A Pilot First-in-Human Study of Embrace,a Polyethylene Glycol-Based Liquid Embolic Agent,in the Embolization of Malignant and Benign Hypervascular Tumors

PurposeTo investigate the safety and efficacy of an aqueous polyethylene glycol-based liquid embolic agent, Embrace Hydrogel Embolic System (HES), in the treatment of benign and malignant hypervascular tumors.Materials and MethodsA prospective, single-arm, multicenter study included 8 patients, 5 males and 3 females, with a median age of 58.5 years (30–85 years), who underwent embolization in 8 tumors between October 2019 and May 2020. Technical success was defined as successful delivery of HES to the index vessel, with disappearance of >90% of the targeted vascular enhancement or, for portal vein embolization, occlusion of the portal branches to the liver segments for future resection. The volume of HES administered, ease of use (5 point Likert scale), administration time, and adverse events (AEs) were recorded. Evaluation was performed at 7, 30, and 90 days via clinical assessment and blood testing, and follow-up imaging was performed at 30 days.ResultsEight patients were enrolled, and 10 embolizations were performed in 8 lesions. Tumors included hepatocellular carcinoma (n = 4), renal angiomyolipoma (n = 3), and intrahepatic cholangiocarcinoma (n = 1). Technical success was 100%, and the average ease of use was 3.3 ± 1.0 SD. The HES delivery time was 1–28 minutes (median, 16.5 minutes), and the HES volume injected was 0.4–4.0 mL (median, 1.3 mL). All patients reached 30-day follow-up with imaging, and 6 patients reached 90-day follow-up. There were 3 serious AEs in 2 patients that were unrelated to the embolic agent.ConclusionHES resulted in a 100% embolization technical success rate. The product ease of use was acceptable, and no target vessel recanalization was noted on follow-up imaging at 30 days.     

载紫杉醇的大黄酸偶联物纳米胶束的制备及初步评价

目的制备载紫杉醇的D-α-生育酚聚乙二醇1000琥珀酸酯(D-α-tocopheryl polyethylene glycol 1000 succinate,TPGS)修饰的羧甲基壳聚糖-大黄酸偶联物(PTX/TPGS-CR)纳米胶束,并对其进行初步评价。方法采用透析法,以载药量、包封率及粒径为指标,通过单因素考察优化PTX/TPGS-CR纳米胶束的制备工艺并进行验证。以溶血实验及血管刺激性实验初步考察PTX/TPGS-CR纳米胶束的安全性。四甲基偶氮唑盐微量酶反应比色法(MTT)法考察PTX/TPGS-CR纳米胶束对Hela细胞的毒性。通过激光扫描共聚焦显微镜定性和流式细胞仪定量考察Hela细胞对PTX/TPGS-CR纳米胶束的摄取情况。结果制备工艺优化后制得的PTX/TPGS-CR纳米胶束粒径为(197.3±4.4)nm,PDI为(0.131±0.021),电位为(-31.8±0.5)mV,载药量为(48.20±3.03)%,包封率为(87.26±4.91)%。溶血实验结果表明,其溶血率低于1.71%;血管静脉注射无明显刺激性。其对Hela细胞的杀伤作用具有浓度和时间依赖性,能被Hela细胞高效摄取。结论PTX/TPGS-CR纳米胶束载药量和包封率高,安全性好,其体外抗肿瘤活性稍优于Taxol?。     

Pediatric bowel preparation: Sodium picosulfate,magnesium oxide,citric acid vs polyethylene glycol,a randomized trial

BACKGROUND Bowel preparation in children can be challenging.AIM To describe the efficacy, safety, and tolerability of sodium picosulfate, magnesium oxide, and citric acid(SPMC) bowel preparation in children.METHODS Phase 3, randomized, assessor-blinded, multicenter study of low-volume, divided dose SPMC enrolled children 9-16 years undergoing elective colonoscopy. Participants 9-12 years were randomized 1:1:1 to SPMC ? dose × 2, SPMC 1 dose × 2, or polyethylene glycol(PEG). Participants 13-16 years were randomized 1:1 to SPMC 1 dose × 2 or PEG. PEG-based bowel preparations were administered per local protocol. Primary efficacy endpoint for quality of bowel preparation was responders(rating of ‘excellent' or ‘good') by modified Aronchick Scale. Secondary efficacy endpoint was participant's tolerability and satisfaction from a 7-item questionnaire. Safety assessments included adverse events(AEs) and laboratory evaluations.RESULTS 78 participants were randomized, 48 were 9-12 years, 30 were 13-16 years. For the primary efficacy endpoint in 9-12 years, 50.0%, 87.5%, and 81.3% were responders for SPMC ? dose × 2, SPMC 1 dose × 2, and PEG groups, respectively. Responder rates for 13-16 years were 81.3% for SPMC 1 dose × 2 and 85.7% for PEG. Overall, 43.8% of participants receiving SPMC 1 dose × 2 reported it was ‘very easy' or ‘easy' to drink, compared with 20.0% receiving PEG. Treatment-emergent AEs were reported by 45.5% of participants receiving SPMC 1 dose × 2 and 63.0% receiving PEG.CONCLUSION SPMC was an efficacious and safe for bowel preparation in children 9-16 years, with comparable efficacy to PEG. Tolerability for SPMC was higher compared to PEG.     

揿针、聚乙二醇 4000 散联合生物反馈疗法治疗功能性便秘临床研究

目的:观察揿针、聚乙二醇4000散联合生物反馈疗法治疗功能性便秘的临床疗效。方法:选取102例功能性便秘患者,按随机数字表法分为对照组和观察组各51例。对照组采用揿针联合聚乙二醇4000散治疗,观察组在对照组基础上加用生物反馈疗法治疗。观察患者治疗后便秘症状改善情况及肛门直肠动力、肛门直肠感觉和生活质量的变化,比较2组临床疗效。结果:观察组总有效率96.08%,高于对照组的80.39%(P<0.05)。治疗后,2组便秘症状评分均较治疗前降低,观察组便秘症状评分低于对照组,差异均有统计学意义(P<0.05)。治疗后,2组直肠最低敏感量、最大耐受量、直肠顺应性均较治疗前降低,观察组以上3项指标值均低于对照组,差异均有统计学意义(P<0.05)。2组治疗前后直肠静息压、肛门括约肌压力比较,差异均无统计学意义(P>0.05)。治疗后,2组躯体不适、心理社会不适、担心和焦虑、满意度及总分均较治疗前降低,观察组躯体不适、心理社会不适、担心焦虑、满意度及总分均低于对照组,差异均有统计学意义(P<0.05)。结论:揿针、聚乙二醇4000散联合生物反馈疗法治疗功能性便秘,可改善患者的便秘症状、肛门直肠动力、肛门直肠感觉及生活质量,提高治疗效果。     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

术中按需喷洒与术前口服二甲硅油 在肠镜检查中的作用研究

〔摘 要〕 目的：探讨术中按需喷洒与术前口服二甲硅油在肠镜检查中的应用效果。 方法：选取 2020 年 1 月至 2021 年 6 月于萍乡市人民医院行肠镜检查的无明显症状患者 90 例，按随机数字表法分为两组，对照组和观察组各 45 例。两组均 使用聚乙二醇电解质散清洁肠道，对照组术前口服二甲硅油，观察组术中按需喷洒二甲硅油。比较两组患者肠道清洁分级、 气泡分级、二甲硅油用量、肠镜检查操作时间、结肠息肉检出率及患者满意度。 结果： 两组患者肠道清洁分级相比，差异无 统计学意义（P ＞ 0.05）。观察组患者气泡分级 1 级率为 80.00 %，高于对照组的 62.22 %，差异具有统计学意义（P ＜ 0.05）。 观察组患者二甲硅油用量为（14.58 ± 2.01）mL，少于对照组的（22.35 ± 2.65）mL，进、退镜时间分别为（8.89 ± 1.14）min、 （8.33 ± 1.08）min，短于对照组的（9.76 ± 1.27）min、（10.27 ± 2.04）min，差异有统计学意义（P ＜ 0.05）。观察组患者 结肠息肉检出率、患者满意度为 17.78 %、97.78 %，高于对照组的 4.44 %、82.22 %，差异具有统计学意义（P ＜ 0.05）。 结论：术中按需喷洒二甲硅油在肠镜检查中效果更佳，可减少二甲硅油用量，提高视野清晰度，缩短肠镜检查操作时间， 并利于结肠息肉的检出，提高患者满意度。     

尿酸性肾病中医分型与氧化应激指标的相关性研究

目的：探讨尿酸性肾病中医分型与氧化应激相关性。方法：采用回顾性分析方法对2017年12月至2019年9月北京中医药大学第三附属医院收治的尿酸性肾病患者105例进行研究，选择同时期正常健康者105例作为对照，参考《中药新药临床研究指导原则》将105例尿酸性肾病和临床常见证型相结合，分成脾肾气虚18例、气阴两虚证19例、肝肾阴虚16例、阴阳两虚12例、湿热蕴结19例、瘀血阻滞17例、痰浊内阻13例，均在入院次日清晨空腹抽取静脉血，检测氧化应激氧化应激、肾功能损害指标，比较不同组别在氧化应激指标含量水平变化情况，比较中医分型和氧化应激、肾功能损害指标水平变化。结果：1）尿酸性肾病组总抗氧化能力（T-ACO）、晚期蛋白氧化物（AOPP）、血清丙二醇（MDA）、超氧化物歧化酶（SOD）含量水平分别为（19.45±3.42）U/mL、（42.45±3.53）μmol/L、（4.52±1.23）nmol/L、（76.78±5.64）U/mL，正常对照组则分别为（10.76±1.31）U/mL、（20.84±1.28）μmol/L、（2.13±0.76）nmol/L、（130.85±16.75）U/mL，尿酸性肾病组T-ACO、AOPP、MDA较正常对照组显著偏高，SOD显著偏低（P<0.05）。2）虚证中阴阳两虚证SOD含量上较其他证型均偏低，而MDA、T-AOC、AOPP、胱抑素C（CysC）、β2微球蛋白、尿微量白蛋白（UMALB）、蛋白尿发生率则较其他证型均偏高，差异均有统计学意义（P<0.05），实证中瘀血阻滞证SOD含量较其他证型均偏低，而MDA、T-AOC、AOPP则较其他证型均偏高，差异均有统计学意义（P<0.05）。结论：尿酸性肾病中医分型的阴阳两虚证、瘀血阻滞证氧化应激水平、肾损害指标均显著升高，可结合该实验室检查进行临床干预。     

经乙二醇诱导的改良型草酸钙肾结石果蝇模型

目的:通过一种改良方法构建果蝇草酸钙肾结石模型。方法:配制标准培养基和造模用培养基，空白对照组果蝇仅予标准培养基，而传统模型组和改良模型组分别从成虫期和幼虫期开始摄入含 0.5%乙二醇( EG)的造模用培养基。于偏光显微镜下观察并评估各组果蝇马氏管内成石情况，分别记录模型组成石率达 100%所花时间，并对成石率 100%时模型组间“ ++”和“ +++”所占比率进行比较；用傅立叶变换拉曼光谱仪鉴定模型组果蝇马氏管内结石成分。绘制各组果蝇生存曲线，并比较生存周期差异。结果:改良模型组和传统模型组分别在果蝇成虫日龄 14 d和 22 d，马氏管内成石率达到 100%。当改良模型组和传统模型组成石率均达到 100%时，两组“ ++”与“+++”所占比率分别为(40.5±4.4)%和(39.0±4.2)%，差异无统计学意义(P＞ 0.05)；拉曼位移的主峰主要集中在 1 462 cm-1、1 463 cm-1和 1 473 cm-1，说明模型组果蝇马氏管内结石成分均为草酸钙。空白对照组、传统模型组和改良模型组的最高寿命分别为 76 d、70 d和 68 d，中位生存时间分别为 35 d、30.5 d和 30 d，与空白对照组相比，模型组生存周期均显著缩短(P均＜ 0.01)，但传统模型组与改良模型组间差异无统计学意义( P＞ 0.05)。结论:改良型造模方法使果蝇在其幼虫期即摄入 0.5% EG，缩短了模型构建周期且具有可重复性，值得进一步研究推广。