Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery ...Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.展开更多
There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 poly...There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.展开更多
The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a pati...The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.展开更多
To solve problems of poor security guarantee and insufficient training efficiency in the conventional reinforcement learning methods for decision-making,this study proposes a hybrid framework to combine deep reinforce...To solve problems of poor security guarantee and insufficient training efficiency in the conventional reinforcement learning methods for decision-making,this study proposes a hybrid framework to combine deep reinforcement learning with rule-based decision-making methods.A risk assessment model for lane-change maneuvers considering uncertain predictions of surrounding vehicles is established as a safety filter to improve learning efficiency while correcting dangerous actions for safety enhancement.On this basis,a Risk-fused DDQN is constructed utilizing the model-based risk assessment and supervision mechanism.The proposed reinforcement learning algorithm sets up a separate experience buffer for dangerous trials and punishes such actions,which is shown to improve the sampling efficiency and training outcomes.Compared with conventional DDQN methods,the proposed algorithm improves the convergence value of cumulated reward by 7.6%and 2.2%in the two constructed scenarios in the simulation study and reduces the number of training episodes by 52.2%and 66.8%respectively.The success rate of lane change is improved by 57.3%while the time headway is increased at least by 16.5%in real vehicle tests,which confirms the higher training efficiency,scenario adaptability,and security of the proposed Risk-fused DDQN.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitatio...Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.展开更多
Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiqu...Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.展开更多
Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase bra...Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase brain-derived neurotrophic factor levels in children and adolescents, the effects of specific types of exercise on brain-derived neurotrophic factor levels are still controversial. To address this issue, we used meta-analytic methods to quantitatively evaluate, analyze, and integrate relevant studies. Our goals were to formulate general conclusions regarding the use of exercise interventions, explore the physiological mechanisms by which exercise improves brain health and cognitive ability in children and adolescents, and provide a reliable foundation for follow-up research. We used the Pub Med, Web of Science, Science Direct, Springer, Wiley Online Library, Weipu, Wanfang, and China National Knowledge Infrastructure databases to search for randomized controlled trials examining the influences of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents. The extracted data were analyzed using Review Manager 5.3. According to the inclusion criteria, we assessed randomized controlled trials in which the samples were mainly children and adolescents, and the outcome indicators were measured before and after the intervention. We excluded animal experiments, studies that lacked a control group, and those that did not report quantitative results. The mean difference(MD;before versus after intervention) was used to evaluate the effect of exercise on brain-derived neurotrophic factor levels in children and adolescents. Overall, 531 participants(60 children and 471 adolescents, 10.9–16.1 years) were included from 13 randomized controlled trials. Heterogeneity was evaluated using the Q statistic and I^(2) test provided by Review Manager software. The meta-analysis showed that there was no heterogeneity among the studies(P = 0.67, I^(2) = 0.00%). The combined effect of the interventions was significant(MD = 2.88, 95% CI: 1.53–4.22, P < 0.0001), indicating that the brain-derived neurotrophic factor levels of the children and adolescents in the exercise group were significantly higher than those in the control group. In conclusion, different types of exercise interventions significantly increased brain-derived neurotrophic factor levels in children and adolescents. However, because of the small sample size of this meta-analysis, more high-quality research is needed to verify our conclusions. This metaanalysis was registered at PROSPERO(registration ID: CRD42023439408).展开更多
Due to the numerous variables to take into account as well as the inherent ambiguity and uncertainty,evaluating educational institutions can be difficult.The concept of a possibility Pythagorean fuzzy hypersoft set(pP...Due to the numerous variables to take into account as well as the inherent ambiguity and uncertainty,evaluating educational institutions can be difficult.The concept of a possibility Pythagorean fuzzy hypersoft set(pPyFHSS)is more flexible in this regard than other theoretical fuzzy set-like models,even though some attempts have been made in the literature to address such uncertainties.This study investigates the elementary notions of pPyFHSS including its set-theoretic operations union,intersection,complement,OR-and AND-operations.Some results related to these operations are also modified for pPyFHSS.Additionally,the similarity measures between pPyFHSSs are formulated with the assistance of numerical examples and results.Lastly,an intelligent decision-assisted mechanism is developed with the proposal of a robust algorithm based on similarity measures for solving multi-attribute decision-making(MADM)problems.A case study that helps the decision-makers assess the best educational institution is discussed to validate the suggested system.The algorithmic results are compared with the most pertinent model to evaluate the adaptability of pPyFHSS,as it generalizes the classical possibility fuzzy set-like theoretical models.Similarly,while considering significant evaluating factors,the flexibility of pPyFHSS is observed through structural comparison.展开更多
Accurate medical diagnosis,which involves identifying diseases based on patient symptoms,is often hindered by uncertainties in data interpretation and retrieval.Advanced fuzzy set theories have emerged as effective to...Accurate medical diagnosis,which involves identifying diseases based on patient symptoms,is often hindered by uncertainties in data interpretation and retrieval.Advanced fuzzy set theories have emerged as effective tools to address these challenges.In this paper,new mathematical approaches for handling uncertainty in medical diagnosis are introduced using q-rung orthopair fuzzy sets(q-ROFS)and interval-valued q-rung orthopair fuzzy sets(IVq-ROFS).Three aggregation operators are proposed in our methodologies:the q-ROF weighted averaging(q-ROFWA),the q-ROF weighted geometric(q-ROFWG),and the q-ROF weighted neutrality averaging(qROFWNA),which enhance decision-making under uncertainty.These operators are paired with ranking methods such as the similarity measure,score function,and inverse score function to improve the accuracy of disease identification.Additionally,the impact of varying q-rung values is explored through a sensitivity analysis,extending the analysis beyond the typical maximum value of 3.The Basic Uncertain Information(BUI)method is employed to simulate expert opinions,and aggregation operators are used to combine these opinions in a group decisionmaking context.Our results provide a comprehensive comparison of methodologies,highlighting their strengths and limitations in diagnosing diseases based on uncertain patient data.展开更多
Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective f...Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.展开更多
BACKGROUND Understanding a patient's clinical status and setting priorities for their care are two aspects of the constantly changing process of clinical decision-making.One analytical technique that can be helpfu...BACKGROUND Understanding a patient's clinical status and setting priorities for their care are two aspects of the constantly changing process of clinical decision-making.One analytical technique that can be helpful in uncertain situations is clinical judgment.Clinicians must deal with contradictory information,lack of time to make decisions,and long-term factors when emergencies occur.AIM To examine the ethical issues healthcare professionals faced during the coronavirus disease 2019(COVID-19)pandemic and the factors affecting clinical decision-making.METHODS This pilot study,which means it was a preliminary investigation to gather information and test the feasibility of a larger investigation was conducted over 6 months and we invited responses from clinicians worldwide who managed patients with COVID-19.The survey focused on topics related to their professional roles and personal relationships.We examined five core areas influencing critical care decision-making:Patients'personal factors,family-related factors,informed consent,communication and media,and hospital administrative policies on clinical decision-making.The collected data were analyzed using the χ^(2) test for categorical variables.RESULTS A total of 102 clinicians from 23 specialties and 17 countries responded to the survey.Age was a significant factor in treatment planning(n=88)and ventilator access(n=78).Sex had no bearing on how decisions were made.Most doctors reported maintaining patient confidentiality regarding privacy and informed consent.Approximately 50%of clinicians reported a moderate influence of clinical work,with many citing it as one of the most important factors affecting their health and relationships.Clinicians from developing countries had a significantly higher score for considering a patient's financial status when creating a treatment plan than their counterparts from developed countries.Regarding personal experiences,some respondents noted that treatment plans and preferences changed from wave to wave,and that there was a rapid turnover of studies and evidence.Hospital and government policies also played a role in critical decision-making.Rather than assessing the appropriateness of treatment,some doctors observed that hospital policies regarding medications were driven by patient demand.CONCLUSION Factors other than medical considerations frequently affect management choices.The disparity in treatment choices,became more apparent during the pandemic.We highlight the difficulties and contradictions between moral standards and the realities physicians encountered during this medical emergency.False information,large patient populations,and limited resources caused problems for clinicians.These factors impacted decision-making,which,in turn,affected patient care and healthcare staff well-being.展开更多
Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity ...Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity rats were randomlydivided into three groups(n=10):normal oxygen concentration quiet group(N),hypoxia quiet group(H),hypoxic exercise group(HE).Exercise training on the horizontal animal treadmill for 1 h/d,5 d/week for a total of 4 week,and the intensity of horizontaltreadmill training was 20 m/min(hypoxic concentration was 13.6%).Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done.And the serum concentrations of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high-densitylipoprotein cholesterol(HDL-C)levels were detected.RT-PCR and Western Blot were used to detect the levels of miR-27,PPARγ,CYP7A1 and CD36.Results Hypoxic exercise decreased the expression levels of miR-27 in the obese rats’liver,however,theexpression level of PPARγwas gradually increased.The expression levels of miR-27 in HE group were significantly lower than Ngroup(P<0.05).The expression levels of PPARγmRNA in N group were significantly lower than H group(P<0.05),especially lowerthan HE group(P<0.01).The protein expression of PPARγprotein in N group was significantly lower than that other groups(P<0.01).The expression of lipid metabolism-related genes and proteins increased in the obese rats’liver.The expression of CYP7A1mRNA in N group was significantly lower than H group(P<0.05),especially lower than HE group(P<0.01).The expression ofCYP7A1 protein in the obese rats’liver in N group was extremely lower than H group and HE group(P<0.01).The proteinexpression of CD36 in N group was significantly lower than that in HE group(P<0.05).Hypoxia exercise improved the relatedphysiological and biochemical indexes of lipid metabolism disorder.The perirenal fat weight of obese rats in HE group wasextremely lower than N group and H group(P<0.01),and the perirenal fat weight in N group was significantly higher than H group(P<0.05).The epididymal fat weight in N group was significantly higher than H group(P<0.05),and extremely higher than HEgroup(P<0.01).The Lee’s index in HE group was extremely lower than N group and H group(P<0.01).The serum concentration ofTC in obese rats in HE group was extremely lower than N group and H group(P<0.01).The serum concentration of TG in HE groupwas extremely lower than N group and H group(P<0.01).The serum concentration of LDL-C in N group was extremely higher thanHE group(P<0.01).The serum concentration of HDL-C in N group was extremely lower than H group(P<0.01).Conclusion Hypoxiaand hypoxia exercise may negatively regulate the levels of PPARγby inhibiting miR-27 in the obese rats’liver,thereby affecting theexpression of downstream target genes CYP7A1 and CD36,and promoting cholesterol,fatty acid oxidation and HDL-C transport inthe liver,and ultimately the lipid levels in obese rats were improved.The effect of hypoxia exercise on improving blood lipid isbetter than simple hypoxia intervention.展开更多
The benefits of regular physical activity are well known.Yet,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary setting.To investigate the incorporat...The benefits of regular physical activity are well known.Yet,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary setting.To investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MSK)anatomy course material.These synchronous sessions were co-taught by a group fitness instructor and an anatomy instructor.The fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously covered.After the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MSK anatomy knowledge,PA levels,and mental wellbeing.Thirty participants completed surveys;a majority agreed that the classes increased understanding of MSK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce stress.The majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social connectedness.Overall,medical students saw benefit in PA based interventions to supplement MSK course concepts.Along with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.展开更多
Objectives:Aerobic exercise training can increase skeletal muscle mitochondrial content.Supine exercise training with legs above the heart potentially augments these increases.However,the impact of supine exercise tra...Objectives:Aerobic exercise training can increase skeletal muscle mitochondrial content.Supine exercise training with legs above the heart potentially augments these increases.However,the impact of supine exercise training on mitochondrial biogenesis and cardiovascular adaptations remains unclear.Methods:In this single-centred,randomized,parallel arm trial,19 recreationally active individuals underwent seven sessions of either supine with legs up(SUP;n=9,6 females)or upright with legs down(UP;n=10,7 females)aerobic training on a recumbent bike at 71±7%and 71±2%of peak work rate(WRpeak),respectively.The study aimed to test the effects of training with decreased muscle oxygenation on indices of muscle mitochondrial remodelling.Secondary outcomes included exercise performance,muscle oxygenation,and cardiovascular responses.Results:Secondary outcomes revealed significant interaction effects for time to fatigue(TTF)and WRpeak in the SUP group during supine testing,suggesting enhanced exercise tolerance and performance.No between group interaction effects were observed for upright testing.No clear effects on mitochondrial biogenesis were observed based on expression of mitochondrial protein subunits and transcriptional regulators.Acutely,HRpeak was lower during the SUP Test compared to the UP Test.No central cardiovascular adaptations were observed following training.Conclusions:Our exploratory analyses showed that supine aerobic training more effectively improves supine exercise tolerance and performance compared with upright training,despite no differences in measured proteins related to mitochondrial biogenesis.Further research is needed to elucidate the mechanisms underlying these postural-specific training effects.Registration:clinicaltrials.gov:NCT04151095.展开更多
Background While Nordic hamstring exercise(NHE)training has been shown to reduce hamstring strains,the muscle-specific adaptations to NHE across the 4 hamstrings remain unclear.This study investigates architectural an...Background While Nordic hamstring exercise(NHE)training has been shown to reduce hamstring strains,the muscle-specific adaptations to NHE across the 4 hamstrings remain unclear.This study investigates architectural and microstructural adaptations of the biceps femoris short head(BFsh),biceps femoris long head(BFlh),semitendinosus(ST),and semimembranosus(SM)in response to an NHE intervention.Methods Eleven subjects completed 9 weeks of supervised NHE training followed by 3 weeks of detraining.Magnetic resonance imaging was performed at pre-training,post-training,and detraining to assess architectural(volume,fiber tract length,and fiber tract angle)and microstructural(axial(AD),mean(MD),radial(RD)diffusivities,and fractional anisotropy(FA))parameters of the 4 hamstrings.Results NHE training induced significant but non-uniform hamstring muscle hypertrophy(BFsh:22%,BFlh:9%,ST:26%,SM:6%)and fiber tract length increase(BFsh:11%,BFlh:7%,ST:18%,SM:10%).AD(5%),MD(4%),and RD(5%)showed significant increases,but fiber tract angle and FA remained unchanged.After detraining,only ST showed a significant reduction(8%)in volume,which remained higher than the pre-training value.While fiber tract lengths returned to baseline,AD,MD,and RD remained higher than pre-training levels for all hamstrings.Conclusion The 9-week NHE training substantially increased hamstring muscle volume with greater hypertrophy in ST and BFsh.Hypertrophy was accompanied by increases in fiber tract lengths and cross-sections(increased RD).After 3 weeks of detraining,fiber tract length gains across all hamstrings declined,emphasizing the importance of sustained training to maintain all the protective adaptations.展开更多
Background:Exercise induces molecular changes that involve multiple organs and tissues.Moreover,these changes are modulated by various exercise parameters—such as intensity,frequency,mode,and duration—as well as by ...Background:Exercise induces molecular changes that involve multiple organs and tissues.Moreover,these changes are modulated by various exercise parameters—such as intensity,frequency,mode,and duration—as well as by clinical features like gender,age,and body mass index(BMI),each eliciting distinct biological effects.To assist exercise researchers in understanding these changes from a comprehensive perspective that includes multiple organs,diverse exercise regimens,and a range of clinical features,we developed Exercise Regulated Genes Database(ExerGeneDB),a database of exercise-regulated differential genes.Methods:ExerGeneDB aggregated publicly available exercise-related sequencing datasets and subjected them to uniform quality control and preprocessing.The data,encompassing a variety of types,were organized into a specialized database of exercise-regulated genes.Notably,Exer-GeneDB conducted differential analyses on this collected data,leveraging curated clinical information and accounting for important factors such as gender,age,and BMI.Results:ExerGeneDB has assembled 1692 samples from rats and mice as well as 4492 human samples.It contains data from various tissues and organs,such as skeletal muscle,blood,adipose tissue,intestine,heart,liver,spleen,lungs,kidneys,brain,spinal cord,bone marrow,and bones.ExerGeneDB features bulk ribonucleic acid sequencing(RNA-seq)(including non-coding RNA(ncRNA)and protein-coding RNA),microarray(including ncRNA and protein-coding RNA),and single cell RNA-seq data.Conclusion:ExerGeneDB compiles and re-analyzes exercise-related data with a focus on clinical information.This has culminated in the crea-tion of an interactive database for exercise regulation genes.The website for ExerGeneDB can be found at:https://exergenedb.com.展开更多
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode...Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM),a chronic metabolic disease with a high global incidence,has become a serious public health challenge.China has the largest number of T2DM patients worldwide,imposing a signif...BACKGROUND Type 2 diabetes mellitus(T2DM),a chronic metabolic disease with a high global incidence,has become a serious public health challenge.China has the largest number of T2DM patients worldwide,imposing a significant economic burden on the healthcare system.T2DM is closely associated with insulin resistance,impaired pancreatic B cell function,and disordered glucose and lipid metabolism,which can lead to various complications,reducing patients'quality of life and increasing the risk of disability and death.Thus,finding effective preventive and intervention measures is crucial.Exercise therapy,a key part of diabetes management,has gained attention in recent years,with many studies indicating its benefits for blood glucose control and other aspects in diabetic patients.AIM To assess the effectiveness of combined resistance and aerobic exercise interventions on blood glucose control and metabolic indicators in patients with T2DM and to explore their application in diabetes management.METHODS Systematic searches were conducted using PubMed,EMBASE,Cochrane Library,and Chinese databases for relevant randomized controlled trials(RCTs).The inclusion criteria were participants aged≥18 years with T2DM and the intervention involved combined resistance and aerobic exercise for≥8 weeks.The primary outcome indicators were fasting blood glucose,low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),glycated hemoglobin A1c(HbA1c),and total cholesterol(TC)levels.Data analysis was performed using RevMan software,and the interventional effects were assessed using weighted mean differences or standardized mean differences(SMD).RESULTS Six RCTs meeting the inclusion criteria were included,with a total sample size of 366 participants.The meta-analysis results showed that combined resistance and aerobic exercise significantly improved several metabolic indicators in patients with T2DM.Specific results were as follows:(1)For fasting blood glucose,combined exercise was more effective than aerobic exercise alone[SMD=1.22;95%confidence interval(95%CI):0.70,1.74;P<0.00001];(2)LDL-C levels were significantly reduced by the combined intervention(SMD=1.45;95%CI:1.18-1.72;P<0.00001);(3)The combined intervention significantly increased HDL-C levels(SMD=1.42;95%CI:0.98-1.87;P<0.00001);(4)The combined intervention significantly reduced TG levels(SMD=1.12;95%CI:0.85-1.39;P<0.00001;(5)No statistically significant difference was observed in HbA1c between the combined and the aerobic exercise group(SMD=-0.03;95%CI:-1.09 to 1.04;P<0.00001);and(6)The combined exercise intervention group significantly reduced TC levels(SMD=2.66;95%CI:1.93-3.38;P<0.00001).The subgroup analysis results suggest that the effect of exercise interventions may be influenced by various factors,including the patient's age,baseline blood glucose levels,and exercise intensity.CONCLUSION Combined resistance and aerobic exercise intervention significantly improved fasting blood glucose,LDL-C,HDL-C,TG,and TC levels in patients with T2DM,especially in terms of blood glucose control and cardiovascular risk,demonstrating better outcomes than aerobic exercise alone.展开更多
Objectives This study aimed to clarify the relationship between the content of proxy decision-making made by families of patients with malignant brain tumors regarding treatment policies and daily care and the cues le...Objectives This study aimed to clarify the relationship between the content of proxy decision-making made by families of patients with malignant brain tumors regarding treatment policies and daily care and the cues leading to those decisions.Methods Semi-structured personal interviews were used to collect data.Seven family members of patients with malignant brain tumors were selected to participate in the study by purposive sampling method from June to August 2022 in the Patient Family Association of Japan.Responses were content analyzed to explore the relationship between the content of decisions regarding“treatment policies”and“daily care”and the cues influencing those decisions.Semi-structured interviews were analyzed by using thematic analysis.Results The contents of proxy decisions regarding“treatment policies”included implementation,interruption,and termination of initial treatments,free medical treatments,use of respirators,and end-of-life sedation and included six cues:treatment policies suggested by the primary physician,information and knowledge about the disease and treatment obtained by the family from limited resources,perceived life threat from symptom worsening,words and reactions from the patient regarding treatment,patient’s personality and way of life inferred from their treatment preferences,family’s thoughts and values hoping for better treatment for the patient.Decisions for“daily care”included meal content and methods,excretion,mobility,maintaining cleanliness,rehabilitation,continuation or resignation from work,treatment settings(outpatient or inpatient),and ways to spend time outside and included seven cues:words and thoughts from the patient about their way of life,patient’s reactions and life history inferred from their preferred way of living,things the patient can do to maintain daily life and roles,awareness of the increasing inability to do things in daily life,family’s underlying thoughts and values about how to spend the remaining time,approval from family members regarding the care setting,advice from medical professionals on living at home.Conclusions For“treatment policies,”guidelines from medical professionals were a key cue,while for“daily care,”the small signs from the patients in their daily lives served as cues for proxy decision-making.This may be due to the lack of information available to families and the limited time available for discussion with the patient.Families of patients with malignant brain tumors repeatedly use multiple cues to make proxy decision-making under high uncertainty.Therefore,nurses supporting proxy decision-making should assess the family’s situation and provide cues that facilitate informed and confident decisions.展开更多
基金supported by the NIH (R01NS103481, R01NS111776, and R01NS131489)Indiana Department of Health (ISDH58180)(all to WW)。
文摘Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.
基金supported by funding from Parkinson Canadafunded by a scholarship from Parkinson Canadaa scholarship from Fonds d’Enseignement et de Recherche (FER) (Faculty of Pharmacy, Université Laval)
文摘There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.
文摘The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.
基金Supported by National Key Research and Development Program of China(Grant No.2022YFE0117100)National Science Foundation of China(Grant No.52102468,52325212)Fundamental Research Funds for the Central Universities。
文摘To solve problems of poor security guarantee and insufficient training efficiency in the conventional reinforcement learning methods for decision-making,this study proposes a hybrid framework to combine deep reinforcement learning with rule-based decision-making methods.A risk assessment model for lane-change maneuvers considering uncertain predictions of surrounding vehicles is established as a safety filter to improve learning efficiency while correcting dangerous actions for safety enhancement.On this basis,a Risk-fused DDQN is constructed utilizing the model-based risk assessment and supervision mechanism.The proposed reinforcement learning algorithm sets up a separate experience buffer for dangerous trials and punishes such actions,which is shown to improve the sampling efficiency and training outcomes.Compared with conventional DDQN methods,the proposed algorithm improves the convergence value of cumulated reward by 7.6%and 2.2%in the two constructed scenarios in the simulation study and reduces the number of training episodes by 52.2%and 66.8%respectively.The success rate of lane change is improved by 57.3%while the time headway is increased at least by 16.5%in real vehicle tests,which confirms the higher training efficiency,scenario adaptability,and security of the proposed Risk-fused DDQN.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
基金supported by STI2030-Major Projects,No.2022ZD0207600(to LZ)the National Natural Science Foundation of China,Nos.32070955(to LZ),U22A20301(to KFS)+3 种基金the Natural Science Foundation of Guangdong Province,No.2021A1515012197(to HO)Guangzhou Core Medical Disciplines Project,No.2021-2023(to HO)Key Research and Development Plan of Ningxia Hui Automomous Region,No.2022BEG01004(to KFS)Science and Technology Program of Guangzhou,China,No.202007030012(to KFS and LZ)。
文摘Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.
基金supported by Project of the Health Shanghai Initiative Special Fund(Medical-Sports Integration,Creating a New Model of Exercise for Health),No.JKSHZX-2022-02(to SC).
文摘Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.
基金supported by the STI 2030-Major Projects,No. 2021ZD0200500 (to XS)。
文摘Brain-derived neurotrophic factor is a crucial neurotrophic factor that plays a significant role in brain health. Although the vast majority of meta-analyses have confirmed that exercise interventions can increase brain-derived neurotrophic factor levels in children and adolescents, the effects of specific types of exercise on brain-derived neurotrophic factor levels are still controversial. To address this issue, we used meta-analytic methods to quantitatively evaluate, analyze, and integrate relevant studies. Our goals were to formulate general conclusions regarding the use of exercise interventions, explore the physiological mechanisms by which exercise improves brain health and cognitive ability in children and adolescents, and provide a reliable foundation for follow-up research. We used the Pub Med, Web of Science, Science Direct, Springer, Wiley Online Library, Weipu, Wanfang, and China National Knowledge Infrastructure databases to search for randomized controlled trials examining the influences of exercise interventions on brain-derived neurotrophic factor levels in children and adolescents. The extracted data were analyzed using Review Manager 5.3. According to the inclusion criteria, we assessed randomized controlled trials in which the samples were mainly children and adolescents, and the outcome indicators were measured before and after the intervention. We excluded animal experiments, studies that lacked a control group, and those that did not report quantitative results. The mean difference(MD;before versus after intervention) was used to evaluate the effect of exercise on brain-derived neurotrophic factor levels in children and adolescents. Overall, 531 participants(60 children and 471 adolescents, 10.9–16.1 years) were included from 13 randomized controlled trials. Heterogeneity was evaluated using the Q statistic and I^(2) test provided by Review Manager software. The meta-analysis showed that there was no heterogeneity among the studies(P = 0.67, I^(2) = 0.00%). The combined effect of the interventions was significant(MD = 2.88, 95% CI: 1.53–4.22, P < 0.0001), indicating that the brain-derived neurotrophic factor levels of the children and adolescents in the exercise group were significantly higher than those in the control group. In conclusion, different types of exercise interventions significantly increased brain-derived neurotrophic factor levels in children and adolescents. However, because of the small sample size of this meta-analysis, more high-quality research is needed to verify our conclusions. This metaanalysis was registered at PROSPERO(registration ID: CRD42023439408).
基金supported by the Deanship of Graduate Studies and Scientific Research at Qassim University(QU-APC-2024-9/1).
文摘Due to the numerous variables to take into account as well as the inherent ambiguity and uncertainty,evaluating educational institutions can be difficult.The concept of a possibility Pythagorean fuzzy hypersoft set(pPyFHSS)is more flexible in this regard than other theoretical fuzzy set-like models,even though some attempts have been made in the literature to address such uncertainties.This study investigates the elementary notions of pPyFHSS including its set-theoretic operations union,intersection,complement,OR-and AND-operations.Some results related to these operations are also modified for pPyFHSS.Additionally,the similarity measures between pPyFHSSs are formulated with the assistance of numerical examples and results.Lastly,an intelligent decision-assisted mechanism is developed with the proposal of a robust algorithm based on similarity measures for solving multi-attribute decision-making(MADM)problems.A case study that helps the decision-makers assess the best educational institution is discussed to validate the suggested system.The algorithmic results are compared with the most pertinent model to evaluate the adaptability of pPyFHSS,as it generalizes the classical possibility fuzzy set-like theoretical models.Similarly,while considering significant evaluating factors,the flexibility of pPyFHSS is observed through structural comparison.
文摘Accurate medical diagnosis,which involves identifying diseases based on patient symptoms,is often hindered by uncertainties in data interpretation and retrieval.Advanced fuzzy set theories have emerged as effective tools to address these challenges.In this paper,new mathematical approaches for handling uncertainty in medical diagnosis are introduced using q-rung orthopair fuzzy sets(q-ROFS)and interval-valued q-rung orthopair fuzzy sets(IVq-ROFS).Three aggregation operators are proposed in our methodologies:the q-ROF weighted averaging(q-ROFWA),the q-ROF weighted geometric(q-ROFWG),and the q-ROF weighted neutrality averaging(qROFWNA),which enhance decision-making under uncertainty.These operators are paired with ranking methods such as the similarity measure,score function,and inverse score function to improve the accuracy of disease identification.Additionally,the impact of varying q-rung values is explored through a sensitivity analysis,extending the analysis beyond the typical maximum value of 3.The Basic Uncertain Information(BUI)method is employed to simulate expert opinions,and aggregation operators are used to combine these opinions in a group decisionmaking context.Our results provide a comprehensive comparison of methodologies,highlighting their strengths and limitations in diagnosing diseases based on uncertain patient data.
基金supported by Cure Alzheimer’s Fund(to RET and SHC)JPB Foundation(to RET),and R56AG072054(to SHC)。
文摘Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.
文摘BACKGROUND Understanding a patient's clinical status and setting priorities for their care are two aspects of the constantly changing process of clinical decision-making.One analytical technique that can be helpful in uncertain situations is clinical judgment.Clinicians must deal with contradictory information,lack of time to make decisions,and long-term factors when emergencies occur.AIM To examine the ethical issues healthcare professionals faced during the coronavirus disease 2019(COVID-19)pandemic and the factors affecting clinical decision-making.METHODS This pilot study,which means it was a preliminary investigation to gather information and test the feasibility of a larger investigation was conducted over 6 months and we invited responses from clinicians worldwide who managed patients with COVID-19.The survey focused on topics related to their professional roles and personal relationships.We examined five core areas influencing critical care decision-making:Patients'personal factors,family-related factors,informed consent,communication and media,and hospital administrative policies on clinical decision-making.The collected data were analyzed using the χ^(2) test for categorical variables.RESULTS A total of 102 clinicians from 23 specialties and 17 countries responded to the survey.Age was a significant factor in treatment planning(n=88)and ventilator access(n=78).Sex had no bearing on how decisions were made.Most doctors reported maintaining patient confidentiality regarding privacy and informed consent.Approximately 50%of clinicians reported a moderate influence of clinical work,with many citing it as one of the most important factors affecting their health and relationships.Clinicians from developing countries had a significantly higher score for considering a patient's financial status when creating a treatment plan than their counterparts from developed countries.Regarding personal experiences,some respondents noted that treatment plans and preferences changed from wave to wave,and that there was a rapid turnover of studies and evidence.Hospital and government policies also played a role in critical decision-making.Rather than assessing the appropriateness of treatment,some doctors observed that hospital policies regarding medications were driven by patient demand.CONCLUSION Factors other than medical considerations frequently affect management choices.The disparity in treatment choices,became more apparent during the pandemic.We highlight the difficulties and contradictions between moral standards and the realities physicians encountered during this medical emergency.False information,large patient populations,and limited resources caused problems for clinicians.These factors impacted decision-making,which,in turn,affected patient care and healthcare staff well-being.
文摘Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity rats were randomlydivided into three groups(n=10):normal oxygen concentration quiet group(N),hypoxia quiet group(H),hypoxic exercise group(HE).Exercise training on the horizontal animal treadmill for 1 h/d,5 d/week for a total of 4 week,and the intensity of horizontaltreadmill training was 20 m/min(hypoxic concentration was 13.6%).Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done.And the serum concentrations of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high-densitylipoprotein cholesterol(HDL-C)levels were detected.RT-PCR and Western Blot were used to detect the levels of miR-27,PPARγ,CYP7A1 and CD36.Results Hypoxic exercise decreased the expression levels of miR-27 in the obese rats’liver,however,theexpression level of PPARγwas gradually increased.The expression levels of miR-27 in HE group were significantly lower than Ngroup(P<0.05).The expression levels of PPARγmRNA in N group were significantly lower than H group(P<0.05),especially lowerthan HE group(P<0.01).The protein expression of PPARγprotein in N group was significantly lower than that other groups(P<0.01).The expression of lipid metabolism-related genes and proteins increased in the obese rats’liver.The expression of CYP7A1mRNA in N group was significantly lower than H group(P<0.05),especially lower than HE group(P<0.01).The expression ofCYP7A1 protein in the obese rats’liver in N group was extremely lower than H group and HE group(P<0.01).The proteinexpression of CD36 in N group was significantly lower than that in HE group(P<0.05).Hypoxia exercise improved the relatedphysiological and biochemical indexes of lipid metabolism disorder.The perirenal fat weight of obese rats in HE group wasextremely lower than N group and H group(P<0.01),and the perirenal fat weight in N group was significantly higher than H group(P<0.05).The epididymal fat weight in N group was significantly higher than H group(P<0.05),and extremely higher than HEgroup(P<0.01).The Lee’s index in HE group was extremely lower than N group and H group(P<0.01).The serum concentration ofTC in obese rats in HE group was extremely lower than N group and H group(P<0.01).The serum concentration of TG in HE groupwas extremely lower than N group and H group(P<0.01).The serum concentration of LDL-C in N group was extremely higher thanHE group(P<0.01).The serum concentration of HDL-C in N group was extremely lower than H group(P<0.01).Conclusion Hypoxiaand hypoxia exercise may negatively regulate the levels of PPARγby inhibiting miR-27 in the obese rats’liver,thereby affecting theexpression of downstream target genes CYP7A1 and CD36,and promoting cholesterol,fatty acid oxidation and HDL-C transport inthe liver,and ultimately the lipid levels in obese rats were improved.The effect of hypoxia exercise on improving blood lipid isbetter than simple hypoxia intervention.
文摘The benefits of regular physical activity are well known.Yet,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary setting.To investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MSK)anatomy course material.These synchronous sessions were co-taught by a group fitness instructor and an anatomy instructor.The fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously covered.After the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MSK anatomy knowledge,PA levels,and mental wellbeing.Thirty participants completed surveys;a majority agreed that the classes increased understanding of MSK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce stress.The majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social connectedness.Overall,medical students saw benefit in PA based interventions to supplement MSK course concepts.Along with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.
基金supported by funding provided to BJG from the Natural Sciences and Engineering Research Council of Canada(NSERCgrant no.402635).
文摘Objectives:Aerobic exercise training can increase skeletal muscle mitochondrial content.Supine exercise training with legs above the heart potentially augments these increases.However,the impact of supine exercise training on mitochondrial biogenesis and cardiovascular adaptations remains unclear.Methods:In this single-centred,randomized,parallel arm trial,19 recreationally active individuals underwent seven sessions of either supine with legs up(SUP;n=9,6 females)or upright with legs down(UP;n=10,7 females)aerobic training on a recumbent bike at 71±7%and 71±2%of peak work rate(WRpeak),respectively.The study aimed to test the effects of training with decreased muscle oxygenation on indices of muscle mitochondrial remodelling.Secondary outcomes included exercise performance,muscle oxygenation,and cardiovascular responses.Results:Secondary outcomes revealed significant interaction effects for time to fatigue(TTF)and WRpeak in the SUP group during supine testing,suggesting enhanced exercise tolerance and performance.No between group interaction effects were observed for upright testing.No clear effects on mitochondrial biogenesis were observed based on expression of mitochondrial protein subunits and transcriptional regulators.Acutely,HRpeak was lower during the SUP Test compared to the UP Test.No central cardiovascular adaptations were observed following training.Conclusions:Our exploratory analyses showed that supine aerobic training more effectively improves supine exercise tolerance and performance compared with upright training,despite no differences in measured proteins related to mitochondrial biogenesis.Further research is needed to elucidate the mechanisms underlying these postural-specific training effects.Registration:clinicaltrials.gov:NCT04151095.
基金financial support from the general electric (GE) healthcareAustralian Research Council Discovery Project (DP200101476)+5 种基金in parts by National Institutes of Health (NIH) grants (R01 AR077604, R01 EB002524, R01 AR079431, P41 EB02706)Stanford Graduate FellowshipThe University of Queensland Graduate ScholarshipNational Health and Medical Research Council of Australia Fellowship (#1194937)Wu Tsai Human Performance Alliance at Stanford Universitythe Joe and Clara Tsai Foundation
文摘Background While Nordic hamstring exercise(NHE)training has been shown to reduce hamstring strains,the muscle-specific adaptations to NHE across the 4 hamstrings remain unclear.This study investigates architectural and microstructural adaptations of the biceps femoris short head(BFsh),biceps femoris long head(BFlh),semitendinosus(ST),and semimembranosus(SM)in response to an NHE intervention.Methods Eleven subjects completed 9 weeks of supervised NHE training followed by 3 weeks of detraining.Magnetic resonance imaging was performed at pre-training,post-training,and detraining to assess architectural(volume,fiber tract length,and fiber tract angle)and microstructural(axial(AD),mean(MD),radial(RD)diffusivities,and fractional anisotropy(FA))parameters of the 4 hamstrings.Results NHE training induced significant but non-uniform hamstring muscle hypertrophy(BFsh:22%,BFlh:9%,ST:26%,SM:6%)and fiber tract length increase(BFsh:11%,BFlh:7%,ST:18%,SM:10%).AD(5%),MD(4%),and RD(5%)showed significant increases,but fiber tract angle and FA remained unchanged.After detraining,only ST showed a significant reduction(8%)in volume,which remained higher than the pre-training value.While fiber tract lengths returned to baseline,AD,MD,and RD remained higher than pre-training levels for all hamstrings.Conclusion The 9-week NHE training substantially increased hamstring muscle volume with greater hypertrophy in ST and BFsh.Hypertrophy was accompanied by increases in fiber tract lengths and cross-sections(increased RD).After 3 weeks of detraining,fiber tract length gains across all hamstrings declined,emphasizing the importance of sustained training to maintain all the protective adaptations.
基金supported by grants from the National Natural Science Foundation of China(82225005, 82020108002 to JX,82200321 to QZ)Science and Technology Commission of ShanghaiMunicipality(23410750100,20DZ2255400,, 21XD1421300 to JX)+1 种基金the“Dawn”Program of Shanghai Educa-tion Commission(19SG34 to JX)Shanghai Sailing Program(21YF1413200 to QZ).
文摘Background:Exercise induces molecular changes that involve multiple organs and tissues.Moreover,these changes are modulated by various exercise parameters—such as intensity,frequency,mode,and duration—as well as by clinical features like gender,age,and body mass index(BMI),each eliciting distinct biological effects.To assist exercise researchers in understanding these changes from a comprehensive perspective that includes multiple organs,diverse exercise regimens,and a range of clinical features,we developed Exercise Regulated Genes Database(ExerGeneDB),a database of exercise-regulated differential genes.Methods:ExerGeneDB aggregated publicly available exercise-related sequencing datasets and subjected them to uniform quality control and preprocessing.The data,encompassing a variety of types,were organized into a specialized database of exercise-regulated genes.Notably,Exer-GeneDB conducted differential analyses on this collected data,leveraging curated clinical information and accounting for important factors such as gender,age,and BMI.Results:ExerGeneDB has assembled 1692 samples from rats and mice as well as 4492 human samples.It contains data from various tissues and organs,such as skeletal muscle,blood,adipose tissue,intestine,heart,liver,spleen,lungs,kidneys,brain,spinal cord,bone marrow,and bones.ExerGeneDB features bulk ribonucleic acid sequencing(RNA-seq)(including non-coding RNA(ncRNA)and protein-coding RNA),microarray(including ncRNA and protein-coding RNA),and single cell RNA-seq data.Conclusion:ExerGeneDB compiles and re-analyzes exercise-related data with a focus on clinical information.This has culminated in the crea-tion of an interactive database for exercise regulation genes.The website for ExerGeneDB can be found at:https://exergenedb.com.
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.
基金Supported by Research Project of Zhejiang Provincial Science and Technology Plan for Traditional Chinese Medicine,No.2024ZL753and Research Project of Zhejiang Provincial Medical and Health Science and Technology Plan,No.2024KY1406.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM),a chronic metabolic disease with a high global incidence,has become a serious public health challenge.China has the largest number of T2DM patients worldwide,imposing a significant economic burden on the healthcare system.T2DM is closely associated with insulin resistance,impaired pancreatic B cell function,and disordered glucose and lipid metabolism,which can lead to various complications,reducing patients'quality of life and increasing the risk of disability and death.Thus,finding effective preventive and intervention measures is crucial.Exercise therapy,a key part of diabetes management,has gained attention in recent years,with many studies indicating its benefits for blood glucose control and other aspects in diabetic patients.AIM To assess the effectiveness of combined resistance and aerobic exercise interventions on blood glucose control and metabolic indicators in patients with T2DM and to explore their application in diabetes management.METHODS Systematic searches were conducted using PubMed,EMBASE,Cochrane Library,and Chinese databases for relevant randomized controlled trials(RCTs).The inclusion criteria were participants aged≥18 years with T2DM and the intervention involved combined resistance and aerobic exercise for≥8 weeks.The primary outcome indicators were fasting blood glucose,low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),glycated hemoglobin A1c(HbA1c),and total cholesterol(TC)levels.Data analysis was performed using RevMan software,and the interventional effects were assessed using weighted mean differences or standardized mean differences(SMD).RESULTS Six RCTs meeting the inclusion criteria were included,with a total sample size of 366 participants.The meta-analysis results showed that combined resistance and aerobic exercise significantly improved several metabolic indicators in patients with T2DM.Specific results were as follows:(1)For fasting blood glucose,combined exercise was more effective than aerobic exercise alone[SMD=1.22;95%confidence interval(95%CI):0.70,1.74;P<0.00001];(2)LDL-C levels were significantly reduced by the combined intervention(SMD=1.45;95%CI:1.18-1.72;P<0.00001);(3)The combined intervention significantly increased HDL-C levels(SMD=1.42;95%CI:0.98-1.87;P<0.00001);(4)The combined intervention significantly reduced TG levels(SMD=1.12;95%CI:0.85-1.39;P<0.00001;(5)No statistically significant difference was observed in HbA1c between the combined and the aerobic exercise group(SMD=-0.03;95%CI:-1.09 to 1.04;P<0.00001);and(6)The combined exercise intervention group significantly reduced TC levels(SMD=2.66;95%CI:1.93-3.38;P<0.00001).The subgroup analysis results suggest that the effect of exercise interventions may be influenced by various factors,including the patient's age,baseline blood glucose levels,and exercise intensity.CONCLUSION Combined resistance and aerobic exercise intervention significantly improved fasting blood glucose,LDL-C,HDL-C,TG,and TC levels in patients with T2DM,especially in terms of blood glucose control and cardiovascular risk,demonstrating better outcomes than aerobic exercise alone.
文摘Objectives This study aimed to clarify the relationship between the content of proxy decision-making made by families of patients with malignant brain tumors regarding treatment policies and daily care and the cues leading to those decisions.Methods Semi-structured personal interviews were used to collect data.Seven family members of patients with malignant brain tumors were selected to participate in the study by purposive sampling method from June to August 2022 in the Patient Family Association of Japan.Responses were content analyzed to explore the relationship between the content of decisions regarding“treatment policies”and“daily care”and the cues influencing those decisions.Semi-structured interviews were analyzed by using thematic analysis.Results The contents of proxy decisions regarding“treatment policies”included implementation,interruption,and termination of initial treatments,free medical treatments,use of respirators,and end-of-life sedation and included six cues:treatment policies suggested by the primary physician,information and knowledge about the disease and treatment obtained by the family from limited resources,perceived life threat from symptom worsening,words and reactions from the patient regarding treatment,patient’s personality and way of life inferred from their treatment preferences,family’s thoughts and values hoping for better treatment for the patient.Decisions for“daily care”included meal content and methods,excretion,mobility,maintaining cleanliness,rehabilitation,continuation or resignation from work,treatment settings(outpatient or inpatient),and ways to spend time outside and included seven cues:words and thoughts from the patient about their way of life,patient’s reactions and life history inferred from their preferred way of living,things the patient can do to maintain daily life and roles,awareness of the increasing inability to do things in daily life,family’s underlying thoughts and values about how to spend the remaining time,approval from family members regarding the care setting,advice from medical professionals on living at home.Conclusions For“treatment policies,”guidelines from medical professionals were a key cue,while for“daily care,”the small signs from the patients in their daily lives served as cues for proxy decision-making.This may be due to the lack of information available to families and the limited time available for discussion with the patient.Families of patients with malignant brain tumors repeatedly use multiple cues to make proxy decision-making under high uncertainty.Therefore,nurses supporting proxy decision-making should assess the family’s situation and provide cues that facilitate informed and confident decisions.
