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.     

鼓膜穿刺加压灌注治疗分泌性中耳炎的临床疗效

目的探讨鼓膜穿刺加压灌注疗法治疗分泌性中耳炎的临床疗效。方法选择确诊为分泌性中耳炎患者88例为研究对象,所有患者采用中耳鼓膜穿刺鼓室灌注加压治疗。比较不同性质分泌物患者的临床疗效及治疗前后患者鼓室导抗图变化。结果胶冻状患者治疗时间最长,浆液性患者治疗时间最短,三组治疗时间比较差异有统计学意义(P<0.01)。浆液性总有效率94.0%,黏液性总有效率86.8%,胶冻状总有效率75.0%,三组比较有显著差异(P<0.05)。治疗前鼓室导图主要是B型,治疗后主要是A型,治疗前后比较差异有统计学意义(P<0.01)。结论鼓膜穿刺加压灌注治疗分泌性中耳炎具有较好的临床疗效。     

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。     

萸竹定眩丸治疗痰浊阻络型眩晕的疗效及对外周血FGF-21水平的影响

目的:评价萸竹定眩丸对痰浊阻络型眩晕的治疗效果及对外周血FGF-21水平的影响。方法:120例患者随机分为治疗组和对照组,对照组口服盐酸氟桂利嗪胶囊10mg,每晚1次;治疗组在对照组的基础上给予萸竹定眩丸,每次1丸,每日2次;两组均治疗14天。14天后比较两组患者临床疗效、血脂及外周血中FGF-21水平。结果:治疗组总有效率为93. 3%,对照组总有效率为66. 7%,两组总有效率比较有统计学差异(P 0. 05);治疗后两组FGF-21水平均较治疗前明显降低(P 0. 01,P 0. 05),且治疗组FGF-21水平比对照组降低更明显(P 0. 05);治疗后,两组的TC、TG、LDL-C水平均较治疗前明显下降,HDL-C水平均较治疗前明显升高(P 0. 01),且治疗组的TC水平比对照组下降更显著,HDL-C水平比对照组上升更显著(P 0. 01)。结论:萸竹定眩丸治疗椎-基底动脉供血不足性眩晕(中医辨证属痰浊阻络型眩晕)具有明确疗效;萸竹定眩丸对改善人体的糖脂代谢水平,降低TC,升高HDL-C疗效明确;萸竹定眩丸在临床应用中未发现严重不良反应,临床应用安全可靠。     

阿帕替尼治疗晚期及术后复发肺肉瘤样癌的疗效分析

目的探索阿帕替尼治疗晚期及术后复发肺肉瘤样癌的疗效。方法收集2016年6月至2019年8月Ⅲ~Ⅳ期及术后复发的肺肉瘤样癌患者21例,口服阿帕替尼(250~425 mg/d)治疗,30 d为1个疗程,观察并分析疗效及评价安全性。结果21例患者中,完全缓解(CR)为0,部分缓解(PR)为14.3%(3例),稳定(SD)为33.3%(7例),疾病进展(PD)为52.4%(11例);客观反应率(ORR)为13.3%(3例),疾病控制率(DCR)为47.6%(10例)。中位总生存期(mOS)为4.6个月,中位无进展生存期(mPFS)为1.0个月。病灶≥6 cm(或≥5 cm)较<6 cm(或<5 cm)平均OS明显缩短,差异有统计学意义(P<0.05);术后分期Ⅰ~Ⅱ期较Ⅲ~Ⅳ期平均OS明显延长(P<0.05)。位于中央的病灶较周围的病灶平均OS明显缩短,差异有统计学意义(P<0.01)。性别、年龄(>60岁,≤60岁)、吸烟史(是/否)对疗效影响差异无统计学意义。常见不良反应包括高血压38.1%(8例)、蛋白尿23.8%(5例)、手足综合征28.6%(6例)、腹泻28.6(6例)、骨髓抑制38.1%(8例)。结论阿帕替尼治疗晚期及术后复发肺肉瘤样癌具有一定疗效,不良反应可控,病灶大小、位置及分期可能是疗效的独立影响因素。     

藿香正气汤抑制新型冠状病毒复制过程的有效成分及机制初探＊

目的 收集藿香正气汤的主要活性成分，通过分子对接及网络药理学探讨其防控新型冠状病毒肺炎（COVID-19）的有效成分及治疗机制。方法 通过基于配体-蛋白质相互作用的计算方法，以瑞德西韦为对照，探索藿香正气汤潜在治疗COVID-19的成分，并选出对接较好成分进行药理学机制预测，初探其药理学机制。结果 本研究筛选出5种与新冠病毒3CLpro结合能力强于瑞德西韦的小分子成分。网络药理学初步预测抗病毒途径可能是通过PI3K-Akt 信号通路影响病毒复制。结论 成分C1-C5与3CLpro结合良好，推测其可能是潜在的3CLpro的抑制剂，为抗病毒天然药物的开发提供了理论依据。     

PCR仪与测序仪应用于丙型肝炎病毒基因型检测的临床效果观察

目的:观察PCR仪与测序仪在丙型肝炎病毒(HCV)基因型检测中的应用。方法:选择2018年1月~2018年12月收治的134例HCV感染患者为研究对象,给予患者PCR仪检测、测序仪检测。结果:测序仪检测134例均可分型,PCR仪检测130例患者可分型,4例未能分型。PCR检测结果:134例HCV感染患者中,1b型59例,2a型47例,3a型6例,3b型15例,6a型3例,4例为分出型别。基因测序结果:134例均可分型:1型59例,2a型40例,2i型7例,3a型6例,3b型15例,6a型3例,6n型4例。PCR仪检测法检测符合率97.0%。结论:PCR仪测序仪检测用于丙型肝炎病毒基因型检测,操作便捷,但其只能检测探针覆盖的型别,个别罕见型别不能分型。     

三级公立医院行政总值班管理现状分析与研究*

探索一套符合现代化医院的行政总值班管理体系，确保医院管理工作安全、稳定运行。分析国内外医院总值班现状和问题，运用系统性、科学性、规范性等综合干预措施，进一步提高值班人员责任意识、分析问题和解决问题能力等综合管理能力，使总值班管理从粗放式向精细化转变，实现目标标准化、过程规范化、结果同质化的服务格局。