Update on adrenal cortical neoplasia

The adrenal cortex gives rise to a biologically heterogenous group of neoplasms, each with a distinct morphology, antigen expression and molecular profile. Adrenal cortical adenomas have excellent prognosis and are usually cured by surgical resection alone, while adrenal cortical carcinomas are very aggressive tumors with a poor prognosis regardless of therapy. These tumors are rare and often challenging for a pathologist to diagnose, as significant overlap exists between benign and malignant lesions in some cases. In this review, we attempt to summarize most important histologic and clinical features of adrenal cortical adenomas and carcinomas, clarify the use of different grading systems, the use of special stains and the differential diagnosis for practicing pathologists. Most relevant hereditary syndromes associated with adrenal cortical tumors are listed. Updates in molecular alterations in adrenal cortical neoplasms and hyperplastic diseases as well as their clinical significance and potential therapeutic implications are also discussed.     

双重实时荧光PCR快速鉴别人参和西洋参＊

目的 建立一种能够快速鉴定人参和西洋参的双重实时荧光PCR方法。方法 通过对人参属及其近似种基因序列的分析比对，设计特异性的引物探针，建立双重实时荧光PCR检测方法。PCR反应体系为Premix Ex Taq （Probe qPCR） 10 μL，人参上下游引物各0.5 μL，西洋参上下游引物各0.3 μL，人参与西洋参特异性探针各0.4 μL，DNA模板2 μL，灭菌去离子水补至20 μL。反应条件为95℃预变性30 s；然后以95℃变性5 s，60℃退火延伸30 s进行40个循环。应用该方法测试了27份DNA样品，包括7份人参、6份西洋参、4份人参与西洋参混合样、10份其他人参属样品及其他常见中药材样品的DNA，以确定该方法的特异性。将人参与西洋参样品DNA混合后10倍稀释成不同浓度后进行检测，用以确定该方法的灵敏度。结果 人参及西洋参样品均在特定的荧光通道下出现典型的阳性扩增曲线，人参与西洋参混合样品均同时出现两条阳性扩增曲线，其它对照样品及空白对照均没有出现阳性扩增曲线。灵敏度检测结果显示该方法检测人参及西洋参的最低检测限均为2 pg DNA/反应。结论 本实验建立的双重实时荧光PCR方法能够同时快速、准确、灵敏地鉴别出人参和西洋参。     

基于网络药理学和分子对接技术探讨黄芪干预腹膜纤维化的机制

目的 运用网络药理学方法及分子对接技术探讨黄芪干预腹膜纤维化的可能机制。方法 利用中药系统药理学数据库及分析平台(TCMSP)检索黄芪的主要化学成分及靶点,并补充文献报道相关药理作用的成分作为潜在活性成分。以"peritoneal fibrosis"为关键词分别在OMIM、Genecards获取目前已知的与腹膜纤维化相关的疾病靶点,后取两者的交集靶点;对交集基因通过STRING数据库与Cytoscape 3.7.2软件构建"药物-成分-靶点-疾病"网络及蛋白互作(PPI)网络并筛选核心网络。基于R软件使用Bioconductor生物信息软件对核心靶点进行GO及KEGG富集分析,最终采用AutoDock软件将主要有效成分与核心靶点进行分子对接,得出其结合能力。结果 筛选出20个黄芪活性成分及文献报道有相关药理作用4个, 457药物作用靶点,与674个腹膜纤维化病靶点取交集,得到86个共同靶点。GO功能富集分析提示黄芪拮抗腹膜纤维化主要参与了蛋白激酶B信号转导的调节、细胞对化学的应激反应、炎症反应的调节等通路; KEGG通路富集分析主要涉及调控肿瘤、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)、人类巨细胞病毒感染、HIF-1信号通路等;分子对接结果显示关键靶点与活性成分具有较好的结合能力。结论 黄芪治疗腹膜纤维化的分子机制,可能与抑制炎症及氧化应激反应、调节多种信号通路等相关。     

中医健康状态辨识模式的研究现状与展望

健康状态的辨识是把握健康的前提。当前学界已存在专家辨识模式、标准辨识模式、数字辨识模式、智能辨识模式以及微观辨识模式等。联合多种辨识方法,构建健康状态辨识体系,形成常态与动态结合、主观与客观结合、人机互参的中医健康状态个体化辨识方法是研究的趋势所在。文章对未来的研究方向进行展望,探讨了多元辨识模式、远程辨识模式、终身辨识模式、自动辨识模式的思路方法,以期促进全民健康事业,助力"健康中国"战略。     

奥扎格雷联合低分子肝素钙治疗脑血栓的临床研究

目的：对应用低分子肝素钙与奥扎格雷联合对患有脑血栓疾病的患者实施治疗的临床效果进行研究。方法整群选择在该院2012年12月—2014年12月就诊的患有脑血栓疾病的患者86例，随机分为对照组和治疗组，每组43例。采用奥扎格雷对对照组患者实施治疗；采用低分子肝素钙与奥扎格雷联合对治疗组患者实施治疗。对比神经功能缺损评分在药物治疗前后的变化幅度、脑神经功能恢复正常时间和脑血栓药物治疗计划实施总时间、脑血栓疾病药物治疗效果、用药期间的不良反应人数。结果治疗组患者神经功能缺损评分在药物治疗前后的变化幅度明显大于对照组；脑神经功能恢复正常时间（9.66±2.41）d和脑血栓药物治疗计划实施总时间（13.28±2.14）d明显短于对照组（13.62±3.47）、（17.39±3.20）d；脑血栓疾病药物治疗效果（总有效率90.6%）明显优于对照组（总有效率69.8%）；用药期间的不良反应人数（1例）明显少于对照组（8例）。结论应用低分子肝素钙与奥扎格雷联合对患有脑血栓疾病的患者实施治疗的临床效果非常明显。     

Colorectal serrated pathway cancers and precursors

The serrated pathway (SP) can be viewed as two parallel, but partially overlapping, arrays of colorectal precursor lesions, and their respective endpoint carcinomas, that are distinct from those of the conventional adenoma–carcinoma sequence (APC‐pathway). In this review we focus at the outset on the clinical impact, pathological features, molecular genetics and biological behaviours of the various SP cancers. Then we summarize the clinicopathological features, classification and molecular profiles of the two main precursor lesions that anchor the respective pathways: (i) sessile serrated adenoma/polyp (SSA/P), also called sessile serrated lesion (SSL), and (ii) traditional serrated adenoma (TSA). Activating mutations of the RAS–RAF–MAPK pathway initiate and sustain the lesions of the SP, and CpG island methylation of the promoter regions of tumour suppressor and DNA repair genes play the major role in their neoplastic progression. The SP includes microsatellite stable (MSS) carcinomas that are among the most biologically aggressive colorectal carcinomas (CRC), and also accounts for the great preponderance of sporadic hypermutated, mismatch repair (MMR)‐deficient or microsatellite instable (MSI) CRC. The identification, removal and appropriate classification of at‐risk SP precursors and surveillance of individuals who harbour these lesions present a challenge and opportunity for CRC prevention and mortality reduction.     

Reactivation of heat-inactivated Ku proteins by heat shock cognate protein HSC73

Purpose: Mouse double-stranded DNA-dependent protein kinase (DNA-PK) activity is heat sensitive. Recovery of heat-inactivated DNA repair activity is a problem after combination therapy with radiation and heat. We investigated the mechanism of recovery of heat-inactivated DNA-PK activity.

Methods: Hybrid cells containing a fragment of human chromosome 8 in scid cells (RD13B2) were used. DNA-PK activity was measured by an in vitro assay. Immunoprecipitation of the nuclear extract was performed with an anti-Ku80 antibody. Proteins co-precipitated with Ku80 were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and detected by Western blotting using anti-heat shock protein (HSP)72 and anti-heat shock cognate protein (HSC)73 antibodies. HSC73 was overexpressed with the pcDNA3.1 vector. Short hairpin (sh)RNA was used to downregulate HSC73 and HSP72.

Results: The activity of heat-inactivated DNA-PK recovered to about 50% of control during an additional incubation at 37?°C after heat treatment at 44?°C for 15?min in the presence of cycloheximide (which inhibits de novo protein synthesis). Maximal recovery was observed within 3?h of incubation at 37?°C after heat treatment. Constitutively expressed HSC73, which folds newly synthesized proteins, reached maximal levels 3?h after heat treatment using a co-immunoprecipitation assay with the Ku80 protein. Inhibiting HSC73, but not HSP72, expression with shRNA decreased the recovery of DNA-PK activity after heat treatment.

Conclusions: These results suggest that de novo protein synthesis is unnecessary for recovery of some heat-inactivated DNA-PK. Rather, it might be reactivated by the molecular chaperone activity of HSC73, but not HSP72.     

藿香正气汤抑制新型冠状病毒复制过程的有效成分及机制初探＊

目的 收集藿香正气汤的主要活性成分，通过分子对接及网络药理学探讨其防控新型冠状病毒肺炎（COVID-19）的有效成分及治疗机制。方法 通过基于配体-蛋白质相互作用的计算方法，以瑞德西韦为对照，探索藿香正气汤潜在治疗COVID-19的成分，并选出对接较好成分进行药理学机制预测，初探其药理学机制。结果 本研究筛选出5种与新冠病毒3CLpro结合能力强于瑞德西韦的小分子成分。网络药理学初步预测抗病毒途径可能是通过PI3K-Akt 信号通路影响病毒复制。结论 成分C1-C5与3CLpro结合良好，推测其可能是潜在的3CLpro的抑制剂，为抗病毒天然药物的开发提供了理论依据。