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Objective: To integrate pharmacovigilance and network toxicology methods to explore the potential adverse drug events (ADEs) and toxic mechanisms of selumetinib, and to provide a reference for quickly understanding the safety and toxicological mechanisms of newly marketed drugs., Methods: Taking selumetinib as an example, this study integrated pharmacovigilance methods based on real-world data and network toxicology methods to analyze its ADE and its potential toxicological mechanism. First, the ADE reports of selumetinib were extracted from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS), and the ADE signals were detected by reporting odds ratio (ROR) and UK medicines and healthcare products regulatory agency (MHRA) methods. The ADE signals were classified and described according to the preferred terms (PTs) and system organ class (SOC) derived from the Medical Dictionary for Regulatory Activities (MedDRA). The network toxicology method was used to analyze the toxicological mechanism of the interested SOCs. The specific steps included predicting the potential targets of selumetinib using TOXRIC, STITCH, ChEMBL, CTD, SwissTargetPreditcion, and Super-PRED databases, collecting the targets of SOC using GeneCards database, conducting protein-protein interaction (PPI) analysis through STRING database, conducting gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis through DAVID database, and testing the molecular affinity using AutoDock software., Results: A total of 1388 ADE reports related to selumetinib were extracted, and 53 positive signals were detected by ROR and MHRA methods, of which 20 signals were not mentioned in the package insert, including ingrowing nail, hyperphosphatemia, cardiac valve disease, hematuria, neutropenia, etc. Analysis of the toxicological mechanism of six SOCs involved in positive ADE signals revealed that the key targets included EGFR, STAT3, AKT1, IL6, BCL2, etc., and the key pathways included PI3K/Akt pathway, apoptosis, ErbB signaling pathway, and EGFR tyrosine kinase inhibitor resistance, etc. Molecular docking assays showed spontaneous binding of selumetinib to key targets in these pathways., Conclusion: The pharmacovigilance analysis identified some new potential ADEs of selumetinib, and the network toxicology analysis showed that the toxic effects of selumetinib may be related to PI3K/Akt pathway, apoptosis, ErbB signaling pathway, EGFR tyrosine kinase inhibitor resistance and other pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiong, Lei, Wang, Zhang, Liu, Wang, Liu and Lai.)

Background: The increase in sedentary behavior (SB) in children and adolescents is one of the major threats to global public health, and the relationship between physical activity (PA) and SB has always been a key topic., Methods: The literature search was conducted through PubMed, Web of Science, CNKI, Wanfang, and Scopus, and 121 pieces of literature were included in this study after screening and evaluation., Results: (1) SB caused by screen time such as mobile phones and TVs has varying degrees of negative impact on obesity, cardiovascular metabolism, skeletal muscle development, and cognitive, and psychological disorders in children and adolescents. (2) Regular physical activity could effectively prevent, offset, or improve the harm of SB to the physical and mental health of children and adolescents, mainly by reducing the incidence of obesity, and cardiovascular and metabolic risks, promoting skeletal muscle development, and improving cognitive function and mental health. (3) The mechanism of physical activity to prevent or ameliorate the harm of SB was relatively complex, mainly involving the inhibition or activation of neurobiomolecules, the improvement of blood and cell metabolic factors, and the enhancement of brain functional connectivity., Conclusions: Children and adolescents should avoid excessive SB, and through a variety of moderate to vigorous physical activity (MVPA) to replace or intermittent SB, which could effectively prevent or improve the harm of SB to physical and mental health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Liu, Zhang and Luo.)

Ethnopharmacological Relevance: Liver fibrosis (LF) is a common reversible consequence of chronic liver damage with limited therapeutic options. Yinchen Gongying decoction (YGD) composed of two homologous plants: (Artemisia capillaris Thunb, Taraxacum monochlamydeum Hand.-Mazz.), has a traditionally application as a medicinal diet for acute icteric hepatitis. However, its impact on LF and underlying mechanisms remain unclear., Aim of the Study: This study aims to assess the impact of YGD on a carbon tetrachloride (CCl 4 ) induced liver fibrosis and elucidate its possible mechanisms. The study seeks to establish an experimental foundation for YGD as a candidate drug for hepatic fibrosis., Materials and Methods: LC-MS/MS identified 11 blood-entry components in YGD, and network pharmacology predicted their involvement in the FoxO signaling pathway, insulin resistance, and PI3K-AKT signaling pathway. Using a CCl 4 -induced LF mouse model, YGD's protective effects were evaluated in comparison to a positive control and a normal group. The underlying mechanisms were explored through the assessments of hepatic stellate cells (HSCs) activation, fibrotic signaling, and inflammation., Results: YGD treatment significantly improved liver function, enhanced liver morphology, and reduced liver collagen deposition in CCl 4 -induced LF mice. Mechanistically, YGD inhibited HSC activation, elevated MMPs/TIMP1 ratios, suppressed the FoxO1/TGF-β1/Smad2/3 and YAP pathways, and exhibited anti-inflammatory and antioxidant effects. Notably, YGD improved the insulin signaling pathway., Conclusion: YGD mitigates LF in mice by modulating fibrotic and inflammatory pathways, enhancing antioxidant responses, and specifically inhibiting FoxO1/TGF-β1/Smad2/3 and YAP signal pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Theoretical studies have suggested that the integration of sports and medicine with one another could positively affect children's health. By monitoring the variation characteristics of children's sleep, body mass index (BMI), and heart rate variability (HRV), we explored and compared the influences of and differences between two interventions - physical exercise and an intervention integrating sports and medicine - on improving children's health., Methods: We conducted a randomised controlled study, where we randomly divided 136 children into the physical exercise group (PEG), the integration of sports and medicine group (ISMG), and the control group. We measured sleep, BMI, and HRV at baseline and week eight., Results: After the eight-week intervention, the sleep scores in the PEG and the ISMG were significantly lower than in the control group, while the scores in the ISMG were significantly lower than in the PEG. After the eight-week intervention, the BMI of both the PEG and the ISMG was significantly lower than that of the control group, without a significand difference between the two intervention groups. After the eight-week intervention, the standard deviation of normal-to-normal intervals (SDNN), root mean square differences of the standard deviation (RMSSD), low-frequency of normal (LFn), and high-frequency of normal (HFn) in the PEG and the ISMG were significantly higher than those in the control group, again without a significant difference between the two intervention groups. After intervention, sleep, BMI, and HRV of the three groups were correlated with one another to different degrees, but the correlation coefficient of the two exercise groups was higher., Conclusions: Based on the interventions, we observed a significant correlation between sleep, BMI, and HRV in children. Regular physical exercise or an intervention integrating sports and medicine could synergistically improve sleep, BMI, and HRV in this population, with the latter having a better effect on improving sleep quality., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Objective: To systematically evaluate the impact of physical exercise intervention on children with acute lymphoblastic leukemia (ALL) during the treatment and rehabilitation consolidation periods., Method: Randomized controlled trials (RCTs) were retrieved from PubMed, Scopus, Web of Science, CNKI, and Cochrane databases, with a search time range from database establishment to September 1, 2023. The quality of the included RCTs was evaluated using the Cochrane risk assessment tool, and a systematic evaluation was conducted using RevMan 5.4. The study has been registered with INPLASY (registration number: 202390100)., Result: A total of 12 RCTs including 423 subjects was included. The meta-analysis results showed that long-term exercise intervention can effectively improve the endurance performance (SMD = 1.37, 95% CI 0.45 to 2.29, p = 0.004), functional mobility (MD =  - 1.17, 95% CI - 1.85 to - 0.49, p = 0.0008), cancer-related fatigue (CRF) (MD =  - 1.25, 95% CI - 1.69 to - 0.80, p < 0.00001), and quality of life (QOL) (MD = 4.93, 95% CI 1.80 to 8.05, p = 0.002) of ALL children during the treatment and rehabilitation consolidation periods. Its promoting effect on the muscle strength (SMD = 0.53, 95% CI - 0.33 to 1.39, p = 0.23) and bone mineral density (BMD) (SMD = 0.48, 95% CI 0.20 to 0.77, p = 0.05) of the subjects was not significant. Further meta-analysis showed that exercise intervention with a duration of less than 1 year (SMD = 0.91, 95% CI 0.55 to 1.28, p < 0.00001) rather than more than 1 year (SMD =  - 0.16, 95% CI - 0.61 to 0.29, p = 0.49) can effectively reduce subject BMD, while in terms of strength, exercise intervention can effectively improve strength during the treatment period (SMD = 0.97, 95% CI 0.40 to 1.54, p = 0.0008) rather than the consolidation period (SMD =  - 0.27, 95% CI - 1.08 to 0.53, p = 0.51)., Conclusion: Long-term regular exercise can effectively improve the endurance, functional mobility, CRF, and QOL of children with ALL in the rehabilitation and treatment consolidation stages. Their strength and BMD may be influenced by the timing of treatment and the intervention cycle, respectively. Considering the limited number of included literature and the instability of some outcome indicators, it is necessary to design more comprehensive and rigorous high-quality RCTs in the future to test the exercise efficacy of ALL children., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The degree of aging in China is deepening, leading to cognitive decline and seriously affecting the health status of the elderly. This article explores the benefits of exergames in improving cognitive function in older adults through a literature review, with aim of contributing to the development of healthy aging., Methods: Using PubMed, Web of Science, CNKI, dimensional spectrum, search for research papers from 2005 to April 2023 by using keywords such as a somatosensory game, cognitive function, execute function, working memory, aged and suppression control. PEDro Scale was used to check the quality of the literature., Results: A total of 16 papers were included in the review. Exergames improve the executive function of the elderly and support the relationship between exergames and cognitive performance in older adults. From a mechanistic perspective, somatosensory play promotes signal transduction of brain neurotrophin, thereby protecting the structure and function of neurons in specific brain regions and delays the decline of executive function in older adults as much as possible., Conclusions: It is recommended to use exergames as an intervention measure for the physical and mental health preservation of older adults. Suggest adopting personalised exergames in the future to explore the impact of cognitive and physical functions in elderly people, as well as measurable changes in brain structure., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

This study investigates the relationship between political connections and firm financial performance during the COVID-19 pandemic. Using a difference-in-differences methodology, we found that politically connected enterprises paid more taxes, employed more employees, and suffered financial performance. This study enriches the literature on the impact of COVID-19 on enterprises and provides suggestions for regulators., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Elsevier B.V. All rights reserved.)

Purpose: It is well known that there is an obvious 24 h diurnal variation in the individual's mood state and physiological activity, and training at different times of the day may lead to different exercise performance and metabolic outcomes; however, the time-dependent effect of emotional state on physical activity and the influence of its circadian rhythm on exercise performance are still not comprehensively understood. Based on this, this study summarizes the rhythmic experimental research in the field of sport psychology, and it aims to provide the basis for coaches to optimize sports training scientifically and to improve the mental health of the related crowd to the greatest extent., Methods: The systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Web of Science, Medline, and CNKI databases for relevant literature; the search scope was research before September 2022., Results: 13 studies comprising 382 subjects examined the effects of exercise timing on mood responses to exercise or the effects of circadian rhythms of mood on exercise performance, which included 3 RCTs and 10 Non-RCTs. The subjects included athletes (both training or retired), college students, and healthy adults. Two studies were designed for long-term exercise intervention (aerobic training and RISE) and the rest for acute intervention (CrossFit training, HIIT, aerobic combined with muscle conditioning training, constant power exhaustion training, and cycling) or physical function tests (RSA + BTV tests, 30 s Wingate test, muscle strength + CMJ + swimming performance test, RSSJA, shooting accuracy tests + 10 × 20 m dribbling sprint, 200 m time trials). All trials reported specific exercise timing; of these, 10 studies reported subjects' chronotypes, most commonly using the MEQ scale, while 1 recorded with the CSM. Mood responses were assessed with the POMS scale in 10 studies, while 3 other studies used the UMACL, PANAS, and GAS scales, respectively., Conclusion: There was much inconsistency between the results, with subjects likely to be exposed to more sunlight (the main timing factor of the circadian rhythm) during early morning exercise, resulting in feeling more positive emotions; however, following a night's rest, delayed responses and poor functioning of the various organ systems of the human body may also lead to higher feelings of fatigue and negative emotions indirectly. Conversely, for athletes, their physical function tests are also more susceptible to the circadian rhythm of emotions, suggesting the importance of synchronizing them. In addition, night owls' emotional state during physical activity seems to be more susceptible to exercise timing than that of early birds. In order to achieve the best emotional state, it is suggested that night owls arrange courses in the afternoon or evening in future training.

Objective: To understand the mechanism of dual activation of the brain and heart in pistol athletes during shooting performances, through synchronized monitoring of electroencephalogram (EEG) and electrocardiogram (ECG)., Methods: Eighteen adolescents air pistol athletes were placed in a simulated competition environment and performed 40 self-paced shooting tasks, and simultaneously monitored the athletes' EEG, ECG, and shooting performance during the preparation period., Results: (1) In the successful performance, the power values of the alpha wave of the athlete's T7 area showed a significant upward trend 6 s before the shot, but there was no significant change in the alpha wave in the T8 area. In the failure performance, the alpha wave in the T7 and T8 areas did not change significantly 6 s before the shot. (2) The Fz theta wave power value of athletes in successful performance showed a significant upward trend in the 6 s before firing, and in the failure performance, it showed an "inverted U-shaped" characteristic of rising first and then decreasing. (3) Regardless of whether it was a success or a failure, the SMR wave power value of the athlete's central area has no significant change before the shot. (4) At 6 s before the shot, the athlete's heart rate and R-R interval (RRI) in the successful performance showed a significant decline and rise, respectively, but there was no significant change in the failure performance. (5) Approaching the firing time, the athletes' EEG and ECG have a more significant correlation in successful performance and a more synchronized trend, while the correlation was lower in failure performance., Conclusions: The psychophysiological state of young air pistol athletes was closely related to shooting performance. If the brain-cardiac system maintains a benign dual activation level during the aiming and firing period, it will be beneficial to the improvement of shooting performance, otherwise, it was easy to reduce shooting performance., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cerebral vascular accident (CVA) is one of the main causes of chronic disability, and it affects the function of daily life, so it is increasingly important to actively rehabilitate patients' physical functions. The research confirmed that the nutrition supplement strategy is helpful to improve the effect of sports rehabilitation adaptation and sports performance. The patients with chronic strokes (whose strokes occur for more than 6 months) have special nutritional needs while actively carrying out rehabilitation exercises, but there are still few studies to discuss at present. Therefore, this paper will take exercise rehabilitation to promote muscle strength and improve muscle protein synthesis as the main axis and, through integrating existing scientific evidence, discuss the special needs of chronic stroke patients in rehabilitation exercise intervention and nutrition supplement one by one. At the same time, we further evaluated the physiological mechanism of nutrition intervention to promote training adaptation and compared the effects of various nutrition supplement strategies on stroke rehabilitation. Literature review pointed out that immediately supplementing protein nutrition (such as whey protein or soybean protein) after resistance exercise or endurance exercise can promote the efficiency of muscle protein synthesis and produce additive benefits, thereby improving the quality of muscle tissue. Recent animal research results show that probiotics can prevent the risk factors of neural function degradation and promote the benefits of sports rehabilitation. At the same time, natural polyphenols (such as catechin or resveratrol) or vitamins can also reduce the oxidative stress injury caused by animal stroke and promote the proliferation of neural tissue. In view of the fact that animal research results still make up the majority of issues related to the role of nutrition supplements in promoting nerve repair and protection, and the true benefits still need to be confirmed by subsequent human studies. This paper suggests that the future research direction should be the supplement of natural antioxidants, probiotics, compound nutritional supplements, and integrated human clinical research.

Purpose: Physical activity is an important non-drug-related method to prevent and treat cardiovascular diseases, but how exercise duration affects the cardiovascular metabolic risk factors in adults remains uncertain. This review systematically examines the time-dependent effects of physical activity on cardiovascular risk factors in adults and aims to further the understanding of the temporal therapeutics of exercise., Methods: Following the PRISMA guidelines, the PubMed, Web of Science, EMBASE, and CNKI databases were systematically searched for relevant scientific studies from January 2000 to June 2022., Results: A total of 16 studies met the inclusion criteria and were included in the systematic review. The sample size ranged from 11-275 participants who were diagnosed with obesity, hypertension, diabetes mellitus type 2 (T2DM), and Coronary Heart Disease (CAD), while the subjects in four studies did not report any metabolic or cardiovascular disease. Four studies conducted trials of acute exercise interventions, while the remaining intervention periods ranged from 12 days to 12 weeks. The exercise interventions included aerobic training, resistance training, aerobic training that was combined with resistance training, compound exercise, and high-intensity interval exercise, and the training frequency varied from 2-5 times/week., Conclusions: Overall, this review found some evidence that the cardiovascular risk factors in adults may be time-dependent in response to physical activity. However, it is limited by the small sample size for each of the outcomes and several methodological issues, leading to poor comparability between studies. A randomized controlled trial with a larger sample size is supposed to be designed for the relevant population to completely test whether synchronizing the exercise time point in the day with the individual's circadian rhythm can amplify the benefits of the exercise for improving cardiovascular health.

In this study, the blood test index, demographic data, and health promotion behavior of adolescents were analyzed to provide a reference for early prevention and treatment of physical decline and abnormal biochemical indexes of adolescents. Using a cross-sectional study design, 1,436 valid samples were obtained by stratified random sampling, and the data were processed by SPSS21.0 statistical analysis software. The results showed that the overall health-promoting lifestyle of adolescents was good, and the interpersonal support behavior was the best, and the health responsibility and sports participation behavior were the worst; the interpersonal support and sports participation behavior of adolescents with normal weight were significantly better than those with overweight or light weight, while the overall health-promoting behavior of adolescents with high fasting blood glucose (FBG) before meals was poor, those with high glutamate pyruvate transaminase (GPT) had poor nutritional behavior and health responsibility behavior, while those with high uric acid (UA) had poor interpersonal support and stress coping behavior. The overweight rate and abnormal detection rate of UA and triglyceride (TG) in boys were significantly higher than those in girls, and the higher BMI of teenagers, the higher abnormal detection rate of GPT, UA, and TG, the better nutritional behavior, health responsibility behavior, and sports participation behavior, the lower abnormal detection rate of GPT, UA, and TG; the higher education level of parents, the better teenagers' sports participation and health responsibility behavior, the lower the incidence of overweight, the more time they spend playing online games and drinking sugary drinks on weekdays (or holidays), the higher the incidence of overweight., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Peng, Yin, Wang, Zhang, Liu, Yang and Luo.)

Objectives: To explore the current situation of knowledge, attitude, and behavior about the correct use of analgesics among adolescents in Western Sichuan and Chongqing and its related factors and to provide a reference for health promotion schools to promote correct medication education and relevant policy-making., Methods: A questionnaire survey was conducted among senior high school students in Sichuan and Chongqing by stratified random sampling. A total of 48 classes were surveyed and 2,280 valid questionnaires were obtained. Descriptive analysis, mean value comparison, and multiple regression analysis were conducted for the data using SPSS17.0 statistical analysis software., Results: (1) It showed that 65.5% of the students used methods other than drugs to deal with pain, 52.9% of the students took analgesics prescribed by doctors, more than 60% of the students got information about pain treatment from medical professionals or their families members, 71.6% of the students read the use label when using drugs, and only about 20% of the students knew the dosage and side effects of analgesics. (2) The higher the grade, the higher the proportion of students who often take analgesics prescribed by doctors, the higher the proportion of students who use methods other than drugs to relieve pain, the higher the proportion of students who read the label of analgesics, and the more information sources are introduced by family members. The better the knowledge, attitude, efficacy, and accomplishment of using analgesics, the better the behavior of using analgesics correctly. (3) Students who had taken analgesics provided by their family or friends and who had taken anti-inflammatory analgesics did not perform well in the correct use of analgesics., Conclusion: The key factors that influence the correct drug use behavior of middle school students are their correct drug use literacy, efficacy, attitude, and reading of analgesics. Therefore, schools should strengthen cooperation with pharmacists and encourage the promotion of parent-child education activities of correct drug use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yin, Wang, Zhang, Liu, Li and Luo.)