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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 | 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 |
| 3 | Microbiota or short-chain fatty acids: which regulates diabetes?显示文摘Diabetes mellitus,with sustained high-sugar levels in the blood,has been steadily rising in prevalence worldwide.Around 12–14%of the US population has been diagnosed with diabetes in recent years.1 One major reason for the rise of diabetes is dietary changes.Increased consumption of processed carbohydrates with inadequate consumption of dietary fiber(DF)has been recognized as a major risk factor for diabetes,as hypothesized several decades ago by Trowell. | Chang H Kim | 2018 | Cellular & Molecular Immunology2018，15，2： | 13 |
| 4 | Use of blood-based biomarkers for early diagnosis and surveillance of colorectal cancer显示文摘Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate because of their high cost and cumbersome preparatory procedures that ultimately lead to a low participation rate. People simply do not like to have colonoscopies. It would be ideal, therefore, to develop an alternative modality based on blood biomarkers as the first line screening test. This will allow for the differentiation of the general population from high risk individuals. Colonoscopy would then become the secondary test, to further screen the high risk segment of the population. This will encourage participation and therefore help to reach the goal of early detection and thereby reduce the anticipated increasing global CRC incidence rate. A blood-based screening test is anappealing alternative as it is non-invasive and poses minimal risk to patients. It is easy to perform, can be repeated at shorter intervals, and therefore would likely lead to a much higher participation rate. This review surveys various blood-based test strategies currently under investigation, discusses the potency of what is available, and assesses how new technology may contribute to future test design. | Ganepola AP Ganepola Joel Nizin John R Rutledge David H Chang | 2014 | World Journal of Gastrointestinal Oncology2014，6，4： | 11 |
| 5 | 退火对ZnO薄膜结构及发光特性的影响显示文摘生长在蓝宝石C面上的ZnO薄膜是通过等离子体金属有机物化学汽相淀积方法获得的 ,由其X光衍射得知 ,生长过程中分段退火和最后退火在薄膜中分别引入了张应力和压应力。通过对样品光致发光光谱研究表明 :分段退火样品在 380nm附近出现了单一激子发射峰 ,而最后退火样品却出现了与应变有关的Γ5和Γ6两激子发射峰 ,同时在两者的光致发光光谱中与深能级有关的荧光峰都未出现。 | 王金忠 杜国同 王新强 闫玮 马燕 姜秀英 杨树人 高鼎三 Chang R P H | 2002 | 光学学报2002，22，2： | 10 |
| 6 | Bis(7)-tacrine attenuates beta amyloid-induced neuronal apoptosis by regulating L-type calcium channels显示文摘 | Fu H Li W Lao Y Luo J Lee NT Kan KK Tsang HW Tsim KW Pang Y Li Z Chang DC Li M Han Y | 2006 | 中国生物学文摘2006，20，10： | 10 |
| 7 | Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer显示文摘AIM:To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage.METHODS:Blood-based circulating microRNAs were profiled by high throughput screening using microarray analysis,comparing differential expression between early stage pancreatic cancer patients(n = 8) and healthy controls(n = 11).A panel of candidate microRNAs was generated based on the microarray signature profiling,including unsupervised clustering and statistical analysis of differential expression levels,and findings from the published literature.The selected candidate microRNAs were then confirmed using TaqMan real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR) to further narrow down to a three-microRNA diagnostic panel.The three-microRNA diagnostic panel was validated with independent experimental proce-dures and instrumentation of RT-qPCR at an independent venue with a new cohort of cancer patients(n = 11),healthy controls(n = 11),and a group of high risk controls(n = 11).Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of the three-microRNA panel.RESULTS:In the initial high throughput screening,1220 known human microRNAs were screened for differential expression in pancreatic cancer patients versus controls.A subset of 42 microRNAs was then generated based on this data analysis and current published literature.Eight microRNAs were selected from the list of 42 targets for confirmation study,and three-microRNAs,miR-642b,miR-885-5p,and miR-22,were confirmed to show consistent expression between microarray and RT-qPCR.These three microRNAs were then validated and evaluated as a diagnostic panel with a new cohort of patients and controls and found to yield high sensitivity(91%) and specificity(91%) with an area under the curve of 0.97(P < 0.001).Compared to the CA19-9 marker at 73%,the three-microRNA panel has higher sensitivity although CA19-9 has higher specificity of 100%.CONCLUSION:The identified panel of three microRNA biomarkers can potentially be used as a diagnostic tool for early stage pancreatic cancer. | Ganepola AP Ganepola John R Rutledge Paritosh Suman Anusak Yiengpruksawan David H Chang | 2014 | World Journal of Gastrointestinal Oncology2014，6，1： | 9 |
| 8 | Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial显示文摘 | Sung-Bum Kang Ji Won Park Seung-Yong Jeong Byung Ho Nam Hyo Seong Choi Duck-Woo Kim Seok-Byung Lim Taek-Gu Lee Dae Yong Kim Jae-Sung Kim Hee Jin Chang Hye-Seung Lee Sun Young Kim Kyung Hae Jung Yong Sang Hong Jee Hyun Kim Dae Kyung Sohn Dae-Hyun Kim Jae H | 2010 | Lancet Oncology2010，，7： | 5 |
| 9 | GENETIC PROGRAMMING TO PREDICT SKI-JUMP BUCKET SPILLWAY SCOUR显示文摘Researchers in the past had noticed that application of Artificial Neural Networks (ANN) in place of conventional statistics on the basis of data mining techniques predicts more accurate results in hydraulic predictions. Mostly these works pertained to applications of ANN. Recently, another tool of soft computing, namely, Genetic Programming (GP) has caught the attention of researchers in civil engineering computing. This article examines the usefulness of the GP based approach to predict the relative scour depth downstream of a common type of ski-jump bucket spillway. Actual field measurements were used to develop the GP model. The GP based estimations were found to be equally and more accurate than the ANN based ones, especially, when the underlying cause-effect relationship became more uncertain to model. | AZAMATHULLA H. MD GHANI A. AB ZAKARIA N. A LAI S. H CHANG C. K LEOW C. S ABUHASAN Z | 2008 | Journal of Hydrodynamics2008，20，4： | 4 |
| 10 | The growth of brain tumors can be suppressed by multiple transplantation of mesenchymal stem cells expressing cytosine deaminase显示文摘Suicide genes have recently emerged as an attractive alternative therapy for the treatment of various types of intractable cancers.The efficacy of suicide gene therapy relies on efficient gene delivery to target tissues and the localized concentration of final geneproducts. | Chang DY Yoo SW Hong Y Kim S Kim SJ Yoon SH Cho KG Paek SH Lee YD Kim SS Suh-Kim H | 2010 | 中国神经肿瘤杂志2010，8，2： | 3 |
| 11 | On the existence and iterative approximation problems of solutions for set-valued variational inchusions in Banach spaces显示文摘 | Chang S S Kim J K Kim K H | 2002 | JMath Anal Appl2002，268，： | 2 |
| 12 | Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: Risk and prognosis prediction显示文摘 | Manal M. Hassan Ahmed Kaseb Carol J. Etzel Hashem El‐Serag Margaret R. Spitz Ping Chang Katherine S. Hale Mei Liu Asif Rashid Mohamed Shama James L. Abbruzzese Evelyne M. Loyer Harmeet Kaur Hesham M. Hassabo Jean‐Nicolas Vauthey Curtis J. Wray Basmah S. H | 2013 | Mol Carcinog2013，，1： | 2 |
| 13 | Plasma endothelin level changes during hemorrhagic shock显示文摘 | Chang H Wu GJ Wang SM | 1993 | J Trauma1993，35，6： | 2 |
| 14 | Maize tapetum xylanase is synthesized as a precursor, processed and activated by a serine protease, and deposited on the pollen显示文摘 | Sherry S H Wu Der Fen Suan Han Chang Chang | 2002 | The Journal of Biological Chemistry2002，277，49： | 2 |
| 15 | The organic precursors affecting the formation of disinfection by - products with chlorine dioxide 显示文摘 | CHANG Chenyu HSIEH Y H LIN Yumin | 2001 | Chemosphere2001，44，： | 2 |
| 16 | Stability of interconnected stochastic delay systems显示文摘 | CHANG M H | 1985 | APPI Math Comput1985，16，： | 2 |
| 17 | Immunomodulation by dietary β-1,3-glucan in the brooders of the black tiger shrimp Penaeus monodon显示文摘 | Chang C F Chen H Y Su M S | 2000 | Fish Shellfish Immun2000，10，： | 2 |
| 18 | 饲料中添加发酵豆粕对岩鱼生长性能、身体组成、抗氧化酶活性和抗病性能的影响显示文摘试验研究用发酵豆粕鱼料(FSM)代替常规鱼料(FM)对幼鱼期和生长期岩鱼(又名许氏鲆鲉)生长性能、身体组成、抗氧化酶活性和抗病能力的影响。FSM含量分别为0、8%、16%、24%和32%的等氮(51%)和等热量(MJ·kg^(-1))鱼料代替FM蛋白质含量约0、10%、20%、30%和40%的鱼料(分别为FSM0组、FSM8组、FSM16组、FSM24组和FSM32组)。每组鱼料分别饲喂3组幼生期岩鱼(1.2±0.04 g;EXPⅠ组)和3组生长期岩鱼(148.2±2.9 g;EXPⅡ组),2次·d^(-1),共8周。与FSM0组、FSM8组和FSM16组相比,饲喂FSM32组幼生期岩鱼的体增重(WG)显著降低。FSM16组、FSM24组和FSM32组的饲料效率(FE)和岩鱼蛋白质功效比值(PER)显著低于FSM0组和FSM8组。FSM24组的日采食量(DFI)显著低于FSM0组和FSM8组。但生长期岩鱼的生长性能和饲料利用率未表现出显著改变。FSM32组幼生期岩鱼的内脏指数(VSI)显著低于其他各组。FSM替代FM量达到40%,对幼生期和生长期岩鱼的整个身体和肌肉指标、氨基酸组成均无显著影响。与对照组相比,鱼料中含有FSM的生长期岩鱼的血清抗氧化酶活性显著提高。腹腔注射迟钝爱德华菌后存活的幼生期岩鱼不受饲料变化的影响。试验结果表明,FSM是一种成功的FM替代品,幼生期岩鱼鱼料中替代量可达10%,生长期岩鱼料中替代量达40%时,对其生长性能仍无不良影响。 | Sang M L Hamid M A Kyung H Chang | 2016 | 饲料博览2016，0，7： | 2 |
| 19 | Novel pharmacological therapy in type 2 diabetes mellitus with established cardiovascular disease: Current evidence显示文摘Cardiovascular diseases(CVDs) remain the leading cause of death in the world and in most developed countries. Patients with type 2 diabetes mellitus(T2DM)suffer from both microvascular and macrovascular diseases and therefore have higher rates of morbidity and mortality compared to those without T2DM. If current trends continue, the Center for Disease Control and Prevention estimates that 1 in 3 Americans will have T2DM by year 2050. As a consequence of the controversy surrounding rosiglitazone and the increasing prevalence of diabetes and CVDs, in 2008 the Food and Drug Administration(FDA) established new expectations for the evaluation of new antidiabetic agents, advising for pre and,in some cases, post-marketing data on major cardiovascular events. As a direct consequence, there has been a paradigm shift in new antidiabetic agents that has given birth to the recently published American Diabetes Association/European Association for the Study of Diabetes consensus statement recommending sodium-glucose cotransporter-2 inhibitors(SGLT2i) and glucagon like peptide-1 receptor agonists(GLP-1RA) in patients with T2DM and established CVD. As a result of over a decade of randomized placebo controlled cardiovascular outcome trials, the aforementioned drugs have received FDA approval for risk reduction of cardiovascular(CV) events in patients with T2DM and established CV disease.SGLT2i have been shown to have a stronger benefit in patients with congestiveheart failure and diabetic kidney disease when compared to their GLP-1RA counterparts. These benefits are not withstanding additional considerations such as cost and the multiple FDA Black Box warnings. This topic is currently an emerging research area and this mini-review paper examines the role of these two novel classes of drugs in patients with T2DM with both confirmed, and at risk for, CVD. | Leonardo Pozo Fatimah Bello Andres Suarez Francisco E Ochoa-Martinez Yamely Mendez Chelsea H Chang Salim Surani | 2019 | World Journal of Diabetes2019，10，5： | 2 |
| 20 | Kinetics of silica particle formation in nonionic W/O microemulsions from TEOS显示文摘 | Chang C L Fogler H S | 1996 | AICHE Journal1996，42，11： | 1 |
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