子宫内膜功能亢进性疾病的“异病同治”诊治研究思路＊

笔者根据现代临床子宫内膜的病理演变过程结合中医“异病同治”理念，提出“子宫内膜功能亢进性疾病”概念，涵盖5种常见的子宫内膜疾病：无排卵性异常子宫出血（Abnormal Uterine Bleeding Ovulatory dysfunction，AUB-O），子宫内膜息肉（Endometrial Polyp，EP），子宫内膜异位症（Endometriosis，EMs），子宫腺肌病（Adenomyosis，AM），子宫内膜癌（Endometrial Carcinoma，EC）。基于文献的汇总，分析得到此类疾病的子宫内膜病理演变与中医病因病机的关联性，为寻找关键通路、创新性治疗此类疾病提供了重要的参考方向，对深化中医妇科学常见疾病的共性病因病机提供了理论依据和探索思路。     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

放疗计划系统DeepPlan光子放疗剂量计算的临床可行性验证

目的:评估DeepPlan放疗计划系统患者计划剂量计算的准确性和临床应用的可行性。方法:剂量算法准确性评估主要是针对YY 0775号和YY/T 0889号报告中的例题内容进行测量验证。临床病例验证是基于Pinnacle计划系统设计的前列腺肿瘤患者9例、胸部肿瘤患者13例和头颈部肿瘤患者5例，试验将各病例原计划优化的子野等信息直接导入DeepPlan进行重新剂量计算，比较不同计划系统得到的靶区和危及器官剂量分布，并用PTW VeriSoft软件对两组计算结果进行全空间剂量γ分析。结果:DeepPlan光子剂量算法通过了剂量计算准确性验证，YY 0775号报告中所有测试例题误差均在2%以内。YY/T 0889号报告中所有患者计划的γ通过率均在96.8%以上，复合野的γ通过率平均值为98.1%。在病例验证中，前列腺肿瘤病例的等中心层面2D γ通过率平均值为97.6%，3D γ通过率平均值为96.9%。胸部肿瘤病例的等中心层面2D γ通过率平均值为98.7%，3D γ通过率平均值为98.3%。头颈部肿瘤病例的中间层面2D γ通过率为98.6%，3D γ通过率平均值为98.8%。结论:通过模体实际测量和临床病例测试，验证了DeepPlan光子放疗剂量计算的准确性和临床应用的可行性。     

Interventions in the diagnosis and adoption of pacemaker therapy in sinus node dysfunction patients: Results from the IMPROVE Brady study

AimsIMPROVE Brady assessed whether a process improvement intervention could increase adoption of guideline-based therapy in sinus node dysfunction (SND) patients.Methods/Results: IMPROVE Brady was a sequential, prospective, quality improvement initiative conducted in India and Bangladesh. Patients with symptomatic bradycardia were enrolled. In Phase I, physicians assessed and treated patients per standard care. Phase II began after implementing educational materials for physicians and patients. Primary objectives were to evaluate the impact of the intervention on SND diagnosis and pacemaker (PPM) implant. SF-12 quality of life (QoL) and Zarit burden surveys were collected pre- and post-PPM implant.A total of 978 patients were enrolled (57.7 ± 14.8 years, 75% male), 508 in Phase I and 470 in Phase II. The diagnosis of SND and implantation of PPM increased significantly from Phase I to Phase II (72% vs. 87%, P < 0.001 and 17% vs. 32%, P < 0.001, respectively). Pacemaker implantation was not feasible in 41% of patients due to insurance/cost barriers which was unaltered by the intervention. Both patient QoL and caregiver burden improved at 6-months post-PPM implant (P < 0.001).ConclusionsA process improvement initiative conducted at centers across India and Bangladesh significantly increased the diagnosis of SND and subsequent treatment with PPM therapy despite the socio-economic constraints.     

淫羊藿（苷）对男性生殖系统的作用和机制

淫羊藿是一种常用的中药材,淫羊藿苷是从淫羊藿中提取的一种黄酮类化合物,也是淫羊藿中最主要的活性物质。研究发现,淫羊藿苷具有促进成骨细胞的生成和活化、调节免疫、抗衰老和抗炎等多种功能。临床上淫羊藿（苷）用于治疗生殖系统、骨关节系统、呼吸系统、神经系统、心血管系统和免疫系统等多种疾病。淫羊藿（苷）对男性生殖系统的作用及机制主要包括具有雄性激素样作用,促进睾内睾酮的合成和分泌。淫羊藿（苷）通过改善精子发生的微环境、增强睾丸抗氧化作用促进精子生成,增加精子密度,改善精子活力,减缓生殖衰退。此外,淫羊藿（苷）可促进阴茎勃起,治疗勃起功能障碍及早泄。     

近端胃切除人工三角瓣成形抗反流术的力学机理仿真分析

目的:对食管胃结合部腺癌近端胃切除术（PG）人工三角瓣成形后残胃食糜进行流体动力学数值模拟，并计算不同性质胃内食糜的流动特征。方法:构建常规PG和人工三角瓣成形术术后胃仿真模型，运用Fluent软件对不同粘度胃内食糜反流问题进行数值模拟。结果:站立位姿态时，相对常规PG方案，人工三角瓣成形手术方案表现出较好的抗反流作用；卧位姿态时，当胃内食糜粘度大于0.145 2 Pa[?s，且胃内食糜不超过人工三角瓣情况下，人工三角瓣成形抗反流手术表现出较好的抗反流效果；人工三角瓣抗反流成形手术方案数值模拟结果与临床上患者表现一致。结论:本研究仿真分析为人工三角瓣成形抗反流手术方案的有效性机理分析、临床患者术后饮食及手术方案的进一步改进提供理论及数值依据。 【关键词】食管胃结合部腺癌；抗反流；人工三角瓣；计算流体力学     

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database

BackgroundConsiderable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization.MethodsThe Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018.ResultsA total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment.ConclusionWe present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.