Deep learning with biopsy whole slide images for pretreatment prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer：A multicenter study

IntroductionPredicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs.Materials and methodsWe retrospectively collected data from four cohorts of 874 patients diagnosed with biopsy-proven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs.ResultsThe WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80).ConclusionOur study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction.     

基于TCGA数据初步探查肝内胆管癌预后相关基因

目的 分析tCGA数据库中肝内胆管癌（ICC）高通量测序数据，寻找其预后相关基因，构建风险模型，并研究其在ICC组织中表达及作用通路。方法 下载tCGA数据库中33例ICC组织和8例癌旁组织中的RNA-seq表达矩阵数据和患者临床资料信息，利用edgeR软件包进行基因差异表达分析，通过单因素Cox回归分析筛选出预后相关差异基因，对差异基因绘制生存曲线，筛选出具有临床意义的基因，经多因素Cox回归分析并构建风险模型，通过京都基因与基因组百科全书（KEGG）通路富集分析了解预后相关基因的作用通路。结果 通过edgeR分析后得到6 617个差异基因（筛选标准为|log2 Fold Change|＞1，P＜0.05），其中高表达组4 094个，低表达组2 523个。通过功能富集发现，这些基因主要集中在化学物致癌作用、药物代谢-细胞色素P450系统、细胞色素P450对异生物质的代谢影响以及视黄醇代谢通路。经单因素Cox回归、R软件“survival”包生存曲线分析显示，UCN2、CST1、PROS1、SLC35E4、PEMT五个基因对ICC患者预后存在显著性影响。通过多因素Cox回归分析，CST1、PEMT、PROS1构建的风险模型对ICC患者预后具有判断作用。结论 UCN2、CST1、PROS1、SLC35E4、PEMT基因可能成为ICC预后判断指标，为后续临床试验提供数据支持。     

IFN-gamma promotes apoptosis of the uterus and placenta in pregnant rat and human cytotrophoblast cells.

Growth and development of placentas in all pregnancy periods and that of fetuses in late pregnancy were inhibited after administration of interferon-gamma (IFN-gamma). Apoptosis can be detected by TUNEL at the maternal-fetal interface during normal rat pregnancy. Apoptosis locations at the maternal-fetal interface changed according to the period of pregnancy. The results of immunohistochemistry and the DNA ladder assay showed that IFN-gamma could promote the apoptosis levels during the entire pregnancy, but it did not change the apoptosis locations. IFN regulatory factor-1 (IRF-1), FasL, and p53 expressions were modulated by IFN-gamma during the entire pregnancy. In vitro cell proliferation assay indicated that IFN-gamma could inhibit proliferation of human cytotrophoblast cells, and flow assay showed that this effect was mainly due to apoptosis induction. TUNEL and Hoechst staining also showed that IFN-gamma could induce apoptosis of human cytotrophoblast cells. Expression of IRF-1 was induced and expression of active caspase-3 was promoted by IFN-gamma treatment, but IFN-gamma did not affect the expression of IFNGR and p53.     

基于ISD模型的突发公共卫生事件全员培训设计与应用分析

目的 北京市某三级医院为提升全员应对突发公共卫生事件的应急处置能力,最大限度保障职工职业安全,实现所有工作人员零感染,开展全员职业培训与考核。方法 采用ISD（instructional system design）模型进行培训课程的系统设计,对全院人员在线学习、电子试卷考核和现场培训、考核结果使用Excel、SPSS 22.0进行分析。结果 参加培训人员经培训后平均得分由84升至100,答题时间由平均308 s缩短为179 s,不同职称人员培训前后考核分数存在差异,不同部门间人员培训前后的考核分数存在差异。结论 在突发公共卫生事件发生时,全员培训及考核是必要的,应用ISD模型有助于快速制定培训方案。在线学习考核的应用是应急全员培训的首选有效方式。     

非特异性相互作用的断裂力与寿命测量

目的　探讨量化非特异性相互作用在特异性选择素－配体分子相互作用中的贡献。方法　利用光镊技术，对牛血清白蛋白(Bovine serum albumin, BSA)封闭的玻璃小球间的非特异性作用进行了系统测量，得出不同加载率下的断裂力以及不同外力作用下的寿命分布。结果　实验结果表明，非特异性作用同样表现出断裂力随加载率增加而增大的趋势。在较低加载率下，非特异性断裂力与选择素－配体特异性断裂力大小、增大趋势基本一致；随着加载率增加，二者的差别逐渐显著，前者的断裂力增加速率远低于后者。同样外力作用下，非特异性作用的寿命平均值比特异性作用要小；不同外力作用下，非特异性作用的寿命随外力增大仅略有下降，与特异性作用中逆锁键－滑移键转化现象有明显不同。结论　该研究结果将为正确评估非特异性相互作用对选择素－配体特异性相互作用实验结果的影响提供基础。     

Arthrobacter scleromae sp. nov. isolated from human clinical specimens

A gram-positive, coryneform bacterium was isolated from swollen scleromata of a dermatosis patient. An analysis of its phenotypic, chemotaxonomic, and genotypic characteristics showed that this bacterium is closely associated with Arthrobacter oxydans and Arthrobacter polychromogenes but that it belongs to a distinct species, for which the name Arthrobacter scleromae sp. nov. is proposed.     

Longitudinal alteration of circulating dendritic cell subsets and its correlation with steroid treatment in patients with severe acute respiratory syndrome

In this study, we found that 74 patients with severe acute respiratory syndrome (SARS) exhibited a rapid, dramatic decrease in numbers of circulating myeloid and plasmacytoid dendritic cells (mDCs and pDCs) during the first 2 weeks of illness (5.3- and 28.4-fold reductions for mDCs and pDCs compared with 25 healthy individuals, respectively), with slow return to normal cell numbers during convalescence (weeks 5–7 of illness on average). In addition, numbers of circulating CD4 and CD8 T cells exhibited milder reductions (2.1- and 1.8-fold at week 1) and earlier return to normal at a mean of weeks 3 and 4, respectively. A significant inverse correlation was found between numbers of DC and T-cell subsets and high-dose steroid treatment. Our novel findings thus suggest that the acute SARS-coronavirus infection probably contributes to the initial reduction of DC and T-cell subsets in blood, and that high-dose steroid administration may subsequently exacerbate and prolong low expression of the cell subsets. These findings will aid the framing of further studies of the immunopathogenesis of SARS.     

Stat5b/Survivin信号转导通路调控结肠癌细胞凋亡的机制

目的: 探讨Stat5b/Survivin信号转导通路调控结肠癌细胞凋亡的作用机制。方法: 用阳离子脂质体介导Stat5反义寡核苷酸转染人结肠癌HT29细胞，MTT法检测细胞增殖状态；流式细胞术检测细胞周期与凋亡；EMSA检测Stat5活性；Western blotting检测Stat5、p-Stat5、cyclin D1、Survivin与Bcl-2凋亡家族成员Bcl-2和Bcl-x_L的表达。结果: 转染Stat5反义寡核苷酸后HT29细胞增殖受抑制，凋亡细胞增多，Stat5、p-Stat5与Survivin表达下降，Bcl-2与Bcl-x_L变化不明显。结论: 阻断Stat5通路可以抑制靶基因Survivin表达并诱导结肠癌细胞凋亡。     

γ型干扰素、CD4+CD25+调节性T细胞与自身免疫病

γ型干扰素在适应性免疫应答中起重要作用.在MHC-Ⅱ类分子限制性自身免疫病中,T细胞反应主要以1型辅助性T细胞(Th1)为主,并伴有IFN-γ水平增高,而剔除小鼠胸腺来源的CD4 CD25 调节性T细胞则导致自身免疫病的发生,有研究认为调节性T细胞在诱导免疫耐受产生的过程中起关键性作用.IFN-γ及其受体缺陷小鼠的CD4 CD25 调节性T细胞的免疫抑制能力明显受损,这表明IFN-γ及其受体在CD4 CD25 调节性T细胞免疫调节作用中以及在自身免疫病发生中可能发挥重要而复杂的免疫调节作用.本文仅就IFN-γ与调节性T细胞及自身免疫病发病三者之间关系的研究进展进行简要综述.     

经椎体后上缘入路椎体后凸成形术治疗腰椎骨质疏松性椎体压缩骨折的临床疗效

【摘要】 目的：分析经椎体后上缘入路椎体后凸成形术（percutaneous kyphoplasty,PKP）的手术设计,并与经双侧椎弓根入路PKP治疗骨质疏松性腰椎椎体压缩性骨折（osteoporotic vertebral compression fracture,OVCF）进行临床疗效对比。方法：回顾性分析符合纳入标准并行PKP治疗的患者67例,共74个椎体,按照患者接受PKP的不同入路手术分为经椎体后上缘入路组（观察组）与经双侧椎弓根入路组（对照组）。其中观察组男6例,女23例,平均年龄76.8±8.8岁;对照组男9例,女29例,平均年龄77.7±10.2岁。对两组患者的椎体高度改善率、骨水泥分布及渗漏情况、穿刺角度、手术时间、术中放射暴露、骨水泥注射量、VAS评分和ODI评分进行对比分析。结果：所有患者均顺利完成手术,术中未发生穿刺相关神经损伤、节段动脉损伤等。两组患者椎体高度改善率[（47.68±23.76）％ vs （48.70±22.10）％]、骨水泥注射量（4.35±1.00ml vs 4.63±0.75ml）、骨水泥单侧分布率（6.1％ vs 0）、椎管内骨水泥渗漏率（27.3％ vs 14.6％）、椎间盘骨水泥渗漏率（12.1％ vs 9.8％）、椎间孔骨水泥渗漏率（3.0％ vs 0）及术后VAS（2.10±0.90 vs 1.92±0.67）相比,差异均无统计学意义（P>0.05）。两组椎旁骨水泥渗漏率（30.3％ vs 61.0%）、放射暴露、手术时间（39.2±4.7min vs 44.8±5.5min）及穿刺角度相比,差异有统计学意义（P＜0.05）。结论：经椎体后上缘入路单侧穿刺即可达到椎体中心实现骨水泥双侧弥散,可减少手术时间与放射暴露,降低骨水泥椎旁渗漏率,可获得与经双侧椎弓根入路PKP相同的椎体复位率及临床疗效。