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。     

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。     

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.     

Patient and clinician experiences with cross-border reproductive care: A systematic review

ObjectivesThis review analyzes the experiences of patients and clinicians with regards to international cross-border reproductive care (CBRC) for the purpose of conception.MethodsElectronic databases PubMed, Embase, Web of Science, and Scopus were searched using ‘medical tourism’ AND ‘assisted reproductive technology’ from 1978 to 2020.ResultsPredominant patient motivators for CBRC were cost and legality of assisted reproduction technology (ART) in one's home country, followed by cultural factors like shared language, religion, and cultural familiarity. Clinicians suggested global laws for CBRC would reduce the potential for exploitation of vulnerable populations but believed the enactment of international regulations unlikely and, even if enacted, difficult to enforce.ConclusionsWhile patient and clinician experiences with CBRC varied, patients frequently cited financial and legal reasons for pursuing CBRC, while many providers had concern for the patient’s safety.Clinical practice implicationsThis review recommends clinicians involved in family planning counsel patients seeking treatment abroad by: (i) informing patients of the risks and benefits of treatment abroad, (ii) establishing guidelines and standards for clinicians on resuming patient care post-CBRC, and (iii) creating a directory of reputable CBRC clinicians and experts.     

金黄色葡萄球菌异质性耐药机制及实验室检测技术

 异质性耐药是一种特殊的细菌耐药类型，常表现为同一克隆来源的不同细菌亚群对某种抗菌药物表现出不一致的耐药特征，大多数亚群对某种抗菌药物敏感，而少部分亚群对其耐药或高度耐药。异质性耐药分离株常会导致特定抗菌药物抗感染治疗失败。针对异质性耐药菌较为深入的研究主要集中于革兰阴性菌，革兰阳性球菌的相关报道较少。近年有研究报道万古霉素、利奈唑胺、苯唑西林等多种类型抗菌药物异质性耐药金黄色葡萄球菌分离株出现，但其实际临床意义尚待进一步评估。此文对金黄色葡萄球菌异质性耐药机制和检测技术最新进展进行综述，为细菌异质性耐药机制研究和新型检测技术研发提供新的思路。     

Involvement of Patients and Medical Professionals in the Assessment of Relative Effectiveness: A Need for Closer Cooperation

ObjectivesInvolvement of patients and medical professionals in assessment of relative effectiveness (relative effectiveness assessment) contributes to an efficient and effective health technology assessment (HTA) process and supports acceptance and implementation of the outcome. This study aimed to analyze stakeholder involvement in assessing relative effectiveness and how the parties involved value this collaboration.MethodsThis is a document analysis of all drug assessments completed in 2019 (20) by the public HTA agency of The Netherlands, enriched with semistructured interviews with employees of the HTA agency (18) and representatives of patient (5) and medical (11) associations involved in these assessments. Data were analyzed, coded, and categorized.ResultsIn almost half of the assessments, there was no coordination with the medical associations at the start of the relative effectiveness assessment and no patient associations involved in this phase. During the assessment procedure, patient and medical associations were always asked to comment on the draft report. Nevertheless, the strict 5-day deadline that the HTA agency uses as a response period often hampered a proper response and involvement. According to interviewees of the HTA agency, this leads to a great diversity in the substantive quality of their input. Patient and medical associations indicated that the HTA agency relies too much on “paper knowledge,” which leads to a (perceived) lack of alignment with clinical practice.ConclusionsThe limited involvement results in a lack of coordination and mutual trust. Optimizing involvement of patients and medical professionals in HTA practice requires effort from all parties involved. Procedural adjustments and better coordination, especially at the start of the assessment, would probably improve cooperation.     

直肠癌新辅助放疗研究进展

在过去的近40年里，直肠癌的治疗方案逐渐标准化。大多数早期直肠癌患者仅通过手术即可得到充分的治疗。然而，相当比例的直肠癌患者处于局部进展期，此类患者需要行新辅助治疗。直肠癌的新辅助放射治疗已被证明能有效地降低患者术前肿瘤分期、改善患者生存以及降低直肠癌局部复发率等，随之而来的是患者放疗后出现的不同程度的放疗不良反应，但随着放射治疗规范化、放射治疗技术及设备的改进，放疗不良反应严重程度在逐渐降低。本文就新辅助放疗中的放疗方案的选择、放射治疗技术、放疗不良反应、放疗后的手术时间以及放疗后的观察与等待等问题的最新研究进展进行了系统性的综述，从而为临床直肠癌新辅助治疗提供有力依据。     

数字化技术在可摘局部义齿和全口义齿制作中的应用现状与未来

数字化技术的发展为可摘局部义齿/全口义齿的设计和制作提供了全新的选择,具有高精度、高质量和高效率的特点。其中,本文就数字化印模、数字化设计与数字化制作这三个关键因素进行了重点讨论。     

TIC en actividad física y parámetros cardiovasculares en mayores: una revisión

IntroductionAgeing is a period of physical and psychological changes. Inactivity is one of the biggest problems among the older adult population increasing the risk of sarcopenia and chronic diseases. Physical activity is an effective intervention to improve health outcomes. In recent years, there has been an increase in the use of technology, with health technology tools (ICT) appearing as an intervention to increase physical activity and improve associated health problems.ObjectiveIn this review, we evaluated the effectiveness of health technology to increase physical activity and to improve cardiovascular parameters in older adults.MethodologyStudies with a great variety of health technology tools to increase physical activity levels, and that evaluated the effect of that increase on cardiovascular parameters were included by searching the main databases.ResultsEleven studies reporting the use of a variety of ICT tools were included in this review. Despite these differences, the effectiveness of health technology tool interventions has been demonstrated in increasing physical activity and reducing cardiovascular parameters.DiscussionThe lack of adherence of older adults to health technology would be a disadvantage, but it has been shown that younger older adults are more familiar with health technology tools and the number using them is increasing.ConclusionHealth technology tools show effectiveness in increasing physical activity in older adults and improving cardiovascular parameters.     

基于网络药理学及分子对接技术研究人参-陈皮配伍治疗慢性阻塞性肺疾病的作用机制＊

目的 研究人参-陈皮配伍治疗慢性阻塞性肺疾病（COPD）的主要活性成分和潜在的分子作用机制。方法 从TCMSP数据库中获取人参、陈皮的活性成分和潜在靶点，疾病靶点利用DrugBank、TTD、GeneCards数据库获取。“药物-化合物-靶点”互作网络可视化由Cytoscape3.6.1软件完成。通过绘制韦恩图得到人参、陈皮和COPD的共有靶点，运用Cytoscape平台获取共有靶点相互作用关系。通过DAVID数据库对共有靶点进行GO、KEGG富集分析。活性成分和关键靶点的分子对接由autodock vina实现，并采用体外抗炎活性实验进行验证。结果 从人参和陈皮中共筛选得到27个活性成分，800个疾病靶点，药物和疾病共有靶点70个。GO功能富集分析得到GO条目213个（P<0.01），KEGG通路富集筛选得到99条信号通路（P<0.01）。分子对接结果显示，甾醇类成分和黄酮类成分与关键靶点有较高的结合性。体外抗炎活性验证结果表明，川陈皮素、山奈酚、柚皮素、人参皂苷rh2能够减少炎症因子的分泌。结论 人参-陈皮配伍可通过多成分、多靶点和多通路调控炎症因子释放，达到治疗COPD的效果。