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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 herbal compound geniposide rescues formaldehyde-induced apoptosis in N2a neuroblastoma cells显示文摘The herbal medicine Tong Luo Jiu Nao(TLJN)contains geniposide(GP)and ginsenoside Rg1 at a molar ratio of 10:1.Rg1 is the major component of another herbal medicine,panax notoginseng saponin(PNS).TLJN has been shown to strengthen brain function in humans,and in animals it improves learning and memory.We have previously shown that TLJN reduces amyloidogenic processing in Alzheimer’s disease(AD)mouse models.Together this suggests TLJN may be a potential treatment for patients with dementia.Because chronic damage of the central nervous system by formaldehyde(FA)has been presented as a risk factor for age-associated cognitive dysfunction,in the present study we investigated the protective effect of both TLJN and GP in neuron-like cells exposed to FA.FA-exposed murine N2a neuroblastoma cells were incubated with TLJN,its main ingredient GP,as well as PNS,to measure cell viability and morphology,the rate of apoptosis and expression of genes encoding Akt,FOXO3,Bcl2 and p53.The CCK-8 assay,cytoskeletal staining and flow cytometry were used to test cell viability,morphology and apoptosis,respectively.Fluorescent quantitative real-time PCR(qRT-PCR)was used to monitor changes in gene expression,and HPLC to determine the rate of FA clearance.Treatment of N2a cells with 0.09 mmol L?1 FA for 24 h significantly reduced cell viability,changed cell morphology and promoted apoptosis.Both TLJN and GP conferred neuroprotection to FA-treated N2a cells,whereas PNS,which had to be used at lower concentrations because of its toxicity,did not.Our data demonstrate that TLJN can rescue neuronal damage caused by FA and that its main ingredient,GP,has a major role in this efficacy.This presents purified GP as a drug or lead compound for the treatment of AD. | CHEN JinYan SUN MengRu WANG XingHua LU Jing WEI Yan TAN Yan LIU Ying GTZ Jürgen HE RongQiao HUA Qian | 2014 | Science China(Life Sciences)2014，57，4： | 15 |
| 3 | Visualizing the microtubule-associated protein tau in the nucleus显示文摘Although tau is mainly known as an axonal microtubule-associated protein,many studies indicate that it is not restricted to this subcellular compartment.Assessing tau’s subcellular distribution,however,is not trivial as is evident from transgenic mouse studies.When human tau is over-expressed,it can be immunohistochemically localized to axons and the somatodendritic domain,modeling what is found in neurodegenerative diseases such as Alzheimer’s disease.Yet,in wild-type mice,despite its abundance,tau is difficult to visualize even in the axon.It is even more challenging to detect this protein in the nucleus,where tau has been proposed to protect DNA from damage.To establish a framework for future studies into tau’s nuclear functions,we compared several methods to visualize endogenous nuclear tau in cell lines and mouse brain.While depending on the fixation and permeabilization protocol,we were able to detect nuclear tau in SH-SY5Y human neuroblastoma cells,we failed to do so in N2a murine neuroblastoma cells.As a second method we used subcellular fractionation of mouse tissue and found that in the nucleus tau is mainly present in a hypophosphorylated form.When either full-length or truncated human tau was expressed,both accumulated in the cytoplasm,but were also found in the nuclear fraction.Because subcellular fractionation methods have their limitations,we finally isolated nuclei to probe for nuclear tau and found that the nuclei were free of cytoplasmic contamination.Together our analysis identifies several protocols for detecting tau in the nucleus where it is found in a less phosphorylated form. | LU Jing LI Ting HE RongQiao BARTLETT Perry F GTZ Jürgen | 2014 | Science China(Life Sciences)2014，57，4： | 11 |
| 4 | 煤灰沉积的传热过程模型及其数值研究显示文摘计算流体力学(CFD)方法的应用在锅炉设计或燃烧设备的改造过程中有着十分重要的作用.本文研究了实际燃烧过程中普遍存在的煤灰沉积现象对数值计算结果的影响,提出了描述煤灰沉积的新型传热模型,比较了新模型采用前后数值计算结果与实测数据的差异,从而验证了该模型的合理性,提高了对炉内积灰、结渣过程数值描述的精度. | 徐明厚 郑楚光 HE X G AZEVEDO J L T CARVALHO M G | 2002 | 工程热物理学报2002，23，1： | 10 |
| 5 | An epigenomic approach to therapy for tamoxifen-resistant breast cancer显示文摘Tamoxifen 是为雌激素受体 alpha 的前线治疗(ERα) 在绝经前的女人的积极的胸肿瘤。然而,到 tamoxifen 的抵抗发生在许多病人。嗯仍然与获得的 tamoxifen 抵抗在乳癌房间的生长起一个关键作用,建议那 ERα为治疗仍然是一个有效目标 tamoxifen 抵抗(Tam-R ) 乳癌。以识别 ERα 的新奇管理者;发信号,通过对 histone 甲基修饰词的一幅小规模的 siRNA 屏幕,我们发现了 WHSC1, histone H3K36 methyltransferase, ERα 的一个积极管理者;在乳癌房间发信号。我们证明 WHSC1 被招募到 ERα由 BET 蛋白质 BRD3/4 的基因,并且便于 ERα基因表示。小分子的赌注蛋白质禁止者 JQ1 potently 压制了经典 ERα发信号的小径和在文化的 Tam-R 乳癌房间的生长。用一个 Tam-R 乳癌异种皮移植老鼠模型,我们与 JQ1 和 ER degrader fulvestrant 由 JQ1 和联合治疗的强壮的长持续的效果在 vivo 反胸癌症活动示威了。一起拿,我们提供 epigenomic 蛋白质 BRD3/4 和 WHSC1 是雌激素受体发信号的必要管理者并且是为 Tam-R 乳癌的治疗的新奇治疗学的目标的证据。 | Qin Feng Zheng Zhang Martin J Shea Chad J Creighton Cristian Coarfa Susan G Hilsenbeck Rainer Lanz Bin He Lei Wang Xiaoyong Fu Agostina Nardone Yongcheng Song James Bradner Nicholas Mitsiades Constantine S Mitsiades C Kent Osborne Rachel Schiff Bert W O'Malley | 2014 | Cell Research2014，24，7： | 10 |
| 6 | 缺血性脑卒中后的中期血压变异性与临床结局的关系显示文摘本研究旨在探讨急性脑卒中患者发病7d内的中期血压变异性(blood pressure variability,BPV)与预后的关系。方法:本研究纳入873例急性缺血性脑卒中患者。通过计算发病7d内的收缩压和舒张压的变异系数来评价中期BPV。 | Wang Y Wang J Meng P Liu N Ji N Zhang G Xu B Zhou X Sun Y Xu Y Hui R He M 陈云 叶鹏 | 2018 | 中华高血压杂志2018，26，5： | 2 |
| 7 | Speciation of heavy metals in marine sediments from the East China Sea by ICP-MS with sequential extraction显示文摘 | Yuan C G Shi J B He B | 2004 | Environment International2004，30，： | 1 |
| 8 | Application of an intelligent classification method to mechanical fault diagnosis显示文摘 | LEI Y G HE Z J ZI Y Y | 2009 | Expert Systems with Applications2009，36，6： | 1 |
| 9 | disturbance attenuation for state delayed systems 显示文摘 | Wang Q G Lee T H | 1998 | System & Control Letters1998，33，： | 1 |
| 10 | Inverse application of charge simulation method in detecting faulty ceramic insulators and processing influence from tower 显示文摘 | HE W YANG F WANG J G | 2006 | IEEE Transactions on Magnetics2006，42，4： | 1 |
| 11 | Newly synthesized dyes and their polymer/Glass composites for one-and two-photon pumped solid-state cavity lasing显示文摘 | Zhao C F He G S Bhawalkar J D | 1995 | Chem Mater1995，，7： | 1 |
| 12 | Location and migration of cations in Cu2+-adsorbed montmorillonite显示文摘 | H P He J G Guo X D Xie | 2001 | Environment International2001，26，： | 1 |
| 13 | Sea surface temperature variability in the north side of the South China Sea over the last 55 years revealed by coral δ^18O records显示文摘 | Peng Z C He J F Chen T G | 2003 | Geochimica et Cosmochimica Acta2003，67，18： | 1 |
| 14 | Ti-based Nano-structure-dendrite Composite with Enhanced Plasticity显示文摘 | G He J Eckert W Loeser L Novel | 2003 | Nature Mater2003，2，1： | 1 |
| 15 | Modeling Rotor Wake Dynamics with Vis- cous Vortex Particle Method 显示文摘 | He C J Zhao J G | 2009 | AIAA Journal2009，47，4： | 1 |
| 16 | MieroRNAs: small RNAs with a big role in gene regulation显示文摘 | HE L HANNON G J | 2004 | Nature Re- views Genetics2004，5，7： | 1 |
| 17 | Repression of Smad4 transcrip- tional activity by SUMO modification显示文摘 | Long J Wang G He D | 2004 | Biochem J2004，379，1： | 1 |
| 18 | Risk factors of obesity in preschool children in an urban area in China显示文摘 | Zhou L He G Zhang J | 2011 | Eur J Pedialr2011，170，11： | 1 |
| 19 | Influence of droplet kinetic energy flux density from fixed spray-plate sprinklers on soil infiltration,runoff and sediment yield显示文摘 | Yan H J Bai G He J Q | 2011 | Biosystems Engineering2011，110，2： | 1 |
| 20 | 查看详情显示文摘 | Zhang J P Yang H P Han K L Deng W Q He G Z Lou N Q | | 0，，： | 1 |
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