凉血通瘀方干预高血压大鼠急性脑出血模型对脑组织中差异miRNA表达的影响＊

目的 研究凉血通瘀方对高血压大鼠急性脑出血模型脑组织miRNA表达的影响，对差异表达的miRNA靶基因进行分析，探索凉血通瘀方可能的药效机制。方法 将自发性高血压大鼠随机分成对照组（B）和实验组（C）。适应性饲养一周后，C组灌胃凉血通瘀方，B组灌胃等体积生理盐水，连续5天，每天1次。构建脑出血模型后收集脑组织，借助全转录组测序技术获得miRNA表达量，与miRBase数据库比对获取已知miRNA，使用miRDeep2预测新miRNA。差异分析软件为DESeq2，筛选阈值为|log₂FC| ≥1 并且P <0.05。对显著差异表达的miRNA进行靶基因预测，对靶基因进行GO功能、KEGG通路富集和PPI网络分析。结果 实验组和对照组对比，共发现21个显著差异表达的miRNA，上调有9个，下调有12个，共预测得到1243个有统计学意义的靶基因。GO富集分析发现，生物过程中突触囊泡分泌的调节、神经递质分泌的调节和神经递质运输的调节占前三位，神经元投射终点、全膜、质膜区域和细胞投射则是主要的细胞成分。分子功能分别为小GTPase绑定、底物特异性跨膜转运蛋白活性和离子跨膜转运体活性。通路分析结果显示，靶基因在癌证通路、pI3K-Akt信号通路、人类乳头瘤病毒感染、神经活性配体-受体相互作用和MAPK通路等分布广泛。采用STRING网站和Cytoscape软件，根据MCC算法筛选出ADRA2C、CASR、CCL28、CCR1、DRD2、GNAT3、GRM2、DYNC1LI1、GABBR1、GNAI1等核心靶基因。结论 凉血通瘀方对脑出血急性期鼠脑组织内miRNA的表达有重要影响；显著差异表达miRNAs可能通过靶向核心基因调控凉血通瘀方干预急性脑出血的病理过程及预后。     

The role of conventional radiography to assess the outcome of oncologic skeletal reconstructions of lower limbs aided by vascularized fibular autograft

IntroductionVascularized fibular autografts (VFA) are used in the oncologic skeletal reconstructions of long bones, alone or combined with massive bone allografts (MBA). Data regarding the role of imaging in assessing these complex skeletal reconstructions are lacking, and have mainly focused on Computed Tomography (CT). Our aim was to evaluate if early conventional radiography (CR) findings are correlated with the outcome of these skeletal reconstructions.Materials and methodsAll consecutive patients who underwent oncologic resection of lower limbs long bones followed by VFA reconstruction were included in this single-center retrospective study. We compared the CR obtained immediately after surgery with the CR at the 6-month control, as well as the CR at 6 months with the CT at 6 months when available. The following scores were assigned to the VFA: 0 (unchanged), 1 (osteopenia-cortical bone thinning), 2 (increase in bone density-cortical thickening). We then investigated whether this score correlated with the implant outcome within 12 months (optimal integration, suboptimal integration, integration requiring further surgery or lack of integration) using Kaplan-Meier and Cox regression analyses, considering the occurrence of integration and the duration time before the surgical removal of the whole bone reconstruction.ResultsForty-five patients were included (32 men [71.1%], mean age 14.6 years), 26 affected by osteosarcoma, 14 by Ewing sarcoma, 3 by adamantinoma and 2 operated for the failure of previous reconstructions for bone sarcoma. VFA changes on 6-month CR were significantly associated with optimal integration of the implants (log-rank P = 0.0137, multivariate Hazard ratio = 7.62, 95% confidence interval = 1.13–51.25). None of the other clinical and surgical features were associated with the implant outcome. The findings on 6-month CR and CT follow-up were not significantly different. CT at 6 months was available in 36 patients (80.0%).ConclusionThe assessment of VFA morphological changes on CR performed at 6 months can predict the outcome of the skeletal implant. This data should be considered for clinical decision-making, selecting patients requiring additional images (CT), and possible subsequent revision surgical procedures.     

前列腺癌早期诊断的研究进展北大核心

前列腺癌(prostate cancer, PCa)是中老年男性常见恶性肿瘤之一,目前尚缺乏有效的晚期癌症治疗方法,因此早期诊断对于降低PCa死亡率至关重要。近年来,较多研究开发出多种新型诊断方法以改善对PCa诊断的准确性,同时避免过度诊疗,但其有效性及实用性尚需进一步验证。本文对目前新型生物标志物、联合成像技术及风险预测模型等的早期诊断技术进行总结,以期为临床研究提供指导作用。     

基于红外热成像技术探讨扶正温阳法对阳虚体质的影响

目的 基于红外热成像技术探讨“扶正温阳法”对阳虚质的影响，探讨阳虚质者红外热图的共性规律，分析判断“扶正温阳法”干预阳虚质人群的疗效。方法 纳入30例阳虚质患者给予益气温阳药物在大椎、肾俞（双侧）、命门等进行穴位贴敷，分别在干预前后运用红外热成像技术测定督脉、腰部、腹部、双手及双足局部温度的变化。结果 干预后阳虚体质患者的督脉、腰部、腹部、双手、双足温度均升高（P<0.05），阳虚体质局部温度得以改善。结论 本研究发现“扶正温阳法”可诱发循经热传导现象，通过调节热能代谢而起到调治阳虚体质的作用，红外热成像技术可用来辅助评价阳虚质的治疗效果，对临床指导制定阳虚质人群的干预方案疗效判定具有指导意义。     

Differences in Evidentiary Requirements Between European Medicines Agency and European Health Technology Assessment of Oncology Drugs—Can Alignment Be Enhanced?

ObjectivesNational health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies’ evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences.MethodsInterviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted.ResultsAcceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements.ConclusionsDifferences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed.