Notch信号通路相关配体在咪喹莫特诱导的银屑病样小鼠模型中的表达

目的：检测Notch信号通路相关配体在咪喹莫特（IMQ）诱导的银屑病样小鼠模型中的表达。方法： 6-8周雌性BALB/c小鼠随机分为IMQ模型组及空白对照组。HE染色观察皮损病理变化。RT-PCR及免疫组化分别检测IMQ模型组及空白对照组皮肤受体Notch1、Notch2、配体Jagged-1、目标基因Hes-1的mRNA和蛋白表达水平。结果：IMQ模型组小鼠皮肤出现典型银屑病样改变。IMQ模型组小鼠皮损中受体Notch 1、Notch2、配体Jagged-1、目标基因Hes-1的mRNA和蛋白表达水平高于对照组（P<0.05）。结论：Notch信号通路在咪喹莫特诱导的银屑病样小鼠模型中被激活。     

银屑病患者骨髓CD34+细胞Notch受体及其靶基因表达的研究

目的 探讨银屑病患者骨髓CD34+细胞表面两种Notch受体的表达及其下游靶基因Hes-1的表达。方法 分离12例银屑病患者及10例正常对照骨髓CD34+细胞,以β-肌动蛋白为内参照,采用Western印迹法半定量检测Notch受体1、2及其下游靶基因Hes-1的蛋白表达水平。结果 银屑病患者CD34+造血细胞Notch1表达水平（0.9488 ± 0.3221）明显高于正常人对照（0.6693 ± 0.1465）;Hes-1蛋白在银屑病患者表达（0.8579 ± 0.3729）亦高于正常人对照（0.5728 ± 0.1787）,两者差异均有统计学意义（P < 0.05）,而Notch2蛋白的表达在患者组（0.7568 ± 0.3461）和正常人对照组（0.8312 ± 0.2887）之间差异无统计学意义（P > 0.05）。结论 Notch1受体及其下游基因Hes-1的高表达可能参与银屑病患者骨髓造血细胞低增殖活性的发生。     

Notch1信号对银屑病患者外周血Th17细胞分化和功能的影响

目的 探讨Notch1信号对银屑病患者外周血Th17细胞分化和功能的影响。方法 取35例寻常性银屑病患者与32例健康对照外周血,流式细胞仪检测单个核细胞（PBMC）中Th17细胞占CD4+ T淋巴细胞的比例,实时荧光定量反转录PCR检测PBMC中维A酸相关孤儿核受体γt（RORγt）、白介素17（IL-17）、Notch1及发状分裂相关增强子1（Hes-1）mRNA表达水平,酶联免疫吸附试验检测血清及培养上清液中IL-17含量。分析Notch1 mRNA的表达与银屑病皮损面积和疾病严重程度评分（PASI）、Th17细胞比例、RORγt mRNA、IL-17 mRNA及蛋白表达水平的相关性。将银屑病患者PBMC分为0（对照组）、2.5、5.0、10.0、20.0 μmol/L γ分泌酶抑制剂（DAPT）处理组,检测DAPT阻断Notch1信号对PBMC中Th17细胞比例、RORγt及IL-17表达水平的影响。结果 银屑病患者PBMC中Th17细胞占CD4+ T细胞比例为2.863% ± 0.969%,RORγt、Notch1、Hes-1、IL-17 mRNA表达水平分别为5.255 ± 0.998、6.743 ± 1.756、6.384 ± 1.665、6.944 ± 1.626,IL-17血清含量为（36.444 ± 5.936） ng/L,均高于健康对照组［分别为0.604% ± 0.124%、1.530 ± 0.485、1.731 ± 0.456、1.627 ± 0.485、1.698 ± 0.329、（11.762 ± 2.260） ng/L,P < 0.01］。银屑病患者Notch1 mRNA表达水平与PASI、Th17细胞比例、RORγt mRNA表达水平、IL-17 mRNA表达水平及血清含量均呈正相关（r值分别为0.584、0.544、0.518、0.549、0.511,均P < 0.05）。5种不同浓度DAPT处理组银屑病患者PBMC中Th17细胞比例、RORγt mRNA表达水平、IL-17 mRNA表达水平及培养上清液含量差异有统计学意义（F值分别为79.527、82.239、78.086、80.558,均P < 0.01）,2.5、5.0、10.0、20.0 μmol/L DAPT组上述指标均低于对照组（均P < 0.05）,且随着DAPT作用浓度的增加,各指标呈降低趋势。结论 Notch1信号可促进银屑病患者外周血Th17细胞的分化及RORγt 、IL-17、Hes-1的表达。     

Notch信号通路在咪喹莫特诱导的银屑病样小鼠模型中的表达

目的:检测Notch信号通路在咪喹莫特(IMQ)诱导的银屑病样小鼠模型中的表达。方法:6～8周雌性BALB/c小鼠随机分为IMQ模型组及空白对照组。HE染色观察皮损病理变化。RT-PCR及免疫组化分别检测IMQ模型组及空白对照组皮肤受体Notch1、Notch2、配体Jagged-1、目标基因Hes-1的mRNA和蛋白表达水平。结果:IMQ模型组小鼠皮肤出现典型银屑病样改变。IMQ模型组小鼠皮损中受体Notch1、Notch2、配体Jagged-1、目标基因Hes-1的mRNA和蛋白表达水平高于对照组(P0.05)。结论:Notch信号通路在咪喹莫特诱导的银屑病样小鼠模型中被激活。     

银屑病患者骨髓CD34~+细胞Hes-1基因的表达研究

目的:观察银屑病患者骨髓CD34~+细胞Hes-1基因的表达.方法:以β-肌动蛋白为内参照,采用反转录(RT)-PCR法半定量检测24例银屑病患者及18名正常人骨髓CD34~+细胞Hes-1 mRNA的表达水平.结果:与正常对照组相比,银屑病患者组Hes-1mRNA表达水平明显升高,二者差别有统计学意义.结论:造血细胞发育过程中重要的转录因子Hes-1的高表达可能与银屑病患者骨髓造血细胞的增殖活性异常有关.     

银屑病患者Jak/STAT信号传导通路基因表达的研究

目的:探讨角质形成细胞Jak/STAT信号传导通路上的STAT1、STAT3、SOCS1、SOCS3 4个相关基因在银屑病发病中的作用。方法:收集10例银屑病患者皮损区和非皮损区组织各一块,用实时荧光定量PCR检测组织角质形成细胞中STAT1、STAT3、SOCS1、SOCS3 mRNA的表达,计算各基因mRNA的相对表达水平,探讨其与银屑病皮损发生的关系。结果:银屑病患者皮损区角质形成细胞STAT1、STAT3、SOCS1、SOCS3基因的mRNA表达水平(△Ct值分别为-1.9±1.6、0.6±1.6、0.1±1.0、-0.6±1.1)较非皮损区(△Ct值分别为1.0±1.6、3.7±1.5、4.2±1.2、3.9±1.3)明显增高(P值均<0.01);银屑病患者中角质形成细胞STAT1、STAT3 mRNA的表达水平分别与SOCS1和SOCS3 mRNA的表达水平呈正相关(r=0.84、0.83,P值均<0.01)。结论:角质形成细胞Jak/STAT信号传导通路相关基因可能与银屑病发病有关,需要进行结构与功能相关性的研究以进一步明确。     

寻常型银屑病患者外周血单个核细胞SOCS-1、SOCS-3 mRNA的表达

目的:检测细胞因子信号抑制因子SOCS-1、SOCS-3mRNA在寻常型银屑病患者外周血单个核细胞(PBMC)中的表达。方法:从20例银屑病患者及20例健康志愿者外周血中分离PBMC,提取RNA,应用逆转录-聚合酶链反应(RT-PCR)方法检测SOCS-1、SOCS-3mRNA的表达。结果:SOCS-1、SOCS-3mRNA在银屑病患者中表达,在正常人中无表达,活动期银屑病患者较静止期患者SOCS-1、SOCS-3mRNA表达增高。结论:SOCS-1、SOCS-3可能在银屑病的Th1免疫反应中发挥作用。     

45例麻风病患者外周血CD4+ T细胞差异表达基因筛查

【摘要】 目的 检测麻风病患者外周血CD4+ T细胞中mRNA表达谱,筛选并验证可能与麻风病发病过程密切相关的基因。方法 2018年7月至2020年5月在湖南省收集45例麻风病患者及45例健康人,以磁珠法分离外周血CD4+ T细胞,提取RNA。在上述受试者中,随机选取6例患者及6例健康人,采用Solexa测序法筛查两组间差异表达基因,将差异倍数2倍以上者（P < 0.05）定义为差异表达基因,并进行KEGG Pathway富集分析,再以实时荧光定量PCR验证基因的表达水平。结果 基因筛查发现4 831个转录本,属于新基因且具有蛋白编码潜能,在两组间筛选出8个差异表达基因,其中,CXCL8、PPBP、RPS18及IL-1β基因mRNA表达水平上调,RNH1、RPL39、RPL15及AMBRA1基因mRNA表达水平下调。实时荧光定量PCR验证结果与上述基因筛查结果一致。KEGG分析显示,麻风病患者与健康对照组差异表达基因主要富集在线粒体自噬及细胞自噬相关通路和人乳头状瘤病毒感染通路。结论 麻风病患者AMBRA1、RNH1基因mRNA表达水平下调,CXCL8、PPBP、IL-1β基因mRNA表达水平上调,可能分别通过线粒体自噬通路和趋化因子介导的信号通路参与麻风病发病。     

寻常性银屑病患者外周血单一核细胞IFN-γ受体和TNF-α受体mRNA表达的研究

目的 探讨寻常性银屑病患者外周血单一核细胞IFN-γ受体mRNA和TNF-α仅受体mRNA的表达及其在银屑病发病机制中的作用.方法 采集50例寻常性银屑病患者外周静脉血,分离单一核细胞后,以RT-PCR法检测其IFN-γ受体mRNA和TNF-α受体mRNA的表达,PASI评分法评估银屑病的严重程度.以24例正常人作对照.结果 50例银屑病患者外周血单一核细胞IFN-γ受体mRNA的表达均值为1.11±0.55,其中37例进行期患者为1.13±0.57,13例静止期患者为1.03±0.52,正常人对照组为0.72±0.17,银屑病患者显著高于正常人对照组(P=0.0034),进行期显著高于正常人对照组(P=0.008),而静止期与正常人对照组差异无统计学意义.正常人对照组和银屑病患者外周血单一核细胞TNF-α受体mRNA的表达水平差异无统计学意义.银屑病患者外周血单一核细胞IFN-γ受体mRNA表达水平与TNF-α受体mRNA表达水平及PASI值均无相关性.结论 IFN-γ受体mRNA在寻常性银屑病患者外周血单一核细胞中异常高表达,但与疾病的活动性无关.     

寻常型银屑病患者皮损中miRNA-34a及其靶基因Notch1的表达及意义

目的:探讨miRNA-34a及其靶基因Notch1在寻常型银屑病患者皮损中的表达水平及意义。方法:实时荧光定量PCR法检测22例寻常型银屑病患者皮损组织及10例正常人皮肤组织中miRNA-34a的表达水平。采用免疫组化EnVision法检测51例寻常型银屑病患者(包括上述22例患者)和29例正常人(包括上述10例正常人)皮损组织中miRNA-34a可能的靶基因Notch1的表达情况。结果:miRNA-34a在寻常型银屑病患者皮损组织中的表达水平为0.162±0.186,高于正常皮肤组织中的表达水平(0.028±0.029),银屑病组为正常对照组的5.786倍,两组比较,差异有统计学意义(t=2.22,P<0.05);Notch1在寻常型银屑病组织中主要为表皮全层细胞质表达,阳性表达率为76.47%(39/51),而在正常皮肤组织中阳性表达率为13.79%(4/29),两者差异有统计学意义(χ~2=29.22,P<0.05)。结论:miRNA-34a在寻常型银屑病皮损组织中的表达高于正常人皮肤组织,其可能通过调控靶基因Notch1参与寻常型银屑病的发病机制。     

Dermatology in private practice in France in 2000

OBJECTIVES: Data regarding French dermatological practice are scarce. Our objective was to identify the skin disorders most commonly diagnosed by office-based dermatologists. We also documented the severity of these skin disorders, as reflected by the repercussions on patient's everyday life, and the way physicians managed patients. DESIGN: We carried out a one-day survey of visits to a randomly selected sample of 900 French office-based dermatologists. The randomization was stratified according to the five French different dialing area codes. RESULTS: Office-based dermatologists saw 6411 patients with 7839 skin disorders during the survey. The daily number of visits to French dermatologists was estimated at 47 000 and the annual number between 12 and 14 millions. Office-based dermatologists mostly managed warts, acne, nevus, dermatitis, malignancies and pre-malignancies, fungal infection and psoriasis. Repercussions on patients'everyday life were assessed by physicians as important or very important in 28 p. 100 of cases. Half of the patients received topical treatment, 20.5 p. 100 a systemic drug and 40 p. 100 a minor surgical procedure (including cryotherapy). CONCLUSION: Although dermatologists frequently see benign skin disorders such as warts or nevus, more severe diseases represent an important part of their activity.     

Pentoxifylline in reactions in leprosy

A study was conducted to assess the response of reactions in leprosy to pentoxifylline therapy. Ten cases were studied; 8 cases had type 2 reaction and 2 cases had type 1 reaction. Pentoxifylline was given orally 400 mg three times daily. In patients with type 2 reaction, good response was observed within one week. There was near complete regression of ENL lesions within one month. Cases with type 1 reaction did not respond to pentoxifylline.     

Leukocyte migration in vivo and in vitro in patients with psoriasis

Leukocyte migration in vivo was studied with a skin chamber technique in 21 patients with active psoriasis vulgaris and 18 with cleared psoriasis vulgaris. Measuring over 24 h, no difference was found between healthy volunteers and most patients with active psoriasis, although a subgroup of patients with long-lasting relapses showed subnormal migration values. In patients with cleared psoriasis on the other hand the in vivo leukocyte migration values were increased. In addition, leukocyte migration in vitro under agarose was studied, but no difference was found between healthy controls and patients with psoriasis, active or cleared.     

Decrease in neutrophils observed in vivo in psoriatics after PUVA therapy

Summary In 56 patients leucocyte and differential counts were done before and at weekly intervals during PUVA treatment of chronic recalcitrant psoriasis. A statistical significant (P<0.01) decrease in the percentage of neutrophils was observed during the first week of the PUVA therapy. This observation could be closely related to the clinical clearing of psoriasis (P=0.02).The effect of PUVA therapy in psoriasis may be due to a decrease in the number of immunocompetent neutrophils demonstrated in psoriatic lesions.