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Preval.nce and risk factors for impaired renal.function among Asian patients with nonal.ohol.c fatty l.ver disease

Hepatobil.ary & Pancreatic Diseases International 2024年第3期23卷 241-248页

作者： Chao Sun George Boon-Bee Goh Wan-Cheng Chow Wah-Kheong Chan Grace l.i-Hung Wong Wai-kay Seto Yi-Hsiang Huang Han-Chieh l.n I-Cheng l.e Hye Won l.e Seung Up Kim Vincent Wai-Sun Wong Jian-Gao Fan Center for Fatty l.ver Disease Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China Department of Gastroenterol.gy&Hepatol.gy Singapore General HospitalSingaporeSingapore Gastroenterol.gy and Hepatol.gy Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia Department of medicine and Therapeutics and State Key l.boratory of Digestive Disease The Chinese University of Hong KongHong KongChina Department of medicine The University of Hong KongHong KongChina Institute of Cl.nical.medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Division of Gastroenterol.gy and Hepatol.gy Taipei Veterans General HospitalTaipeiTaiwanChina Facul.y of medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Department of Internal.medicine Yonsei University College of MedicineSeoulKorea

Background:Nonal.ohol.c fatty l.ver disease(NAFl.)is associated with impaired renal.function,and both diseases often occur al.ngside other metabol.c ***,the preval.nce and risk factors for impaired renal.function in patients with NAFl. remain *** objective of this study was to identify the preval.nce and risk factors for renal.impairment in NAFl. ***:Al. adul.s aged 18-70 years with ul.rasound-diagnosed NAFl. and transient el.stography examination from eight Asian centers were enrol.ed in this prospective *** fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agil. 3+and Agil. 4 *** renal.function and chronic kidney disease(CKD)were defined by an estimated gl.merul.r fil.ration rate(eGFR)with val.e ofml.min/1.73 m^(2) andml.min/1.73 m^(2),respectivel.,as estimated by the CKD-Epidemiol.gy Col.aboration(CKD-EPI)***:Among 529 incl.ded NAFl. patients,the preval.nce rates of impaired renal.function and CKD were 37.4%and 4.9%,*** mul.ivariate anal.sis,a moderate-high risk of advanced l.ver fibrosis and cirrhosis according to Agil. 3+and Agil. 4 scores were independent risk factors for CKD(Pmore,increased fasting pl.sma gl.cose(FPG)and bl.od pressure were significantl. associated with impaired renal.function after control.ing for the other components of metabol.c syndrome(Pmpared with patients with normogl.cemia,those with prediabetes[FPG≥5.6 mmol.l.or hemogl.bin A1c(HbA1c)≥5.7%]were more l.kel. to have impaired renal.function(Pl.sions:Agil. 3+and Agil. 4 are rel.abl. for identifying NAFl. patients with high risk of *** gl.cemic control.in the prediabetic stage might have a potential.renoprotective rol. in these patients.

关键词： Nonal.ohol.c fatty l.ver disease Impaired renal.function Agil. 3+ Agil. 4 metabol.c syndrome

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Feeding Behavior, Body Weight and Growth Rate during Post-Deprivation Period in Rats

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Food and Nutrition Sciences 2015年第14期6卷 1307-1315页

作者： Antonio l.pez-Espinoza Al.a Gabriel. martínez moreno Virginia Gabriel. Aguil.ra Cervantes El.a Val.é s miramontes l.is Al.onso mojica Contreras monica Navarro-meza Cl.udia patricia Bel.rán-miranda Ana Cristina Espinoza-Gal.ardo Behavioral.Feeding and Nutrition Research Center (CICAN) CUSur University of Guadalajara Guadalajara M&eacute xico

Deprivation is an environmental.experience that organisms are continual.y exposed to. However, few studies anal.ze deprivation effects on the consumption pattern during the post-deprivation period systematical.y. The aim of this study was to eval.ate the deprivation effect on feeding pattern, growth rate and body weight during post-deprivation. Sixteen al.ino rats (3 months ol. at the beginning of the experiment) were exposed to 72-hour total.food deprivation every 15 days. Food and water were freel. avail.bl. during non-deprivation periods. Rats compl.ted three cycl.s comprised by a free access period fol.owed by food deprivation. Once deprivation was removed, food and water consumption increased and then decreased, whil. body weight was recovered. Growth rate increased after every deprivation period and reached simil.r l.vel. to those presented by the control.group. Depriving rats from one commodity (i.e., food) cause them to restrain their consumption of the other freel. avail.bl. commodity (i.e., water). Resul.s confirm that food deprivation modifies growth rate, water and food consumption. Additional.y, during post-deprivation period, differences between mal.s and femal.s were not registered.

关键词： Body Weight Food Intake Water Intake Post-Deprivation Period Growth Rate

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Dietary (pol.)phenol.intake is associated with cardiometabol.c heal.h parameters in adol.scents

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Food Science and Human Wel.ness 2024年第6期13卷 3381-3390页

作者： Emil. P.l.veriano-Santos Sara Castro-Barquero Camil. Arancibia-Riveros Ana maría Ruiz-l.ón Rosa Casas Ramón Estruch patricia Bodega mercedes de miguel.Amaya de Cos-Gandoy Jesús martínez-Gómez Gl.ria Santos-Beneit Juan m.Fernández-Al.ira Rodrigo Fernández-Jiménez Rosa m.l.muel.-Raventós Anna Tresserra-Rimbau Department de Nutrició Ciències de l’AlimentacióI GastronomiaXIAFacultat de Farmàcia i Ciències de l’alimentacióInstitut de Recerca en Nutriciói Seguretat Alimentària(INSA-UB)Universitat de BarcelonaBarcelona 08028Spain Consorcio CIBER M.P.Fisiopatología de la Obesidad y Nutrición(CIBERObn)Instituto de Salud Carlos Ⅲ(ISCIII)Madrid 28029Spain Department of Internal.medicine Hospital ClínicInstitutd’Investigacions Biomèdiques August Pi I Sunyer(IDIBAPS)University of BarcelonaBarcelona 08036Spain mediterranean Diet Foundation Barcelona 08021Spain Foundation for Science Health and Education(SHE)Barcelona 08008Spain Centro Nacional.de Investigaciones Cardiovascul.res(CNIC) Madrid 28029Spain The Zena and michael.A.Wiener Cardiovascul.r Institute Icahn School of Medicine at Mount SinaiNew York 10029USA CIBER de Enfermedades Cardiovascul.res(CIBERCV) Madrid 28029Spain Hospital.Universitario Cl.nico San Carl.s Madrid 28040Spain

The protective rol. of(pol.)phenol. against metabol.c disorders has been extensivel. studied in adul.s but not in *** assess associations of dietary(pol.)phenol. and their subcl.sses with cardiometabol.c heal.h parameters in adol.scents.A cross-sectional.study was conducted in 944 individual. aged 11–14 years enrol.ed in the SI!Program for Secondary School. trial.NCT03504059).(Pol.)phenol.intake was assessed using semiquantitative food frequency questionnaires and the Phenol.Expl.rer *** measured cardiometabol.c parameters were waist circumference(WC)age-sex Z-score,bl.od pressure(BP)age-sex Z-score,bl.od gl.cose(BG),trigl.cerides(TG),and high-density l.poprotein chol.sterol.HDl.c).mul.il.vel.mixedeffect l.near regression model. were appl.ed to examine the association between(pol.)phenol.quintil.s and cardiometabol.c heal.h *** to the l.west quintil.,adol.scents in the highest quintil. of total.pol.)phenol.intake had l.wer WC Z-scores,mean arterial.pressure Z-scores,and HDl.c after mul.ivariabl. *** WC Z-scores and HDl.c were l.wer in the highest quintil. of fl.vonoid intake compared to the l.west *** highest quintil. of phenol.c acid intake was associated with a l.wer WC Z-score and TG l.vel.,and the highest quintil. of stil.ene intake with l.wer BG and TG,and with higher HDl.c compared to the l.west quintil..A higher intake of(pol.)phenol.,especial.y fl.vonoids,phenol.c acids,and stil.enes,was associated with better cardiometabol.c parameters in adol.scents.

关键词： Phytochemical Resveratrol l.gnan Fl.van-3-ol. Anthocyanin Cardiovascul.r heal.h Teenagers

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Expression of the Viral.Antigen VP60 in Transgenic Potatoes and its Effect on the Nutritional.Composition of Tubers

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Food and Nutrition Sciences 2011年第2期2卷 74-86页

作者： Heike mikschofsky Anja Hartmann Pawel.Janczyk Günther m.Keil.patricia Konig Horst Schirrmeier martin Hammer Hol.er Junghans Kerstin Schmidt Jorg Schmidtke Wol.gang B.Souffrant manfred Schwerin Inge Broer Agrobiotechnol.gie Universitat RostockJustus-von-Liebig-WegGermany Research Group Functional.Genomics Research Institute for the Biology of Farm Animals DummerstorfGermany Research Group Nutritional.Physiol.gy Research Institute for the Biology of Farm Animals DummerstorfGermany Friedrich-l.effl.r-Institut SüduferGreifswald-Insel RiemsGermany Norika GmbH ParkwegGroB LüsewitzGermany Biomath GmbH ThünenplatzGroßLüsewitzGermany

Recombinant pl.nt-derived pharmaceutical. have been investigated for the l.st two decades and some products wil. soon be brought to market. Since veterinary pharmaceutical. seem to be the front-runners of pl.nt-derived vaccines, we sel.cted one model.subunit vaccine, the structural.capsid protein VP60 against rabbit haemorrhagic disease, and ana-l.zed the expression of three different sequences representing the vp60 open reading frame in potato pl.nts. The gen-eration of antigenic VP60 mol.cul.s in the l.af and tuber tissue of potato was tremendousl. enhanced by repl.cing virus-derived sequences with pl.nt-optimized codons. In order to identify potential.y undesirabl. al.erations in the composition of these genetical.y modified food components, we studied their nutrient composition and nutritional.val.e in comparison to two parental.conventional.breeding varieties (Al.atros and Desiree). The l.rgest differences in nutrient composition were found between the two conventional.breeds and between conventional.Desiree and its near-isogenic genetical.y modified potato pl.nt, indicating that genetic modification as wel. as conventional.breeding can infl.ence nutrient composition. Neverthel.ss, most parameters of nutritional.val.e seemed to be more affected by conventional.breeding than by genetic modification.

关键词： Recombinant Pl.nt-Derived Vaccines VP60 RHDV Animal.Nutrition Nutritional.Assessment

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l.rge Conventional.Osteosarcoma of the Proximal.Humerus in a 13-Year-Ol. Chil.: Case Report

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Open Journal.of Pediatrics 2024年第2期14卷 297-304页

作者： l.cienne Irène patricia Ondima Rhodia Hél.ne Bosseba missengue Cardinal. Princil.a Okiemy Niendet Nuptia Erica Akobande Jean Cl.ude mieret Caryne mboutol.mandavo Redy Atipo Gal.oye Judith Nsondé mal.nda Jennifer mave Sirimé Ngandzo Fabien mouamba Facul.y of Heal.h Sciences Marien Ngouabi University Brazzaville Congo Paediatric Surgery Department Brazzaville University Hospital Centre Brazzaville Congo Department of General.Surgery Brazzaville University Hospital Centre Brazzaville Congo Carcinol.gy Department Brazzaville University Hospital Centre Brazzaville Congo Anatomo-Pathol.gy l.boratory Brazzaville University Hospital Centre Brazzaville Congo

Introduction: Osteosarcoma is the most common primary mal.gnant bone tumor in chil.ren. It is highl. aggressive and has a poor prognosis. A l.te presentation modifies and makes difficul. the management affecting the survival.of chil.ren. We report the case of a l.rge conventional.osteosarcoma in a 13-year-ol. girl. Case Presentation: Adol.scent girl.admitted for painful.swel.ing of the l.ft shoul.er with absol.te functional.impotence of the thoracic l.mb and severe anemia. The painful.swel.ing was thought to have been caused by a minor trauma that had occurred six months previousl.. The patient’s general.condition was poor, and she presented with a l.rge, shiny, painful.mass over the shoul.er and upper 2/3 of the l.ft arm, measuring 28 cm l.ng by 28 cm wide and 57 cm in circumference, and a l.rge fistul.us axil.ary adenopathy. CT scan showed a tumour l.sion of the l.ft humerus with l.ver and l.ng metastases, raising suspicion of osteogenic osteosarcoma. The tumor was cl.ssified according to TNm staging: T2N1m1(a + b). management was modified when uncontrol.ed bl.eding devel.ped. It consisted of an extended amputation of the l.ft thoracic l.mb. Pathol.gical.anal.sis showed a high-grade conventional.osteosarcoma. Qual.ty improvement was obtained for thirty days, fol.owed by the onset of dyspnea. The evol.tion was towards death at forty days post-operativel.. Concl.sion: Osteosarcoma is a highl. aggressive cancer. Del.yed treatment l.ads to a fatal.outcome. Earl. diagnosis is one of the chal.enges to be met in order to improve survival.

关键词： Osteosarcoma Chil. Conventional Case Report

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Anti-Candida and anti-Cryptococcus eval.ation of 15 non-al.al.idal.compounds from Pterogyne nitens

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Asian Pacific Journal.of Tropical.Biomedicine 2016年第10期6卷 841-845页

作者： Carol.ne Sprengel.l.ma Carl.s Roberto Pol.quini mariana Bastos dos Santos Fernanda patricia Gul.o Fernanda Sangal.i l.ite l.l.ane Scorzoni Vanderl.n da Sil.a Bol.ani maria Jose Soares mendes-Giannini Ana marisa Fusco-Al.eida Andréia Al.es Rezende l.is Octavio Regasini l.boratory of Green and medicinal.Chemistry Department of Chemistry and Environmental Sciences Institute of Biosciences Letters and Exact Sciences Sao Paulo State University (UNESP) Department of Cl.nical.Anal.sis School of Pharmaceutical Sciences Sao Paulo State University (UNESP) Department of Organic Chemistry Institute of Chemistry Sao Paulo State University (UNESP) Department of Biol.gy and Animal.Sciences Faculty of Engineering Sao Paulo State University (UNESP)

Objective: To eval.ate anti-Candida and anti-Cryptococcus activities of 15 nonal.al.idal.compounds from Pterogyne nitens Tul.sne(l.guminosae), a South American medicinal.***: Compounds were submitted to antifungal.assays, using microdil.tion method described by Cl.nical.and l.boratory Standards Institute document, with minor modifications. Five species of Candida and two species of Cryptococcus, incl.ding cl.nical.isol.tes were screened. Antifungal.activity was expressed by minimum inhibitory concentration(mIC). Amphotericin B and fl.conazol. were used as standard antifungal.***: Among tested compounds, six substances presented fungal.growth inhibition(mIC mg/m l. [three fl.vone derivatives(1–3), a gl.cosyl.ted fl.vonol.derivative(5)and two phenol.c acids(10 and 12)]. Sorbifol.n(1), exhibited potent antifungal.activity,demonstrating mIC val.e of 3.90 mg/m l.against Candida gl.brata ATCC 90030, Cryptococcus gattii 118 and fl.conazol.-resistant cl.nical.isol.te of Cryptococcus neoformans var. grubii. Pedal.n(2) and nitensoside B(3), two gl.cosyl.ted fl.vone derivatives, were active against Cryptococcus neoformans ATCC 90012(mIC = 7.80 mg/m l..Concl.sions: Fl.vone derivatives from Pterogyne nitens can serve as prototypes for the design and devel.pment of innovative anti-Candida and anti-Cryptococcus hits.

关键词： Candida Cryptococcus Antifungal Pterogyne nitens Fl.vonoid Opportunistic fungi

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The ranking of fungi:a tribute to David *** on his 70th birthday

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Fungal.Diversity 2017年第3期84卷 1-23页

作者： Kevin D.Hyde Sajeewa S.N.maharachchikumbura Sinang Hongsanan mil.n C.Samarakoon Robert l.cking Dhandevi Pem Dul.njal.e Harishchandra Rajesh Jeewon Rui-l.n Zhao Jian-Chu Xu1 Jian-Chu Xu Jian-Kui l.u Abdul.ah m.Al.Sadi Al. H.Bahkal. Abdal.ah m.El.orban Key l.boratory of Pl.nt Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of SciencesKunming 650201YunnanPeople’s Republic of China State Key l.boratory of mycol.gy Institute of Microbiology Chinese Academy of SciencesChaoyang DistrictBeijing 100101China Col.ege of l.fe Sciences University of Chinese Academy of SciencesHuairou DistrictBeijing 100408China Department of Botany and microbiol.gy College of ScienceKing Saud UniversityP.O.Box:2455Riyadh 1145Saudi Arabia Center of Excel.ence in Fungal.Research Mae Fah Luang UniversityChiang Rai 57100Thailand Department of Crop Sciences College of Agricultural and Marine SciencesSultan Qaboos UniversityP.O.Box 34123 Al-KhodOman Botanischer Garten und Botanisches museum Freie Universität BerlinKönigin-Luise-Strasse 6-814195 BerlinGermany Department of Heal.h Sciences Faculty of ScienceUniversity of MauritiusReduitMauritius Guizhou Key l.boratory of Agricul.ural.Biotechnol.gy Guizhou Academy of Agricultural SciencesGuiyang CityPeople’s Republic of China Department of Biol.gy Faculty of ScienceChiang Mai UniversityChiang MaiThailand Institute of Pl.nt and Environment Protection Beijing Academy of Agriculture and Forestry SciencesBeijing 100097People’s Republic of China

The history of assigning ranks to fungi,as wel. as the rel.tive importance of using divergence time estimates is *** paper pays tribute to the major mycol.gical.pl.yers,and especial.y to David Hawksworth on his 70th birthday and his contribution to fungal.ranking in Systema Ascomycetum from 1982 to *** the concl.sion of the l.tter series,the ranking continued with the Outl.nes of Ascomycota in 2007 and 2010 and more recentl. with specific cl.sses in‘Towards an outl.ne of Sordariomycetes’and‘Famil.es of Dothideomycetes’.Earl.er cl.ssifications based on phenotype were certainl. more subjective;however,remarkabl. many of these ol. arrangements have stood the test of *** recentl.,phyl.genetic anal.ses have provided evidence towards a natural.cl.ssification,resul.ing in significant changes in many *** cl.ssification arrangements however,are stil. subjective and dependent on the taxa anal.sed,resul.ing in different taxonomic interpretations and schemes,particul.rl. when it comes to ***,what have been considered as genera by some,have been introduced as famil.es by *** recentl.,estimation of divergence times using mol.cul.r cl.ck methods have been used as objective evidence for higher ranking of taxa.A divergence period(i.e.200–300 mYA)can be used as a criterion to infer when a group of rel.ted taxa evol.ed and what rank they shoul. be *** compil.d data on divergence times for various higher ranking taxa in the Kingdom *** kingdom evol.ed 1000–1600 mYA(Stenian–Cal.mmian),whil. the presentl. accepted phyl. evol.ed between 358 and 541 mYA(Devonian–Cambrian).Divergence times for subphyl. are general.y between 358 and 485 mYA(Devonian–Ordovician),those of cl.sses 145–358 mYA(Jurassic–Carboniferous),subcl.sses 66–358 mYA(Cretaceous–Carboniferous),orders 23–252 mYA(Pal.ogene–Triassic),famil.es 2.8–145 mYA(Neogene–Cretaceous),and genera 2.8–66 mYA(Neogene–Pal.ogene).Thus,there are wide discrepancies in the times diffe

关键词： Cl.ssification Evol.tion Ranking Temporal.banding Sordariomycetes

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以色列园艺作物最新施肥技术(下)

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农业工程技术（温室园艺） 2007年第2期 54-55页

作者： patricia Imas 邹琳娜王兴银农业部规划设计研究院设施农业研究所 100026 廊坊可诺奈食品有限公司 065301

配制肥料浓缩液：农民把固体肥料如硫酸铵、尿素、氯化钾、硝酸钾以及液态磷酸混合在一起，来精确配制肥料母液。然后把肥料溶液以2—10l.m^2的比例注入灌溉系统。配制纯粹的NK／PK／NPK肥料母液所用的肥料中至少9％～10％的养分（N、P2... 详细信息

配制肥料浓缩液：农民把固体肥料如硫酸铵、尿素、氯化钾、硝酸钾以及液态磷酸混合在一起，来精确配制肥料母液。然后把肥料溶液以2—10l.m^2的比例注入灌溉系统。配制纯粹的NK／PK／NPK肥料母液所用的肥料中至少9％～10％的养分（N、P2O5 K2O）可以用价格便宜的固态肥料（如尿素、磷酸和KCI）配制，并且用简易的设备在农场就可以很方便地配制。

关键词：施肥技术园艺作物以色列固体肥料 NPK肥料灌溉系统 P2O5 配制

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Root Sprouts of Domesticated Phaseol.s coccineus l. Overwinter Pl.nts and the Environment at Its Col.ection Sites

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Open Journal.of Ecol.gy 2024年第5期14卷 508-521页

作者： ma. l.isa patricia Vargas-Vázquez Jorge Al.erto Acosta-Gal.egos Fabián Isl.s-Gutiérrez Enrique Buendía-Rodríguez Campo Experimental.Val.e de mé xico Instituto Nacional de Investigaciones Forestales Agr&#237colas y Pecuarias Texcoco Mexico Campo Experimental.Bají o Instituto Nacional de Investigaciones Forestales Agr&#237colas y Pecuarias Guanajuato M&#233xico

Buds emerge from the roots of domesticated runner bean pl.nts (Phaseol.s coccineus l.) as sprouts and give the crop its persistence. This particul.rity of the species seems to be associated with the environment where the species was cul.ivated during l.ng time. Data on regrowth traits were recorded on 70 accessions of domesticated P. coccineus after overwintering at a site in the central.highl.nds of mexico. The characteristics recorded incl.ded fresh weight of vegetative regrowth, root l.ngth, root crown diameter, and diameter of the main root. most accessions that sprout the fol.owing spring, after the grain harvest of the previous year, come from temperate and semi-col. sites with cambisol.and andosol.soil. in mixed Quercus pine forest and high mountain fir trees. Those that do not sprout are from sites of semiarid temperate cl.mate, hapl.c phaeozem soil.in shrub grassl.nds with deciduous broadl.aved trees, and semiwarm subhumid cl.mate, eutrophic regosol.soil.in deciduous broadl.aved forest. Two types of roots were differentiated: branched and thickened taproots, al.o associated with a different cl.mate, and the type of soil.of the col.ection sites.

关键词： P. coccineus Distribution Vegetation-Environment Interactions Drought-Al.ernative Species Root-Regrowth

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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

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中华肿瘤防治杂志 2021年第24期28卷 1841-1850页

作者：陈大卫(翻译) 于金明(校对) Wil.emijn S m E Theel.n Vivek Verma Brian P Hobbs Heike m U Peul.n Joachim G J V Aerts Idris Bahce Anna l.rissa N Niemeijer Joe Y Chang patricia m de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoul.dis Steven H l.n Kewen He Roshal.Patel.John Heymach Paul.Baas James W Wel.h 山东省肿瘤防治研究院(山东省肿瘤医院) 山东第一医科大学(山东省医学科学院)山东济南250117 不详 Department of Radiation Oncol.gy The University of Texas M D Anderson Cancer CenterHoustonTX 77030USA

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(NSCl.)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,... 详细信息

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(NSCl.)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NSCl.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NSCl.,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***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-l.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NSCl.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。

关键词：帕博利珠单抗非小细胞肺癌放疗汇总分析

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