目的 观察葛根芩连汤对2,4-二硝基氟苯(2,4-dinitrofluorobenzene,DNFB)诱导的特应性皮炎(atopic dermatitis,AD)模型小鼠的干预作用及潜在作用机制.方法 24只雄性BALB/c小鼠随机分为正常组、模型组、中药组(葛根芩连汤治疗)和对照组(糠酸莫米松治疗).DNFB反复刺激皮肤致敏诱导AD小鼠模型.观测各组小鼠皮损评估、皮肤组织病理学、皮肤pH值、经皮水分流失、搔抓行为及血清总免疫球蛋白E(immunoglobulin E,IgE)、白细胞介素6(interleukin-6,IL-6)、白细胞介素10(interleukin-10,IL-10)含量.逆转录—聚合酶链式反应(quantitative Real-time PCR,qRT-PCR)法测定丝聚合蛋白、密封蛋白1的mRNA的表达;蛋白免疫印迹法(Weston blot,WB)检测丝聚合蛋白、密封蛋白1的蛋白表达水平.结果(1)治疗前,与正常组相比,模型组背部皮肤有明显的红斑水肿,并可见结痂、鳞屑、皮肤肥厚增生;搔抓次数明显增多,经皮失水及皮肤pH值显著升高;经治疗,与模型组比较,中药组与对照组皮肤损伤情况改善,搔抓次数、经皮失水、皮肤pH值显著降低(P<0.05);(2)治疗前,模型组小鼠血清总IgE、IL-6、IL-10水平均与正常组有显著差异;经治疗,中药组、对照组总IgE、IL-6水平与模型组相比含量降低(P<0.05);(3)与正常组比较,模型组qRT-PCR显示丝聚合蛋白、密封蛋白1的表达水平降低;WB显示丝聚合蛋白、密封蛋白1蛋白的含量降低;经治疗,中药组、对照组丝聚合蛋白、密封蛋白1的基因表达水平增高;丝聚合蛋白、密封蛋白1蛋白含量增高(P<0.05);(4)皮肤病理学显示与正常组相比,模型组表皮层存在不完全角化,颗粒层和棘层皮肤增厚,表皮、真皮层均有大量炎细胞浸润;经治疗,中药组及对照组小鼠表皮层角化不全程度较轻,颗粒层、棘层皮肤轻微增厚,炎细胞浸润减轻.结论 葛根芩连汤可以减轻AD模型小鼠皮损程度,减少搔抓次数,有效降低经皮失水、皮肤pH值,下调小鼠血清IgE、IL-6水平,上调丝聚合蛋白、密封蛋白1的表达,抑制炎症反应和改善皮肤屏障,为中医"皮应大肠"理论和皮肤病从肠论治提供了实验依据.

目的:探讨麻黄连轺赤小豆汤对不同时期特应性皮炎(atopic dermatitis,AD)模型小鼠皮肤屏障功能的影响.方法:采用随机数字表法将120只雄性BALB/c小鼠随机分为正常组、模型组、糠酸莫米松组和麻黄连轺赤小豆汤组.除正常组外,其余组小鼠采用2,4-二硝基氟苯(2,4-dinitrofluorobenzene,DNFB)反复刺激皮肤建立AD动物模型.于实验第4、18、32、39天4个时间点分别进行药物干预,麻黄连轺赤小豆汤组灌胃给予麻黄连轺赤小豆汤(11.98 g·kg-1·d-1),每日2次;糠酸莫米松组于小鼠皮损处均匀涂抹适量0.1％糠酸莫米松凝胶,每日2次;正常组和模型组给予等量常温蒸馏水灌胃,每日2次;每个时间点连续干预7 d.于第11、25、39、46天4个时间点分别考察各组小鼠皮损评分、皮肤组织病理学、皮肤酸碱度(pondus hydrogenii,pH)及经皮水分散失(trans epidermal water loss,TEWL)情况.结果:与正常组相比,AD模型组小鼠整个观察周期各时间点皮损评分、TEWL值均明显升高(P＜0.01);第11、25、39天3个观测点pH值均明显升高(P＜0.01).与模型组相比,麻黄连轺赤小豆汤组小鼠第39、46天两个时间点TEWL值显著下降(P＜0.01);第11、25、39天3个观测点皮肤pH值均明显降低(P＜0.01).HE染色发现AD模型组小鼠四个观察点皮肤组织表现依次为:表皮增厚,以棘细胞层增厚为主→表皮增厚,棘细胞层增生变厚→表皮增厚,棘细胞层显著增厚→表皮增厚减轻,棘细胞层增生减轻等;而麻黄连轺赤小豆汤可明显改善模型小鼠皮肤病理改变.皮损评分、TEWL值、pH值的相关分析发现,皮损评分、pH值、TEWL值三者呈正相关关系,可共同加重皮肤屏障功能障碍.结论:麻黄连轺赤小豆汤可有效改善AD模型小鼠皮肤屏障功能,以亚急性期治疗效果最佳.

Objective:To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis（AD） by studying the effects of Mahuang Lianqiao Chixiaodou decoction（MLCD） on skin damage and inflammation factors in an AD-like mouse model.Methods:Ninety-six male BALB/c mice were divided into normal,model,positive control（mometasone furoate）,and traditional Chinese medicine treatment（MLCD） groups by a random number table.2,4-dinitrofluorobenzene was used to induce AD-like mice in all groups except the normal group.The treatment or intervention was administered for seven consecutive days on days 4,18,32,and 39.The mRNA relative expressions of interleukin-4（IL-4）,IL-10,interferon-γ（IFN-γ）,thymic stromal lymphopoietin（TSLP）,and the TSLP receptor（TSLPR） were measured using quantitative real-time polymerase chain reaction,and the serum immunoglobulin E,IL-4,IL-10,and IFN-γ levels were detected using enzyme-linked immunosorbent assay.Results:Compared with the normal group,the hematoxylin-eosin staining of the skin lesions of the mice in the model group was significantly thickened on days 11,25,and 39.Compared with the model group,the epidermal thickness of the positive control group was significantly alleviated on day 39（P ＜.001）,and that of the MLCD group was significantly improved on days 25 and 39（P ＜.001）.Compared with the four observation time points,MLCD had the best treatment effect on day 39 of the experiment and significantly improved the skin damage performance and relieved pathological lesions.On day 39,compared with the model group,MLCD downregulated the skin mRNA relative expressions of IL-4（P=.009）,TSLP（P=.030）,and TSLPR（P ＜.001）,and reduced the mouse serum levels of IL-4（P=.003）.For other serum indicators,no significant difference was observed between the model and MLCD groups.Conclusion:MLCD improved AD-like mice skin damage by regulating the Th1/Th2 immune imbalance.

目的:探索构建适用于中医学领域的分词模型.方法:采用基于SentencePiece的无监督学习分词方法,提出利用出版教材、名家著作及中医临床病历这3种不同类型的文献构建中医学分词模型;选择中医临床病历、名医医案作为测试集进行模型测试.结果:中医学分词模型在测试集中的Kappa系数为0.79(一致性程度很高),准确率为0.84,宏观精确率为0.84,宏观召回率为0.83,宏观f1得分为0.83.结论:所构建的分词模型对于中医学专业术语有着较好的切分效果,表明该方法可运用于中医学领域的分词模型的构建,可为进一步地研究中医学分词提供方法学参考.

Currently, a broad diversity of fluorescent proteins among marine organisms range from cyano-red emissions. Fluorescent proteins differ in their DNA sequences from green fluorescent protein (GFP). We identified cDNA encoding the gene of a new protein from the reef coral Hydnophora rigida of the Merulinidae family. Both the spectral properties and putative primary sequence of the protein has been determined. The cloned cDNA encode peptide we call HriCFP is comprised of 134 amino acids. It has characteristics of a cyano fluorescent protein (HriCFP) and its sequence is markedly different from known GFP from the hydroid jellyfish Aequorea victoria. HriCFP was cloned, expressed, purified and exist as monomer. The peptide mass finger print on the purified protein confirmed identity of HriCFP.