In vitro dissolution and oral bioavailability study of fenofibrate nanomatrix system prepared by hot-melt extrusion

Solvent evaporation method for preparation of nanomatrix has the disadvantages, such as residual organic solvent, environmental pollution, explosion-proofing and so on. To overcome these shortcomings, a series of fenofibrate nanomatrix drug delivery system (NDDS) consisting of nano-porous silica Sylysia^®350 (S350) and pH sensitive material Eudragit^® L100-55 (EL100-55) were prepared using hot-melt extrusion (HME), and their in vitro dissolution and in vivo bioavailability were compared. Finally, the formulation with the highest in vivo bioavailability was selected as the optimized formulation for DSC and PXRD characterization. The results showed that the optimized NDDS showed a higher bioavailability than the reference formulation, although there was crystalline form drug remaining in NDDS. The relative bioavailability of the optimized formulation was 157.1% compared with the commercial product Lipanthyl^®. In addition, the relative bioavailability of the optimized formulation was 124.8% in comparison with the formulation prepared by solvent evaporation method, showing that the NDDS prepared by the HME method was effective in improving the bioavailability of fenofibrate. In conclusion, HME was a promising method to prepare NDDS.     

Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

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广泛期小细胞肺癌一线化疗肿瘤缓解深度与生存期的相关性

目的:分析广泛期小细胞肺癌一线化疗后肿瘤缓解深度与患者生存期的相关性。方法:回顾性分析符合入组条件的50例初治广泛期小细胞肺癌患者的临床资料。通过Spearman秩相关检验评价广泛期小细胞肺癌化疗后肿瘤缓解深度与生存期的相关性，应用Log-rank检验比较不同肿瘤缓解深度对生存期的影响，应用COX比例回归模型进行多因素分析。结果:Spearman秩相关分析显示肿瘤缓解深度与PFS及OS均呈中等程度相关。不同缓解深度患者的生存期存在统计学差异。体重减少（P＜0.000 1）、缓解深度（P＜0.001）为无进展生存期的独立影响因素；体重减少（P＜0.000 1）、体力状态（P=0.001 2）、缓解深度（P＜0.001）、化疗周期（P=0.000 2）、二线治疗（P=0.006 7）为总生存期的独立预后因素。结论:广泛期小细胞肺癌一线化疗后肿瘤缓解深度对患者生存期有一定的预测价值。     

Seminar教学法在普通外科住院医师规范化培养中的应用

目的 探讨 Seminar 教学法在普通外科住院医师规范化培养中的应用价值。方法 将首都医科大学宣武医院普通外科接受住院医师规范化培训的 35 名学员（自 2016 年 9 月至 2018 年 8 月）采用 Seminar 教学法分为实验组即男生 30 人 , 女生 5 人 , 平均年龄 (25.0±1.7) 岁 , 均为大学本科学历，将 2014 年 9 月至 2016 年8 月的前期住院医师采用传统教学法的 35 名住院医师 ( 男生 29 人 , 女生 6 人 , 平均年龄 (25.0±1.8) 岁 , 均为大学本科学历 ) 作为对照组采用传统教学法。采用客观结构化临床考试 (OSCE) 及学生满意度调查评价教学效果。结果 实验组 OSCE 考试中病史采集和查体、病例分析、基本操作技能及辅助检查结果判读得分均高于对照组 (P ＜ 0.01), 学员对教学方式的满意度评分中对 Seminar 教学模式满意 , 认为通过这种教学方式激发了学习兴趣 , 提高了自学能力 , 口头表达、总结、临床思维、专业知识理解等各方面综合能力。结论 Seminar 教学法有助于提高普通外科住院医师规范化培训质量。     

小青龙汤古今应用与方证探析

小青龙汤出自《伤寒杂病论》,是疗效确切、使用广泛的经典方剂,一直以来被归为辛温解表剂范畴。本文通过梳理历代的医籍论述,结合古代医案、现代研究、临床应用情况,探讨小青龙汤证的因机证治与方药特点。认为"饮"邪往往是小青龙汤证的病机关键,且治"饮"是小青龙汤组方用药的核心意图所在。若囿于"外寒内饮"之说,恐不能充分发挥其应有的疗效。     

Safety of a quadrivalent human papillomavirus vaccine in a Phase 3, randomized,double-blind,placebo-controlled clinical trial among Chinese women during 90 months of follow-up

Background

A quadrivalent human papillomavirus (qHPV) vaccine (HPV6/11/16/18) has demonstrated efficacy and acceptable safety in international studies. However, these studies did not include participants from mainland China, which has a substantial burden of HPV-related disease. This is the first safety report with a follow-up period of up to 90?months from a randomized, double-blind, placebo-controlled trial of qHPV vaccine in Chinese women 20–45?years of age.

Effects and long‐term follow‐up of using umbilical cord blood–derived mesenchymal stromal cells in pediatric patients with severe BK virus‐associated late‐onset hemorrhagic cystitis after unrelated cord blood transplantation

This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood–derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus–associated late‐onset hemorrhagic cystitis (BKV‐HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV‐HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 10⁶/kg once a week until the symptoms improved. The median follow‐up time was 1432 (89‐2080) days. The median frequency of MSC infusion was 2 (1‐3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36‐56.9) ×10⁸/mL before MSC infusion and 2.67 (0‐56.3) ×10⁸/mL after MSC infusion; the difference was not significant (P = .219). There were no significant differences in the overall survival, disease‐free survival, and the incidence of relapse and acute and chronic graft‐versus‐host disease between the MSC infusion group and non‐MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein‐Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood–derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV‐HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long‐term infection, or survival of patients with leukemia.     

妊娠早期胎儿颈部透明层厚度与胎儿预后的前瞻性队列研究

目的探讨妊娠早期胎儿颈部透明层(NT)厚度与胎儿预后的关系。方法收集2015年12月至2018年12月于南京大学医学院附属鼓楼医院行妊娠早期胎儿NT厚度测量的单胎孕妇,共4958例建立前瞻性研究队列,进行妊娠早期胎儿结构超声筛查、妊娠早期血清学筛查、妊娠中期超声筛查及对新生儿出生后28 d的体格检查。根据妊娠早期超声筛查的结果,分为胎儿NT增厚(≥3.0 mm)者167例与NT厚度正常者4791例;将胎儿NT增厚的孕妇,分为胎儿单纯NT增厚者86例与NT增厚合并结构异常者81例。分析不同NT厚度胎儿的预后,并重点对单纯NT增厚与NT增厚合并结构异常胎儿的妊娠结局进行分析。妊娠早期超声筛查发现胎儿结构异常或血清学筛查结果为高风险的孕妇,经绒毛穿刺取样术行染色体微阵列分析(CMA)检测以明确产前诊断。结果(1)胎儿NT厚度正常孕妇的妊娠结局:共4791例孕妇,包括胎儿NT厚度正常且无结构异常者4726例,其中妊娠中期及产后新诊断结构异常83例,4688例活产;胎儿NT厚度正常但结构异常的孕妇65例,其中61例孕妇终止妊娠,4例活产。(2)胎儿单纯NT增厚孕妇的妊娠结局:86例孕妇中,66例(76.7%,66/86)行CMA检测,3例胎儿诊断为21三体综合征;除7例孕妇选择终止妊娠外,余79例行妊娠中期超声检查、新生儿出生后28 d体格检查、新生儿电话随访至6~21个月均未发现发育异常。(3)胎儿NT增厚合并结构异常孕妇的妊娠结局:81例孕妇中,73例(90.1%,73/81)行CMA检测,其中32例的胎儿为染色体非整倍体异常。70例选择终止妊娠,2例妊娠中期自然流产,9例活产。(4)NT增厚是否合并结构异常胎儿的产前诊断结果及预后比较:单纯NT增厚的胎儿染色体非整倍体的发生率为3.5%(3/86),合并结构异常者为39.5%(32/81),两者比较,差异有统计学意义(χ2=32.7,P<0.01);胎儿单纯NT增厚孕妇的健康新生儿存活率为91.9%(79/86),合并结构异常者为9.9%(8/81),两者比较,差异有统计学意义(χ2=112.3,P<0.01)。结论妊娠早期,超声筛查胎儿NT及结构,能提高出生缺陷的产前筛查率。单纯NT增厚胎儿的染色体非整倍体的发生率较低,新生儿健康存活率较高。