白术饮片不同贮藏条件包装材料和包装方式的比较研究

目的:确定白术饮片的储藏条件、年限及最佳包装,为饮片的保管与使用提供依据。方法:分别用牛皮淋膜纸袋、塑料袋、塑料袋真空密封、铝塑袋、铝塑复合袋真空密封,存放于阴凉库和药品稳定性试验箱(40℃,湿度75%)中,开展为期6个月的阴凉稳定性和加速稳定性试验,观察性状,分别测定水分、浸出物、挥发油、白术内酯Ⅰ、白术内酯Ⅱ、白术内酯Ⅲ及总量的变化情况,考察温湿度、包装对白术饮片各指标的影响。结果:阴凉稳定性试验中,各包装白术饮片外观性状无明显变化;加速稳定性试验中,部分样品出现发霉、变软现象。水分均呈上升趋势。浸出物和挥发油含量基本保持不变。从白术内酯含量来看,在阴凉库环境下,白术内酯Ⅰ含量小幅度下降,白术内酯Ⅱ、白术内酯Ⅲ含量先下降后平缓,总和下降后趋于平缓;在高温高湿环境下,白术内酯Ⅰ含量小幅度下降,白术内酯Ⅱ、白术内酯Ⅲ含量先下降后趋于平缓后上升,总和先下降后上升。通过气质联用,5种包装中均未发现白术内酯Ⅰ、白术内酯Ⅱ、白术内酯Ⅲ的残留,但塑料、真空塑料、铝塑复合袋、牛皮淋膜纸袋4种包装上均有苍术酮的残留。结论:白术受湿度影响大,受温度影响相对较小,最适宜的包装为铝塑复合袋真空或非真空形式。     

基于真实世界中刺五加注射液应用于心血管病的复杂网络分析＊

为分析真实世界刺五加注射液治疗心管病的联合用药治疗方案，提取全国19家三甲医院信息系统（HIS）数据库中使用刺五加注射液治疗心血管疾病患者的一般信息、中西医诊断信息、医嘱记录，采用Tabu算法挖掘不同子结构之间的关系，并用复杂网络分析将结果可视化。全国19家医院5904例患者纳入分析，优效人群为2595，占44%。刺五加注射液治疗心血管疾病常与西药的抗心绞痛药、抗心律失常药、心血管扩张药、抗血栓药、降血脂药及中药祛瘀剂联合应用，使用频次最高的是单硝酸异山梨酯和中药的速效救心丸。优效人群的联合用药方案中不仅有对症治疗，还有针对基础病的用药，在临床中取得较为理想的疗效。通过对不同子结构之间关系的深入分析，可以为联合用药以及研发用药提供支持和借鉴。     

Hematological toxicities in immune checkpoint inhibitors: A pharmacovigilance study from 2014 to 2019

Immune checkpoint inhibitors (ICIs) have shown remarkable clinical effects in many cancer types. However, ICIs could also induce severe organ system toxicities, including those of the hematological system. The present study aimed to extensively characterize the hematological toxicities of ICIs immunotherapy. Data were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1, 2014, to March 31, 2019. Disproportionality analysis, including information component (IC) and reporting odds ratio (ROR), was used to detect potential disproportionality signal. The lower boundary of the 95% confidence interval of IC (IC₀₂₅) exceeding zero or that of ROR (ROR₀₂₅) exceeding one was considered statistically significant for detecting disproportionality signal. A total of 29 294 335 records were extracted from the database, with 132 573 related to ICIs. Overall, hematological adverse events (AEs) were more frequently reported in ICIs (IC₀₂₅: 0.81; ROR₀₂₅: 1.80). On further analysis, hematological AEs were overreported in female patients (female vs male, ROR₀₂₅: 1.04) and anti-CTLA-4 monotherapy groups (anti-CTLA-4 vs anti-PD-1, ROR₀₂₅: 1.33) and polytherapy groups (polytherapy vs monotherapy, ROR: 1.20, ROR₀₂₅: 1.11). Moreover, class-specific hematological AEs were also detected and differed in unique ICI regimens. Notably, disseminated intravascular coagulation had the highest proportion of death outcomes among the top 10 most frequently reported ICI-associated hematological AEs. Our study shows a high reporting frequency of hematological AEs induced by ICI monotherapy (especially by anti-CTLA-4 therapy) and reinforced by polytherapy. A spectrum of class-specific disproportionality signal was also detected; some were fatal and reported for the first time. The heterogeneous clinical spectrum of hematological toxicities, including the non-negligible proportion of death as reported outcome, are warranted to be reminded by clinicians. Early recognition and management of ICI-related hematological AEs are highly important and further studies are needed to confirm the results of our study.     

A technical review of canonical correlation analysis for neuroscience applications

Collecting comprehensive data sets of the same subject has become a standard in neuroscience research and uncovering multivariate relationships among collected data sets have gained significant attentions in recent years. Canonical correlation analysis (CCA) is one of the powerful multivariate tools to jointly investigate relationships among multiple data sets, which can uncover disease or environmental effects in various modalities simultaneously and characterize changes during development, aging, and disease progressions comprehensively. In the past 10 years, despite an increasing number of studies have utilized CCA in multivariate analysis, simple conventional CCA dominates these applications. Multiple CCA‐variant techniques have been proposed to improve the model performance; however, the complicated multivariate formulations and not well‐known capabilities have delayed their wide applications. Therefore, in this study, a comprehensive review of CCA and its variant techniques is provided. Detailed technical formulation with analytical and numerical solutions, current applications in neuroscience research, and advantages and limitations of each CCA‐related technique are discussed. Finally, a general guideline in how to select the most appropriate CCA‐related technique based on the properties of available data sets and particularly targeted neuroscience questions is provided.     

注射氨基酮戊酸光动力疗法对大鼠痤疮样炎性结节模型的疗效及组织病理学影响

【摘要】 目的 探讨注射氨基酮戊酸（ALA）光动力疗法对大鼠痤疮样炎性结节模型的疗效及组织病理改变。方法 40只SPF级SD大鼠分为正常对照组、模型对照组、注射ALA组、外敷ALA组，每组10只。除正常对照组不处理外，其余3组大鼠右耳廓内侧接种痤疮丙酸杆菌，建立大鼠痤疮样炎性结节模型。造模成功后，模型对照组不处理，注射ALA组将5%ALA注射入结节内再予红光照射，外敷ALA组直接外敷5%ALA于鼠耳痤疮样结节处再予红光照射，均为每周1次，共2次。末次治疗24 h后观察各组大鼠耳部大体表现和组织病理学变化，测量耳廓厚度，并检测肝肾功能。采用单因素方差分析和LSD-t检验比较各组差异。结果 正常对照组、模型对照组、外敷ALA组、注射ALA组大鼠耳廓厚度分别为（0.435 ± 0.006）、（1.269 ± 0.071）、（1.088 ± 0.098）、（0.699 ± 0.095） mm，差异有统计学意义（F = 235.60，P < 0.001），模型对照组耳廓厚度高于正常对照组、外敷ALA组和注射ALA组（t 值分别为24.18、5.24、16.48，均P < 0.01）；注射ALA组低于外敷ALA组（t = 11.24，P < 0.01）。外敷ALA组和注射ALA组大鼠耳廓局部红肿程度、结节数均低于模型对照组，真皮及皮下组织浸润炎症细胞数量减少，注射ALA组结节消退更明显，亦未见团块状分布的炎症细胞或微脓肿形成。各组大鼠丙氨酸转氨酶、天冬氨酸转氨酶、肌酐、尿素氮水平差异均无统计学意义（均P > 0.05）。结论 注射ALA光动力疗法治疗大鼠痤疮样炎性结节模型较外敷ALA光动力疗法治疗更有效。     

如何正确运用t检验——相关系数与0比较t检验及SAS实现

本文目的是介绍Pearson相关系数、Spearman秩相关系数和Kendall’s tau-b秩相关系数的概念及应用场合。首先介绍三种相关系数的计算及其假设检验的基本原理,然后使用SAS程序对实例进行分析,最后对分析结果进行解释和讨论。     

Poly(ADP-ribose) glycohydrolase silencing down-regulates TCTP and Cofilin-1 associated with metastasis in benzo(a)pyrene carcinogenesis

Benzo(a)pyrene (BaP) is a ubiquitously distributed environmental pollutant. BaP is a known carcinogen and can induce malignant transformation of rodent and human cells. Many evidences suggest that inhibitor of poly(ADP-ribose) glycohydrolase (PARG) is potent anticancer drug candidate. However, the effect of PARG on BaP carcinogenesis remains unclear. We explored this question in a PARG-deficient human bronchial epithelial cell line (shPARG cells) treated with various concentration of BaP for 15 weeks. Soft agar assay was used to examine BaP-induced cell malignancy of human bronchial epithelial cells and shPARG cells. Mechanistic investigations were used by 2D-DIGE and mass spectrometry. Western blot analysis and Double immunofluorescence detection were used to confirm some of the results obtained from DIGE experiments. We found that PARG silencing could dramatically inhibit BaP-induced cell malignancy of human bronchial epithelial cells in soft agar assay. Altered levels of expression induced by BaP were observed within shPARG cells for numerous proteins, including proteins required for cell mobility, stress response, DNA repair and cell proliferation pathways. Among these proteins, TCTP and Cofilin-1 involved in malignancy, were validated by western blot analysis and immunofluorescence assay. PARG inhibition contributed to down-regulation of TCTP and Cofilin-1. This is the first experimental demonstration of a link between PARG silencing and reduced cell migration after BaP exposure. We propose that PARG silencing might down-regulate TCTP and Cofilin-1 associated with metastasis in BaP carcinogenesis.