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。     

MSCT在对比剂外渗的急性腹部创伤性动脉损伤诊断中的应用价值

目的探讨MSCT在对比剂外渗的急性腹部创伤性动脉损伤诊断中的应用价值。方法回顾性分析本院2016年1月～2018年12月收治的44例急性创伤性腹部动脉损伤患者及58例腹部非创伤性动脉病变患者影像资料,分析急性腹部创伤性和非创伤性动脉病变所致对比剂外渗的相关性。结果 44例创伤性腹部损伤患者通过MSCT及图像后处理技术共检出59支动脉损伤,其中对比剂外渗34支、非对比剂外渗共25支;58例急性腹部非创伤组共检出58支动脉病变,其中8支存在对比剂外渗。对比剂外渗征象创伤组出现率明显高于非创伤性组(χ~2=24.42,P0.05)。结论与非创伤组相比,急性腹部创伤性动脉损伤对比剂外渗征象较为常见,MSCT可以较好地显示创伤性对比剂外渗的直接及间接征象。     

Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

建设世界一流科技期刊的策略——基于Nature、Science、The Lancet和Cell的分析

【目的】 探索建设世界一流科技期刊的策略,以助力中国科技期刊冲刺世界一流水平。【方法】 通过研读相关政策和研究文献,结合对Nature、Science、The Lancet、Cell等不同类型的世界一流科技期刊的分析,解析世界一流科技期刊的概念及内涵,探讨建设世界一流科技期刊的充分条件和必要条件,提出建设世界一流科技期刊的建议。【结果】 卓越的办刊理念、全方位的国际化水平、世界一流的人才队伍、先进的经营管理水平以及汇聚一流前沿成果、卓著的科学声望是建设世界一流科技期刊的必要条件。“高、精、尖”和“稳、准、狠”的办刊策略,是建设世界一流科技期刊的充分条件。建设世界一流科技期刊要理性且准确地认知其内涵,始终坚持卓越的办刊理念、国际化战略、人才战略、质量战略和集群化战略。【结论】 中国科技期刊既要扎根祖国大地,又要学习世界一流期刊的成功经验,从办刊的硬实力和软实力方面吸收借鉴,才能探索出具有中国特色的世界一流科技期刊建设路径。     

直肠癌淋巴结转移的深度神经网络评判研究进展

正目前,临床上对于直肠癌常用的影像评估方法有MRI、螺旋CT、PET-CT、直肠腔内超声(ERUS)等。而MRI作为首选检查方式,对肿瘤位置、浸润深度、淋巴结转移、血管侵犯、环周切缘及周围器官侵犯等方面的评估均具有明显优势~([1-2])。通过MRI诊断淋巴结的方法通常是影像科医师逐层浏览每一幅图像,从中识别淋巴结的形状、界限及密度来判断,这种传统方式耗时较长且存在主观偏倚,导致     

Predefined vs data-guided training prescription based on autonomic nervous system variation: A systematic review

Monitoring variations in the functioning of the autonomic nervous system may help personalize training of runners and provide more pronounced physiological adaptations and performance improvements. We systematically reviewed the scientific literature comparing physiological adaptations and/or improvements in performance following training based on responses of the autonomic nervous system (ie, changes in heart rate variability) and predefined training. PubMed, SPORTDiscus, and Web of Science were searched systematically in July 2019. Keywords related to endurance, running, autonomic nervous system, and training. Studies were included if they (a) involved interventions consisting predominantly of running training; (b) lasted at least 3 weeks; (c) reported pre- and post-intervention assessment of running performance and/or physiological parameters; (d) included an experimental group performing training adjusted continuously on the basis of alterations in HRV and a control group; and (e) involved healthy runners. Five studies involving six interventions and 166 participants fulfilled our inclusion criteria. Four HRV-based interventions reduced the amount of moderate- and/or high-intensity training significantly. In five interventions, improvements in performance parameters (3000 m, 5000 m, Loadmax, Tlim) were more pronounced following HRV-based training. Peak oxygen uptake () and submaximal running parameters (eg, LT1, LT2) improved following both HRV-based and predefined training, with no clear difference in the extent of improvement in . Submaximal running parameters tended to improve more following HRV-based training. Research findings to date have been limited and inconsistent. Both HRV-based and predefined training improve running performance and certain submaximal physiological adaptations, with effects of the former training tending to be greater.     

中药生产过程质量控制关键技术研究进展

中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。     

How structural and functional MRI can inform dual-site tACS parameters: A case study in a clinical population and its pragmatic implications

BackgroundAbnormalities in frontoparietal network (FPN) were observed in many neuropsychiatric diseases including substance use disorders. A growing number of studies are using dual-site-tACS with frontoparietal synchronization to engage this network. However, a computational pathway to inform and optimize parameter space for frontoparietal synchronization is still lacking. In this case study, in a group of participants with methamphetamine use disorders, we proposed a computational pathway to extract optimal electrode montage while accounting for stimulation intensity using structural and functional MRI.MethodsSixty methamphetamine users completed an fMRI drug cue-reactivity task. Four main steps were taken to define electrode montage and adjust stimulation intensity using 4x1 high-definition (HD) electrodes for a dual-site-tACS; (1) Frontal seed was defined based on the maximum electric fields (EF) predicted by simulation of HD montage over DLPFC (F3/F4 in EEG 10–10), (2) frontal seed-to-whole brain context-dependent correlation was calculated to determine connected regions to frontal seeds, (3) center of connected cluster in parietal cortex was selected as a location for placing the second set of HD electrodes to shape the informed montage, (4) individualized head models were used to determine optimal stimulation intensity considering underlying brain structure. The informed montage was compared to montages with large electrodes and classic frontoparietal HD montages (F3-P3/F4-P4) in terms of tACS-induced EF and ROI-to-ROI task-based/resting-state connectivity.ResultsCompared to the large electrodes, HD frontoparietal montages allow for a finer control of the spatial peak fields in the main nodes of the FPN at the cost of lower maximum EF (large-pad/HD: max EF[V/m] = 0.37/0.11, number of cortical sub-regions that EF exceeds 50% of the max = 77/13). For defining stimulation targets based on EF patterns, using group-level head models compared to a single standard head model results in comparable but significantly different seed locations (6.43 mm Euclidean distance between the locations of the frontal maximum EF in standard-space). As expected, significant task-based/resting-state connections were only found between frontal-parietal locations in the informed montage. Cue-induced craving score was correlated with frontoparietal connectivity only in the informed montage (r = ?0.24). Stimulation intensity in the informed montage, and not in the classic HD montage, needs 40% reduction in the parietal site to reduce the disparity in EF between stimulation sites.ConclusionThis study provides some empirical insights to montage and dose selection in dual-site-tACS using individual brain structures and functions and proposes a computational pathway to use head models and functional MRI to define (1) optimum electrode montage for targeting FPN in a context of interest (drug-cue-reactivity) and (2) proper transcranial stimulation intensity.