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.     

探究128层CT血管造影心肌桥-壁冠状动脉图像特征及与冠脉动脉粥样硬化的相关性

目的探讨128层CT血管造影心肌桥-壁冠状动脉(MB-MCA)图像特征及与冠脉动脉粥样硬化的相关性。方法收集2018年1月至12月于我院进行冠状动脉成像检查的126例患者临床及影像学资料,总结所有患者MB-MCA检出率情况及与冠状动脉硬化的相关性。结果126例患者MB-MCA检出率为65.08%,其中LAD中段检出率最高,浅表型最为多见;CT检出位于MB-MCA近侧动脉硬化斑块发生率最高(63.41%,P<0.05),检出MB-MCA患者斑块检出率为(52.22%)与未检出MB-MCA患者斑块检出率(45.45%)比较无差异(P>0.05);且CT检出MB-MCA患者累及段数和斑块的狭窄程度与未检出MB-MCA患者相比较无统计学意义(P>0.05),但检出MB-MCA患者的斑块主要分布于动脉近段,而未检出MB-MCA患者的斑块主要位于中段和远段(P<0.05)。结论128层CT血管造影可较好地检出MB-MCA,且主要好发于LAD,以浅表型更为多见。但MB-MCA的形成与冠状动脉硬化无直接联系,当MB出现收缩和功能血流减少的时候可能会导致冠状动脉硬化的形成。     

Position paper on stress cardiac MRI in chronic coronary syndrome: Endorsed by the Société Française de Radiologie (SFR) the Société Française d’Imagerie CardioVasculaire (SFICV) and the Société Française de Cardiologie (SFC)

This position paper was intended to update the former consensus between the French Societies of Radiology and Cardiology about the use of stress cardiac magnetic resonance imaging (MRI) in chronic coronary syndrome published in 2009. The Delphi method was used to build the present consensus. This expert panel consensus includes recommendations for indications, procedure with patient preparation, stress inducing drugs, acquisition protocol, interpretation and risk stratification by stress MRI.     

连续性肾脏替代疗法叠加全血吸附改善脓毒性休克患者心肌抑制的疗效研究

目的探讨连续性肾脏替代疗法（CRRT）叠加全血吸附对脓毒性休克患者心肌抑制的改善效果。 方法选择2016年5月至2019年6月收治于绍兴市人民医院重症医学科、心脏指数（CI）< 3.0 L·min^-1·m^-2的60例脓毒性休克患者，按随机区组法分为对照组（30例）与试验组（30例），两组患者按照脓毒症/脓毒性休克标准化操作程序治疗，试验组在标准治疗基础上加用CRRT +全血吸附，连续治疗3 d。所有入选病例均应用脉波指示剂连续心排出量监测进行血流动力学监测，记录并评价两组患者入组时及治疗后第3、5天的CI、中心静脉压（CVP）、血管外肺水指数（EVLWI）、日去甲肾上腺素剂量、日液体总量及急性病生理学和长期健康评价（APACHE）Ⅱ评分。 结果两组脓毒性休克患者在不同时间点CI、CVP、EVLWI、日去甲肾上腺素剂量、日液体总量和APACHEⅡ评分的比较，差异均有统计学意义（F = 12.543、10.213、12.840、9.765、10.821、19.466，P均< 0.05）。两组患者入组时上述各指标的比较，差异均无统计学意义（P均> 0.05）；治疗后CI均有不同程度改善，试验组第3、5天CI均高于对照组[（3.0 ± 1.7）L·min^-1·m^-2 vs.（2.6 ± 1.6）L·min^-1·m^-2，（3.2 ± 1.8）L·min^-1·m^-2 vs.（2.7 ± 1.8）L·min^-1·m^-2，P均< 0.05]；两组患者的CVP治疗后均呈现下降趋势，且试验组第3、5天CVP值均显著低于对照组[（11.9 ± 5.9）cmH₂O vs.（13.5 ± 3.1）cmH₂O，（10.6 ± 3.7）cmH₂O vs.（12.6 ± 2.6）cmH₂O，P均< 0.05]；两组患者EVLWI在治疗后第3、5天回落至正常水平，且治疗后第3天试验组EVLWI显著低于对照组[（9.8 ± 2.4）mL/kg vs.（11.4 ± 3.3）mL/kg，P < 0.05]；治疗后第3、5天试验组日去甲肾上腺素剂量[（11.4 ± 3.4）mg vs.（18.9 ± 5.3）mg，（7.5 ± 2.1）mg vs.（13.2 ± 3.2）mg，P均< 0.05]和日液体总量[（2 954 ± 537）mL vs.（3 624 ± 453）mL，（2 446 ± 484）mL vs.（3 243 ± 675）mL，P均< 0.05]均少于对照组。两组患者APACHEⅡ评分治疗后呈下降趋势，试验组第3、5天APACHEⅡ评分均显著低于对照组[（13 ± 4）分vs.（18 ± 4）分，（11 ± 3）分vs.（13 ± 4）分，P均< 0.05]。 结论CRRT叠加全血吸附可在早期改善脓毒性休克患者心肌抑制状态，一定程度上改善患者预后。     

Clinical evaluation of Ortho Clinical Diagnostics high-sensitivity cardiac Troponin I assay in patients with symptoms suggestive of acute coronary syndrome

BackgroundAs more companies obtain regulatory approval for high-sensitivity cardiac troponin (hs-cTn) assays there is an urgent need for independent analytical and clinical evaluations. To this end, we have evaluated Ortho Clinical Diagnostics’ hs-cTnI assay and compared it to their contemporary cTnI-ES assay in emergency department (ED) patients with suspected acute coronary syndrome (ACS).MethodsThe study cohort consisted of ED patients (n = 906) with symptoms suggestive of ACS who had Ortho hs-cTnI and cTnI-ES results at presentation and 3 h (with calculated delta (0–3 h) defined as the absolute concentration difference between paired results). The primary composite outcome was 7-day myocardial infarction (MI) or cardiovascular death, with secondary analyses performed for 7-day MI and index-MI. Analytical imprecision testing (i.e., coefficient of variation; CV), receiver-operating characteristic (ROC) curve analyses with area under the curve (AUC), and diagnostic parameters (sensitivity/specificity/predictive values) were calculated.ResultsThe hs-cTnI assay had superior precision compared to the cTnI-ES assay below 5 ng/L in EDTA plasma (hs-cTnI CV ≤ 15% versus cTnI-ES CV ≥ 85%). The AUCs were higher for hs-cTnI as compared to cTnI-ES at 0 h (0.88 vs. 0.85), 3 h (0.94 vs. 0.92), and the delta (0–3 h) value (0.91 vs. 0.85) for the primary composite outcome (p < 0.05). At 3 h, the sensitivity/specificity for index-MI was ≥97%/≥82%, for 7-day MI was ≥89%/≥84%, and for the primary composite outcome was ≥90%/≥85% using the manufacturer’s sex-specific 99th-percentile cutoffs.ConclusionThe Ortho hs-cTnI assay has superior analytical and clinical performance over their contemporary cTnI-ES assay in evaluating ED patients with symptoms suggestive of ACS.