Mixed Polyethylene Glycol-Modified Breviscapine-Loaded Solid Lipid Nanoparticles for Improved Brain Bioavailability: Preparation,Characterization, and In Vivo Cerebral Microdialysis Evaluation in Adult Sprague Dawley Rats

Breviscapine is used in the treatment of ischemic cerebrovascular diseases, but it has a low bioavailability in the brain due to its poor physicochemical properties and the activity of P-glycoprotein efflux pumps located at the blood–brain barrier. In the present study, breviscapine-loaded solid lipid nanoparticles (SLN) coated with polyethylene glycol (PEG) derivatives were formulated and evaluated for their ability to enhance brain bioavailability. The SLNs were either coated with polyethylene glycol (40) (PEG-40) stearate alone (Bre-GBSLN-PS) or a mixture of PEG-40 stearate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 (DSPE-PEG₂₀₀₀) (Bre-GBSLN-PS-DSPE) and were characterized both in vitro and in vivo. The mean particle size, polydispersity index, and entrapment efficiency for Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE were 21.60 ± 0.10 and 22.60 ± 0.70 nm, 0.27 ± 0.01 and 0.26 ± 0.04, and 46.89 ± 0.73% and 47.62 ± 1.86%, respectively. The brain pharmacokinetic parameters revealed that the brain bioavailability of breviscapine from the Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE was significantly enhanced (p < 0.01) with the area under concentration–time curve (AUC) of 1.59 ± 0.39 and 1.42 ± 0.58 μg h/mL of breviscapine, respectively, in comparison to 0.11 ± 0.02 μg h/mL from the commercial breviscapine injection. The ratios of the brain AUC for scutellarin in comparison with the plasma scutellarin AUC for commercial breviscapine injection, Bre-GBSLN-PS, and Bre-GBSLN-PS-DSPE were 0.66%, 2.82%, and 4.51%, respectively. These results showed that though both SLN formulations increased brain uptake of breviscapine, Bre-GBSLN-PS-DSPE which was coated with a binary combination of PEG-40 stearate and DSPE-PEG₂₀₀₀ had a better brain bioavailability than Bre-GBSLN-PS. Thus, the coating of SLNs with the appropriate PEG derivative combination could improve brain bioavailability of breviscapine and can be a promising tool for brain drug delivery.KEY WORDS: breviscapine, microdialysis, mixed PEGylation, P-glycoprotein (P-gp), solid lipid nanoparticles     

双源CT冠状动脉血管成像诊断心肌桥的价值探讨

目的：研究双源CT冠状动脉血管成像诊断心肌桥的临床价值。方法：选择260例具有典型心前区不适的患者进行双源CT冠脉血管成像检查,观察其发生部位,测量其长度和深度并进行分析。结果：260例受检患者中,62例共70段存在心肌桥,检出率达20.76%,高于文献报道的检出率18.2%。所有心肌桥均发生于左前降支,其中近段17段（24.4%）,中段43段（61.4%）,远段10段（14.2%）。心肌桥平均长度为15.8±6.4mm,深度为1.4±0.85mm。结论：双源CT冠状动脉血管成像因其便捷无创,不受心率严格限制且价格低廉可作为心肌桥筛查的理想检查手段。     

选择性5-羟色胺再摄取抑制剂的临床应用进展

5-羟色胺（5-hydroxy tryptamine,5-HT）是中枢及外周神经系统中一种重要的神经递质。5-羟色胺转运体（5-HT transporter,5-HTT）可将5．HT再摄取,降低细胞外5-HT浓度,从而调节神经信号传导。5-HTT异常在某些精神疾病的发病中起重要作用。近年来选择性5．羟色胺再摄取抑制剂（selective serotonin reuptake inhibitors,SSRIs）在临床上的应用日趋广泛,如治疗抑郁症、焦虑症、抑郁和焦虑共病等常见的精神疾病。氟西汀、帕罗西汀、舍曲林、氟伏沙明和西酞普兰是目前临床上最常用的五种SSRIs,被誉为抗抑郁药的“五朵金花”。本文详细介绍近年来在临床上药物治疗抑郁症取得的成果以及这类药物的药效学、药动学、不良反应和相互作用等,并简要介绍SSRIs在其它疾病领域取得的应用进展。     

Modification of Bombyx mori silk fabrics by tyrosinase‐catalyzed grafting of chitosan

Tyrosinase could oxidize tyrosyl residues in silk fibroin and result in the production of activated o‐quinone residues, which could facilitate the grafting of the functional amino‐compounds onto silk fibers. In this study, the enzymatic modifications of Bombyx mori silk fibroin with tyrosinase and chitosan were investigated, aiming at improving the properties of silk fabrics, including dyeability, crinkling resistance, and antibacterial activity. The grafting grades of chitosan were evaluated by a color‐development method using bromocresol green. The result indicated that chitosan molecules were not only adsorbed on silk fibers via electrostatic interactions, they also could react with the oxidized silk fibers with tyrosinase. For the silk fabric combinedly treated with tyrosinase and chitosan, tensile strength and crinkling resistance were noticeably increased as compared to that of the chitosan‐treated. The antibacterial activity and its durability measurements revealed the actions of the tyrosinase‐catalyzed grafting of chitosan. The efficacy of the graft reaction might be further enhanced by increasing the accessibility of reactive sites in silk fibers.     

B超引导下甲状腺肿块细针穿刺细胞学诊断的临床病理分析

目的：比较B超引导下细针吸取穿刺和传统细针吸取穿刺在甲状腺肿块性质确定中意义。方法：使用B超引导下细针吸取穿刺（UG-FNAB）和传统细针吸取穿刺技术（C-FNAB）对225例甲状腺肿块进行穿刺活检,然后进行涂片,染色,镜检,结合临床作出细胞学诊断,并与组织切片诊断对照,比较两种方法的确诊率。结果：在UG—FNAB检测病例中59.3％的结节位于甲状腺右叶,40．7％肿块位于左叶和峡部。87％的患者甲状腺机能正常,结节最长径平均为2．8±1．1cm,部分病例符合甲状腺恶性肿瘤的超声影像学改变。在本研究中诊断为甲状腺乳头状癌的病例细胞学和组织学特点均符合甲状腺癌形态学特点。在225例研究病例中,总确诊率为72．89％（164／225）,其中UG-FNAB组确诊率为90．58％（77／85）,C-FNAB组确诊率为62．14％（87／140）,两组确诊率比较有显著性差异（P〈0．05）。结论：本组研究数据显示比较C—FNAB,UG—FNAB在诊断甲状腺复杂性结节中具有更高的确诊率,特别是在C—FNAB方法不能得出明确诊断时。     

河北省华北落叶松河北群体遗传多样性分析

以来自河北8个群体共312个华北落叶松天然个体为材料,利用10对SSR引物对群体进行扩增,所得数据用于其遗传多样性和遗传结构的研究。结果表明:10对SSR位点共检测到42个位点,平均每个位点有4.2个等位基因,位点的等位基因数(Na)为2~6个。群体平均等位基因数为3.36,Shannon指数(I)平均为0.749,观察杂合度Ho为0.405、期望杂合度He为0.423,来自河北北部的围场台子水和吉字以及兴隆雾灵山的多样性水平最高,南部的阜平群体多样性水平最低。AMOVA分子差异分析显示3%的遗传变异存在于群体间,97%的遗传变异则存在于群体内,基因分化系数Gst仅为0.028,表明华北落叶松在河北的群体分化很低。聚类结果表明河北围场两个群体为一类,蔚县、隆化和涿鹿为一类,阜平和赤城为一类,兴隆雾灵山群体距离其他较远。多样性北部群体较高,南部较低,表明华北落叶松可能的衍化方向是从北向南,印证了北部可能是起源中心的结论。