+,FG Duchenne 29G trolgroupatthe4clinicvisitswere38 2±7 5,37 0±8 0,36 2±7 6,and36 6±7 7,whilethoseofthetreat mentgroupwere37 7±6 1,39 1±6 4,40 3±5 9,a

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1 MedicalJournalofPekingUnionMedicalColegeHospital Duchenne,,,,, :!" #$: ,E " %&' ()*+,-./01 Duchenne 2 (Duchennemusculardystrophy, DMD) #$ :; <9 5~10= DMD3 >?@ABC DE 9, FGH H FGH3 IJKLM 0 75mg/(kg d), HIJNO, C0 3mg/d FG 3, 1 B 1P,B 3,%& 4PQ R78 S +T %& U 31V DMD3 :;WX,YFGH 17V, H 14V H3 4PQ 9 4% P 38 2± ± ± ±7 7,FGH 37 7± ± ± ±5 6, HFG FGZ 49[\]^,[_ 0`abc (P=0 024,P=0 000,P=0 002) H 4PQ 9 m9 P (7 7±2 5) (7 6±2 8) (8 1±2 4) (7 6±2 8) s,fgh (8 5±3 4) (7 2±3 3) (7 6±3 1) (7 1±2 8)s, HFG 2 3 FGZ 9m 9[\]^,[_ 0`abc (P= 0 013,P=0 003) H 4PQ 9 4R (forcedvitalcapacity,fvc) P (1 24±0 28) (1 13± 0 26) (1 21±0 31) (1 16±0 26)L,FGH (1 14±0 37) (1 40±0 35) (1 42±0 36) (1 52±0 37)L, HFG FGZ FVC9[\]^,[_ 0`abc (P=0 000,P=0 006,P=0 000) HFG 1 FGZ9 S+T9[\]^,[_ 0`abc (P=0 035) 3 FGH+, 2, Y 2 % ' KLMFG DMD 3 4, 3 56 R78 ' Duchenne 2;()*+,;KLM;FG ( R746 2 )*+,- A )./( (2014) DOI: /j isn EficacyofLowDoseCorticosteroidTherapyinDuchenneMuscularDystrophy MAMing sheng,zhangxü de,weimin,zhaoshi min,qiuzheng qing DepartmentofPediatrics,PekingUnionMedicalColegeHospital,ChineseAcademyofMedicalSciences& PekingUnionMedicalColege,Beijing100730,China Corespondingauthor:QIUZheng qing Tel: ,E mail:zhengqingqiu33@aliyun.com Abstract Objective Toaseswhetherlowdosecorticosteroidcouldimprovemusclestrengthandmotor functioninchildrenwithduchennemusculardystrophy(dmd).methods Inthisrandomizeddouble blindcon troledtrial,patientswithdmdattheageof5-10diagnosedfromseptember2005todecember2008inpeking UnionMedicalColegeHospitalwereenroled.Thepatientsweredividedintotreatmentgroupandcontrolgroup randomly.thetreatmentgroupwasgivenprednisoneatadosageof0 75mg/(kg d)forthreemonths,andthe controlgroupwasgivenvitaminc0 3mg/dasplacebointhesameperiod.Everypatientwasfolowed uponcea monthforatotalof4times,testingmusclestrength,motorfunction(9 meterwalktest),respiratoryfunction [forcedvitalcapacity(fvc)],andserumcreatinekinase.results Thirty oneeligibledmdpatientswereen roled,including17inthetreatmentgroupand14inthecontrolgroup.themeanmusclestrengthscoresofthecon 384 October,2014

2 +,FG Duchenne 29G trolgroupatthe4clinicvisitswere38 2±7 5,37 0±8 0,36 2±7 6,and36 6±7 7,whilethoseofthetreat mentgroupwere37 7±6 1,39 1±6 4,40 3±5 9,and40 0±5 6,respectively.Thechangesinmuscle strengthscoresat1,2,3monthsaftertreatmentcomparedwiththescoresatdiagnosiswerealsignificantlylarger inthetreatmentgroupthaninthecontrolgroup(p=0 024,P=0 000,P=0 002).Themeantimeof9 meter walkatthe4visitsinthecontrolgroupwere(7 7±2 5),(7 6±2 8),(8 1±2 4),and(7 6±2 8)s,and thoseinthetreatmentgroupwere(8 5±3 4),(7 2±3 3),(7 6±3 1),and(7 1±2 8)s,showingsignifi cantlylargerchangesoftimeinthetreatmentgroupthaninthecontrolgroupat2and3monthsaftertreatmentcom paredwiththetimeatdiagnosis(p=0 013,P=0 003).ThefourmeanFVCsinthecontrolgroupwere(1 24± 0 28),(1 13±0 26),(1 21±0 31),and(1 16±0 26)L,andthemeanFVCsinthetreatmentgroupwere (1 14±0 37),(1 40±0 35),(1 42±0 36),and(1 52±0 37) L,showingsignificantlylargerchangesin thetreatmentgroupthaninthecontrolgroupat1,2,and3monthsaftertreatmentcomparedwiththefvcsatdiag nosis(p=0 000,P=0 006,P=0 000).Thedecreaseofcreatinekinaseinthetreatmentgroupwassignificantly largerafter1 monthtreatmentthanthatinthecontrolgroup(p=0 035).Therewerenoseriousadverseefectsin thetreatmentgroupexceptweightgain.conclusions Short termapplicationoflowdoseprednisoneinchildren withdmdcanincreasemusclestrength,improvemotorandrespiratoryfunctions. Keywords Duchennemusculardystrophy;glucocorticoid;prednisone;treatment MedJPUMCH,2014,5(4): Duchenne 2 (Duchennemusculardys trophy,dmd)- 4 9 X, - DMD 9 dystrophin9, 1/3500 D 4, 10~12 = 8,20~30= 78 [1] Z DMD F, ()* +,- BC >? 0 DMD3 4 9 [2 4], Z Z WX WX@ BC DE >?,' +, DMDFG9 01 #$ 01 :; DMD3 V; : 5~10=, DMD9 < [5], T! DMD " #$ % dystrophin &' :(1) +, FG;(2) 0+, ( )*;(3) +4, -. >? WX /01 (, 0WX ( 23 4b5 WX #$ 6 7 5~6= 7~8= 9~10= :H, ; 3,82 * 4 0 < 1 0 9=>?; BC@A 1 =>, 1 0 AB 3 >?C KLM (FGH) DE NO, C ( H) 2$ KLMNO, C> : FGY H I4 JK L9 M 6 HA NO ( O 5 % ( ), 2 5 % 9 O 3 34#$ FGH: 3 IJ 0 75mg/(kg d) 9KLM, PQRS ; H:IJ 0 3mg/d NO, C> (0 1mg/>), PQRS FG (1) T :U V W X Y ;(2) 4:5 4 % 9 [3], AZ < 1~10, 8 V3 Q T[\ ] ]^_ ` Vol 5No 4 385

3 a bc_ 5 4% 3 PQ 49 % ; (3) 5678: 9m ; (4) R78:A 4R (forcedvitalca pacity,fvc) R78; (5) S+T (creatin kinase,ck);(6) : Y 8 0;H3 9B 1P,B 3 U 4P%& 9:; C `a SSPS17 0, H ]^@ t?,p<0 05 [_0`a bc % & WXU:; 5~10= DMD3 31V,Y 5~6=3 8V,7~8= 14V,9~10= 9 V, 7 5= Y 29V, DMD " ;2V dystrophin H DMD 31V3,17VBC F GH,Y 14V H, H [_ `abc (P>0 05) 3, E < H3 4PQ 9 4% P 38 2± ± ± ±7 7,F G H 4 PQ 9 4 % P 37 7± ± ± ±5 6 HFG FGZ 49[\]^,[_ 0`ab c (P=0 024,P=0 000,P=0 002); HFG [\]^ FG [\]^,[_ `abc (P= 0 066,P=0 303,P=0 161) =>?@ H 4PQ 9m9 P (7 7± 2 5) (7 6±2 8) (8 1±2 4) (7 6±2 8) s,f GH9 P (8 5±3 4) (7 2±3 3) (7 6±3 1) (7 1±2 8) s HFG 2 3 FGZ 9m 9[\]^,[_ 0` abc (P=0 013,P=0 003); FG 1 [_0`abc A?@ H 4P Q 9 FVC P (1 24± 0 28) (1 13±0 26) (1 21±0 31) (1 16± 0 26)L,FGH 4PQ 9 FVC P (1 14± 0 37) (1 40±0 35) (1 42±0 36) (1 52± 0 37)L HFG FGZ FVC9 [\ ] ^,[ _ 0 ` a b c (P=0 000,P= 0 006,P=0 000) BC PQ H F G H 9 CK \ A ( ±4733 7)U/L ( ±5723 1)U/L, FG 1 H CK \ A ( ± ) U/L ( ±4293 9) U/L, HF G 1 FGZ9 CK[\]^,[_0`a bc(p=0 035); HFG ] ^ FG 3 2 ]^,CK [_ ` abc (P=0 070,P=0 073,P=0 065) DE FGH0 10V3 FG 3 ( 9 10%, H 0 1V3 FG 2 ( 9 10%;3 H3 \ 0 305kg, FGH3 \ 0 684kg,FGH # H (P=0 01) FGH3 0 4VFG 3 Y^ 20%, H3 Y 20%, H Y [_ `abc (P=0 06) FGH0 1V3 ;2V 3 # DMD O 9 1/3500, # 9 UV 2~5= -, 4, 10~12= 8,20~30= 78 [2] WX 5~10=93 WX, 78 9 O ;YP,5= !>,! [;, DMD,10= 3 8 " #, !> Z DMD 0 F 7, 30 YFG <, > DMD 9,()*+,- BC >? 80 DMD October,2014

4 +,FG Duchenne 29G 9 [6] ()*+,FG DMD9C 80 :(1) ), ()*+, ( Z, O, $, [7] (2) DMD3 O N,()*+, ( 9 H 9, [8] (3)? 9 ;KL C #1 [9], dystophin0 9,DMD3 dsytrophin9 CK?;X,X CK WX K LMFG 1 CK #,!()*+,F G DMD C, 0 ()*+,FG DMD9 G, Z ` b Connoly [10] (BC HWX+, 4 FG DMD O9 2 :, I 0 75mg/(kg d),fg 3 4 #, 1 5mg/(kg d)9g, 2 ; 0 75mg/(kg d) - FG Moxley [6] !"9 DMD +,FG>? #$, % & ':+,FG # , +,9 0 75mg/(kg d) WX 0 75mg/(kg d) KLMFG DMD3, 4 ' # R78 Fenichel [11] KL M 0 75mg/(kg d)fg 10d, 4,3 4, 4 () FG 3 3, C DMD3 478* 9 # 3 WX KLMFG R78 %+ #1, WX9, # Moxley [12] ( 2-./WX0,B 73V ()* +,2 FG9 DMD3, 2 ()*+,F G 2 2~5, 1 9, R78, C2 3C,2O " 1 O * ()*+,FG9G 3 2,945 WX 6 KLMF G 3, 0, # ()*+,FG DMD 8 2 WX ()*+,9 2 FG 6 [12], 9b:!;W XY Y ( X, NO, D [13] 3,<= 2 9 O WX5 0 DMD+,FG 9 >?a,@abc DE 9 & B,' KLMFG DMD R78, Y 2 - C 9 6!"D 致谢 : 感谢参加本研究的患儿及家长 ) * [1] KhiraniS,RamirezA,AubertinG,etal.Respiratorymus cledeclineinduchennemusculardystrophy[j].pediatr Pulmonol,2014,49: [2] HofmanEP,ReevesE,DamskerJ,etal.Novelapproaches tocorticosteroidtreatmentinduchennemusculardystrophy [J].PhysMedRehabilClinNAm,2012,23: [3] BeenakkerEA,FockJM,VanTolMJ,etal.Intermitent prednisonetherapyinduchennemusculardystrophy:aran domizedcontroledtrial[j].archneurol,2005,62: [4] MendelJR,MoxleyRT,GriggsRC,etal.Randomized, double blindsix monthtrialofprednisoneinduchenne smus culardystrophy[j].nengljmed,1989,320: [5] EmeryAE,MuntoniF.Duchennemusculardystrophy[M]. Oxford:OxfordUniversityPres,2003. [6] MoxleyRT3rd,AshwalS,PandyaS,etal.Practiceparame ter:corticosteroidtreatmentofduchennedystrophy:reportof thequalitystandardssubcommiteeoftheamericanacademy ofneurologyandthepracticecommiteeofthechildneurolo gysociety[j].neurology,2005,64: [7] UpadhayaR,BurczynskiFJ,WangG,etal.Nitricoxide donorsimproveprednisoneefectsonmusculardystrophyin themdxmousediaphragm [J].Am JPhysiolCelPhysiol, 2011,300: [8] Emslie SmithAM,ArahataK,EngelAG.Majorhistocom patibilitycomplexclasiantigenexpresion,immunolocaliza tionofinterferonsubtypes,andtcel mediatedcytotoxicityin myopathies[j].humpathol,1989,20: [9] WelerC,ZschüntzschJ,MakoschG,etal.Motorperform anceofyoungdystrophicmdxmicetreatedwithlong circulat ingprednisoloneliposomes[j].jneuroscires,2012,90: [10] ConnolyAM,SchierbeckerJ,RennaR,etal.Highdose weeklyoralprednisoneimprovesstrengthinboyswithduch Vol 5No 4 387

ennemusculardystrophy[j].neuromusculdisord,2002, 1210:917 925. [11] FenichelGM,FlorenceJM,PestronkA,etal.Long term benefitfromprednisonetherapyinduchennemusculardystro phy[j].

j ChildNeurol,2010,25:1116 1129. [13] BianchiML,MorandiL,AndreucciE,etal.Lowboneden sityandbonemetabolism alterationsinduchennemuscular dystrophy:responsetocalciumandvitamindtreatment[j].

5 ennemusculardystrophy[j].neuromusculdisord,2002, 1210: [11] FenichelGM,FlorenceJM,PestronkA,etal.Long term benefitfromprednisonetherapyinduchennemusculardystro phy[j].neurology,1991,41: [12] MoxleyRT3rd,PandyaS,CiafaloniE,etal.Changein naturalhistoryofduchennemusculardystrophywithlong term corticosteroidtreatment:implicationsformanagement[j].j ChildNeurol,2010,25: [13] BianchiML,MorandiL,AndreucciE,etal.Lowboneden sityandbonemetabolism alterationsinduchennemuscular dystrophy:responsetocalciumandvitamindtreatment[j]. OsteoporosInt,2011,22: (E : ) 櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒櫒 F 5 Creasy& ResnikGHI;: JKL (M 7N) Creasy& Resnik smaternal FetalMedicine:PrinciplesandPractice(7thed.)(2014) :Creasy,RobertK,Resnik,Eds :Elsevier Creasy& Resnik 母胎医学 : 理论与实践自 1984 年首次出版以来, 受到广大产科医生和母胎医学同仁的认可与好评, 在大家的关注和期待下, 第 7 版于 2014 年问世本书着重于整合基础医学和临床实践, 并对相关临床研究给予恰当评价, 以力求读者对相关专题和内容有深入系统的了解, 文字深入浅出全面系统条理分明, 更有插图表格图示等形式进行归纳总结全书分为 6 部分, 共 72 章第 1 部分为妊娠生理学基础, 从人类基础遗传学及遗传模式胚胎的早期发育羊水动力学多胎妊娠生理分娩机制妊娠免疫学妊娠内分泌学孕妇各系统 ( 心血管呼吸泌尿系统 ) 对妊娠的适应哺乳生理孕妇营养健康与疾病的起源胎儿心血管生理学胎儿行为与胎儿健康和发育的关系胎盘的气体交换和胎儿氧供以及胎儿肺发育和表面活性物质这些方面进行生动详细的阐述, 并在最后 1 章介绍围产期循证医学试验的相关内容, 倡导科研与临床的结合第 2 部分为产科影像学, 是第 7 版新增内容此部分介绍产科超声的基本内容, 详细地阐述了胎儿各器官系统病变的超声图像特征及相关的发病机制诊断治疗和预后, 还介绍了胎盘和脐带子宫和附件相关疾病的超声图像特点以及妊娠早期的超声表现第 3 部分介绍胎儿疾病的诊断与治疗, 包括先天性畸形的产前诊断胎儿畸形与环境暴露的关系胎儿健康评估产时胎儿监测胎儿肺成熟的评估与促进有创性的胎儿治疗胎儿和新生儿溶血性疾病, 非免疫性胎儿水肿以及多胎妊娠的临床特点与处理第 4 部分介绍早产异常分娩等母胎并发症, 值得一提的是, 作者采用了 GAPPS 对早产的新分类法, 认为早产是一种综合征, 分类系统以临床表型为基础第 5 部分主要介绍孕妇合并症, 第 7 版新增加了 2 章 : 产科患者的安全孕妇死亡 ; 患有并发症或合并症孕妇的麻醉注意事项以及危重产妇的重症监护第 6 部分为新生儿, 主要阐述产科决策与新生儿结局早产的相关并发症及新生儿疾病的产前和围生期起源女性是维护家庭社会和谐的重要因素, 妊娠和分娩更是凝聚了全家几代人的希望和期待, 守护孕产妇和新生儿平安健康是母胎医学医务人员的职责所在, Creasy&Resnik 母胎医学 : 理论与实践一书能够满足母胎医学医务人员所需知识和技能, 值得推荐 ( 2F G H) ( IJK L ) 388 October,2014

!"#$ % & ())$ $ +,-./0)1)1/.21/.$ 3 4$ 5 4$ 6 789:;9< $ = :; A B CD ()) E )FG(? H$ $ $ $ $ $ $ $ $ $ % IJ!"#% &$ KLMNO 2( H 2G))(2 $ PQ R

!#$ % & ())*$ $ +,-./0)1)1/.21/.$ 3 4$ 5 4$ 6 789:;9< $ = :; A B CD ())* E )FG(*? H$ $ $ $ $ $ $ $ $ $ % IJ!#% &$ KLMNO 2(* H 2G))(2 $ PQ R !"#$ % & ())*$ $ +,-./0)1)1/.21/.$ 3 4$ 5 4$ 6 789:;9< $ = >?((@0$ :; A B CD ())* E )FG(*? H$ $ $ $ $ $ $ $ $ $ % IJ!"#% &$ KLMNO 2(* H 2G))(2 $ PQ R STU$ VW ;XY Z [$ \] ^_ a\]b$ c ())* d G ee 2 $ H +,-./0)1)1/.21/.