Baicalin-loaded PEGylated lipid nanoparticles: characterization,pharmacokinetics, and protective effects on acute myocardial ischemia in rats

Context: Baicalin has many pharmacological activities, including protective function against myocardial ischemia by antioxidant effects and free radical scavenging activity. However, its rapid elimination half-life in plasma and poor water solubility limits its clinical efficacy.

Objective: Novel baicalin-loaded PEGylated nanostructured lipid carriers (BN-PEG-NLC) were developed to improve bioavailability of BN, to prolong retention time in vivo and to enhance its protective effect.

Methods: In this study, BN-PEG-NLC were prepared by the emulsion-evaporation and low temperature-solidification method using a mixture of glycerol monostearate and polyethylene glycol monostearate as solid lipids, and oleic acid as the liquid lipid. The physicochemical properties of NLC were characterized. The pharmacokinetic and pharmacodynamic behaviors of BN-PEG-NLC or BN-NLC were evaluated in acute MI rats.

Results and discussion: The particle size, zeta potential, and entrapment efficiency for BN-PEG-NLC were observed as 83.9?nm, ?32.1?mV, and 83.5%, respectively. The release profiles of BN from both BN-PEG-NLC and BN-NLC were fitted to the Ritger–Peppas modal, which presented burst release initially and prolonged release afterwards. Pharmacokinetics results indicated that BN-PEG-NLC exhibited a 7.2-fold increase in AUC in comparison to BN solution, while a 3-fold increase in comparison to BN-NLC. Biodistribution results revealed that BN-PEG-NLC exhibited higher heart drug concentration compared with BN-NLC as well as BN solution. In the present study, BN-PEG-NLC significantly ameliorated infarct size.

Conclusion: The results of the present study imply that PEG-NLC could be the biocompatible carriers for heart-targeted drug delivery to improve myocardial ischemia.     

新型四腔水箱在腹外科腔镜电凝线清洗消毒中的应用研究

摘要〓目的〓研究四腔水箱在腹外科腔镜电凝线擦拭法清洗消毒中的应用效果。方法〓通过目测法和ATP生物荧光法,对本研究的四腔水箱用于腹外科腔镜电凝线的清洗效果进行评价。结果〓传统治疗碗清洗的206件腔镜电凝线清洗质量合格率为86.4%,四腔水箱清洗的206件腹腔镜电凝线清洗质量合格率为94.6%,差异有统计学意义（P＜0.01）。用四腔水箱清洗腔镜电凝线擦拭过程中的护理人员满意度较高。结论〓四腔水箱可提高腹外科腔镜电凝线清洗质量和护理人员满意度。     

丙泊酚麻醉对老龄大鼠认知功能和海马神经元γ-氨基丁酸A受体表达的影响

目的观察丙泊酚麻醉对老龄大鼠认知功能及海马神经元γ-氨基丁酸A(GABA)受体表达的影响。方法50只SD老年大鼠随机分为丙泊酚组和对照组,每组25只。丙泊酚组大鼠腹腔注射1%丙泊酚中/长链脂肪乳注射液6 mL/kg,对照组腹腔注射等体积的生理盐水。麻醉后1 d进行Morris水迷宫实验,分别采用HE染色和尼氏体染色观察海马区神经细胞及尼氏体(Nissl体)形态学变化,Western Blot检测GABA蛋白量表达。结果麻醉后,2组大鼠肛温、心率、呼吸频率、血氧饱和度比较,差异均无统计学意义(P>0.05)。随着实验时间的延长,2组大鼠逃逸潜伏期、总里程数逐渐减小,丙泊酚组大鼠各时间点逃逸潜伏期、总里程均高于对照组,差异有统计学意义(P<0.05)。丙泊酚组大鼠穿越平台区域次数、时间小于、短于对照组,差异有统计学意义(P<0.05)。对照组海马区Nissl体存在于细胞浆及树突,染色较深,神经细胞排列整齐,形态规则;丙泊酚组Nissl体消失,神经细胞数量减少,细胞核破裂、丢失。丙泊酚组大鼠海马GABA蛋白表达量低于对照组,差异有统计学意义(P<0.05)。结论丙泊酚对大鼠认知功能有影响,并与海马区GABA的表达相关。     

Comparison between a new platelet count drop method PL-11, light transmission aggregometry,VerifyNow aspirin system and thromboelastography for monitoring short-term aspirin effects in healthy individuals

Platelet function has been described by many laboratory assays, and PL-11 is a new point-of-care platelet function analyzer based on platelet count drop method, which counts platelet before and after the addition of agonists in the citrated whole blood samples. The present study sought to compare PL-11 with other three major more established assays, light transmission aggregometry (LTA), VerifyNow? aspirin system and thromboelastography (TEG), for monitoring the short-term aspirin responses in healthy individuals. Ten healthy young men took 100?mg/d aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA, VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2 hour, 1 day during the aspirin treatment and 1 day, 5?±?1 days, 8?±?1 days after the aspirin withdrawal. Moreover, 90 additional healthy subjects were recruited to establish a reference range for PL-11. Platelet function of healthy subjects decreased significantly 2 hours after 100?mg/d aspirin intake and began to recover during 4–6 days after the aspirin withdrawal. Correlations between methods were PL-11 vs. LTA (r?=?0.614, p?<?0.01); PL-11 vs. VerifyNow (r?=?0.829, p?<?0.01); PL-11 vs. TEG (r?=?0.697, p?<?0.001). There was no significant bias between PL-11 and LTA at baseline (bias?=?1.94%, p?=?0.804) using Bland-Altman analysis, while the data of PL-11 were significantly higher than LTA (bias?=?24.02%, p?<?0.001) during the aspirin therapy. The reference range for PL-11 in healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low-responsiveness was defined as LTA?>?20%, the cut-off values for each method were, respectively: PL-11?>?50%, VerifyNow?>?533 ARU, TEG?>?60.2%. The results of different platelet function assays were uninterchangeable for monitoring aspirin response and correlations among them were also varied. Correlations among PL-11 and other three major assays suggested the ability of PL-11 to assess the treatment effects of aspirin. But a large cohort study is needed to confirm the cut-off value of aspirin response detected by PL-11.     

乳腺炎性肌纤维母细胞瘤的研究进展

炎性肌纤维母细胞瘤（inflammatory myofibroblastic tumor，IMT）作为一种低度恶性潜能的间叶组织来源的肿瘤，病因及发病机制不明。主要见于儿童和青少年,最常见的部位是肺、肠系膜、网膜，发生于乳腺的比较罕见，且往往单发。乳腺炎性肌纤维母细胞瘤的临床症状及影像学特点均不典型，术前易造成误诊，本文复习国内外文献报道的乳腺炎性肌纤维母细胞瘤，从发病机制、临床表现、影像学特征、病理学特征、鉴别诊断、治疗及预后等方面作一系统综述。     

我国日间手术开展现状与前景展望

日间手术在国外已有上百年的发展历史，现已成为欧美国家重要手术模式。我国于20世纪初开始开展日间手术，但目前尚未普及，发展不平衡问题比较突出，存在认识不清、开展不规范、与医保支付对接不畅等问题。日间手术是一种使国家、医院和病人三方均受益的新型手术模式。近年来，国家相关管理部门积极引导，开展日间手术的医院明显增多，可以预见，我国日间手术即将进入快速发展的新阶段。因此，有条件的医院可以从简单、易操作的病种开始，落实临床路径，积累经验，再逐步稳妥展开。在保证质量的前提下，不断拓展日间手术范围，提高三、四级手术比例。同时，积极与医保支付政策对接，采取灵活的方式，获得医保的支持，更好地促进我国日间手术的快速发展。