不同阻滞阶段非梗阻性无精子症的生物信息学分析

目的：利用生物信息学筛选不同阻滞阶段非梗阻性无精子症（NOA）相关的调控因子及其调控途径,为后续的功能研究提供依据。方法：从GEO（Gene Expression Omnibus）数据库中获得GSE45885的基因表达谱矩阵,筛选其中的正常样本以及不同阻滞阶段NOA样本,包括4例正常生精样本和20例NOA患者样本,20例NOA患者中有2例患者处于减数分裂前期阻滞阶段（PRE）,7例处于减数分裂期阻滞阶段（MEI）,11例处于减数分裂后期阻滞阶段（POST）。将正常生精样本设置为对照组（CON）,使用GEO2R在线工具鉴定正常生精样本与不同阻滞阶段NOA样本之间的差异基因,对GEO芯片中不同阻滞阶段的NOA数据整合归一化并进行矫正后取交集。对差异表达的基因以及其靶基因进行GO（Gene Ontology）和KEGG（Kyoto Encyclopedia of Genes and Genomes）富集分析,获取关键通路;基于在线工具（STRING）构建蛋白质相互作用（PPI）网络图。然后利用Cytoscape中的CytoHubba插件对枢纽基因进行筛选。结果：在PRE中筛选出463个上调基因,12个下调基因;在MEI和POST中分别发现2个和3个下调基因,无上调基因。PRE中上调基因通过一些重要途径,如精子发生、精子细胞发育、精子的运动、纤毛运动和微管形成等功能来调控生精过程。在上述的3个阻滞阶段NOA中筛选出2个共同差异基因,均为微小RNA（miRNA）,2个miRNA有58个共同靶基因。利用在线生物信息学工具STRING成功构建PRE中上调基因的PPI网络图,并使用Cytoscape筛选出网络中前10个枢纽基因,包括DNAI1、DNAI2、PGK2、ROPN1L、ARMC4、DRC1、DNAAF3、CABYR、ZMYND10和CCDC65。结论：识别枢纽基因和共同差异基因及其通路为后续研究NOA的发生机制提供了有价值的参考,DRC1、ARMC4、MIR15A和MIR509-3可作为后续NOA发病机制研究的潜在靶点。     

Axillary management based on American college of surgeons oncology group Z0011 criteria makes it possible to omit intraoperative diagnosis of sentinel lymph nodes in early breast cancer patients

The ACOSOG Z0011 trial has resulted in the omission of axillary lymph node dissection (ALND) in early breast cancer patients with one or two metastatic sentinel lymph nodes (SLNs). There has been increasing interest in the necessity of intraoperative assessment of SLNs in patients treated based on the Z0011 criteria. We evaluated the utility of intraoperative assessment in these eligible patients. A total of 1396 patients were treated following the Z0011 criteria from April 2012 to December 2019. We examined the proportion and clinicopathological features of patients who underwent ALND due to three or more metastatic SLNs and the sensitivity of intraoperative assessment. Only 16 (1.1%) patients had three or more metastatic SLNs diagnosed by intraoperative assessment, and they immediately underwent ALND. Of the clinicopathological factors, high clinical tumor stage (p = 0.002) and high Ki-67 labeling index value (p = 0.056) were more likely to be associated with the presence of three or more metastatic SLNs. The major independent risk factor for three or more metastatic SLNs was high clinical tumor stage (OR 3.94 [95% CI 1.42–11.0]; p = 0.009). Intraoperative assessment had low sensitivity (70.5%) and a high false-negative rate (29.5%) in detecting SLN metastases. The main finding of our study was the small proportion of patients who required ALND due to three or more metastatic SLNs according to the Z0011 criteria. The Z0011 strategy enables intraoperative assessment of SLNs to be omitted in early breast cancer patients.     

胆管癌免疫检查点抑制剂治疗研究进展

胆管癌是一种罕见的恶性肿瘤,总体预后较差。根治性手术治疗是目前唯一可使早期胆管癌病人获得长期生存的策略。对于多数晚期胆管癌病人,系统治疗成为主要手段,但目前可用于治疗胆管癌的一线药物选择有限,疗效有限。近年来,免疫检查点抑制剂等免疫治疗策略利用宿主免疫系统进行有效的抗肿瘤反应,在多种实体肿瘤中取得令人鼓舞的结果。笔者回顾并总结免疫检查点抑制剂在治疗胆管癌中的研究进展。     

重视供肝机械灌注研究,推动肝移植高质量发展

随着器官捐献数量不断增加和扩大标准供者(ECD)供肝定义不断拓展,供肝质量必然成为影响肝移植高质量发展的突出问题,也是相关领域的研究重点。最大限度解决器官短缺和推动器官移植高质量发展是我国器官捐献与移植事业发展的方向。近年来,利用机械灌注(MP)对供肝进行灌注、保存、评估及修复,已成为当前国际上提高肝移植质量的研究热点。本文针对国内外ECD供肝的不同应用情况,结合国际上MP研究进展和本中心有关研究经验,探讨整合器官保护技术建设器官重症监护室(ICU)的可行性,拟在推动我国器官移植高质量发展同时,进一步丰富器官捐献与移植“中国模式”的技术内涵。     

Parathyroid Carcinoma: A Single-Institution Experience with an Emphasis on Histopathological Features

Parathyroid carcinoma (PC) is a rare malignancy that poses a diagnostic challenge on histologic examination. We analyzed various clinicopathologic features of PC. Pathology reports and slides were reviewed to evaluate the diagnostic histopathologic features of archived cases of PC from the years of 2004–2018. The study cohort comprised twenty cases of PC. The median age was 49 years (range 21–73 years) with equal gender distribution (M:F = 1:1). Most patients presented with symptoms of hypercalcemia (n = 7, 54%). Serum calcium and serum parathyroid hormone were elevated in all but one patient. The right inferior parathyroid was commonly involved (n = 8/14, 57%). The mean tumor size was 2.4 cm (range 0.8–3.5 cm). On frozen section examination, PC was diagnosed in 8 out of 9 cases. Vascular (n = 19/20, 95%) and soft tissue invasion (n = 10/20, 50%) were the most common characteristic histologic findings. Capsular invasion was identified in all cases. Perineural invasion or metastasis at presentation was absent in all cases. Other histological features noted were intratumoral fibrous bands (70%), nodular growth pattern (70%), moderate nuclear atypia (30%), prominent nucleoli (20%), and necrosis (20%). Regional lymph nodes were negative for metastatic disease in all cases (n = 10). Eight out of 16 patients received adjuvant radiotherapy. Follow-up was available in 16 cases (median 21.5 months). Two patients died of disease. Vascular and soft tissue invasion are the most common diagnostic histologic features of PC. Capsular invasion is important to distinguish PC from its benign counterparts. Intraoperative frozen section examination can be used for accurate diagnosis and surgical management.     

Good practices in health promotion for older people – Significance for evidence in health policy

This article is devoted to convincing policy makers to use good practices in encouraging older people to pursue adequate and effective health policies. Long-term scientific research focused on the effects of health promotion programmes is rarely undertaken, although its scope is still expanding. At the same time, it is strongly desirable to form health policy based on scientific evidence. In this situation, an indication of good practices characterised by precisely defined features and their systematic evaluation could be an alternative to an insufficient number of empirical studies. The first step of the methodology was a literature review on health promotion for older people, aimed at defining good practices and criteria used for their selection. The authors searched the following databases: PubMED, Embase and Cochrane Library, as well as international databases dedicated to health promotion programmes for older people (e.g. Age-friendly World ( https://extranet.who.int/agefriendlyworld/age-friendly-practice-database-launched ); HealthProElderly ( www.healthproelderly.com/database/index.php?id=16 ); JA-CHRODIS ( www.chrodis.eu ); EuroHealthNet ( www.eurohealthnet.eu ) and ProFouND; ( www.profound.eu.com ). As relevant health policy information is usually available in national languages, the authors then approached national experts in 10 European countries, who filled in a dedicated survey on health promotion programmes for older people and indicated examples of good practices from their countries. Practical evidence, based on real implemented programmes, is valuable as inspiration for health promotion programmes, their planning and management. Selecting good practices from among implemented and evaluated actions makes it possible to establish their value. The significance of good practices in health promotion is to deliver real benefits and health effects for a target group, which, in the case of evident benefits, renders the practices credible and worthy of further dissemination. The EU already successfully shares good practices in migrant health and environmental protection. Creating databases on good practices helps policy makers promote the sustainability of already implemented activities and enhances their applicability by other organisations and in different settings.     

食管癌调强放疗靶区与肺体积比和处方剂量的关系

目的 研究食管癌调强放射治疗中能够做出既定目标的放疗计划时,靶区体积与肺体积比值和处方剂量的关系,从而帮助临床医生根据靶区情况,选择适合的处方剂量。方法 随机选取临床上已进行放射治疗的食管癌患者80例;其中病变范围包括全部食管癌类型,靶区根据ICRU（International Commission Radiological Units）50、62号文件进行勾画;设定统计参数及计划目标。根据参数的统计结果进行统计学分析;通过拟合计算求出满足既定目标的体积比临界值。结果 体积比与肺V₅、V₂₀、V₃₀以及肺平均受量具有线性正相关关系。给予60 Gy的处方剂量时,体积比的临界值为10%;给予50 Gy的处方剂量时,体积比的临界值为13%。结论 根据研究结果可以预见：食管癌调强放疗中当靶区体积与肺体积比值超过10%时,考虑给予的处方剂量不高于60 Gy;当靶区体积与肺体积比值超过13%时,给予处方剂量时应谨慎选择,但对于各段食管癌靶区超出肺段的患者可适当放宽。这为临床医生勾画靶区期间在处方剂量和靶区范围的选择上提供了参照。     

神经系统轴突三维定向生长的数值模拟

目的研究轴突在三维组织中的定向生长问题,探讨轴突沿非平坦基底定向生长时基底的低起伏程度对轴突的生长速率、成束和解束速率的影响。方法根据实验观察,设轴突生长的牵引力与靶细胞分泌的可扩散吸引分子的浓度梯度成正比,轴突成束和解束的侧向力与生长锥分泌的可扩散吸引分子和排斥分子的浓度梯度成正比,并且,吸引力指向浓度高的方向,排斥力指向浓度低的方向,浓度满足扩散方程。对于非平坦基底,有效力为沿基底轮廓线的切向分量。数值计算采用三维有限差分法和改进的Euler法。结果(1)轴突在三维组织中定向生长的基本特征与在二维培养基实验中的观察是一致的,只是在形态上有三维与二维之分;(2)非平坦基底的低起伏程度影响轴突的生长,随着起伏加剧,生长锥的前进速率减小、侧向速率增加。结论(1)许多基于二维培养实验所揭示的轴突生长的基本规律在三维情况下仍然是成立的;(2)基底的几何性质是影响轴突生长速率的重要因素之一。