Abstract:BACKGROUND:Due to the decline in estrogen levels within the body,postmenopausal women face a significantly increased risk of developing alveolar bone osteoporosis.Raloxifene,as a potential treatment,has shown preliminary positive effects on alveolar bone osteoporosis. OBJECTIVE:To study the effect of raloxifene on alveolar bone resorption in ovariectomized rats. METHODS:Forty-five female Sprague-Dawley rats were divided into three groups:a sham-operated group,a model group,and a raloxifene group.Ovariectomy was performed to establish animal models in the latter two groups.Rats in the raloxifene group received intraperitoneal injections of 10 μL of raloxifene hydrochloride(5 mg/kg).The injection was repeated once 2 weeks after the first dose,and there were two injections in total.After 2 months,the rat molars and alveolar bone were scanned using Micro-CT to analyze bone microstructural parameters,including bone mineral density,bone volume fraction,trabecular thickness,trabecular number,and trabecular separation.Subsequently,alveolar bone samples were subjected to hematoxylin-eosin staining,immunohistochemical staining for osteocalcin,and tartrate-resistant acid phosphatase staining. RESULTS AND CONCLUSION:(1)Compared with the model group,the raloxifene group exhibited an increasing trend in bone mineral density of the rat alveolar bone(P<0.05).Bone volume fraction and trabecular thickness were significantly increased in the raloxifene group(P<0.05),while trabecular separation and trabecular number were significantly decreased(P<0.05).(2)Hematoxylin-eosin staining results showed that,compared with the model group,the alveolar bone structure of rats in the raloxifene group was significantly improved,with a marked increase in the number of new bone formation areas(P<0.05).(3)Immunohistochemical staining results showed that,compared with the model group,the number of osteocalcin-positive cells in the raloxifene group was significantly increased(P<0.05),and the staining intensity was also markedly enhanced.(4)In addition,tartrate-resistant acid phosphatase staining revealed that raloxifene significantly reduced bone loss by inhibiting the activity of osteoclasts.To conclude,raloxifene can significantly inhibit alveolar bone resorption in ovariectomized rats,prevent structural damage to the alveolar bone,and thereby effectively delay the progression of alveolar bone osteoporosis..

Abstract:OBJECTIVE:Enhancing sports performance remains a central focus in sports science.Ischemic preconditioning,as a non-pharmacological intervention,has been reported to improve performance.However,the results vary across different studies,and the influencing factors remain unclear.This study aimed to conduct a systematic meta-analysis of original research on ischemic preconditioning combined with exercise,to evaluate its true effects and identify potential moderators. METHODS:Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search was conducted on September 4,2024,across the Web of Science Core Collection,PubMed,Embase,and CNKI databases using the Mesh keywords"ischemic preconditioning,""performance,"and"sport."The inclusion criteria were:(1)studies involving non-clinical populations;(2)sham ischemic preconditioning or non-ischemia treatment as the control for ischemic preconditioning;(3)outcomes including balance,jump performance,strength,accumulated oxygen deficit,power output,maximal repetitions,time trial,time to exhaustion,and oxygen consumption;(4)study designs limited to randomized crossover or randomized controlled trials.Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool,and the quality of evidence was evaluated with the GRADE approach.Multilevel meta-analyses were conducted using the"meta,""metafor"and"clubSandwich"packages in R version 4.3.3,along with publication bias tests,subgroup analyses,and meta-regressions. RESULTS:A total of 90 studies involving 1 439 participants aged 18-70 years were included.Compared with sham ischemic preconditioning or non-ischemia treatment,ischemic preconditioning significantly improved sports performance[effect size(ES)=0.13,95%confidence interval(CI)(0.06,0.21),P<0.01;Q=427;I²-Level 2=0%,I²-Level 3=9.13%,I²-Level 4=5.74%;PI=-0.18 to 0.44;low certainty].Subgroup analysis revealed that ischemic preconditioning had a greater effect versus blank control than versus sham ischemic preconditioning(P=0.02)[ESCON=0.22,95%CI(0.12,0.33],P<0.01;ESSHAM 0.10,95%CI(0.02,0.18),P<0.01].(3)No significant between-group differences were found in terms of metabolic characteristics(aerobic/anaerobic),training level,or sex.(4)Among ischemic preconditioning protocols,the 1×5 minutes design showed a significantly greater effect(P=0.01),though it was reported in only one study.Within-subgroup analyses indicated that 3×5 minutes[ES=0.14,95%CI(0.03,0.26),P<0.01]and 4×5 minutes[ES=0.10,95%CI(0.00,0.21),P=0.02]were statistically significant.(5)Ischemic preconditioning significantly benefited sedentary participants[ES=0.14,95%CI(-0.10,0.39),P=0.03],recreationally active participants[ES=0.15,95%CI(0.03,0.27),P=0.02],and participants undergoing general training[ES=0.19,95%CI(0.04,0.33),P=0.01],but not highly trained,elite,or world-class athletes.Significant effects were found only in male participants[ES=0.20,95%CI(0.10,0.30),P<0.01]. CONCLUSION:Ischemic preconditioning shows a small effect on sports performance,with a significant placebo effect(psychological effect).Ischemic preconditioning protocols(the duration of ischemic preconditioning),particularly protocols of 3×5 minutes or 4×5 minutes,emerge as a key moderating factor.More benefits appear in male participants with low exercise experience,though current evidence does not conclusively support sex,training experience level or age as moderators.Future studies should adopt standardized ischemic preconditioning protocols and rigorously control for placebo effects to better delineate the boundaries and mechanisms underlying the effects of ischemic preconditioning.

Abstract:BACKGROUND:Stable animal insomnia models serve as crucial tools for investigating insomnia mechanisms and developing anti-insomnia drugs.The combination of chemical and physical methods provides an effective approach for establishing animal insomnia models. OBJECTIVE:To compare chemical methods(p-chlorophenylalanine),physical methods(water environment sleep deprivation method),and combined methods(p-chlorophenylalanine combined with water environment sleep deprivation method)for constructing insomnia mouse models,thereby exploring the optimal modeling method. METHODS:C57 mice were randomly divided by sex into the following groups:control(untreated),p-chlorophenylalanine,water platform,and p-chlorophenylalanine+water platform,with 12 mice per group(equal numbers of males and females).Mice in the p-chlorophenylalanine group received intraperitoneal injections of 400 mg/kg p-chlorophenylalanine suspension daily for 3 consecutive days;those in the water platform group were placed in a water environment sleep deprivation platform for 3 consecutive days;and those in the p-chlorophenylalanine+water platform group were placed in the sleep deprivation platform and received intraperitoneal injections of 400 mg/kg p-chlorophenylalanine suspension for 3 consecutive days.After 3 days of modeling,mice were subjected to the open field test,and the number of neurons in the hypothalamus and hippocampus was examined via Nissl staining.Serum levels of 5-hydroxytryptamine,gamma-aminobutyric acid,and dopamine were measured using enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION:(1)Compared with the control group,male mice in the three model groups exhibited an upward trend in total distance,number of entries into the central area,average speed,and number of stand-up episodes.The most pronounced changes were observed in the p-chlorophenylalanine+water platform group(P<0.05 or P<0.01).Female mice in the three model groups also showed an upward trend in total distance,number of entries into the central area,average speed,and number of stand-up episodes.(2)All three modeling methods could reduce the number of neurons in the mouse hypothalamus and hippocampus,with the highest reduction and most severe neuronal damage observed in female mice in the p-chlorophenylalanine+water platform group.(3)Compared with female mice in the control group,changes in three serum indicators were more pronounced in the female mice in the p-chlorophenylalanine+water platform group.5-Hydroxytryptamine and gamma-aminobutyric acid levels were significantly reduced(P<0.05),while dopamine levels were significantly elevated(P<0.01).To conclude,the insomnia model established in female mice using p-chlorophenylalanine combined with the water platform is relatively more reliable and stable,providing an ideal animal model for insomnia research.

Abstract:BACKGROUND:Although the role of non-coding RNAs and ferroptosis in the development of osteoarthritis has been initially established and has become a research hotspot,current studies still face many challenges. OBJECTIVE:To systematically analyze and review the role of non-coding RNAs in regulating ferroptosis during osteoarthritis pathogenesis and summarize related research advances. METHODS:Literature searches were performed in CNKI,WanFang,VIP Chinese Journal Database,and PubMed.The search timeline was from database inception to December 2024.Search terms included"osteoarthritis,non-coding RNA,microRNA,long non-coding RNA,circular RNA,ferroptosis"in both Chinese and English.After excluding outdated or redundant publications,86 relevant articles were ultimately selected for review and analysis. RESULTS AND CONCLUSION:(1)Long non-coding RNAs and circular RNAs can act as competitive endogenous RNAs by binding to microRNAs,thereby regulating the expression levels of ferroptosis-related genes and influencing osteoarthritis development.(2)The mechanisms of ferroptosis primarily involve dysregulated iron metabolism,accumulation of lipid peroxidation,and collapse of the antioxidant defense system,with lipid peroxidation accumulation being the core biochemical feature.(3)Ferroptosis in chondrocytes has been shown to exacerbate osteoarthritis pathological progression.(4)Current research on non-coding RNAs influencing osteoarthritis by regulating ferroptosis is still in its early stages.Future studies are needed to extensively validate their feasibility as diagnostic biomarkers and therapeutic targets.

Abstract:BACKGROUND:The PI3K/Akt pathway,as an intracellular signal transduction pathway,plays a crucial role in regulating cell proliferation,growth,and metabolism.Semen Cuscutae,a traditional Chinese medicine used for kidney tonification,possesses potential bone-protective effects due to its total flavonoids;however,the specific molecular mechanisms remain unclear. OBJECTIVE:To investigate the protective effect of total flavonoids from Semen Cuscutae against dexamethasone-induced osteoblast apoptosis and its potential molecular mechanisms through a combination of network pharmacology and in vitro experiments. METHODS:Network pharmacology was used to predict potential targets and signaling pathways for Semen Cuscutae in the treatment of dexamethasone-induced femoral head avascular necrosis.hFOB1.19 cells were cultured in vitro and treated with different concentrations of total flavonoids from Semen Cuscutae(0,25,50,100,200,400,and 600 μg/mL)for 24 hours.Cell viability was assessed using the cell counting kit-8 assay to select the optimal treatment dose for subsequent experiments.hFOB1.19 cells were divided into six groups:control,dexamethasone,total flavonoids from Semen Cuscutae at 100,200,400 μg/mL plus 2 μmol/L dexamethasone,and total flavonoids from Semen Cuscutae plus LY294002 groups(400 μg/mL total flavonoids from Semen Cuscutae and 10 μmol/L LY294002,a PI3K inhibitor).Cell viability was determined using the cell counting kit-8 assay,apoptosis rate was measured by flow cytometry,apoptosis-related protein expression was assessed by immunofluorescence,reactive oxygen species levels were quantified using the DCFH-DA probe,and expression of proteins related to the PI3K/Akt pathway was analyzed by western blot assay after treatment,. RESULTS AND CONCLUSION:(1)Network pharmacology results indicated that the potential targets of Semen Cuscutae may be related to the regulation of tumor necrosis factor,p53,interleukin-6,serine/threonine protein kinase 1,vascular endothelial growth factor A,caspase-3,interleukin-1β,hypoxia-inducible factor 1α expression,and the PI3K/Akt pathway.(2)CCK-8 results showed that total flavonoids from Semen Cuscutae promoted the proliferation of hFOB1.19 cells within a certain range and alleviated the inhibitory effect of dexamethasone on the proliferation of hFOB1.19 cells.(3)Total flavonoids from Semen Cuscutae inhibited dexamethasone-induced apoptosis and increased reactive oxygen species levels,reduced the expression of cleaved caspase-3 and Bax,and decreased reactive oxygen species levels,while increased the protein expression of Bcl-2.(4)Compared with the dexamethasone group,total flavonoids from Semen Cuscutae enhanced the expression of p-PI3K and p-Akt proteins.(5)The PI3K inhibitor LY294002 reversed the effects of total flavonoids from Semen Cuscutae on apoptosis and reactive oxygen species levels in dexamethasone-treated cells.The results indicate that total flavonoids from Semen Cuscutae can attenuate dexamethasone-mediated apoptosis in hFOB1.19 cells,and the mechanism may be related to the activation of the PI3K/Akt pathway.

Abstract:BACKGROUND:Cervi Cornus Colla,which contains bioactive proteoglycans and other bone-targeting components,demonstrates therapeutic potential by modulating gut microbiota composition and bile acid metabolism.Through the gut-bone axis signaling pathway,Cervi Cornus Colla effectively ameliorates bone metabolic disorders associated with steroid-induced osteonecrosis of the femoral head. OBJECTIVE:To investigate the intervention effect of Cervi Cornus Colla on steroid-induced osteonecrosis of the femoral head in rat models and its potential protective mechanism through the"gut-bone axis." METHODS:Thirty Sprague-Dawley rats were randomly divided into three groups:control,model and Cervi Cornus Colla treatment groups.To establish a steroid-induced osteonecrosis of the femoral head model,rats in the model and Cervi Cornus Colla groups received intramuscular gluteal injections of methylprednisolone sodium succinate during the first 3 days of each week for 3 consecutive weeks.Concurrently,the rats in the Cervi Cornus Colla group were administered Cervi Cornus Colla via oral gavage,and those in the control group and the model group received equal volume of purified water via oral gavage for 6 consecutive weeks.Pathological changes in the femoral head were evaluated using hematoxylin-eosin and Masson staining.The serum interleukin-1β level was detected by ELISA.Western blot analysis assessed the expression of Runt-related transcription factor 2 and type Ⅰ collagen a1 protein in the femoral head.Gut microbiota diversity was analyzed via 16SrDNA sequencing,and integrated with prior fecal metabolomics data to explore potential mechanistic correlations. RESULTS AND CONCLUSION:(1)Compared with the model group,Cervi Cornus Colla significantly reduced empty lacunae rate and adipocyte infiltration,increased collagen fiber content and improved trabecular bone structure(P<0.05).Additionally,Cervi Cornus Colla markedly downregulated serum interleukin-1β levels and upregulated Runt-related transcription factor 2 and type Ⅰ collagen a1 protein expressions(P<0.05).(2)Gut microbiota analysis revealed that compared with the model group,Cervi Cornus Colla intervention significantly reduced the relative abundance of Firmicutes at the phylum level and markedly altered the abundances of Candidatus_Saccharimonas,Turicibacter,Fusobacterium,and UCG_007 at the genus level.(3)Spearman correlation analysis showed that Candidatus_Saccharimonas was positively correlated with β-muricholic acid,cholic acid,and bile acids,while Turicibacter,Fusobacterium,and UCG_007 were negatively correlated with β-muricholic acid,cholic acid,and taurine.(4)Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis further revealed significant enrichment in secondary bile acid biosynthesis,primary bile acid biosynthesis,and taurine metabolism pathways(P<0.05).To conclude,Cervi Cornus Colla may alleviate glucocorticoid-induced femoral head injury by regulating gut microbiota and its related metabolites,thereby influencing bile acid and taurine metabolic pathways.

Abstract:BACKGROUND:Acupuncture is an important therapeutic method for ulcerative colitis;however,its mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of electroacupuncture in regulating the pathological progression of ulcerative colitis and the imbalance of Th17/Treg immune homeostasis in mice with ulcerative colitis,and to analyze the remodeling effect of electroacupuncture on the dynamic balance of the proinflammatory-anti-inflammatory cell subpopulations and its interaction with the nuclear receptor signaling pathway. METHODS:Sixty male C57BL/6 mice were randomly divided into five groups(n=12):control,model,sham electroacupuncture,electroacupuncture,and conventional drug treatment.Except for the control group,the other groups were induced with ulcerative colitis by continuous free access to a 3%sodium dextran sulfate solution for 7 days.The mice in the electroacupuncture group received stimulation at the Zusanli(ST36)and Tianshu(ST25)acupoints(20 minutes per day×7 days).The mice in the sham electroacupuncture group underwent superficial needle insertion at Zusanli and Tianshu to subcutaneous tissue,and the electrode device was left in a non-activated state.Mesalazine solution(33.4 g/kg)was administered by gastric gavage to the mice in the conventional drug treatment group.Following treatment,mouse body mass and colon length were measured.Disease activity and colonic mucosal injury severity were assessed.Colonic histopathology of mice was determined using hematoxylin-eosin staining.Colon-related gene and protein expression were detected by qPCR,western blot,immunohistochemistry,and immunofluorescence.The imbalance in Th17/Treg cell subsets was quantified using flow cytometry. RESULTS AND CONCLUSION:(1)Mouse body mass was significantly decreased,colon length was significantly shortened,disease activity index scores was significantly elevated,colon mucosal damage index scores and inflammatory cell infiltration density were significantly increased in the model group compared with the normal group(P<0.01).The expression levels of proinflammatory mediators cyclooxygenase-2,CC chemokine ligand 2,and CXC chemokine ligand 2,hypoxia-inducible factor 1α and its downstream targets matrix metalloproteinase-3,matrix metalloproteinase 9,and nuclear factor κB P65,and blood Th17 cell percentage were significantly increased(P<0.01),while the expression levels of peroxisome proliferator-activated receptor γ,retinoic acid-related orphan receptor γt(a key factor in Th17 differentiation),and regulatory T cell percentage were significantly decreased in the model group compared with the normal group(P<0.01).(2)The aforementioned pathological changes were improved in both the electroacupuncture and conventional drug treatment groups compared with the model group(P<0.01),especially inflammatory cell infiltration was reduced and crypt structural integrity was improved in the colon tissues.Decreased Th17 cell percentage and increased regulatory T cell percentage in the blood were found in the electroacupuncture group compared with the model group(P<0.01).The findings suggest that electroacupuncture stimulation of Zusanli and Tianshu acupoints may remodel the intestinal immune microenvironment by regulating the bidirectional regulatory network involving the peroxisome proliferator-activated receptor gamma/nuclear factor-κB signaling pathway and mediating the immune balance between Th17 and regulatory T cells,thereby offering a novel treatment strategy for ulcerative colitis.

Abstract:BACKGROUND:Studies have shown that different lipid types can affect knee osteoarthritis,but the causal relationship remains unclear. OBJECTIVE:To explore the causal relationship between lipid types and knee osteoarthritis using Mendelian randomization. METHODS:Based on the genome-wide association analysis statistics from the GWAS Catalog,179 types of lipids were derived from the GeneRISK cohort,and whole genome analysis data for knee osteoarthritis included 2 227 cases and 454 121 controls.Single nucleotide polymorphisms were used as instrumental variables and a strict screening was conducted with a liposome significance threshold of P<1×10⁻⁵,a knee osteoarthritis significance threshold of P<5×10-6 and a linkage disequilibrium threshold of r²<0.001.The inverse variance weighted method was mainly used for analysis.The results were evaluated based on the odds ratio(OR)and its 95%confidence interval(CI).MR-Egger regression,weighted median method,and simple mode method were used as supplementary analyses.The robustness of the results was verified through sensitivity analyses including leave-one-out analysis,heterogeneity test,pleiotropy test,and reverse Mendelian randomization analysis. RESULTS AND CONCLUSION:Diacylglycerol(18:1/18:2,OR=0.900 5,95%CI:0.810 9-1.000 0,P=0.049 9),phosphatidylinositol(18:0/18:2,OR=0.895 4,95%CI:0.808 9-0.991 2,P=0.033 2),and phosphatidylcholine(16:0/20:2,OR=0.918 3,95%CI:0.845 8-0.997 1,P=0.042 5)were negatively correlated with knee osteoarthritis,while phosphatidylcholine(O-16:0/18:2,OR=1.221 9,95%CI:0.909 8-1.641 0,P=0.198 7)was positively correlated with knee osteoarthritis.To conclude,specific lipids may influence the risk of knee osteoarthritis by regulating inflammatory or cartilage metabolic pathways,providing genetic evidence for lipid metabolism-targeted intervention strategies.

Abstract:BACKGROUND:Limb lymphedema lacks a specific treatment in modern medicine,and the efficacy of existing drugs is limited.Traditional Chinese medicine (TCM)has a profound accumulation in the treatment of edema,and ancient texts contain a wealth of prescription experience.However,the differences in the views of various schools of thought have led to the dispersal of formulas,and their mechanisms of action are not yet understood.In particular,there is a lack of systematic investigation of the treatment pattern of TCM formulas in ancient books. OBJECTIVE:Based on the cloud platform of ancient and modern medical cases and CytoScape,to analyze the medication patterns of Chinese medical texts for the treatment of limb lymphedema,and to explore the mechanism of action of core drugs through network pharmacology and molecular docking. METHODS:We collected the edema-reducing TCM formulas for the treatment of limb lymphedema in the database of"imedbooks"as of May 1,2024,and screened the core drugs that met the criteria.The components and targets of the core drugs were obtained by TCMSP,and the disease targets were screened by GeneCards,TTD,and OMIM.The drug-component-target network and protein-protein interactions network were constructed,and the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed by Metascape and verified by molecular docking. RESULTS AND CONCLUSION:Finally,223 formulas(containing 355 Chinese herbal medicines)were included,and the core drug combination was identified by pairing and complex network analysis:dried tangerine peel-Poria cocos-Betel nut-Atractylodis Macrocephalae-Mucuna pruriens.Network pharmacological analysis showed that the core targets(e.g.,tumor protein 53,non-receptor tyrosine kinase,protein kinase B1)were enriched in the pathways of phosphatidylinositol 3-kinase-protein kinase B,mitogen-activated protein kinase,hypoxia-inducible factor 1,and cancer-related pathways.Molecular docking verified the strong binding activity of 3′,5,7-trihydroxy-4-methoxyflavone and brewer's sterol with non-receptor tyrosine kinase and protein kinase B1.The study suggests that this core combination may treat limb lymphedema by modulating non-receptor tyrosine kinase,protein kinase B1 and the above pathways.

Abstract:BACKGROUND:Recent studies have shown that the endocannabinoid system has a positive effect on the release of dopamine in the mesocorticolimbic,and the reward mechanism of dopamine is a key factor influencing exercise motivation. OBJECTIVE:To systematically investigate the composition of the endocannabinoid system and its important role in neurotransmitter regulation,emotion regulation and pain perception,and to focus on exploring how the endocannabinoid system promotes the improvement of exercise motivation through the dopamine reward system,signal integration in motor control regions and fatigue recovery mechanism. METHODS:Computerized searches were conducted in CNKI,WanFang,VIP,PubMed,MedReading and Web of Science databases.The search terms included"endocannabinoid system,exercise motivation,dopamine reward system,neuromodulation,cannabinoid receptor,anandamide,2-arachidonoylglycerol"in Chinese and English.According to the inclusion and exclusion criteria,84 articles were finally included for review. RESULTS AND CONCLUSION:This study reveals the significant role of the endocannabinoid system in promoting exercise motivation.(1)In the reward pathway,the endocannabinoid system acts on the mesolimbic dopamine pathway and stimulates dopamine release through downstream cannabinoid type 1 receptors,thereby enhancing the rewarding effect of the dopaminergic pathway and ultimately increasing the pleasure during exercise.(2)In terms of motor control,the endocannabinoid system achieves an optimal state by regulating synaptic plasticity changes in the ventromedial prefrontal cortex,and it precisely transmits signals to the striato-cortical circuit through spatial positioning to maintain the stability of exercise motivation.Moreover,the anti-inflammatory mechanism mediated by cannabinoid type 2 receptors can protect the nervous system from damage by inhibiting the excessive activation of microglial M1 polarization.(3)In terms of fatigue recovery,the endocannabinoid system,on the one hand,alleviates post-exercise discomfort and reduces fatigue caused by exercise by inhibiting the body's pain receptors through cannabinoid type 1 or type 2 receptors.On the other hand,it can increase the plasticity of brain neurons and improve the structure of muscle fibers through the action of anandamide-brain-derived neurotrophic factor to help restore physical strength quickly.In conclusion,targeting the endocannabinoid system can effectively enhance people's desire to engage in sports activities,which has important clinical value and significance,especially for those who have not participated in physical exercise for a long time or those suffering from depression.However,more experimental evidence is needed to support this conclusion.

Abstract:BACKGROUND:After a stroke,damage to the central nervous system can lead to abnormalities in motor control.Lesions in the visual,proprioceptive,and vestibular systems can cause abnormalities in sensory integration,and attention deficits and unilateral neglect can also affect sensory input. OBJECTIVE:To investigate the status quo of balance function in patients with hemiplegia after stroke and to analyze its influencing factors. METHODS:A total of 166 inpatients with stroke who were treated in the Department of Rehabilitation of Shandong Provincial Hospital of Traditional Chinese Medicine from January 2023 to October 2024 were selected by the convenience lottery method.The survey was performed using the General Information Questionnaire,Berg Balance Scale,Simplified Fugl-Meyer Scale of the Lower Extremity,National Institutes of Health Stroke Scale,Visual Analogue Scale,Modified Ashworth Scale,Concise International Fall Efficacy Scale,and Functional Walking Grading.Multiple linear regression was used to analyze the main influencing factors of balance function in stroke patients with hemiplegia. RESULTS AND CONCLUSION:The balance function score of post-stroke hemiplegia patients was(28.39±8.69)points.The results of multiple linear regression analysis showed that the motor function,neurological deficit,spasticity of the lower limb,fall efficacy,unilateral neglect,and visual function were included in the regression equation(F=131.142,P<0.001),which explained 90.4%of the total variation in balance function.In conclusion,the balance function of stroke patients with hemiplegia is at a low and medium level,with the lower limb motor function,neurological deficit,lower limb spasticity,fall efficiency,unilateral neglect and visual function as the main influencing factors.

Abstract:BACKGROUND:Surface electromyography,as a non-invasive neuromuscular monitoring technique,enables real-time quantification of muscle function status.It offers significant advantages in musculoskeletal pain diagnosis and treatment,efficacy assessment,and therapeutic optimization,providing objective evidence for precision diagnosis and treatment of musculoskeletal pain. OBJECTIVE:To analyze the current research status,hotspots,and evolutionary trends of surface electromyography application in musculoskeletal pain rehabilitation through bibliometric analysis. METHODS:Relevant literature on surface electromyography in musculoskeletal pain rehabilitation from 2000 to 2025 was retrieved from the Web of Science Core Collection database.CiteSpace 6.4.R1 software was used to analyze countries,institutions,authors,journals,key words,etc. RESULTS AND CONCLUSION:A total of 507 articles were included in the bibliometric analysis.From 2000 to 2025,the number of publications on surface electromyography in musculoskeletal pain rehabilitation exhibited a fluctuating upward trend.China produced the highest number of publications,while Italy exhibited the highest centrality.Aalborg University ranked first in both highest number and centrality of publications.Anders Christoph from Germany was the most prolific author,and the journal with the highest co-citation frequency was Journal of Electromyography&Kinesiology.Application research on surface electromyography in musculoskeletal pain rehabilitation exhibits interdisciplinary characteristics,spanning neurology,molecular science,biology,sports medicine,rehabilitation,and physical education.Core keywords in this field include musculoskeletal pain,surface electromyography,and low back pain,with current research hotspots focusing on muscle performance,spine,and therapeutic exercise.Over the past two decades,surface electromyography has been widely adopted as a non-invasive monitoring technique in musculoskeletal pain rehabilitation.Research has expanded from fundamental theory to clinical applications and occupational health,indicating that future academic exploration will unfold in diverse and multifaceted directions.

Abstract:BACKGROUND:The free peroneal muscle flap is currently an important method for repairing unilateral maxillary defects.In clinical practice,both single-layer free peroneal muscle flaps and double-layer folded free peroneal muscle flaps are commonly used to address these defects.However,there is still a lack of relevant biomechanical studies on the restoration of the bony struts of the maxilla following the reconstruction with either technique. OBJECTIVE:To analyze the biomechanical characteristics of unilateral maxillary defects repaired with a single-layer free fibular flap and a double-layer folded free fibular flap,and to simulate the biomechanical properties of each structure after implant restoration using the three-dimensional finite element method. METHODS:CT data of the maxilla and fibula from a 52-year-old male patient scheduled for"subtotal maxillectomy with simultaneous vascularized fibular osteomyocutaneous flap reconstruction"were collected.The data were imported into Mimics 21.0 software to digitally simulate subtotal maxillectomy and to establish 3D models of single-layer and double-layer folded fibular flap reconstructions.The models were then imported into Geomagic Studio 2014,SolidWorks 2019,and Ansys 18.0 to construct three-dimensional finite element models:a normal maxillary complex(Model A),a unilateral maxillary defect reconstructed with a single-layer free fibular flap and simulated implant restoration(Model B),and a unilateral maxillary defect reconstructed with a double-layer folded free fibular flap and simulated implant restoration(Model C).The stress distribution and biomechanical stability of the maxilla,miniplates,and implant prostheses under bilateral posterior vertical loading were compared among the models. RESULTS AND CONCLUSION:(1)In Models A,B,and C,maxillary stress was primarily distributed in the healthy maxilla near the zygomatic region,the reconstructed fibular region,and the bilateral lateral orbit,medial orbit,and nasal root areas.Model B exhibited significantly higher stress at the left piriform aperture margin compared with Model C,with a prominent red stress concentration zone in this area.(2)Under various loads,the displacement at the junction between the fibula and the alveolar process in Model B was greater than that in Model C.The maximum displacement occurred under a 250 N load on the affected side:30 μm for Model B and 23 μm for Model C.(3)In both Models B and C,the maximum stress on the miniplates was located at the bending points connecting the fibular segments.The peak stress values were similar between the two models.The maximum displacement of the miniplates occurred at the first screw hole of the miniplate connecting the fibula and the alveolar process,with the highest displacement(27 μm)observed in Model B under a 250 N load on the affected side.(4)Under three loading conditions,stress in the implants of Models B and C was concentrated at the neck regions,with the highest stress occurring in the distal implants.Model C exhibited significantly greater stress(160.6 MPa)than Model B(58.5 MPa).Meanwhile,the maximum displacement occurred in the anterior implants of both models,increasing with load magnitude,and Model C showed slightly lower displacement than Model B.(5)The results confirmed that both single-layer and double-layer folded free fibular flaps effectively restored the biomechanical support of the maxilla after unilateral defect reconstruction.However,the single-layer reconstruction led to stress concentration near the nasal region,increasing the risk of fracture under high external forces.Therefore,the double-layer folded fibular reconstruction is more favorable for restoring nasomaxillary support.Between the two methods,the double-layer folded fibular flap provided better stability,though it resulted in higher localized stress on the implant prostheses.

Abstract:BACKGROUND:Studies have indicated that multi-modal exercise training can effectively improve the endurance walking ability and cognitive processing speed of patients with moderate to severe mobility impairments caused by multiple sclerosis.This effect appears to be related to the optimization of cardiorespiratory function;however,there is a lack of literature review in this area. OBJECTIVE:To identify research hotspots and explore the thematic evolution in the field of exercise interventions for multiple sclerosis through a bibliometric analysis. METHODS:A literature search was conducted in the Web of Science Core Collection database using the query:TS=("multiple sclerosis")AND TS=("physical activity"OR exercise OR sport),limited to English-language publications.A total of 3 761 articles regarding exercise interventions for multiple sclerosis were included for visualized analysis using CiteSpace. RESULTS AND CONCLUSION:(1)The evolving landscape of key research domains in exercise and multiple sclerosis demonstrates a notable transition toward interdisciplinary collaboration,marked by a paradigm shift from conventional therapeutic approaches to cutting-edge digital rehabilitation solutions.Current research trends reveal a progressive movement from fundamental immunological studies and disease progression monitoring to more investigations focusing on rehabilitation interventions and quality-of-life enhancements.(2)Thematic classifications encompass three key dimensions:intervention methodologies,research design frameworks,and intervention indicators.Notably,advancements in modern rehabilitation technologies have facilitated the application of virtual reality systems,virtual reality games,and robotic-assisted training protocols as therapeutic interventions for patients with multiple sclerosis.Exercise intervention for multiple sclerosis is shifting from empirical practices toward a more precise,theory-driven approach.(3)Early research focused on the clinical manifestations of multiple sclerosis,common comorbidities(such as depression and fatigue),and the initial examination of exercise interventions.Mid-to-late stage research emphasized the standardized validation of exercise rehabilitation effects,including an increasing number of randomized controlled trials and meta-analyses,while the research scope expanded to cognitive impairment,behavioral adjustment,and other aspects.The latest stage of research,building on previous achievements,combines new technologies such as virtual reality and adopts patient-experience-centered methods,thus forming a more comprehensive and evidence-based treatment strategy.The development of research themes can be divided into four periods:"macro-benefit verification,""theoretical modeling and initial exploration of mechanisms,""behavioral motivation construction and participation promotion,"and"precision and technology integration."This study provides a solid theoretical foundation for the formulation and improvement of exercise intervention plans in clinical practice for multiple sclerosis.

Abstract:BACKGROUND:Under hypertensive conditions,exosome communication between endothelial progenitor cells and brain endothelial cells is impaired,which may be a key mechanism leading to poor prognosis in patients with hypertensive stroke.Exercise rehabilitation is an important non-drug means of preventing and treating hypertensive stroke,but the specific mechanism is unclear. OBJECTIVE:To investigate the effect of high-intensity interval training on the function of exosomes from endothelial progenitor cells in spontaneously hypertensive rats and explore the possible mechanism. METHODS:Twenty-four male spontaneously hypertensive rats were randomly assigned into exercise group or control group.The animals in the exercise group underwent 6 weeks of high-intensity interval training,while those in the control group were kept quietly in cage.After the experiment,bone marrow endothelial progenitor cells were isolated and cultured,and exosomes were obtained to detect the expression of miR-27a using qPCR.After treating neuroblastoma N2a(Neuro-2a)with angiotensin Ⅱ and hypoxia,they were co-incubated with endothelial progenitor cell-derived exosomes and a miR-27a inhibitor.The cells were then divided into the following groups:a blank group(cultured in normoxic high-glucose DMEM medium),an injury group(treated with angiotensin Ⅱ combined with hypoxia),an injury+control exosome group,an injury+exercise exosome group,and an injury+exercise exosome+miR-27a inhibitor group.The following parameters were assessed:exosome uptake rate,cell viability,reactive oxygen species levels,and the expression levels of cytochrome C and NADPH oxidase 4 protein. RESULTS AND CONCLUSION:(1)Exercise could increase the uptake efficiency of endothelial progenitor cell exosomes by Neuro-2a cells.(2)Exercise up-regulated the expression of miR-27a in endothelial progenitor cell exosomes and Neuro-2a cells(P<0.05).(3)Exercise-induced endothelial progenitor cell exosomes improved the survival of Neuro-2a cells(P<0.05),reduced the level of reactive oxygen species(P<0.05)and down-regulated the protein expression of cytochrome C and NADPH oxidase 4(P<0.05),while the above effects were weakened after administration of miR-27a inhibitor(P<0.05).To conclude,high-intensity interval training-induced exosomes from endothelial progenitor cells in spontaneously hypertensive rats alleviate the oxidative stress of damaged neurons through the miR-27a pathway.

Abstract:BACKGROUND:Cystic degeneration is a critical pathological feature of steroid-induced osteonecrosis of the femoral head and exhibits unusual reparative responses.Studies have shown that immune cell infiltration and upregulation of inflammatory cytokines in cystic areas may be closely related to bone regeneration during repair.Therefore,investigating the role of the immune microenvironment in cystic lesion repair has important clinical significance. OBJECTIVE:To explore the immune microenvironment in cystic degeneration of steroid-induced osteonecrosis of the femoral head based on single-cell sequencing and to elucidate the role of inflammation in the repair process as well as to validate the effects of glucocorticoids on macrophage polarization and inflammatory responses via in vitro cellular experiments. METHODS:(1)Single-cell RNA sequencing was used to analyze the immune microenvironment of cystic regions in steroid-induced osteonecrosis of the femoral head.Pathologic observation of cystic degeneration specimens was also performed.(2)In addition,an in vitro cell model was established.In vitro cultured RAW 264.7 macrophages were divided into control group(normal culture of RAW cells),lipopolysaccharide group(lipopolysaccharide intervention for 24 hours),and dexamethasone+lipopolysaccharide group(dexamethasone pretreatment for 72 hours and lipopolysaccharide intervention for 24 hours).RT-qPCR was used to detect the expression of cellular M1 polarization markers(inducible nitric oxide synthase,tumor necrosis factor α,and interleukin 6)and M2 polarization markers(arginase 1 and interleukin 10).ELISA was used to detect the levels of inflammatory factors in the cell culture supernatants.Flow cytometric assay was performed to detect the levels of cellular reactive oxygen species. RESULTS AND CONCLUSION:(1)Single-cell sequencing results revealed a diverse infiltration of immune cells in the cystic region,with significant upregulation of inflammatory cytokines such as tumor necrosis factor α and interleukin 6.(2)Observation of the pathologic specimen showed the presence of multiple inflammatory cell infiltrates in the cystic degeneration.(3)In vitro experiments demonstrated that combined treatment with dexamethasone and lipopolysaccharide significantly induced M1 polarization of RAW 264.7 macrophages,inhibited the expression of anti-inflammatory M2 phenotype and promoted the generation of reactive oxygen species,thereby enhancing the local inflammatory response(significant upregulation of tumor necrosis factor α,interleukin 6 and interleukin 1β).Overall,the immune microenvironment in the cystic regions of steroid-induced osteonecrosis of the femoral head plays a critical role in bone repair.Immune cell infiltration and inflammatory cytokine expression may exert dual effects during the reparative process.Excessive immune activation may lead to repair failure.Thus,modulating immune responses—especially balancing M1/M2 macrophage polarization—may serve as a potential therapeutic strategy for enhancing cystic repair in steroid-induced osteonecrosis of the femoral head.

Abstract:BACKGROUND:Developmental dysplasia of the hip is the most common skeletal deformity in children and is an important risk factor for osteoarthritis in young adulthood.Severe cases require hip replacement,which seriously affects the quality of life of patients. OBJECTIVE:To investigate the expression of secreted modular calcium-binding protein 2(SMOC2)in the cartilage acetabular roof of rats with developmental dysplasia of the hip and its effect on chondrocyte autophagy. METHODS:(1)Newborn Sprague-Dawley rats were randomly divided into disease group and control group(normal rats).A developmental dysplasia of the hip model was established in rats of the disease group.At 2 weeks of age,the expression of SMOC2 as well in the cartilage tissues of the acetabular top wall was detected by real-time quantitative polymerase chain reaction and Western blot.Autophagy-related protein expression was assessed via Western blot.(2)Chondrocytes were isolated from rat acetabular tissue and divided into three groups:Sh-NC,Sh-SMOC2-1,and Sh-SMOC2-2 groups.The expression of autophagy related proteins was detected by Western blot,and the number of autophagosomes was observed using a transmission electron microscope.(3)Rat acetabular tissue chondrocytes were extracted,and the cells were divided into three groups:Sh-NC,Sh-SMOC2,and Sh-SMOC2+740 Y-P(phosphatidylinositol 3-kinase activator)groups.The expression of autophagy-related proteins was detected using western blot to investigate whether SMOC2 regulates autophagy-related proteins of chondrocytes through the PI3K/AKT pathway. RESULTS AND CONCLUSION:(1)Compared with the control group,there was a decrease in the expression of SMOC2,a decrease in the expression of autophagy-associated protein P62,an increase in the expression of Beclin,and no difference in the expression of microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ in cartilage tissues of the rat acetabular top wall in the disease group.(2)Compared with the Sh-NC group,P62 expression was decreased,microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ ratio was increased,and Beclin1 expression was decreased in chondrocytes of the Sh-SMOC2-1 and Sh-SMOC2-2 groups.(3)Compared with the Sh-SMOC2 group,P62 expression was elevated,microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ ratio was decreased,and there was no difference in Beclin1 expression in chondrocytes of the Sh-SMOC2+740 Y-P group.In conclusion,autophagy is enhanced in acetabular chondrocytes of 2-week-old rats with developmental dysplasia of the hip,and SMOC2 can regulate autophagy in rat chondrocytes through the phosphatidylinositol 3-kinase/AKT signaling pathway.

Abstract:BACKGROUND:As a typical representative of neurodegenerative diseases,Parkinson's disease manifests with an intricate web of pathogenic attributes.In the field of programmed cell death,several novel molecular mechanisms have been unveiled in recent years,including but not limited to mitochondrial selective autophagy,iron-dependent cell death,copper ion-mediated apoptosis,and cell damage patterns caused by aberrant disulfide bonds.Studies have indicated that these pathological changes not only contribute to the development of typical clinical symptoms in Parkinson's disease but also exhibit significant correlations with disease progression.From this,it becomes apparent through scholarly works that these mechanisms exert pivotal roles in neuronal dysfunction manifestation.However,uncharted scientific inquiries regarding detailed interactions at the molecular level among these interconnected pathways need to be solved urgently. OBJECTIVE:To review the molecular mechanisms of novel forms of programmed cell death(mitophagy,ferroptosis,cuproptosis,and disulfidptosis)and the roles of their interactions and synergistic effects in Parkinson's disease,and to explore the potential impact and therapeutic prospects of these novel forms of programmed cell death in the pathogenesis of Parkinson's disease. METHODS:The first author conducted a computer-based search of literature indexed in the CNKI and PubMed databases from 2015 to 2025 using the keywords of"Parkinson's disease,mitophagy,ferroptosis,disulfidptosis,cuproptosis,apoptosis,necroptosis,pyroptosis"in Chinese and English,respectively.Literature that is inconsistent with the research content,outdated,or duplicative was excluded.A total of 1 368 relevant articles were retrieved,and 87 articles were ultimately included in the review analysis. RESULTS AND CONCLUSION:(1)The new types of programmed cell death,including mitophagy,ferroptosis,cuproptosis,and disulfidptosis,are essential regulatory pathways for maintaining normal cellular renewal and homeostasis,making them a currently hot research area in life sciences.(2)Mitophagy is a selective autophagic process that can clear damaged mitochondria,thereby maintaining mitochondrial homeostasis in neuronal cells during Parkinson's disease,and playing a crucial role in regulating neuronal health and function.(3)Ferroptosis is a novel form of programmed cell death characterized by iron accumulation and lipid peroxidation,which can regulate Parkinson's disease through various pathways,including cystine/glutamate,iron metabolism,and polyunsaturated fatty acids.(4)Cuproptosis,as a newly discovered mode of cell death,involves the role of copper chelators and heat shock proteins in regulating α-synuclein aggregation and cell survival,potentially providing new targets for the treatment of Parkinson's disease.(5)Disulfidptosis is associated with the aggregation of α-synuclein,which is considered an important feature of Parkinson's disease.Its specific role in Parkinson's disease requires further research.(6)The interactive and synergistic effects of various cell death mechanisms in Parkinson's disease(such as Fe/Cu synergistic regulation of Parkinson's disease)hold great potential for the future.

Abstract:OBJECTIVE:Through a network meta-analysis integrating direct and indirect evidence,this study compared the effects of different non-invasive brain stimulation techniques and parameters on gait and balance functions of patients with Parkinson's disease,and ranked the best intervention schemes. METHODS:A literature search of CNKI,WanFang,VIP,CBM,PubMed,Cochrane Library,Embase and Web of Science was conducted to screen the randomized controlled trials related to non-invasive brain stimulation for gait and balance disorders in patients with Parkinson's disease.The search time limit was up to June 16,2025.Data of the included studies were extracted for statistical processing using RevMan 5.4.1 software and Stata 17.0 software. RESULTS:(1)A total of 47 trials were conducted,involving 2 767 patients(1 399 in the trial group and 1 368 in the control group).(2)The results of traditional meta-analysis indicated that high-frequency repetitive transcranial magnetic stimulation could reduce the scores on the third part of the Unified Parkinson's Disease Rating Scale and the Freezing of Gait Questionnaire,shorten the Timed Up and Go Test time,increase step length,improve gait speed,and raise the Berg Balance Scale score,all of which were superior to conventional treatment(P<0.05).Transcranial direct current stimulation could lower the Freezing of Gait Questionnaire score,shorten the Timed Up and Go Test time,increase step length,improve gait speed,and raise the Berg Balance Scale score,all of which were superior to conventional treatment(P<0.05).Low-frequency repetitive transcranial magnetic stimulation could reduce the Unified Parkinson's Disease Rating Scale Ⅲ score,and there was a significant difference compared with conventional treatment(P<0.05).There was no statistically significant improvement in step frequency for all three methods(P>0.05);however,due to the small number of studies,further verification is required.(3)The results of the network Meta-analysis indicated that in terms of reducing the Unified Parkinson's Disease Rating Scale Ⅲ score:high-frequency repetitive transcranial magnetic stimulation targeting bilateral regions of the primary motor cortex and dorsolateral prefrontal cortex produced cumulative probability ranking is the highest(95.2％),followed by stimulation on the primary motor cortex(72.5％);in terms of shortening the Timed Up and Go Test time:high-frequency repetitive transcranial magnetic stimulation produced cumulative probability ranking was the highest on the dorsolateral prefrontal cortex(85.5％),followed by stimulation on the primary motor cortex(69.0％);in terms of improving gait speed:high-frequency repetitive transcranial magnetic stimulation produced cumulative probability ranking was the highest on the dorsolateral prefrontal cortex(92.5％),followed by stimulation on the primary motor cortex(76.7％);in terms of increasing the Berg Balance Scale score:high-frequency repetitive transcranial magnetic stimulation produced cumulative probability ranking was the highest on the primary motor cortex(79.9％),followed by transcranial direct current stimulation on the cerebellum(79.8％).(4)The GRADE evidence quality assessment results show that the evidence levels for the Unified Parkinson's Disease Rating Scale Ⅲ,Freezing of Gait Questionnaire score,Timed Up and Go Test time,and stride length were moderate,while those for gait speed,step frequency,and Berg Balance Scale score were low. CONCLUSION:Different types of non-invasive brain stimulation can all improve the gait and balance functions of patients with Parkinson's disease.High-frequency repetitive transcranial magnetic stimulation targeting the dorsolateral prefrontal cortex is superior to that targeting the primary motor cortex in improving gait function(moderate evidence),high-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex is superior to transcranial direct current stimulation targeting the cerebellum in improving balance function(low-level evidence).

Abstract:BACKGROUND:Existing studies have shown that extracorporeal shock wave intervention can effectively inhibit the formation of tissue fibrosis.However,there are limited experimental studies and summaries regarding the anti-fibrotic effects of extracorporeal shock wave,and no comprehensive review of the associated signaling pathways has been conducted. OBJECTIVE:To review current clinical or preclinical primary studies and summarize the applications of extracorporeal shock wave in fibrotic tissues and the relevant molecular mechanisms,thereby providing novel insights for the clinical treatment of fibrotic diseases. METHODS:The relevant literatures in PubMed,Web of Science,CNKI,WanFang and VIP databases were searched.The search time was from January 2014 to September 2024,and the search terms were"extracorporeal shockwave therapy,shock wave therapy,shock wave,fibrosis,fibroses"in English and"shock wave,extracorporeal shockwave therapy,fibrosis,anti-fibrosis"in Chinese.A combination of subject headings and free terms was used for the search.After screening and excluding studies based on predefined inclusion and exclusion criteria,a total of 67 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)Extracorporeal shock wave intervention is beneficial for various fibrosis-related diseases,including scars,musculoskeletal disorders,and organ diseases.It can effectively reduce the degree of tissue fibrosis and improve clinical symptoms in patients.(2)Extracorporeal shock wave mainly influences the expression of fibrosis-related cytokines and extracellular matrix composition by modulating signaling pathways such as transforming growth factor-β1,mitogen-activated protein kinases,vascular endothelial growth factor,and inflammatory signaling pathways,thereby inhibiting excessive fibrosis formation.(3)The current review identifies a limited number of clinical studies with insufficient data to support robust conclusions.Additionally,due to the singularity of experimental results and significant differences in intervention subjects and extracorporeal shock wave intervention protocols across studies,there may be an impact on the clarification of the specific dose-response mechanisms and the overall molecular action system of extracorporeal shock wave in anti-fibrosis.To conclude,extracorporeal shock wave may serve as an effective therapeutic approach for the clinical treatment of fibrosis-related diseases in the future.