基于“整体观”探讨中药的研究思维和方法

中药源于自然，治疗疾病有自身的优势和特点，其作用方式一直是中药研究者们不断研究和探索的重要内容。本文从中医的“整体观”对中药起效机制进行深入思考，认为中药成分多样可契合生物多靶，而生物靶标之间的协同作用是中药起效机制的重要补充；此外，中药对情志及肠道菌群稳态的调节作用也不容忽视，或许可为今后开展中药作用机制的研究提供新的思维和方法。     

基于FPGA的神经突触的硬件实现及放电性能比较

目前专门对化学突触硬件实现的研究较少,采用FPGA芯片技术硬件实现化学突触,对神经元网络的硬件实现具有重要价值。运用DSP Builder软件,对以Hodgkin-Huxley神经元为突触前神经元和突触后神经元的化学突触数学模型进行建模。在DSP Builder模型的基础上,将化学突触的DSP Builder模型进行合理的拆分,然后分别将各个模块在FPGA所对应的软件环境下进行编译运行,最后下载到FPGA核心芯片中,硬件实现5种基于不同机理的化学突触模型。采用相关系数法,对仿真结果和硬件结果在同一个周期内的突触前神经元动作电位、突触后神经元动作电位以及突触电流的幅值进行对比,验证硬件实现的准确性。5种硬件实现的化学突触均可以较好地传递动作电位,但是各个模型消耗资源不同,模型3所消耗的内部乘法器资源(69%),约为模型5资源(31%)的2倍,表明突触模型数学复杂度越高,其消耗的乘法器资源越多。相关系数法的对比结果显示,模型3相关度最高,为0.791 3,模型4相关度最低,为0.693 5。虽然模型3数学复杂度高、硬件资源消耗多,但是其表现的生物性最好。硬件实现的5种突触模型均能较好地呈现化学突触的单向传递性,其中模型5硬件资源消耗少、相关度高,建议以其作为化学突触硬件实现的首选。     

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.     

基于行动研究理论的健康教育在体外受精胚胎移植术后异位妊娠病人中的应用

[目的]探讨基于行动研究理论的健康教育对体外受精胚胎移植术后异位妊娠病人生育压力和生活质量的影响。[方法]采用随机数字表法将2018年1月—2018年9月深圳市某三级甲等综合医院生殖医学中心的102例体外受精胚胎移植术后异位妊娠病人分为观察组和对照组各51例,对照组采用常规护理健康教育,观察组采用基于行动研究理论的健康教育方法。采用生育压力量表(FPI)和生活质量量表(FertiQoL)比较两组病人干预后生育压力和生活质量状况。[结果]观察组病人干预后FPI评分低于对照组,FertiQoL评分高于对照组,差异有统计学意义(P<0.05)。[结论]基于行动研究理论的健康教育方法有利于改善体外受精胚胎移植术后异位妊娠病人的压力状况,提高其生活质量。     

Epigenetic regulation of insulin action and secretion – role in the pathogenesis of type 2 diabetes

The prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide. Obesity, physical inactivity and ageing increase the risk of T2D. Epigenetic modifications can change due to environmental exposures and may thereby predispose to disease. This review aims at summarizing recent advances in epigenetics related to T2D, with a special focus on impaired insulin action and secretion in humans. There will be an emphasis on analyses in human tissues; both from T2D case‐control cohorts and intervention studies. Current data support an important role for epigenetics in the pathogenesis of T2D. Numerous studies have found differential DNA methylation and gene expression in skeletal muscle, adipose tissue, the liver and pancreatic islets from subjects with T2D compared with nondiabetic controls. For example, PDX1 has increased DNA methylation and decreased expression in pancreatic islets from patients with T2D compared with nondiabetic controls. Nongenetic risk factors for T2D such as ageing, unhealthy diets and physical activity do also impact the epigenome in human tissues. Interestingly, physical activity altered DNA methylation of candidate genes for T2D such as THADA in muscle and FTO, KCNQ1 and TCF7L2 in adipose tissue. There is also a strong interaction between genetic and epigenetic factors that together seem to affect T2D. mQTL studies in human adipose tissue and pancreatic islets showed that SNPs associated with DNA methylation levels in numerous sites. Several of these SNPs are also associated with T2D. Recent data also support that DNA methylation of some sites in blood may be developed into biomarkers that predict T2D since methylation of, for example TXNIP, ABCG1 and SREBF1 associated with future T2D. Future studies should use this information for development of new therapies and biomarkers and thereby improve prediction, prevention and treatment of T2D and its complications.     

In silico repurposing the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing clear cell renal carcinoma

The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients' overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC.     

白术的化学成分与药理作用及复方临床应用进展

白术作为一味传统中药,在历代本草著作中广泛记载,其功效有一定演变。现代研究发现,其主要化学成分有挥发油、多糖、内酯类等,具有抗肿瘤、抗炎、调节消化系统等药理作用。临床以中药复方的形式应用于胃肠道疾病、心血管疾病、免疫系统疾病、肝脏疾病等治疗。对近5年SCI收录的白术相关文章进行分析,简述其化学成分,重点围绕着药理作用以及复方的临床应用展开论述,为其进一步开发利用提供参考。     

Pharmacological management of cardiovascular risk in chronic inflammatory rheumatic diseases

ABSTRACT

Introduction

Cardiovascular comorbidity is a major burden in patients with chronic inflammatory rheumatic diseases and a significant determinant of their outcome. In addition to optimal management of the underlying inflammatory condition according to current guidelines, individual cardiovascular risk factors, particularly dyslipidaemia, hypertension, and impaired glucose tolerance should be assessed regularly and guide risk stratification and requirement for treatment.