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| 1 | YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA显示文摘 | Hailing Shi Xiao Wang Zhike Lu Boxuan S Zhao Honghui Ma Phillip J HSU Chang Liu Chuan He | 2017 | Cell Research2017，27，3： | 156 |
| 2 | 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 |
| 3 | Petawatt and exawatt class lasers worldwide显示文摘In the 2015 review paper‘Petawatt Class Lasers Worldwide’a comprehensive overview of the current status of highpower facilities of>200 TW was presented.This was largely based on facility specifications,with some description of their uses,for instance in fundamental ultra-high-intensity interactions,secondary source generation,and inertial confinement fusion(ICF).With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification(CPA),which made these lasers possible,we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed.We are now in the era of multi-petawatt facilities coming online,with 100 PW lasers being proposed and even under construction.In addition to this there is a pull towards development of industrial and multi-disciplinary applications,which demands much higher repetition rates,delivering high-average powers with higher efficiencies and the use of alternative wavelengths:mid-IR facilities.So apart from a comprehensive update of the current global status,we want to look at what technologies are to be deployed to get to these new regimes,and some of the critical issues facing their development. | Colin N.Danson Constantin Haefner Jake Bromage Thomas Butcher Jean-Christophe FChanteloup Enam A.Chowdhury Almantas Galvanauskas Leonida A.Gizzi Joachim Hein David I.Hillier Nicholas W.Hopps Yoshiaki Kato Efim A.Khazanov Ryosuke Kodama Georg Korn Ruxin Li Yutong Li Jens Limpert Jingui Ma Chang Hee Nam David Neely Dimitrios Papadopoulos Rory R.Penman Liejia Qian Jorge J.Rocca andrey A.Shaykin Craig W.Siders Christopher Spindloe Sándor Szatmári Raoul M.G.M.Trines Jianqiang Zhu Ping Zhu Jonathan D.Zuegel | 2019 | High Power Laser Science and Engineering2019，7，3： | 33 |
| 4 | 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 |
| 5 | Miocene Bahean stratigraphy in the Longzhong Basin, northern central China and its implications in environmental change显示文摘Fossil mammal-riched Neogene strata are widely distributed in the southeast corner of the huge Longzhong Basin at Tianshui, Gansu Province, northern central China. Hipparion weihoense, a typical member of late Middle Miocene Bahean stage, was recently excavated at Yaodian along a well-exposed outcrop. Owing to the importance of the Bahean stage in the mammalian evolution and its potential for environmental change, we suggested a name of Yaodian Formation for the stratigra- phy, which is correlated to the Bahe Formation at Lantian, Shaanxi. High resolution paleomagnetic dating of the section shows that the Yaodian Formation covers the period between 11.67 Ma and 7.43 Ma, with the site bearing Hipparion weihoense being estimated at about 10.54―10.30 Ma, providing first magnetostratigraphic chronology for the Bahean Stage. The Yaodian Formation consists of fluvial channel deposits (11.67―10.40 Ma) at the bottom, floodplain deposits in the middle (10.40―9.23 Ma) and shallow lake sediments at the top (9.23―7.43 Ma). This upward fining sequence suggests that the relief in nearby mountain ranges such as West Qinling to the south and Huajia Ling to the north was greatly reduced after long-term denudation, fluvial transport capacity was low, and finally the drainage system was disintegrated, replaced with broad-shallow lakes in which only fine sediments like mud and marlite were deposited, indicating an old stage of development of a planation surface. A remarkable shift in ecology and climatic environment was found at 7.4―7.7 Ma when paleoclimate changed from early warm humid to late dry as indicated by sedimentary facies changed from early shallow lake sequence to late eolian red clays and a former coniferous-deciduous mixed forest was replaced by grassland, leading to great growth of Hipparion Fauna of Baodean stage in the region. Therefore, it is estimated that the present high relief of Qinling and drainage pattern did not come into being until Late Pliocene in response to intensive neotectonism and climate change. | LI Jijun1,2, ZHANG Jun1, SONG Chunhui1, ZHAO Zhijun2, ZHANG Yong1, WANG Xiuxi 1, ZHANG Jianming1 & CUI Qiaoyu1 1. Key Laboratory of Western China’s Environmental Systems (Ministry of Education) & College of Earth and Environment Sciences, Lanzhou University, Lanzhou 730000, China 2. Jiangsu Key Laboratory of Environmental Change and Ecological Construction & College of Geography, Nanjing Normal University, Nanjing 210097, China | 2006 | Science China Earth Sciences2006，49，12： | 12 |
| 6 | A basic helix-loop-helix transcription factor, PhFBH4, regulates flower senescence by modulating ethylene biosynthesis pathway in petunia显示文摘The basic helix-loop-helix(bHLH)transcription factors(TFs)play important roles in regulating multiple biological processes in plants.However,there are few reports about the function of bHLHs in flower senescence.In this study,a bHLH TF,PhFBH4,was found to be dramatically upregulated during flower senescence.Transcription of PhFBH4 is induced by plant hormones and abiotic stress treatments.Silencing of PhFBH4 using virus-induced gene silencing or an antisense approach extended flower longevity,while transgenic petunia flowers with an overexpression construct showed a reduction in flower lifespan.Abundance of transcripts of senescence-related genes(SAG12,SAG29)was significantly changed in petunia PhFBH4 transgenic flowers.Furthermore,silencing or overexpression of PhFBH4 reduced or increased,respectively,transcript abundances of important ethylene biosynthesis-related genes,ACS1 and ACO1,thereby influencing ethylene production.An electrophoretic mobility shift assay showed that the PhFBH4 protein physically interacted with the G-box cis-element in the promoter of ACS1,suggesting that ACS1 was a direct target of the PhFBH4 protein.In addition,ectopic expression of this gene altered plant development including plant height,internode length,and size of leaves and flowers,accompanied by alteration of transcript abundance of the gibberellin biosynthesis-related gene GA2OX3.Our results indicate that PhFBH4 plays an important role in regulating plant growth and development through modulating the ethylene biosynthesis pathway. | Jing Yin Xiaoxiao Chang Takao Kasuga Mai Bui Michael S Reid Cai-Zhong Jiang | 2015 | Horticulture Research2015，2，1： | 7 |
| 7 | Pollen assemblage characteristics of lakes in the monsoon fringe area of China显示文摘This paper presents the pollen assemblages from 108 surface sediment samples from 4 lakes(the Lake Daihai,Lake Hongjiannao,Lake Hulunnao and Lake Duikounao) in the monsoon fringe area of China.The herb pollen taxa Artemisia,Chenopodiaceae,Poaceae and Compositae are the major components of pollen assemblages of the 4 lakes and Pinus,Betula,Quercus,Ulmus,Populus,Ostryopsis and Elaeagnaceae are frequently presented,which reflect regional and local vegetation well.The mean similarity coefficients for samples from the Lake Daihai,Lake Hongjiannao,Lake Hulunnao and Lake Duikounao are 0.66 ± 0.17,0.71 ± 0.11,0.73 ± 0.12 and 0.67 ± 0.12 respectively,so pollen assemblages are relatively consistent in each lake,which shows that focusing and mixing effects have occurred before and after pollen deposition.However,pollen assemblages do differ between sampling sites in each lake.The largest difference is seen in the Lake Daihai,followed by the Lake Duikounao,Lake Hulunnao and Lake Hongjiannao(The mean Euclidean distance is 20.09 ± 11.11,11.22 ± 3.64,10.67 ± 4.03 and 8.44 ± 4.51 respectively).These differences are possibly caused by the differences of focusing and mixing effects,pollen source areas,drainage areas and regional vegetation compositions.The Lake Daihai and Lake Hongjiannao have water deeper than 5 m and strong re-suspension,focusing and mixing effects occur in the lakeshore and shallow water areas,where pollen concentrations are lower than in deeper lake areas.In the Lake Hulunnao and Lake Duikounao,with depths less than 5 m,re-suspension and mixing effects are obvious across the whole lake area,so pollen assemblages and pollen concentra-tions are more consistent among sampling sites in each lake.Comparison between the lake samples and samples from the inflowing river reveals that wind is primary pollen transportation force in the Lake Hongjiannao,where the consistency of pollen assemblage is conspicuous,while there is greater variation in lakes where pollen input is dominated by waterborne sources. | TIAN Fang1,2,XU QingHai1,2,3,LI YueCong1,2,CAO XianYong1,2,WANG XueLi1,2 & ZHANG LiYan1,2 1 College of Resources and Environmental Sciences,Hebei Normal University,Shijiazhuang 050016,China 2 Hebei Key Laboratory of Environmental Change and Ecological Construction,Shijiazhuang 050016,China 3 Key Laboratory of Western China’s Environmental System(Ministry of Education),Lanzhou University,Lanzhou 730000,China | 2008 | Chinese Science Bulletin2008，53，21： | 7 |
| 8 | Evolution of permafrost in China during the last 20 ka显示文摘The formation and evolution of permafrost in China during the last 20 ka were reconstructed on the basis of large amount of paleo-permafrost remains and paleo-periglacial evidence, as well as paleo-glacial landforms, paleo-flora and paleofauna records. The results indicate that, during the local Last Glacial Maximum(LLGM) or local Last Permafrost Maximum(LLPMax), the extent of permafrost of China reached 5.3×106-5.4×106 km2, or thrice that of today, but permafrost shrank to only0.80×106-0.85×106 km2, or 50% that of present, during the local Holocene Megathermal Period(LHMP), or the local Last Permafrost Minimum(LLPMin). On the basis of the dating of periglacial remains and their distributive features, the extent of permafrost in China was delineated for the two periods of LLGM(LLPMax) and LHMP(LLPMin), and the evolution of permafrost in China was divided into seven periods as follows:(1) LLGM in Late Pleistocene(ca. 20000 to 13000-10800 a BP)with extensive evidence for the presence of intensive ice-wedge expansion for outlining its LLPMax extent;(2) A period of dramatically changing climate during the early Holocene(10800 to 8500-7000 a BP) when permafrost remained relatively stable but with a general trend of shrinking areal extent;(3) The LHMP in the Mid-Holocene(8500-7000 to 4000-3000 a BP)when permafrost degraded intensively and extensively, and shrank to the LLPMin;(4) Neoglaciation during the late Holocene(4000-3000 to 1000 a BP, when permafrost again expanded;(5) Medieval Warming Period(MWP) in the late Holocene(1000-500 a BP) when permafrost was in a relative decline;(6) Little Ice Age(LIA) in the late Holocene(500-100 a BP), when permafrost relatively expanded, and;(7) Recent warming(during the 20 th century), when permafrost continuously degraded and still is degrading. The paleo-climate, geography and paleopermafrost extents and other features were reconstructed for each of these seven periods. | Huijun JIN Xiaoying JIN Ruixia HE Dongliang LUO Xiaoli CHANG Shaoling WANG Sergey S MARCHENKO Sizhong YANG Chaolu YI Shijie LI Stuart A HARRIS | 2019 | Science China Earth Sciences2019，62，8： | 6 |
| 9 | Treatment of malignant digestive tract obstruction by combined intraluminal stent installation and intra-arterial drug infusion显示文摘AIM To study the palliative treatment of malignant obstrution of digestive tract with placement of intraluminal stent combined with intra-arterial infusion of chemotherapeutic drugs.METHODS A total of 281 cases of digestive tract malignant obstruction were given per oral (esophagus,stomach, duodenum and jejunum), per anal (colon and rectum ) and percutaneous transhepatic ( biliary )installation of metallic stent. Among them, 205 cases received drug infusion by cannulation of tumor supplying artery with Seldingers technique.RESULTS Altogether 350 stents were installed in 281 cases, obstructive symptoms were relieved or ameliorated after installation. Occurrence of restenotic obstruction was 8 - 43 weeks among those with intraarterial drug infusion, which was later than 4 - 26 weeks in the group with only stent installation. The average survival time of the former group was 43 (3 - 105) weeks,which was significantly longer than 15 (3- 24) weeks of the latter group.CONCLUSION Intraluminal placement of stent combined with intra-arterial infusion chemotherapy is one of the effective palliative therapies for malignant obstruction of the digestive tract with symptomatic as well as etiological treatment. | Ai-Wu Mao Zhong-Du Gao Jia-Yu Xu Ren-Jie Yang Xiang-Seng Xiao Ting-Hui Jiang Wei-Jun Jiang Department of Interventional Radiology,Shanghai S.T,Luke’s Hospital,768 Yu Yuan Road,Shanghai 200050,ChinaDepartment of Gastroenterology Rui Jin Hospital,Shanghai Second Medical University,Departrnent of Tumor Hospital,Beijing Medical UniversityDepartment of Imaging Chang Zheng Hospital,Shanghai Second Military Medical University | 2001 | World Journal of Gastroenterology2001，7，4： | 6 |
| 10 | 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 |
| 11 | The strigolactone receptor D14 targets SMAX1 for degradation in response to GR24 treatment and osmotic stress显示文摘The effects of the phytohormone strigolactone(SL)and smoke-derived karrikins(KARs)on plants are generally distinct,despite the fact that they are perceived through very similar mechanisms.The homologous receptors DWARF14(D14)and KARRIKIN-INSENSITIVE2(KAI2),together with the F-box protein MORE AXILLARY GROWTH2(MAX2),mediate SL and KAR responses,respectively,by targeting different SMAX1-LIKE(SMXL)family proteins for degradation.These mechanisms are putatively well-insulated,with D14-MAX2 targeting SMXL6,SMXL7,and SMXL8 and KAI2-MAX2 targeting SMAX1 and SMXL2 in Arabidopsis thaliana.Recent evidence challenges this model.We investigated whether D14 can target SMAX1 and whether this occurs naturally.Genetic analysis indicates that the SL analog GR24 promotes D14-SMAX1 crosstalk.Although D14 shows weaker interactions with SMAX1 than with SMXL2 or SMXL7,D14 mediates GR24-induced degradation of SMAX1 in plants.Osmotic stress triggers SMAX1 degradation,which is protective,through SL biosynthesis and signaling genes.Thus,D14-SMAX1 crosstalk may be beneficial and not simply a vestige of the evolution of the SL pathway. | Qingtian Li Elena Sánchez Martín-Fontecha Aashima Khosla Alexandra R.F.White Sunhyun Chang Pilar Cubas David C.Nelson | 2022 | Plant Communications2022，3，2： | 5 |
| 12 | The ratio of MMP-2 to TIMP-2 in hilar cholangiocarcinoma:a semi-quantitative study显示文摘BACKGROUND: Hilar cholangiocarcinoma is associated with low resectability and poor survival. The aim of this study was to evaluate the roles of matrix metalloproteinases- 2 (MMP-2 ) and its tissue inhibitor of metalloproteinase-2 (TIMP-2) in tumor invasion or as a prognostic factor in patients with human hilar cholangiocarcinoma. METHODS: The expressions of MMP-2 and TIMP-2 were investigated in patients. Paraffinized tissue sections ob- tained from 50 patients with human hilar cholangiocarcino- ma were analysed. The expressions of MMP-2 and TIMP-2 were examined immunohistochemically. Image analysis with image-pro plus analysis software was used to semi- quantitatively determine the ratio of MMP-2 to TIMP-2. RESULTS: The expression levels of MMP-2 and TIMP-2 were strongly associated with tumor hepatic invasion in pa- tients with hilar cholangiocarcinoma. Significant diffe- rences in the ratio of MMP-2 to TIMP-2 between some pathologic factors were observed in patients with hilar cholangiocarcinoma. CONCLUSIONS: MMP-2 plays an essential role in tumor invasion and metastasis,while TIMP-2 is shown to strongly inhibit cancer invasion and metastasis. The ratio of MMP-2 to TIMP-2 may be a prognostic indicator for patients with hilar cholangiocarcinoma. | Mei Xiao, Nin-Xing Zhou,Zhi-Qiang Huang,Ya-Li Lu, Ling-Hong Chen, Dian-Jun Wang and Wei-Lin Chang Beijing, China Department of Hepatobiliary Surgery, General Air- force of Hospital, Beijing 100036, China and General Hospital of People’ s Liberation Army, Beijing 100853 , China | 2004 | Hepatobiliary & Pancreatic Diseases International2004，3，4： | 5 |
| 13 | Plecanatide-mediated activation of guanylate cyclase-C suppresses inflammation-induced colorectal carcinogenesis in Apc+/Min-FCCC mice显示文摘AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC) mice with dextran sodium sulfate(DSS)-induced inflammation. METHODS Inflammation driven colorectal carcinogenesis was induced in Apc^(+/Min-FCCC) mice by administering DSS in their drinking water. Mice were fed a diet supplemented with plecanatide(0-20 ppm) and its effect on the multiplicity of histopathologically confirmed polypoid,flat and indeterminate dysplasia was evaluated. Plecanatide-mediated activation of guanylate cyclase-C(GC-C) signaling was assessed in colon tissues by measuring cyclic guanosine monophosphate(cG MP) by ELISA, protein kinase G-II and vasodilator stimulated phosphoprotein by immunoblotting. Ki-67, c-myc and cyclin D1 were used as markers of proliferation. Cellular levels and localization of b-catenin in colon tissues were assessed by immunoblotting and immunohistochemistry, respectively. Uroguanylin(UG) and GC-C transcript levels were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR). A mouse cytokine array panel was used to detect cytokines in the supernatant of colon explant cultures. RESULTS Oral treatment of Apc^(+/Min-FCCC) mice with plecanatide produced a statistically significant reduction in the formation of inflammation-driven polypoid, flat and indeterminate dysplasias. This anti-carcinogenic activity of plecanatide was accompanied by activation of cG MP/GC-C signaling mediated inhibition of Wnt/b-catenin signaling and reduced proliferation. Plecanatide also decreased secretion of pro-inflammatory cytokines(IL-6, IL-1 TNF), chemokines(MIP-1, IP-10) and growth factors(GCSF and GMCSF) from colon explants derived from mice with acute DSS-induced inflammation. The effect of plecanatidemediated inhibition of inflammation/dysplasia on endogenous expression of UG and GC-C transcripts was measured in intestinal tissues. Although GC-C expression was not altered appreciably, a statistically significant increase in the level of UG transcripts was detected in the proximal small intestine and colon, potentially due to a reduction in intestinal inflammation and/or neoplasia. Taken together, these results suggest that reductions in endogenous UG, accompanied by dysregulation in GC-C signaling, may be an early event in inflammation-promoted colorectal neoplasia; an event that can potentially be ameliorated by prophylactic intervention with plecanatide.CONCLUSION This study provides the first evidence that orally administered plecanatide reduces the multiplicity of inflammation-driven colonic dysplasia in mice, demonstrating the utility for developing GC-C agonists as chemopreventive agents. | Wen-Chi L Chang Shet Masih Anusha Thadi Viren Patwa Apoorva Joshi Harry S Cooper Vaseem A Palejwala Margie L Clapper Kunwar Shailubhai | 2017 | World Journal of Gastrointestinal Pharmacology and Therapeutics2017，8，1： | 5 |
| 14 | 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 |
| 15 | Down-scaled regional ocean modeling system (ROMS) for high-resolution coastal hydrodynamics in Korea显示文摘A down-scaled operational oceanographic system is developed for the coastal waters of Korea using a regional ocean modeling system(ROMS).The operational oceanographic modeling system consists of atmospheric and hydrodynamic models.The hydrodynamic model,ROMS,is coupled with wave,sediment transport,and water quality modules.The system forecasts the predicted results twice a day on a 72 h basis,including sea surface elevation,currents,temperature,salinity,storm surge height,and wave information for the coastal waters of Korea.The predicted results are exported to the web-GIS-based coastal information system for real-time dissemination to the public and validation with real-time monitoring data using visualization technologies.The ROMS is two-way coupled with a simulating waves nearshore model,SWAN,for the hydrodynamics and waves,nested with the meteorological model,WRF,for the atmospheric surface forcing,and externally nested with the eutrophication model,CE-QUAL-ICM,for the water quality.The operational model,ROMS,was calibrated with the tidal surface observed with a tide-gage and verified with current data observed by bottom-mounted ADCP or AWAC near the coastal waters of Korea.To validate the predicted results,we used real-time monitoring data derived from remote buoy system,HF-radar,and geostationary ocean color imager(GOCI).This down-scaled operational coastal forecasting system will be used as a part of the Korea operational oceanographic system(KOOS) with other operational oceanographic systems. | LIM Hak-Soo KIM Chang S PARK Kwang-Soon SHIM Jae Seol CHUN Insik | 2013 | Acta Oceanologica Sinica2013，32，9： | 4 |
| 16 | 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 |
| 17 | Short-segment Barrett's esophagus and cardia intestinal metaplasia:A comparative analysis显示文摘AIM:To investigate the endoscopy and histology of short-segment Barrett's esophagus (SSBE) and cardia intestinal metaplasia (CIM),and their correlation with Helicobacter pylori (H. pylori) gastritis and gastroesophageal reflux disease (GERD). METHODS:Biopsy specimens were taken from 32 SSBE patients and 41 CIM patients with normal appearance of the esophagogastric junction. Eight biopsy specimens from the lower esophagus,cardia,and gastric antrum were stained with hematoxylin/eosin,Alcian blue/periodic acid-Schiff,Alcian blue/high iron diamine and Gimenez dye. Results were graded independently by one pathologist. RESULTS:The SSBE patients were younger than the CIM patients (P < 0.01). The incidence of dysplasia and incomplete intestinal metaplasia subtype was higher in SSBE patients than in CIM patients (P < 0.01). H. pylori infection was correlated with antral intestinal metaplasia (P < 0.05),but not with reflux symptomatic,endoscopic,or histological markers of GERD in CIM patients. SSBE was correlated with reflux symptomatic and endoscopic esophagitis (P < 0.01),but not with H. pylori infection and antral intestinal metaplasia. CONCLUSION:Dysplasia risk is significantly greater in SSBE patients than in CIM patients. CIM is a manifestation of H. pylori-associated and multifocal atrophic gastritis,whereas SSBE may result from GERD. | Ying Chang,Digestive Endoscopic Center,Shanghai Sixth Hospital,Shanghai Jiao Tong University,Shanghai 200233,China Bin Liu,Department of Emergence Surgery,Shaanxi Provincial People’s Hospital,Xi’an 710068,Shaanxi Province,China Gui-Sheng Liu,Department of Gastroenterology,Shaanxi Provincial People’s Hospital,Xi’an 710068,Shaanxi Province,China Tao Wang,Department of Gastroenterology,First Hospital of Xi’ an Jiaotong University,Xi’an 710061,Shaanxi Province,China Jun Gong,Department of Gastroenterology,Second Hospital of Xi’an Jiaotong University,Xi’an 710004,Shaanxi Province,China | 2010 | World Journal of Gastroenterology2010，16，48： | 3 |
| 18 | Role of observation of live cases done by Japanese experts in the acquisition of ESD skills by a western endoscopist显示文摘AIM:To evaluate the role of observation of experts performing endoscopic submucosal dissection(ESD)in the acquisition of ESD skills.METHODS:This prospective study is documenting the learning curve of one Western endoscopist.The study consisted of three periods.In the first period(preobservation),the trainee performed ESDs in animal models in his home institution in the United States.The second period(observation)consisted of visit to Japan and observation of live ESD cases done by experts.The observation of cases occurred over a 5-wk period.During the third period(post-observation),the trainee performed ESD in animal models in a similar fashion as in the first period.Three animal models were used:live40-50 kg Yorkshire pig,explanted pig stomach model,and explanted pig rectum model.The outcomes from the ESDs done in the animal models before and after observation of live human cases(main study intervention)were compared.Statistical analysis of the data included:Fisher’s exact test to compare distributions of a categorical variable,Wilcoxon rank sum test to compare distributions of a continuous variable between the two groups(pre-observation and post-observation),and Kruskal-Wallis test to evaluate the impact of lesion location and type of model(ex-vivo vs live pig)on lesion removal time.RESULTS:The trainee performed 38 ESDs in animal model(29 pre-observation/9 post-observation).The removal times post-observation were significantly shorter than those pre-observation(32.7±15.0 min vs 63.5±9.8 min,P<0.001).To minimize the impact of improving physician skill,the 9 lesions post-observation were compared to the last 9 lesions pre-observation and the removal times remained significantly shorter(32.7±15.0 min vs 61.0±7.4 min,P=0.0011).Regression analysis showed that ESD observation significantly reduced removal time when controlling for the sequence of lesion removal(P=0.025).Furthermore,it was also noted a trend towards decrease in failure to remove lesions and decrease in complications after the period of observation.This study did not find a significant difference in the time needed to remove lesions in different animal models.This finding could have important implications in designing training programs due to the substantial difference in cost between live animal and explanted organ models.The main limitation of this study is that it reflects the experience of a single endoscopist.CONCLUSION:Observation of experts performing ESD over short period of time can significantly contribute to the acquisition of ESD skills. | Peter V Draganov Myron Chang Roxana M Coman Mihir S Wagh Qi An Takuji Gotoda | 2014 | World Journal of Gastroenterology2014，20，16： | 3 |
| 19 | 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 |
| 20 | In vivo anti-tumor activity of murine hematopoietic stem cells expressing a p185HER2-specific chimeric T-cell receptor gene显示文摘We have confirmed efficient anti-tumor activities of the peripheral lymphocytes transduced with a p185HER2-specific chimeric T-cell receptor gene both in murine and in human in our previous studies. To further test the feasibility of chimeric T-cell receptor in a bone marrow transplantation model, we first, made two murine tumor cell lines: MT901 and MCA-205, to express human p185HER2 by retroviral gene transduction. Murine bone marrow cells were retrovirally transduced to express the chimeric T-cell receptor and gene-modified bone marrow cells were transplanted into lethally irradiated mouse. Six months post transplantation, p185HER2-positive tumor cells:MT-901/HER2 or MCA-205/ HER2 was subcutaneously or intravenously injected to make mouse models simulating primary breast cancer or pulmonary metastasis. The in vivo anti-tumor effects were monitored by the size of the subcutaneous tumor or counting the tumor nodules in the lungs after India ink staining. The size of the subcutaneous tumor was significantly inhibited and the number of pulmonary nodules were significantly decreased in mouse recipients transplanted with chimeric T-cell receptor modified bone marrow cells compared with the control group. Our results suggest the efficient in vivo anti-tumor activities of chimeric T-cell receptor gene modified bone marrow cells. | JIAN MIN YANG MICHAEL S FRIEDMAN MARIANNE T HUBEN JENNIFER FULLER QIAO LI ALFRED E CHANG JAMES J MULE KEVIN T MCDONAGH | 2006 | Journal of Microbiology and Immunology2006，4，2： | 3 |
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