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.     

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。     

25-羟维生素D_3治疗2型糖尿病患者早期肾损害的临床观察

目的观察25-羟维生素D3(Vit D3)对2型糖尿病(T2DM)患者早期肾损害的临床疗效。方法纳入T2DM早期肾损伤患者80例,采用随机数字表法等分为治疗组与对照组,对照组继续原有降糖方案,治疗组在既往用药基础上,肌肉注射Vit D3注射液,疗程均为10个月,治疗结束后进行疗效评价。结果 1与治疗前相比,治疗组糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平上调,微量白蛋白(MA)、β2-微球蛋白(β2-M)及肾脏损伤分子-1(KIM-1)水平下调,治疗组低于对照组差异有统计学意义(P<0.05)。2与治疗前相比,治疗组治疗后Vit D3水平上调,治疗组高于对照组差异有统计学意义(P<0.01)。3T2DM患者Vit D3水平与MA(r=-0.432),β2-M(r=-0.615),及KIM-1(r=-0.763)水平均呈负相关(P<0.05)。结论 Vit D3可有效减轻T2DM患者的早期肾损害,对肾脏具有保护作用。     

血清窖蛋白-1在慢性阻塞性肺疾病相关肺动脉高压患者中的表达及意义

目的 研究血清窖蛋白-1 （Cav-1） 在慢性阻塞性肺疾病 （COPD） 相关肺动脉高压 （PAH） 患者中的表达及其意义。方法 选取稳定期COPD患者65例， 根据是否合并PAH分成COPD组 ［肺动脉收缩压 （PASP） ＜40 mmHg， 35例］ 及COPD-PAH组 （PASP ≥40 mmHg， 30例）。另选取在本院健康体检的志愿者30例作为对照组。对比各组基线资料、 动脉血气分析、 肺功能指标， 以及血清Cav-1、 白细胞介素 （IL） -6和肿瘤坏死因子-α （TNF-α） 的表达水平。绘制受试者工作特征 （ROC） 曲线， 评价Cav-1对COPD合并PAH的诊断价值。结果 COPD-PAH组与COPD组第一秒用力呼吸容积 （FEV1） /用力肺活量 （FVC）、 FEV1占预计值百分比 （FEV1%） 及氧分压 ［p （O2 ）］ 低于对照组， 而二氧化碳分压 ［p （CO2 ）］、 PASP均高于对照组 （P＜0.01）。COPD-PAH组p （O2 ） 低于COPD组， p （CO2 ）、 PASP均高于COPD 组 （P＜0.01）。对照组、 COPD组及COPD-PAH组Cav-1表达水平呈逐渐降低趋势， 而IL-6、 TNF-α表达水平呈逐渐升高趋势 （P＜0.01）。血清Cav-1诊断COPD合并PAH的ROC曲线下面积为0.902 （0.821～0.955）， 最佳截断值为 6.66 μg/L， 此时诊断敏感度为76.7%， 特异度为85.7%， 与多普勒超声诊断仪测量PASP结果比较一致性较好 （Kappa 值=0.627）。结论 血清Cav-1在COPD相关PAH患者表达明显下调， 可以作为预测COPD相关PAH的新型血清标志物。     

接受机械取栓治疗的急性脑梗死患者血栓特征研究进展

急性脑梗死是威胁我国人民健康的重大疾病,其致死率及致残率均较高,造成了沉重的社会负担。及时开通导致梗死的责任血管以恢复脑灌注是治疗该病的关键。机械取栓技术的应用使得患者的血栓组织能够被获取并得到研究。本文介绍了近年来通过机械取栓术获取的血栓的相关研究发现,以纤维蛋白为主的血栓是造成取栓困难的重要组织学原因,影像学方法可以在术前评估血栓特征。这些发现提示临床工作者可以积极开发新型血栓取出装置用于处理难治性血栓,并有必要探索精确便捷的血栓特征影像学评价方法,从而提高机械取栓疗效。     

生化汤加味促进剖宫产后子宫复旧随机对照试验的系统评价及Meta分析＊

目的 对生化汤加味促进剖宫产后子宫复旧的有效性与安全性进行系统评价，为其在临床应用提供循证医学证据。方法 检索中国生物医学文献数据库（CBM）、中国知网（CNKI）、万方资源数据库（WanFang）、维普期刊数据库（VIP）、Cochrane Library、PubMed、Web of Science等，检索时限为建库至2020年7月，选择生化汤加味促进剖宫产后子宫复旧的随机对照试验（RCT），采用Cochrane系统评价员手册提供的偏倚风险评估工具进行文献质量评价，应用RevMan5.3软件进行Meta分析。结果 共纳入12篇RCT文献，共计1804例剖宫产产妇；Meta分析结果显示，生化汤加味联合缩宫素组在产后第1、3、5天子宫底高度［MD = -0.75，95%CI（-1.35， -0.15），P < 0.00001；MD = -1.92，95%CI（-3.13， -0.72），P < 0.00001；MD = -1.92，95%CI（-3.79， -0.06），P < 0.00001］低于单用缩宫素组，联合用药组血性恶露时间［MD = -1.52，95%CI（-2.71，-0.34），P < 0.00001］和产后恶露持续时间［MD = -4.47，95%CI（-6.20，-2.75），P < 0.00001］均短于单用缩宫素组。结论 生化汤加味联合缩宫素与单用缩宫素比较，更能促进产后子宫复旧；不良反应少，报道的仅有4例出现轻微腹泻，安全性较高；但由于纳入文献质量较低，上述结论尚需更多的随机对照临床研究加以证实。