智力和发展性残疾儿童青少年身体活动效益：基于ICF的系统综述

目的 基于《国际功能、残疾和健康分类》(ICF)构建智力和发展性残疾儿童青少年身体活动效益系统综述的范畴和PICO架构，探讨智力和发展性残疾儿童和青少年参加身体活动的健康效益。     

Shikonin from Chinese herbal medicine induces GSDME-controlled pyroptosis in tumor cells

ObjectiveTo investigate the potential anti-tumor mechanisms of naphthoquinone compound shikonin (SKN) extracted from the root of Chinese herbal medicine plant lithospermum (Lithospermum erythrorhizon Sieb. & Zucc.).MethodsWe first observed that SKN treatment led to swelling and bubbles in HeLa cells that were similar to the phenotype of cell pyroptosis. Subsequently, the HeLa cells experienced a pyroptotic process with SKN, and this was then assessed using lactate dehydrogenase (LDH) release and propidium iodide (PI)/Hoechst double staining experiments. Pyroptosis is defined as gasdermin-mediated programmed necroptosis. To identify the potential pyroptosis machinery, two strategies were utilized that included a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 screening experiment and a pyroptosis reconstitution assay executed by each of the five known gasdermins (GSDMA-E). Moreover, endogenous cleavage was also detected in a panel of tumor cell lines.ResultsCompared with the control, both the LDH release and PI/Hoechst double-staining experiments suggested that SKN induced perforation and enhancement of the permeability of the cell membranes that resulted in pyroptosis in HeLa cells (P = .028 and P = .032, respectively). In addition, the reconstitution assays in human embryonic kidney 293T (HEK-293T) cells and endogenous cleavage assays in HeLa cells indicated that the pyroptosis was controlled by GSDME. In addition, we also found SKN could trigger pyroptosis in a panel of tumor cell lines in which the cellular morphologies were proportional to the GSDME expression levels. Additionally, the cleavage of GSDME was also detected, and this was indicative of a similar GSDME-mediated mechanism.ConclusionOur study not only explained the molecular mechanism of cytotoxicity of SKN to various tumor cells, but also provided additional information for the potential clinical application of natural naphthoquinone compounds against cancer.     

Effect of chlorhexidine digluconate on antimicrobial activity,cell viability and physicochemical properties of three endodontic sealers

ObjectiveAssess the biological and physicochemical properties of AH Plus, BioRoot RCS and Pulp Canal Sealer (PCS) leachates with and without chlorhexidine (CHX).MethodsThe sealers were studied in no contact and 1-minute contact with CHX. For biological properties (antibacterial activity and cytotoxicity), leachates were formed in saline of freshly mixed, 1-, 7- and 28 days set sealers. The antibacterial properties of sealer leachates were investigated for planktonic and biofilm growth of E. faecalis, S. mutans, S.epidermidis and S.aureus. The 3-(4,5 dimethylthiazolyl-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate murine fibroblast cell viability after exposure to the leachates. The physical properties (water uptake, sorption, solubility, porosity, surface characteristics) of sealers and the pH of the immersion liquid (saline or distilled water) were also assessed over a 28-days period.ResultsCHX improved the antibacterial properties of the sealer leachates and reduced cell viability for all sealer leachates, except for freshly mixed PCS. BioRoot RCS leachates presented the highest antibacterial properties and cell viability with and without CHX contact. PCS was the material most affected by CHX in terms of physical properties, whereas for AH Plus, solubility was increased. CHX did not affect the physical properties of BioRoot RCS, except for solubility that was decreased. CHX contact did not change sealers’ alkalinity in distilled water whereas it increased it for AH Plus and BioRoot RCS in saline.SignificanceCHX improved the antibacterial efficacy of sealer leachates and either compromised or did not affect cell viability. CHX affected to various extent sealers’ physicochemical properties.     

Delineating the geographic context of physical activities: A systematic search and scoping review of the methodological approaches used in social ecological research over two decades

BackgroundThe social ecological approach suggests that the spatial context among other factors influence physical activity behavior. Ample research documents physical environmental effects on physical activity. Yet, to date inconsistent associations remain, which might be explained by conceptual and methodological challenges in measuring the spatial dimensions of health behavior. We review methods applied to measure the spatial contexts in the social ecological physical activity literature.MethodsOnline databases and selected reviews were used to identify papers published between 1990 and 2020. A total of 2167 records were retrieved, from which 412 studies that used physical activity as a primary outcome variable, included measures of the physical environment and applied the main principles of the social ecological approach, were included.ResultsSubjective approaches were the dominant method to capture the spatial context of physical activities. These approaches were applied in 67% (n=279) of the studies. From the objective approaches an administrative unit was most prevalent and was applied in 29% (n=118) of the studies. The most comprehensive objective spatial methods that capture the true environmental exposure, were used only in 2% (n=10) of the studies.ConclusionsCurrent social ecological physical activity research applies simple conceptualizations and methods of the spatial context. While conceptual and methodological concerns have been repeatedly expressed, no substantive progress has been made in the use of spatial approaches. To further our understanding on place effects on health, future studies should carefully consider the choice of spatial approaches, and their effect on study results.     

Effects of virtual Reality-Based Training and aerobic training on gaming disorder,physical activity,physical fitness,and anxiety: A randomized,controlled trial

Background and aimThe effects of physical activity and exercise on gaming disorder severity in individuals with gaming disorder are unknown. The present study aimed to address the empirical gap in the current literature by comparing the effects of virtual reality-based training (VRT) and aerobic training (AT) exercise programs on gaming disorder severity, physical activity, physical fitness, and anxiety versus control group.Materials and methodsForty-four young male adults (18–28 years) with gaming disorder and a sedentary lifestyle were included in the study. The primary outcomes of the study were changes in gaming disorder severity and physical activity, and secondary outcomes included changes in physical fitness and anxiety levels. The participants were randomly assigned to VRT (n = 15), AT (n = 14) and control (n = 15) groups. Training sessions were performed at 50–70% of the maximal heart rate. Exercise programs consisted of 6 weeks of training 3 times a week for 30 min.ResultsThere was a decrease in the severity of gaming disorder as well as an increase in the level of physical activity in the VRT and AT exercise groups compared to the control group. In addition, a reduction was observed in the gaming time and sedentary time in both exercise groups versus control group. VRT group experienced greater improvements in physical fitness parameters than the AT group.ConclusionVRT and AT were effective in reducing gaming time and the severity of gaming disorder in individuals with gaming disorder. The therapeutic effects of VRT and AT can be used for reducing the severity of gaming disorder.     

基于网络药理学和分子对接法探索复方一枝蒿颗粒治疗新型冠状病毒肺炎的潜在分子机制

目的 通过网络药理学及分子对接技术探寻复方一枝蒿颗粒治疗新型冠状病毒肺炎的作用机制。方法 应用TCMSP数据库、BATMAN-TCM数据库及文献收集复方一枝蒿颗粒活性成分及潜在靶点。通过TTD、GeneCards和OMMI数据库检索新型冠状病毒肺炎相关的靶点。将复方一枝蒿颗粒药物靶点和新型冠状病毒肺炎相关基因取交集，使用String数据库构建靶蛋白相互作用（PPI）网络。通过Cytoscape构建“药物–活性成分–靶点基因–疾病”网络。对交集靶点进行GO功能、KEGG通路富集分析。利用Autodock_vina软件对活性成分和靶点进行分子对接。结果 共筛选92个活性成分，1 627个靶点，新型冠状病毒肺炎疾病靶点464个，两者取交集筛选出87个潜在靶点。GO功能富集得到2 040个条目（P＜0.05），与病毒过程、参与共生相互作用的生物过程、活性氧代谢过程的调节、与宿主相互作用的生物过程、病毒生命周期、炎症反应的调节等生物学过程有关。KEGG通路分析共得到150条通路，与新冠肺炎密切相关的有人巨细胞病毒感染、结核、COVID-19、IL-17信号通路等。分子对接结果证实，筛选的靶点受体蛋白与活性成分可以较好地结合。结论 复方一枝蒿颗粒可通过多组分、多靶点和多途径的方式对新型冠状病毒肺炎产生治疗作用。     

School physical activity policies and associations with physical activity practices and behaviours: A systematic review of the literature

The development and implementation of school policies is considered a key strategy for the promotion of physical activity (PA) in children and adolescents. This study aimed to systematically review and synthesise existing literature focusing on the associations between formal written school-based PA policies and (a) school PA practices and (b) PA behaviours of school-aged children and adolescents. Fifty-one papers reporting on 52 studies met the eligibility criteria. All but two studies were from high income countries, most used cross-sectional designs and demonstrated fair methodological quality, and just over a third examined language aspects of policies. Findings predominantly indicated a lack of or inconclusive associations between the various characteristics examined and PA outcomes. Inconclusive associations were identified between both PA practice and behaviour outcomes and state level policies, policies focusing on PE and school-day PA, and in studies examining language aspects of policies. Inconclusive associations with both types of outcomes were more likely to be identified compared to a lack of associations in studies using self-report measures and in studies not providing information about the quality of exposure and outcome measures used. Overall, findings highlight the need for further research that acknowledges the complex relationship between school policies and PA outcomes and employs robust methodological approaches to enhance our understanding of this area.     

Longitudinal associations of subjectively-measured physical activity and screen time with cognitive development in young children

PurposeTo examine the longitudinal associations of subjectively-measured physical activity (PA) and screen time with multiple domains of cognitive development in a sample of young children.MethodsParticipants were 96 children (baseline age: 3.69 ± 0.78 years) and their parents from Edmonton, Canada in the Physical Activity and Cognition in Early Childhood (PACE) study. Different types of PA (organized, non-organized) and screen time (television viewing, video games) were measured using a parental questionnaire at baseline and at 6- and 12-month follow-ups. Total proxy-reported PA, total screen time, and meeting/not meeting the screen time recommendations (2–4 years: ≤1 h/d; 5 years: ≤2 h/d) of the Canadian 24-Hour Movement Guidelines were also calculated. Working memory (Nebraska Barnyard task) and inhibitory control (Fish-Shark Go/No-Go task) were assessed at the three time points. Intellectual ability, including language development, inductive reasoning, and perceptual speed, were assessed using the Woodcock-Johnson III test battery at 6- and 12-month follow-ups. Multilevel growth modeling was conducted.ResultsOrganized PA (B = 1.26; 95%CI: 0.19,2.33), non-organized PA (B = 0.89, 95%CI: 0.08, 1.71), and total proxy-reported PA (B = 1.03, 95%CI: 0.41,1.66) were positively associated with intellectual ability. In particular, positive associations in regard to language development and inductive reasoning were observed. As for screen time, most associations were not significant, except for positive associations of meeting the screen recommendation with intellectual ability (B = 3.19; 95%CI: 0.002,6.38) and language development (B = 4.32; 95%CI: 0.34,8.30).ConclusionFor young children, promoting PA participation in organized and non-organized activities, as well as meeting the screen time recommendations, appears important for cognitive development.     

基于网络药理学和实验验证探讨香菇多糖抑制三阴乳腺癌的作用机制

目的 基于网络药理学研究香菇多糖抑制三阴乳腺癌（TNBC）的作用机制并采用细胞和动物实验进行验证。方法 通过GeneCards数据库和DisGeNET数据库筛选与TNBC相关基因靶点，利用TCMID、PubChem、SwissTargetPrediction和GeneCards数据库查询香菇多糖相关基因靶点。使用Sangerbox软件进行基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）通路富集分析。结合STRING数据库与Cytoscape 3.7.0软件将共同靶点进行可视化处理，筛选核心靶点，构建"化合物-靶点-通路"网络。利用Metascape软件进行转录因子及相关调控基因特异富集。体外培养小鼠TNBC细胞4T1和人TNBC细胞MDA-MB-231，磺酰罗丹明B染色法观察香菇多糖（31.25、62.5、125、250、500、1 000μg·mL^-1）对细胞存活率的影响；健康雌性BABLC小鼠sc接种1×10⁶个4T1-Luc细胞构建TNBC模型，通过小动物活体成像系统观察香菇多糖（100、200 mg·kg^-1）对肿瘤生长的影响，实时荧光定量PCR （qRT-PCR）技术检测肿瘤组织信号转导和转录活化因子3（STAT3）和血管内皮生长因子A （VEGFA） mRNA表达。结果 数据库及软件分析得到香菇多糖治疗TNBC关键靶点52个，靶点主要涉及PI3K-Akt、AGE-RAGE、HIF-1、MAPK信号通路和肿瘤蛋白多糖相关通路，PPI分析得到VEGFA、STAT3、MAPK1、IL2、TNF、RELA、AKT1、MAPK3、BCL2L1和HSP90AA1 10个hub基因。与对照组比较，香菇多糖对4T1和MDA-MB-231细胞存活率均有显著抑制作用（P<0.05、0.01），且作用呈浓度相关性；在给药14、21d后，与模型组比较，香菇多糖能够剂量相关性地抑制小鼠TNBC肿瘤的生长，高剂量组差异显著（P<0.05、0.01），21 d抑制率达到（91.9±4.7）%；与对照组比较，香菇多糖给药后能够剂量相关性抑制STAT3和VEGFA的mRNA表达，高剂量组差异显著（P<0.05、0.01）。结论 香菇多糖可通过多靶点、多途径协同作用抑制TNBC的生长。