Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

丹参酮生物合成相关SmERF108转录因子的鉴定及其靶基因分析＊

目的 鉴定与丹参酮合成相关转录因子AP2/ERF家族中SmERF108转录因子，并分析转录因子SmERF108的靶基因。方法 利用生物信息学在线分析平台如NCBI、PFAM等分析SmERF108的序列特征；MEGA-X软件用于构建SmERF108与不同功能转录因子的系统进化树；拟南芥原生质体转化法鉴定SmERF108蛋白的亚细胞定位；通过实时荧光定量PCR（Real-time qPCR）对SmERF108基因在丹参不同器官和组织差异表达进行检测；利用酵母体系对SmERF108的转录激活活性进行探究并用酵母单杂技术确定其靶基因。结果 SmERF108具有典型的AP2/ERF保守结构域，属于ERF-B3亚组，系统进化树和保守基序分析显示SmERF108与丹参中SmERF128、青蒿中AaERF2亲缘关系较近且保守基序分布一致；亚细胞定位显示SmERF108蛋白定位于细胞核；SmERF108基因在周皮中表达最高，且呈现周皮（R1）>韧皮部（R2）>木质部（R3）的规律；酵母自激活验证SmERF108具有转录激活活性，同时酵母单杂交确认其能与关键酶基因SmCPS1启动子结合。结论 鉴定到丹参中一个新转录因子SmERF108，生物信息学分析及差异表达分析预测与丹参酮合成相关，分子互作初步证实靶基因为SmCPS1二萜环化酶。     

Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

基于CiteSpace可视化分析代谢组学在中医药领域的研究现状及趋势＊

目的 应用可视化方法分析代谢组学在中医药领域的现状及趋势。方法 检索中国知网数据库（CNKI）和Web of Science 核心合集数据库2021年3月15日之前收录的中医药领域代谢组学研究的相关文献，应用CiteSpace软件对纳入的文献进行关键词、作者、研究机构等内容进行可视化分析。结果 共纳入中文文献247篇，英文文献350篇。文献数量在波动中迅速上升。中、英文文献作者合作网络显示，张爱华是中医药领域代谢组学研究发文量最多的作者，并形成了核心研究团队。发文机构显示，中国医学科学院是该领域的重要研究机构，机构间合作紧密。中、英文文献关键词分析显示，研究内容主要集中在核磁共振、代谢标记物、冠心病、质谱技术、代谢通路等相关领域。结论 中医药领域代谢组学研究的热点主要为中医药治疗代谢性疾病的机制研究。研究趋势为卵泡代谢组学研究及中药有效成分的研究。     

基于CiteSpace的结直肠癌患者生命质量研究

目的：通过中英文文献了解结直肠癌患者生命质量研究现状及发展趋势。方法：运用CiteSpace对中国知网（CNKI）、万方数据知识服务平台、中国生物医学文献数据库、Web of Science核心数据集、PubMed、Cochrane Library中收录的关于结直肠癌患者生命质量研究的中英文文献进行可视化分析。结果：检索得到中文文献1 285篇，英文文献871篇，中英文文献发文量均呈上升趋势，相关研究关注的重点主要是结直肠癌患者造口、抑郁、免疫、肠道功能、化疗及化疗药物，但机构之间、学者之间合作程度及研究类型等方面存在一定差异。结论：中文文献相关研究起步晚、发展快，但在研究质量与研究深度等方面与英文文献相比还有一定差距；国内学者之间、机构之间应加强合作，关心患者肠道功能、心理状况，提高患者体力活动水平，开展更多高质量研究。     

Reacreditación o recertificación de los cirujanos generales en España: esa es la cuestión. Resultados de una encuesta nacional

IntroductionThe Law for the Regulation of Health Professions (LOPS) indicates that health professionals will carry out continuous training throughout their professional life, and will regularly prove their professional competence. The objective of the study was to carry out a national survey to find out the opinion of Spanish surgeons and thus be able to prepare a recertification project by the Spanish Association of Surgeons (AEC).MethodsCross-sectional observational study carried out in June-July 2020, through a survey sent to the members of the AEC.ResultsThe survey had a total of 1230 visits and an overall completion rate of 784 responses (67.3%). 69.6% were unaware of the LOPS forecasts and 83.4% were unaware of similar initiatives in other specialties and 95.5% agreed to demand adequate information. 71.4% believed it necessary but only 57% believed that it should be mandatory. 82.9% would agree that it should be regulated through an objective and predictable official procedure.ConclusionsThe concept of re-accreditation is not well known in our specialty and in view of the results obtained, adequate and reliable information seems necessary. Therefore, it would be pertinent to propose by the AEC a specific project to assess activities and skills.     

Evaluating the use of anti-scatter grids in adult knee radiography

IntroductionAnti-scatter grids efficiently reduce scatter radiation from reaching the imaging receptor, enhancing image quality; however, the patient radiation dose increases in the process. There is disagreement regarding the thickness thresholds for which anti-scatter grids are beneficial. This study aims to establish a thickness threshold for the use of anti-scatter grids to optimise adult knee radiography.MethodsThe study consisted of two phases. In Phase 1 phantom knee radiographs were acquired at varying thicknesses (10–16 cm) and tube voltages (60–80 kV). For each thickness and tube voltage, images with and without an anti-scatter grid were obtained. In Phase 2, two radiologists and three radiographers, evaluated the image quality of these images. Visual Grading Analysis (VGA) scores were analysed using Visual Grading Characteristics (VGC) based on the visualisation of five anatomic criteria.ResultsThe average DAP decreased by 72.1% and mAs by 73.1% when removing the anti-scatter grid. The VGC revealed that overall images taken with an anti-scatter grid have better image quality (AUC ≥0.5 for all comparisons). However, the anti-scatter grids could be removed for thicknesses 10, 12 and 14 cm in conjunction with using 80 kVp,.ConclusionAnti-scatter grids can be removed when imaging adult knees between 10 and 12 cm using any kVp setting since the radiation dose is reduced without significantly affecting image quality. For thicknesses >12 cm, the use of anti-scatter grids significantly improves image quality; however, the radiation dose to the patient is increased. The exception is at 14 cm used with 80 kVp, where changes in image quality were insignificant.Implications for practiceOptimisation by removing anti-scatter grids in adult knee radiography seems beneficial below 12 cm thickness with any kVp value. Since the average knee thickness ranges between 10 and 13 cm, anti-scatter grid can be removed for most patients. Nevertheless, further studies are recommended to test if this phantom-based threshold applies to human subjects.