子痫前期胎盘组织中SMARCA5基因的表达及其与滋养细胞侵袭、凋亡的相关关系

目的检测子痫前期胎盘组织中SMARCA5基因的表达,探讨其表达量与子痫前期滋养细胞侵袭、凋亡活力的内在联系。方法选取2016年2月至2018年4月在枣阳市第一人民医院分娩的91例子痫前期患者作为研究对象。根据病情严重程度分为轻度子痫前期组(n=63)、重度子痫前期组(n=28),另取同期进行分娩的100例健康产妇作为对照组。比较三组孕妇胎盘组织中SMARCA5基因表达量,以及滋养细胞相关侵袭基因、凋亡基因的表达,采用Pearson检验评估子痫前期胎盘组织中SMARCA5基因表达量与滋养细胞侵袭、凋亡活力的相关基因表达量的关系。结果三组研究对象胎盘组织中SMARCA5 mRNA表达量,滋养细胞侵袭相关基因CCL28、Gadd45α、GPR30、RASA1、HIF-2α及凋亡相关基因HtrA1、Survivin、SHBG、XIAP mRNA表达量的差异均具有统计学意义(均P0.05)。随子痫前期病情加重,胎盘组织中SMARCA5基因表达量增加;胎盘组织中CCL28、GPR30 mRNA表达量下降,Gadd45α、RASA1、HIF-2αmRNA的表达量增加;胎盘组织中HtrA1 mRNA的表达量增加,Survivin、SHBG、XIAP mRNA的表达量下降,差异具有统计学意义(P0.05)。相关性分析发现,子痫前期胎盘组织中SMARCA5基因表达量与滋养细胞的侵袭及凋亡相关基因表达量均直接相关,差异具有统计学意义(P0.05)。结论子痫前期胎盘组织中SMARCA5基因表达量异常降低,且具体表达量与滋养细胞的侵袭活力及凋亡进度密切相关,对子痫前期发生发展具有重要意义。     

HGF和MMP-9在妊娠期高血压患者中的临床意义

目的:研究分析正常晚孕妇女与子痫前期妇女胎盘组织中基质金属蛋白酶-9(MMP-9)和肝细胞生长因子(HGF)在妊娠期高血压疾病中的意义与作用。方法:在同一时期选择86例子痫前期孕妇作为病例组(其中轻度子痫前期孕妇44例,重度子痫前期孕妇42例),选择45例正常晚孕期妇女作为对照组,对照组与病例组均在临产前进行剖宫产手术,并在胎盘娩出后去除钙化区和坏死区。在30min内取1cm3大小用生理盐水充分清洗后的胎盘绒毛组织,用福尔马林溶液固定,酒精浸洗脱水,最后将胎盘组织用石蜡包埋及切片备用。两组孕妇胎盘组织中MMP-9与HGF的阳性表达结果用免疫组织法染色测定,测定结果根据切片中细胞染色的深浅和阳性细胞的数目进行分级计分并作统计学分析。结果:(1)病例组重度子痫前期孕妇的HGF、MMP-9的表达水平存在正相关性(r=0. 6733,P 0. 05)。(2)对照组孕妇胎盘组织中HGF的总阳性数为32(71. 1%)、MMP-9的总阳性数为36(80. 0%),均呈强阳性;病例组轻度子痫前期孕妇胎盘组织中HGF的总阳性数为29(65. 9%)、MMP-9的总阳性数为33(75. 0%),阳性表达率较低;病例组重度子痫前期孕妇胎盘组织中HGF的总阳性数为16(39. 1%)、MMP-9的总阳性数为14(33. 3%),阳性表达率明显降低。(3)对照组与病例组(包括轻度与重度子痫前期)的HGF、MMP-9阳性表达率比较,差异均有统计学意义(均P 0. 05);对照组与病例组轻度子痫前期孕妇的HGF、MMP-9阳性表达率比较,差异均无统计学意义(均P﹥0. 05);对照组与病例组重度子痫前期孕妇的HGF、MMP-9阳性表达率比较,差异均有统计学意义(均P 0. 05);病例组重度子痫前期孕妇与轻度子痫前期孕妇的HGF、MMP-9阳性表达率比较,差异均有统计学意义(均P 0. 05)。结论:病例组孕妇胎盘中MMP-9与HGF的表达比对照组明显减少,MMP-9与HGF的表达愈低,病情愈重,子痫前期病情严重程度和妊娠过程中胎盘绒毛表达的HGF和MMP-9密切相关。     

黄芪甲苷对光老化小鼠皮肤中转化生长因子-β信号通路的影响北大核心CSCD

目的探讨黄芪甲苷对皮肤光老化的保护机制。方法BALB／c小鼠分为模型组、模型＋基质组、模型＋黄芪甲苷组、正常对照组。RT—PCR测定转化生长因子β受体Ⅱ（TGF—βRⅡ）、Smad7的mRNA表达水平,免疫组化观察TGF-βRⅡ、Smad7在小鼠皮肤组织中的蛋白表达情况。结果正常对照组中,TGF-βRⅡ、Smad7的灰度值比值分别为0．5688±0．0439、0．5900±0．0585,阳性表达率分别为（53．00±4．72）％、（47．50±3．81）％;模型组中,TGF-βRⅡ、Smad7的灰度值比值分别为0．2588±0．0283、0．8637±0．0514,阳性表达率分别为（28．20±5．24）％、（82．06±2．18）％;模型＋基质组中,TGF-βRⅡ、Smad7的灰度值比值分别为0．2653±0．0456、0．8553±0．0575,阳性表达率分别为（28．74±2．28）％、（82．62±4．02）％;模型＋黄芪甲苷组中TGF-βRⅡ、Smad7的灰度值比值分别为O．3767±0．0374、0．7131±0．0410,阳性表达率分别为：（41．64±2．59）％、（64．36±2．62）％。皮肤组织中TGF-βRⅡ和Smad灰度值比值4组小鼠间比较,F值分别为80．98和736．80,TGF-βRⅡ和Smad7的阳性表达率4组小鼠间比较,F值分别为45．36和132．25,P值均〈0．01。与正常对照组相比,模型组TGF-βRⅡmRNA和蛋白表达明显降低,Smad7mRNA和蛋白表达显著升高（P值均〈0．01）。与模型组和模型＋基质组比较,模型＋黄芪甲苷组TGF-βRⅡmRNA和蛋白表达明显升高,Smad7mRNA和蛋白表达显著下调（P值均〈0．01）。模型＋基质组TGF-βRⅡ、Smad7的mRNA和蛋白表达与模型组相比差异无统计学意义（P值均〉0．01）。结论黄芪甲苷可以通过上调TGF-βRⅡ表达和下调Smad7表达而改变TGF—β通路的信号转导参与抗光老化。     

超敏C反应蛋白,维生素D、A、E与妊娠期高血压疾病的相关性研究

目的探究维生素D,A,E以及超敏C反应蛋白与妊娠期高血压疾病的相关性。方法从徐州医科大学附属连云港医院2017年1月至2018年1月期间进行产检的孕早期单胎初孕妇中,随机抽取97名孕妇,根据妊娠结局分为正常妊娠组26例,妊娠期高血压组37例,子痫前期组22例,重度子痫前期组12例。所有研究对象均进行维生素D、维生素A、维生素E及超敏C反应蛋白水平检测。结果重度子痫前期组、子痫前期组、妊娠期高血压组患者体内维生素D、维生素A、维生素E含量均低于正常妊娠组患者,且重度子痫前期组各水平含量低于子痫前期组与妊娠高血压组,妊娠期高血压组各水平含量与子痫前期组患者、重度子痫前期组比较结果均具有统计学意义(均P 0. 05);正常孕妇、妊娠期高血压孕妇、轻度子痫前期孕妇及重度子痫前期孕妇超敏C反应蛋白水平呈依次升高,差异具有统计学意义(P 0. 05)。结论维生素D、维生素A、维生素E及超敏C反应蛋白对于妊娠期高血压疾病有很好的预测作用,孕期一旦发现可以及早处理,防止不良妊娠结局的发生。     

环氧合酶-2反义寡核苷酸对Colo-16细胞增殖及环氧合酶-2表达的影响

目的　研究环氧合酶（COX）-2反义寡核苷酸（AsODN）对人皮肤鳞状细胞癌细胞株Colo-16细胞体外增殖的抑制作用及COX-2表达的影响。方法　人工合成COX-2 AsODN,利用脂质体将不同浓度（50,100,200,400 nmol/L）反义寡核苷酸转染入Colo-16细胞,免疫荧光显微镜观察转染情况;采用噻唑蓝（MTT）法检测Colo-16细胞的增殖情况;Western印迹及半定量逆转录PCR检测Colo-16细胞COX-2蛋白和mRNA表达水平。结果 不同浓度的COX-2 AsODN对Colo-16细胞体外增殖均具有抑制作用（P < 0.05）,400 nmol/L反义组在48 h抑制率最高,达60.3%;COX-2 AsODN转染Colo-16细胞后,COX-2蛋白和mRNA表达明显下调,50、100、200、400 nmol/L组COX-2蛋白灰度值分别为0.763 ± 0.070、0.600 ± 0.065、0.430 ± 0.074、0.251 ± 0.045,与阴性对照组相比差异均有统计学意义（P < 0.05）;COX-2 mRNA表达量随COX-2 AsODN浓度的增加而减少,50、100、200、400 nmol/L组COX-2 mRNA灰度值分别是0.778 ± 0.025、0.602 ± 0.041、0.417 ± 0.031、0.297 ± 0.051,各组间COX-2 mRNA表达差异有统计学意义（F = 132.48,P < 0.01）。结论 COX-2 AsODN对Colo-16细胞的体外增殖有抑制作用,并能下调COX-2蛋白及其mRNA在Colo-16细胞中的表达,提示COX-2 AsODN有潜在治疗皮肤鳞状细胞癌的作用。     

不同预后尖锐湿疣组织中Toll样受体3、9的表达

目的 探讨不同预后尖锐湿疣（CA）患者皮损局部Toll样受体3（TLR3）和Toll样受体9（TLR9）表达定位及TLR3 mRNA、TLR9 mRNA的表达情况。方法 免疫组化SP法及反转录聚合酶链反应（RT-PCR）法检测10例CA复发者、14例CA无复发者及10例包皮组织中TLR3 及TLR9表达情况。结果 TLR3、TLR9在无复发CA皮损中表达以棘层、颗粒层为主;在复发组CA皮损中表达以基底层、棘层为主。无复发组CA组织中TLR3mRNA表达较对照组及复发组均明显升高（P ＜ 0.01、P ＜ 0.05）,TLR9 mRNA较对照组明显升高（P ＜ 0.05）,较复发组差异无统计学意义。结论 表皮TLR3 及TLR9的表达部位和表达量的改变可能与CA预后有关,TLR3的影响可能更大。     

SPRY4-IT1在子痫前期患者胎盘中的表达及对滋养层细胞增殖、侵袭的影响

目的探讨SPRY4内含子转录本1(SPRY4-IT1)在子痫前期(PE)患者胎盘中的表达及对滋养层细胞增殖、侵袭的影响。方法选取2017年6月至2019年6月在宜宾市第二人民医院产科行剖宫产术的34例PE患者(PE组)和32例正常妊娠孕妇(对照组)作为研究对象。采用实时荧光定量PCR(qRT-PCR)法检测胎盘中SPRY4-IT1表达水平。将HTR8/SVneo细胞分为空白对照组(不转染)、无义转染组(转染空载体)和上调组(转染SPRY4-IT1过表达载体);检测各组HTR8/SVneo细胞增殖、周期分布、细胞凋亡、侵袭情况及细胞中基质金属蛋白酶(MMP)-2、MMP-9蛋白表达情况。结果 PE组胎盘组织中SPRY4-IT1表达水平较对照组显著下调(P0.05);上调组HTR8/SVneo细胞OD值,S期、G_2/M期HTR8/SVneo细胞比例、穿膜细胞数,MMP-2、MMP-9蛋白表达水平均较无义转染组、空白对照组显著升高(P0.05),HTR8/SVneo细胞凋亡率、G_0/G_1期HTR8/SVneo细胞比例均较无义转染组、空白对照组显著降低(P0.05)。结论 SPRY4-IT1在PE患者胎盘组织中呈低表达,SPRY4-IT1可能通过上调MMP-2、MMP-9表达,调控细胞周期,参与促进HTR8/SVneo细胞增殖、侵袭及抑制其凋亡过程。     

天冬氨酸/半胱氨酸组织蛋白酶在光老化成纤维细胞中的表达变化

目的 探讨天冬氨酸组织蛋白酶（cathepsin D）及半胱氨酸组织蛋白酶（cathepsin K）在光老化成纤维细胞中的表达变化。方法 培养原代人皮肤成纤维细胞,在50 mg/L的8-甲氧沙林（8-MOP）培养基中避光孵育24 h后,用80 kJ/m2 UVA照射,体外诱导培养细胞光老化。衰老相关-β-半乳糖苷酶（SA-β-Gal）染色证明老化诱导成功。Western印迹及实时定量RT-PCR对比检测光老化成纤维细胞及正常成纤维细胞cathepsin K和cathepsin D蛋白及基因表达。结果 Western印迹结果显示,光老化组表达的cathepsin D的灰度值为3.25 ± 0.33,对照组为14.18 ± 2.25,t = 30.61,P < 0.01,两组间差异有统计学意义;光老化组表达的cathepsin K灰度值为2.39 ± 0.66,对照组为29.38 ± 4.62,t = 12.63,P < 0.01,两组差异有统计学意义。光老化组cathepsin D mRNA的ΔCt值为2.79 ± 0.17,对照组为4.54 ± 0.34,根据2-ΔΔCt值计算得cathepsin D mRNA在光老化组的表达下调为对照组的0.24 ± 0.021（t = 20.78,P < 0.01）;光老化组cathepsin K mRNA的ΔCt值为-0.92 ± 0.06,对照组为2.57 ± 0.13,根据2-ΔΔCt值计算得cathepsin K mRNA在光老化组的表达下调为对照组的0.09 ± 0.005（t = 28.50,P < 0.01）。结论 cathepsin D及cathepsin K在光老化成纤维细胞中表达均下调。     

紫外线对光化性角化病和正常皮肤p53、基质金属蛋白酶2、9表达的影响

目的 探讨不同剂量紫外线对光化性角化病（AK）与正常皮肤组织中增殖与凋亡、及p53、基质金属蛋白酶（MMP）2和MMP9表达的影响。方法 AK与正常皮肤组织分别分为4个组,对照组（照射剂量为0 J/cm2）、5 J/cm2组、10 J/cm2组、20 J/cm2组。每块组织连续照射4 d,继续培养24 h后取材。TUNEL检测细胞凋亡、Ki-67检测细胞增殖情况,定量PCR及免疫组化法检测p53、MMP2及MMP9表达。 结果 紫外线照射后,与对照组相比,凋亡细胞百分比在正常皮肤组织 10、20 J/cm2组（46.8 ± 2.1,56.7 ± 2.4）增加,在AK 20 J/cm2（43.5 ± 1.5）组增加,正常皮肤组织10、20 J/cm2组比AK同剂量组增加（P < 0.05）;Ki-67阳性细胞百分比在正常皮肤组织20 J/cm2组（3.34 ± 0.76）表达减少（P < 0.05）,在AK中无明显变化（P > 0.05）;p53 mRNA（5 J/cm2：1.106 ± 0.025;10 J/cm2：1.259 ± 0.045;20 J/cm2：1.425 ± 0.053）及蛋白（10 J/cm2：0.1169 ± 0.0032;20 J/cm2：0.1454 ± 0.0047）在正常皮肤组织中表达增加,在AK中,mRNA（10 J/cm2：0.611 ± 0.050;20 J/cm2：0.578 ± 0.070）及蛋白（20 J/cm2：0.0404 ± 0.0027）表达减少（P < 0.05）;正常皮肤组织中MMP2 mRNA及蛋白（10 J/cm2：1.086 ± 0.013,0.0843 ± 0.0024;20 J/cm2：1.417 ± 0.036,0.1236 ± 0.0042）、MMP9 mRNA及蛋白（20 J/cm2：1.395 ± 0.026,0.3065 ± 0.0162）表达增加,AK中MMP2 mRNA及蛋白（20 J/cm2：1.296 ± 0.028,0.0744 ± 0.0032）、MMP9 mRNA及蛋白（10 J/cm2：1.298 ± 0.035,0.0992 ± 0.0053;20 J/cm2：1.286 ± 0.032,0.1010 ± 0.0063）表达增加（P < 0.05）。结论 紫外线促进AK进展可能与其下调p53表达,上调MMP2和MMP9有关。     

早幼粒细胞白血病基因在寻常性银屑病患者外周血淋巴细胞中表达的研究

目的 检测寻常性银屑病患者外周血淋巴细胞中早幼粒细胞白血病（PML）基因的表达,以探索PML基因与银屑病之间的相互关系。方法 收集年龄18 ~ 65岁、未经系统治疗的寻常性银屑病患者50例,健康人对照45例。分离外周血淋巴细胞,使用RNAprep pure 血液总RNA提取试剂盒提取淋巴细胞RNA,用实时荧光定量逆转录聚合酶链反应检测外周血淋巴细胞PML基因mRNA的表达;流式细胞仪检测30例银屑病患者和25例健康人对照外周血淋巴细胞PML蛋白荧光强度值。分别用独立样本t检验对检测结果进行统计分析。结果 50例银屑病患者和45例健康人对照外周血淋巴细胞PML mRNA相对定量（RQ）值分别为14.98 ± 3.64和5.50 ± 1.10,银屑病患者组显著高于健康人对照组（两组比较,t = 16.79,P ＜ 0.05）。30例银屑病患者和25例健康人对照外周血淋巴细胞PML蛋白荧光强度值分别为3.13 ± 0.27和2.43 ± 0.21,银屑病患者组亦显著高于健康人对照组（两组比较,t = 6.93,P ＜ 0.05）。结论 PML基因mRNA及蛋白在银屑病患者外周血淋巴细胞中高表达,提示PML基因可能在银屑病的发病中起一定作用。     

Squamous cell carcinoma arising in Hailey-Hailey disease of the vulva

A 61-year-old woman, who was known to have Hailey-Hailey disease, presented with increasing vulval soreness. Biopsy showed vulval intraepithelial neoplasia (VIN) 3 and subsequent histology from a vulvectomy specimen showed extensive VIN with early invasive squamous cell carcinoma. This may be another example of chronic inflammation of the vulval area leading to the development of squamous cell carcinoma. However, in this case, chronic human papillomavirus may also have played a part, leading to VIN and reactivation of the Hailey-Hailey disease. We can find no previous reports of squamous cell carcinoma developing in the setting of Hailey-Hailey disease.     

Determination of plasma fibronectin in congenital epidermolysis bullosa

Comme il est possible que la fibronectine (FN) ait un rapport avec la formation ou la guérison des bulles dans des cas d'épidermolyse bulleuse congénitale (É.B.C.), nous avons effectué les dosages de FN plasmatique dans 10 cas d'É.B.C. (3 É.B. simples, 2 É.B. dystrophiques dominantes, 5 É.B. dystrophiques recessives). Les taux de FN plasmatique ne sont pas fonction de l'âge et du sexe, mais ils sont en corrélation avec la gravité de la maladie. Résultats selon les types d'épidermolyses; pour celles de type simple, les taux se classent en trois groupes, très bas, bas, normal et leur moyenne est basse aussi, pour celles de type dominant, les taux sont presque normaux, pour celles de type récessif, les taux se classent en deux groupes, normal et bas. Tous les cas, où l'on rencontre des taux de FN bas, sont a l'état évolutif, et l'abaissement de la FN plasmatique est en corrélation inverse avec la gravité (p<0,01).     

Distichiasis-lymphoedema: clinical features, venous function and lymphoscintigraphy

Distichiasis-lymphoedema is a rare variant of the genetically determined lymphoedemas; distichiasis is the abnormal development of the meibomian glands causing aberrant growth of eyelashes. However, a better understanding of this clinically distinct subgroup may provide useful information on the genetic inheritance of all types of lymphoedema. This report provides phenotype data on a very large family with distichiasis-lymphoedema. Lymphoscintigraphy and light reflection rheography (venous function) were undertaken to identify the phenotype more clearly. As a result of lymphoscintigraphy several subjects were reclassified phenotypically (unaffected or affected) with implications for genetic linkage studies. Associated congenital abnormalities were found and venous abnormalities were almost always present in affected limbs. A dominant inheritance with incomplete penetrance was confirmed.     

TLR9的生物学特性及其在生殖器疱疹发病中的意义

Toll样受体9属于模式识别受体(pattern recognition receptor,PRR)的一种,属于天然免疫系统的一部分,人体可能通过TLR9来识别HSV-2基因中的CpGDNA,启动天然免疫系统,活化DCs,以依赖MyD88的信号传导通路促使IFN-α分泌,诱导Th1型细胞免疫应答,以对抗生殖器疱疹病毒感染。深入认识TLR9的作用机理为DNA疫苗的应用提供理论依据。     

A novel mutation of keratin 9 in a large Chinese family with epidermolytic palmoplantar keratoderma

BACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant inherited skin disorder characterized by diffuse yellow thickening of the skin of the palms and soles, sharply bordered with erythematous margins. Histologically and ultrastructurally, EPPK presents cytolysis of keratinocytes and abnormal aggregation of tonofilaments in the suprabasal layers of the epidermis. To date, 15 different mutations of the keratin 9 gene (KRT9) have been demonstrated to cause most cases of EPPK. OBJECTIVES: To identify the KRT9 mutation in a large Chinese family with EPPK. METHODS: Denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and allele-specific polymerase chain reaction (AS-PCR) were used to screen exon 1 of the KRT9 gene for sequence variations. RESULTS: The DHPLC elution profiles of the DNA fragments amplified from the affected samples differed from those obtained from unaffected individuals, indicating that a sequence variation existed within the analysed fragment of KRT9. DNA sequencing revealed a novel insertion-deletion mutation in the exon 1 of KRT9, 497delAinsGGCT, resulting in the change of tyrosine(166) to tryptophan and leucine (Y166delinsWL). AS-PCR confirmed the mutation was not a common polymorphism. CONCLUSIONS: The results suggest the molecular basis of EPPK in this Chinese family and provide further evidence that mutations in the helix initiation motif of keratin 9 underlie Chinese EPPK.     

Teaching non-specialist health care professionals how to identify the atypical mole syndrome phenotype: a multinational study

The atypical mole syndrome (AMS) phenotype is the strongest known risk factor for cutaneous melanoma but recognition of the phenotype has been claimed to be problematic and to require specialist assessment. This study determined the ability of previously unskilled doctors and nurses in five countries to recognize the phenotype after brief training. The system used was the AMS scoring system. This incorporates melanocytic naevus counts, clinical atypia of naevi and distribution of naevi. The agreement in scoring between the dermatologist and trained personnel was determined in 986 patients; overall agreement in diagnosis was 94.5% (kappa 0.70, P < 0.0001). The kappa scores in different countries ranged from 0.65 to 0.77 for individual naevus characteristics, indicative of good agreement. Accurate diagnosis of the atypical mole syndrome phenotype is possible by non-specialists. This has implications for collaborative studies of naevi, for screening and for both primary and secondary prevention of melanoma.     

Topical 9-cis-retinaldehyde for delivery of 9-cis-retinoic acid in mouse skin

The 9-cis-retinoic acid (9cRA) is an endogenous ligand of retinoid X nuclear receptors (RXRs). Although the epidermis contains five times more RXRs than RARs, little is known on the activity of topical 9cRA. In order to circumvent surface isomerization of topically applied 9cRA into all-trans-retinoic acid (atRA), we used topical 9-cis-retinaldehyde (9cRAL) as a precursor of 9cRA, hypothesizing that keratinocytes would metabolize 9cRAL into 9-cis-retinoic acid (9cRA). Retinoid content was determined by HPLC analysis of mouse tail skin that had been washed after the application of 9cRAL (0.05% for 14 days) to evaluate the metabolites produced within the epidermis. Biologic activities of 9cRAL and atRAL were analysed by assessing hyperplastic and metaplastic responses, by determining epidermal thickness and the levels of mRNAs encoding for specific keratins. atRAL and derived retinoids were found in skin treated with either atRAL or 9cRAL. The metabolite pattern obtained with 9cRAL was similar to that obtained with atRAL except the presence in 9cRAL samples of an unidentified nonpolar metabolite. However, treatment with 9cRAL yielded higher atRAL and lower retinyl ester concentrations. The biologic activities (hyperplastic and metaplastic responses) resulting from topical application of 9cRAL were lower than those induced by atRAL or atRA at similar concentrations. Taken together, these data show that topical 9cRAL does not deliver significant amounts of 9cRA and exerts less biologic activity than atRAL. Contrary to atRAL, 9cRAL does not appear therefore as a pertinent candidate for topical use in humans.     

浆细胞样树突状细胞和TLR9及其mRNA在银屑病患者皮损中的表达

目的：探讨浆细胞样树突状细胞（Plasmacytoid dendritic cells,PDCs）和toll样受体9（TLR9）在银屑病发病中的表达状态。方法：采用免疫组织化学SP法和逆转录-聚合酶链反应（RT-PCR）方法检测了22例银屑病患者皮肤损害中PDCs和TLR9及其mRNA的表达。15例整形外科患者的皮肤作为正常对照。结果：免疫组化结果显示银屑病组皮损中PDCs、TLR9的表达明显增多,而在正常对照组没有表达;RT-PCR检测显示银屑病皮损中TLR9mRNA的表达明显高于正常对照组（P〈0.01）。结论：银屑病患者皮损中有PDCs浸润,TLR9及其mRNA的表达水平上调,可能与银屑病的发病相关。     

Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy

Cyclosporin (CyA) has been shown to be highly effective and well tolerated in the short-term treatment of severe childhood atopic dermatitis; however, there is limited experience in its longer-term use. The aim of this study was to compare multiple short courses of CyA with continuous therapy for 1 year, with respect to efficacy, safety, tolerability and quality of life. Children aged 2-16 years, with a diagnosis of severe atopic dermatitis refractory to topical steroid therapy, were randomly assigned to receive short course therapy (multiple courses of 12 weeks) or continuous therapy. The starting dose and maximum dose for all patients was 5 mg/kg per day. Disease activity was monitored using the Six Area Six Sign Atopic Dermatitis score and the 'Rule of Nines' area score. Pruritus, sleep disturbance and irritability were measured using visual analogue scales, and topical therapy was monitored. Safety measurements included monitoring of serum creatinine, blood pressure and adverse events. Forty patients were included in the efficacy analysis, 21 of whom were randomized to the short course group (of whom six were withdrawn) and 19 to the continuous group (of whom five were withdrawn). Significant improvements were seen in all efficacy parameters at every time-point. There were no significant differences between groups, although the improvement was more consistent in the continuous arm. In the short course arm, 7 out of 21 patients could be managed by at least two short courses. The remaining 14 patients includes 12 who could not be controlled by at least two short courses, one patient who failed to return after week 12 and another patient who was withdrawn at week 4 due to an adverse event. Quality of life improved for both the children and their families. Tolerability was considered good or very good in at least 80% of the patients at week 12 and at the end of the study. No clinically significant change was seen in mean serum creatinine and no change was seen in mean blood pressure in either group. CyA is effective in controlling severe atopic dermatitis in children over a 1-year period and is well tolerated. More consistent control is achieved with continuous treatment; however, short course therapy was adequate for some patients, indicating that treatment should be tailored to the individual patient's needs. Short course treatment may produce prolonged remission in some cases and reduce the cumulative exposure to the drug.