS W G SULLIVAN M | 1986 | Clin Endocrinol Metab1986，62，： | 2 |
| 9 | Wide diameter of butterfly networks 显示文摘 | LIAW S C CHANG G J | 1999 | Taiwanese Journal of Mathematics1999，3，： | 2 |
| 10 | Rabin numbers of butterfly networks 显示文摘 | LIAW S C CHANG G J | 1999 | Discrete Mathematics1999，196，： | 2 |
| 11 | Generalized diameters and Rabin numbers of networks 显示文摘 | LIAW S C CHANG G J | 1999 | Journal of Combinatorial Optimization1999，4，： | 2 |
| 12 | Spatially adaptive wavelet thresholding with context modeling for image denoising显示文摘 | Chang S G Yu B Vetterlim M | 2000 | IEEE Transactions on Image Processing2000，9，9： | 2 |
| 13 | The rule of thumb of the permeability calculation by Φ, Ss and SWT, in the carbonate stone显示文摘 | Chilingazian G V Chang Jincai Bagrintseva K J | 1990 | Journal of Petroleum Science and Engineering1990，14，4： | 1 |
| 14 | Cooperative Caching for Chip Multiprocessors显示文摘 | Chang Jichuan Sohi G S | 2006 | ACM SIGARCH Computer Architecture News2006，34，2： | 1 |
| 15 | Observations on changes in ultrasonically treated waste-activated sludge显示文摘 | Chu C P Chang B V Liao G S | 2001 | Wat Res2001，35，4： | 1 |
| 16 | A full-duplex radio-over-fiber system based on optical carrier suppr -ession and reuse显示文摘 | JIA Zhen-sheng YU Jian-jun CHANG G K | 2006 | IEEE Photon Technol Lett2006，18，16： | 1 |
| 17 | A prospective randomized clinical trial of phacoemulsi- fication vs manual sutureless small-incision extracapsular cataract surgery in Nepal显示文摘 | Ruit S Tabin G Chang D Bajracharya L Kline DC Richheimer W | 2007 | Am J Ophthalmol2007，143，1： | 1 |
| 18 | Behavior of double skin composite wall subjected to in- plane cyclic loading显示文摘 | Eom T S Park H G Lee C H Kim J H Chang I H | 2009 | Journal of Structural Engineering ASCE2009，135，10： | 1 |
| 19 | The RING finger protein RNF4, a co-regulator of transcription, interacts with the TRPSI transcription factor 显示文摘 | Kaiser F J Moroy T Chang G T | 2003 | J Biol Chem2003，278，： | 1 |
| 20 | Energy efficient coverage control in wireless sensor networks based on multi-objective genetic algorithm显示文摘 | Jia J Chen J Chang G | 2009 | Computers and Mathematics with Applications2009，57，1112： | 1 |
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