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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 | 体内腺相关病毒-常间回文重复序列丛集及其相关蛋白9介导的基因编辑可改善家族性高胆固醇血症的动脉粥样硬化显示文摘低密度脂蛋白受体(low-density lipoprotein receptor,Ldlr)基因突变是家族性高胆固醇血症的主要原因之一,可导致动脉粥样硬化,并具有很高的终生心血管病风险。常间回文重复序列丛集(clustered regularly interspaced short palindromic repeats,CRISPR)/CRISPR相关蛋白9(CRISPR-related protein 9,Cas9)系统是基因编辑纠正基因突变从而改善疾病的有效工具。该研究的目的是通过腺相关病毒(adeno-associated virus,AAV)携带的CRISPR/Cas9系统进行体内体细胞基因编辑,以确定其能否在小鼠模型中治疗由Ldlr突变体引起的家族性高胆固醇血症。 | 刘青(译) 叶鹏(审校) Zhao H Li Y He L Pu W Yu W Li Y Wu YT Xu C Wei Y Ding Q Song BL Huang H Zhou B | 2020 | 中华高血压杂志2020，28，3： | 22 |
| 3 | On the combined effect of soil fertility and topography on tree growth in subtropical forest ecosystems—a study from SE China显示文摘Aims The aim of our research was to understand small-scale effects of topography and soil fertility on tree growth in a forest biodiversity and ecosystem functioning(BEF)experiment in subtropical SE China.Methods Geomorphometric terrain analyses were carried out at a spatial resolution of 5×5 m.Soil samples of different depth increments and data on tree height were collected from a total of 566 plots(667 m2 each).The soils were analyzed for carbon(soil organic carbon[SOC]),nitrogen,acidity,cation exchange capacity(CEC),exchangeable cations and base saturation as soil fertility attributes.All plots were classified into geomorphological units.Analyses of variance and linear regressions were applied to all terrain,soil fertility and tree growth attributes.Important Findings In general,young and shallow soils and relatively small differences in stable soil properties suggest that soil erosion has truncated the soils to a large extent over the whole area of the experiment.This explains the concurrently increasing CEC and SOC stocks downslope,in hollows and in valleys.However,colluvial,carbon-rich sediments are missing widely due to the convexity of the footslopes caused by uplift and removal of eroded sediments by adjacent waterways.The results showed that soil fertility is mainly influenced by topography.Monte-Carlo flow accumulation(MCCA),curvature,slope and aspect significantly affected soil fertility.Furthermore,soil fertility was affected by the different geomorphological positions on the experimental sites with ridge and spur positions showing lower exchangeable base cation contents,especially potassium(K),due to leaching.This geomorphological effect of soil fertility is most pronounced in the topsoil and decreases when considering the subsoil down to 50 cm depth.Few soil fertility attributes affect tree height after 1-2 years of growth,among which C stocks proved to be most important while pH_(KCl)and CEC only played minor roles.Nevertheless,soil acidity and a high proportion of Al on the exchange complex affected tree height even after only 1-2 years growth.Hence,our study showed that forest nutrition is coupled to a recycling of litter nutrients,and does not only depend on subsequent supply of nutrients from the mineral soil.Besides soil fertility,topography affected tree height.We found that especially MCCA as indicator of water availability affected tree growth at small-scale,as well as aspect.Overall,our synthesis on the interrelation between fertility,topography and tree growth in a subtropical forest ecosystem in SE China showed that topographic heterogeneity lead to ecological gradients across geomorphological positions.In this respect,small-scale soil-plant interactions in a young forest can serve as a driver for the future development of vegetation and biodiversity control on soil fertility.In addition,it shows that terrain attributes should be accounted for in ecological research. | Thomas Scholten Philipp Goebes Peter Kühn Steffen Seitz Thorsten Assmann Jürgen Bauhus Helge Bruelheide Francois Buscot Alexandra Erfmeier Markus Fischer Werner Härdtle Jin-Sheng He Keping Ma Pascal A.Niklaus Michael Scherer-Lorenzen Bernhard Schmid Xuezheng Shi Zhengshan Song Goddert von Oheimb Christian Wirth Tesfaye Wubet Karsten Schmidt | 2017 | Journal of Plant Ecology2017，10，1： | 22 |
| 4 | Unusual life-threatening Rosai-Dorfman disease of the trachea. role of NF-kappa B显示文摘 | Zhou, LF Chen, LA Zhu, QA Wang, C Xu, H Cui, XF Jiang, LF He, Ski Huang, M Yin, KS | 2010 | 南京医科大学学报(自然科学版)2010，30，11： | 21 |
| 5 | Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis.显示文摘 | Zhang J Liu Q Chen Q Liu NQ Li FL Lu ZB Qin C Zhu H Huang YY He W Zhao BL | 2006 | 中国生物学文摘2006，20，9： | 17 |
| 6 | The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. | Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid | 2019 | Genes & Diseases2019，6，3： | 15 |
| 7 | Transcriptomic landscape regulated by the 14 types of bone morphogenetic proteins(BMPs)in lineage commitment and differentiation of mesenchymal stem cells(MSCs)显示文摘Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and myocytes.MSCs represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult tissues.At least 14 BMPs have been identified in mammals.Different BMPs exert distinct but overlapping biological functions.Through a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of MSCs.Nonetheless,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully elucidated.Here,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of BMPs.Hierarchical clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 cluster.We also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase pathway.Furthermore,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,Notch and PI3K/AKT/mTOR pathways.While the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs. | Linghuan Zhang Qing Luo Yi Shu Zongyue Zeng Bo Huang Yixiao Feng Bo Zhang Xi Wang Yan Lei Zhenyu Ye Ling Zhao Daigui Cao Lijuan Yang Xian Chen Bin Liu William Wagstaff Russell R*Reid Hue H*Luu Rex C*Haydon Michael J*Lee Jennifer Moriatis Wolf Zhou Fu Tong-Chuan He Quan Kang | 2019 | Genes & Diseases2019，6，3： | 11 |
| 8 | Multivariate statistical analysis of clinicopathologic factors influencing survival of patients with bile duct carcinoma显示文摘AIM: To evaluate the influence of various clinicopathologicfactors on survival of patients with bile duct carcinoma aftercurative resection.METHODS: A retrospective analysis was made for 86 casesof bile duct carcinoma treated from January 1981 toSeptember 1995. Fifteen clinicopathologic factors possiblyinfluencing survival were selected. Independent variableswere first analyzed by univariate methods. Survival forvariable was estimated by the method of Kaplan and Meier.The variables that were statistically significant by univarlateanalysis were included in a multivariate analysis, which wereconfirmed using the Cox stepwise proportion hazard modelwith the help of SPSS 10.0 for Windows software.RESULTS: The overall cumulative survival rate was 72.6 %at 1 year, 32.4 % at 3 years, and 18.7 % at 5 years. Theresults of univariate analysis showed that the majorsignificant prognostic factors influencing survival of thesepatients were histological type of lesion, lymph nodemetastasis, pancreatic invasion, duodenal invasion, pedneuralinvasion, macroscopic vessel involvement, resected surgicalmargin and depth of cancer invasion (P=0.02, 0.02, 0.004,0.005, 0.01, 0.43, 0.03 and 0.04). Age, sex, location of tumor,size of tumor, macroscopic type of lesions, hepaticmetastasis, and hepatic invasion were not significantlyassociated with prognosis (P>0.05). Pancreatic invasion,perineural invasion and lymph node metastases were thethree most important prognostic factors by multivariateanalysis using the Cox proportional hazards model.CONCLUSION: Pancreatic invasion, pedneural invasion andlymph node metastases are the most important prognosticfactors for bile duct carcinoma after curative resection. | He, P Shi, JS Chen, WK Wang, ZR Ren, H Li, H | 2002 | World Journal of Gastroenterology2002，8，5： | 10 |
| 9 | Expression and release of IL-29 by mast cells and modulation of mast cell behavior by IL-29显示文摘 | He, S Zhang, H Chen, H Yang, H Huang, T Chen, Y Lin, J Wang, F Chen, X Li, TL Yang, P | 2010 | 南京医科大学学报(自然科学版)2010，30，11： | 6 |
| 10 | 血清netrin-1增加与缺血性脑卒中预后改善相关显示文摘先前的实验研究表明,血清netrin-1与缺血性脑卒中进展相关。进一步了解缺血性脑卒中患者中netrin-1的变化可能为缺血性脑卒中的预后评估提供新的思路。该研究旨在探讨血清netrin-1与缺血性脑卒中预后的关系。研究人员测定3346例中国急性缺血性脑卒中抗高血压试验(China antihypertensive trial in acute ischemic stroke,CATIS)中缺血性脑卒中患者基线血清netrin-1水平,所有患者均在脑卒中发病后3个月进行随访。主要观察指标是脑卒中发病后3个月内死亡和严重残疾(改良Rankin 量表评分≥3)。 | 刘莉 叶鹏 Guo D Zhu Z Zhong C Peng H Wang A Xu T Peng Y Xu T Chen CS Li Q Ju Z Geng D Chen J Zhang Y He J | 2019 | 中华高血压杂志2019，27，5： | 6 |
| 11 | Efficient therapeutic gene expression in cultured rat hippocampal neurons mediated by human foamy virus vectors: a potential for the treatment of neurological diseases显示文摘 | Liu W He X Cao Z Sheng J Liu H Li Z Li W | 2006 | 中国生物学文摘2006，20，10： | 5 |
| 12 | Vitamin C Enhances the Generation of Mouse and Human Induced Pluripotent Stem Cells显示文摘 | Miguel Angel Esteban Tao Wang Baoming Qin Jiayin Yang Dajiang Qin Jinglei Cai Wen Li Zhihui Weng Jiekai Chen Su Ni Keshi Chen Yuan Li Xiaopeng Liu Jianyong Xu Shiqiang Zhang Feng Li Wenzhi He Krystyna Labuda Yancheng Song Anja Peterbauer Susanne Wolbank H | 2010 | Cell Stem Cell2010，，： | 3 |
| 13 | 基于FeCoNiCrMn高熵合金的晶粒生长和霍尔-佩奇关系研究取得新进展显示文摘高熵合金是一种新型的合金设计理念,这种合金一般含有5种或5种以上的合金元素,且每种元素含量都相同或者相似。高熵效应抑制了金属间化合物的出现,促使元素间相互混合,最终形成体心立方结构(BCC)或面心立方结构(FCC)等较为简单的结构。 | 吴渊 Liu W H Wu Y He J Y | 2015 | 中国表面工程2015，28，3： | 3 |
| 14 | Four multidetector-row helical CT: image quality and volume coverage speed显示文摘 | Hu H He H D Foley W D | 2000 | Radiology2000，215，1： | 2 |
| 15 | Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells显示文摘AIM:To investigate the impact of arachidonic acid (AA) and docosahexaenoic acid (DHA) and their combination on colon cancer cell growth.METHODS:The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. Cell viability was assessed in XTT assays. For analysis of cell cycle and cell death,flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 (COX-2),p21 and bcl-2 in cells incubated with AA or DHA was examined by real-time RT-PCR. Prostaglandin E2 (PGE2) generation in the presence of AA and DHA was measured using a PGE2-ELISA.RESULTS:AA increased cell growth,whereas DHAreduced viability of LS 174T cells in a time-and dose-dependent manner. Furthermore,DHA down-regulated mRNA of bcl-2 and up-regulated p21. Interestingly,DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE2 formation. DHA also down-regulated COX-2 expression. In addition to the effect on PGE2 formation,DHA directly reduced PGE2-induced cell proliferation in a dose-dependent manner. CONCLUSION:These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE2. | Piet Habbel Karsten H Weylandt Katja Lichopoj Johannes Nowak Martin Purschke Jing-Dong Wang Cheng-Wei He Daniel C Baumgart Jing X Kang | 2009 | World Journal of Gastroenterology2009，15，9： | 2 |
| 16 | Study on incisional implantation of tumor cells by carbon dioxide pneumoperitoneum in gastric cancer of a murine model显示文摘 | Wang H Zheng MH Zhang HB Zhu J He JR Lu AG Ji YB Zhang MJ Jiang Y Yu BM Li HW | 1999 | World Journal of Gastroenterology1999，5，6： | 2 |
| 17 | Effects of panax notosinseng sapoins on the receptor operated Ca2+ channel显示文摘 | Guan YY Kwan CY He H | 1994 | Act Pharmacol Sin1994，15，5： | 2 |
| 18 | Synthesis, microstructure, and mechanical properties of TiO2/Ni nanocomposite coatings显示文摘 | Li J Jiang J He H | 2002 | Journal of Materials Science Letters2002，21，： | 2 |
| 19 | Studies on solid-solid phase transition of polyols by infrared spectroscopy 显示文摘 | Feng H Y Liu X D He S M | 2000 | Thermochim Acta2000，348，： | 2 |
| 20 | Molecular diversity of microbial community in acid mine drainages of Yunfu sulfide mine显示文摘 | He ZG Xiao SM Xie XH Zhong H Hu YH Li QH Gao FL Li GY Liu JS Qiu GZ | 2007 | 中国生物学文摘2007，21，6： | 2 |
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