Abstract:BACKGROUND:Adipocyte differentiation is a complex biological process involving the transformation of preadipocytes into mature adipocytes.This process plays a key role in the development and progression of obesity and related metabolic diseases.In recent years,the complement C1q/tumor necrosis factor-related protein family,as a new member of the adipokine family,has become a research hotspot in the field of metabolic regulation. OBJECTIVE:To investigate the effect of complement 1q/tumor necrosis factor-related protein 4 on the differentiation of 3T3-L1 preadipocytes and its underlying mechanism. METHODS:The CCK-8 assay was used to determine the effects of different concentrations of complement 1q/tumor necrosis factor-related protein 4 on the viability of 3T3-L1 preadipocytes,and a safe concentration was selected for intervention.3T3-L1 preadipocytes were divided into a control group,an inducer group,and a complement 1q/tumor necrosis factor-related protein 4 group.3T3-L1 preadipocytes were first contact-inhibited for 2 days,followed by adipogenic inducer and complement 1q/tumor necrosis factor-related protein 4 treatment.On day 10 of differentiation,lipid droplet formation was observed using Oil Red O staining.The mRNA and protein expression levels of CCAAT/enhancer binding protein α,peroxisome proliferator-activated receptor γ,and fatty acid binding protein 4 were determined by RT-qPCR and western blot assay.Intracellular triglyceride and total cholesterol levels were measured using triglyceride and total cholesterol detection kits. RESULTS AND CONCLUSION:The safe maximum concentration of complement 1q/tumor necrosis factor-related protein 4 without toxicity to 3T3-L1 preadipocytes was 1 000 ng/mL.Compared with the control group,the inducer group showed increased intracellular lipid droplet formation,elevated triglyceride and total cholesterol levels(P<0.05),and significantly upregulated mRNA and protein expression levels of CCAAT/enhancer binding protein α,peroxisome proliferator-activated receptor γ,and fatty acid binding protein 4(P<0.05).Compared with the inducer group,the complement 1q/tumor necrosis factor-related protein 4 group showed reduced intracellular lipid droplet formation,lower triglyceride and total cholesterol levels(P<0.05).The mRNA and protein expression levels of CCAAT/enhancer binding protein α,peroxisome proliferator-activated receptor γ,and fatty acid binding protein 4 were significantly downregulated(P<0.05).These results suggest that complement 1q/tumor necrosis factor-related protein 4 inhibits the differentiation of preadipocytes into mature adipocytes,and its mechanism of action may be related to downregulating the expression of CCAAT/enhancer binding protein α,peroxisome proliferator-activated receptor γ,and fatty acid binding protein 4.

Abstract:BACKGROUND:The anterior transpedicular screw fixation system can achieve adequate decompression and strong fixation in a single anterior surgery.However,due to its unique anatomical structure,the risk of screw placement is relatively high.Previous domestic and international scholars have confirmed the feasibility of this approach through anatomical measurements,but there are some drawbacks such as relatively small sample sizes,difficulties in locating the pedicle axis,and limitations in measurement methods. OBJECTIVE:To perform morphological measurements of the adult cervical spine based on imaging to provide anatomical guidance for anterior transpedicular pedicle screw fixation. METHODS:3D CT scan data of 50 adult cervical vertebrae were imported into the Mimics system for 3D reconstruction.Morphological data were measured,including pedicle axis distance,pedicle width,pedicle height,pedicle horizontal axial angle,pedicle sagittal angle,distance from the entry point in the transverse plane,distance to the entry point in the sagittal plane,axial vertebral length and axial pedicle length. RESULTS AND CONCLUSION:(1)Positioning of nail entry points:C3 and C4 were located on the opposite side of the median sagittal plane of the vertebral body,with distances from the median sagittal line of approximately 2.060 mm and 2.310 mm.C5 could be located on the same side of the median sagittal line as or opposite to the median sagittal line,with an average value of approximately 1.224 mm.C6-C7 were located on the same side of the body,with distances from the center of the vertebral body of 1.132 mm and 2.538 mm;the distances of C3-C7 from the vertebral body of the upper endplates increasd gradually,with average values ranging from 2.362-7.350 mm.(2)In the direction of the entry point,the cross-sectional pinch angles:C3-4 gradually increased to 46.32°-47.36°,and C5-7 gradually decreased from 44.03° to 37.80°;the sagittal pinch angles:C3-C4 needed to be shifted caudally,with the angles of 95.75° and 100.93°;C5-C7 angles needed to be shifted toward the cephalad,with angles of 104.38°,110.34°,and 104.86°,respectively.(3)There was no statistical significance in the positioning and orientation of the entry point between genders and sides(P>0.05).For screw selection,except for individual patients with abnormal cervical vertebral development,the vast majority of the lower cervical pedicle screws were selected to be at least 30-mm-long,4.0-mm-diameter screws for males,and at least 28-mm-long,3.5-mm-diameter screws for females for anterior transpedicular pedicle screw fixation,which could ensure their safety and reliability while to achieve bicortical screws.(4)Morphological measurements confirm that anterior transpedicular screw fixation of the lower cervical spine is feasible,but a personalized fixation plan should be developed based on individual needs.

Abstract:BACKGROUND:Neuropathic pain has a complex pathogenesis and limited clinical intervention outcomes.In recent years,exosomes have gradually emerged as a focal point in the study of neuropathic pain due to their unique intercellular communication functions and molecular delivery capabilities. OBJECTIVE:To systematically review research progress on exosomes in the field of neuropathic pain using bibliometric methods,summarize the knowledge framework and research hotspots,and provide theoretical foundations and translational strategies for advancing this field. METHODS:Based on the Web of Science Core Collection(WOSCC)database,relevant literature on exosomes and neuropathic pain was retrieved over the time span from January 1,2012,to March 31,2025.Keyword co-occurrence analysis,clustering analysis,outbreak detection,and collaboration network visualization were performed using VOSviewer and CiteSpace software. RESULTS AND CONCLUSION:A total of 313 articles were included in this study.Among 42 countries or regions,the United States and China made significant contributions.Shanghai Jiao Tong University and Nantong University were the research institutions with the highest number of publications.The journals with the most publications and the highest number of citations were Neural Regeneration Research and International Journal of Molecular Sciences,respectively.The study identified 382 authors,with Zhang Zheng Gang having the highest number of publications and Zhang Yi having the highest number of citations.Keywords of particular interest included"nerve regeneration,""neuroinflammation,""Schwann cell,""regenerative medicine,"and"spinal cord injury,"all of which are key areas for future research.Bibliometric analysis revealed research trends of exosomes in the field of neuropathic pain.Exosomes hold great promise in elucidating the underlying mechanisms and developing novel precision therapies for neuropathic pain.Future studies may combine multi-omics and engineered exosome platforms to advance the development of this field.

Abstract:BACKGROUND:Non-infectious poor wound healing following lumbar surgery is a significant clinical complication that prolongs hospitalization and increases the risk of reoperation.However,its predictive indicators remain unclear.Based on the hypothesis that paraspinal muscle degeneration may impede tissue repair by altering the local microenvironment,this study aimed to investigate the predictive value of preoperative paraspinal muscle fatty infiltration for non-infectious poor wound healing and its association with osteoporosis. OBJECTIVE:To quantify the degree of paraspinal muscle fatty infiltration using preoperative MRI and evaluate its predictive value for non-infectious poor wound healing after lumbar surgery. METHODS:A retrospective analysis was conducted on medical records of 4 368 patients who underwent traditional open posterior lumbar surgery at Third Affiliated Hospital of Guangzhou University of Chinese Medicine between 2019 and 2024.We screened 190 patients with a postoperative hospital stay of 15 days or longer.Based on postoperative wound healing and infection indicators,patients with non-infectious poor healing were identified from these 190 patients and placed in a poor healing group(41 patients).The remaining 4 178 surgical patients were screened and their medical records and blood tests were reviewed.Patients with good healing were selected and placed in a good healing group(40 patients).The non-infectious poor healing group was further divided into an osteoporosis group and a non-osteoporosis group.Preoperative lumbar MRI images were analyzed using ImageJ software to measure and calculate the cross-sectional area of the psoas major muscle and the percentage of fat infiltration in the erector spinae and multifidus muscles. RESULTS AND CONCLUSION:(1)No significant differences were observed in baseline characteristics such as gender,age,or diabetes status between the poor healing group and the good healing group(P>0.05).(2)There were significant differences in the functional cross-sectional area and fat infiltration percentage of the psoas major,erector spinae,and multifidus muscles between the poor healing group and the good healing group(P<0.05).(3)Logistic regression analysis showed that the fat infiltration percentage was an independent risk factor for poor wound healing.(4)Receiver operating characteristic curve analysis showed that the fat infiltration percentage had a high predictive value for poor wound healing(area under the curve>0.7).(5)One-way analysis of variance suggested that osteoporosis may be a risk factor for the degree of fatty infiltration of the L4 multifidus muscle(P<0.05).(6)The results indicate that the percentage of fatty infiltration of the paraspinal muscles is an important indicator for predicting poor wound healing in patients undergoing traditional posterior open lumbar spine surgery,providing a clinical reference.Osteoporosis has also been shown to be a risk factor for the degree of fatty infiltration of the L4 multifidus muscle.However,due to the small sample size in this subgroup,further clinical trials are needed to confirm whether osteoporosis affects non-infectious poor wound healing after lumbar spine surgery.

Abstract:BACKGROUND:The scarcity of bone trabecular structures caused by osteoporosis is not enough to maintain screw holding power,which often leads to the failure of internal fixation surgery.The screw holding power is often increased by increasing the diameter and length of screws,changing the surface coating of screws,and reinforcing the nail track with bone cement.The cement reinforced cortical bone track nailing technique and the modified cortical bone track nailing technique using a new type of variable diameter screw have been proven to have good fixation effects,and now the related mechanical properties of the two need to be analyzed and compared. OBJECTIVE:Finite element analysis was used to compare the mechanical properties of bone cement-strengthened cortical bone trajectory nailing technology,cortical bone trajectory nailing technology,and modified cortical bone trajectory nailing technology using a new variable-diameter total cortical bone thread screw in lumbar spine internal fixation surgery. METHODS:Based on the CT scan data processing of three osteoporotic vertebrae,the L4 lumbar spine model was constructed,and the innovative variable-diameter all-cortical bone screw was applied in the modified cortical bone nailing technique,with the screw having a total length of 45 mm and a variable diameter of 5.5-4.3 mm as the modified cortical bone trajectory screw group.It was compared with the standard cortical bone trajectory screw group(5.5 mm in diameter and 40 mm in length)and the bone cement-augmented cortical bone trajectory screw group(5.5 mm in diameter,40 mm in length,and 1 mm in diameter in the center opening).The fixation strength of the screws in each group was compared by measuring the axial withdrawal force,screw stability(upper,lower,left,and right load displacement ratio),and vertebral body mobility. RESULTS AND CONCLUSION:(1)Axial pullout strength:The bone cement-augmented cortical bone trajectory screw group showed greater axial pullout strength than the modified cortical bone trajectory screw group(P=0.024 6).Additionally,both the bone cement-augmented cortical bone trajectory screw group and the modified cortical bone trajectory screw group exhibited significantly higher axial pullout strength compared with the standard cortical bone trajectory screw group(P=0.000 1 and P=0.002 64,respectively).(2)Screw stability:Under inferior loading conditions,the load-displacement ratio of the screws was highest in the bone cement-augmented cortical bone trajectory screw group,followed by the standard cortical bone trajectory screw group and the modified cortical bone trajectory screw group(all P<0.05).The modified cortical bone trajectory screw group showed a higher stability compared with the standard cortical bone trajectory screw group(P<0.05).(3)Vertebral mobility:Under five different loading conditions,the bone cement-augmented cortical bone trajectory screw group exhibited less vertebral mobility than the modified cortical bone trajectory screw group,and no significant difference was detected(P>0.05).Furthermore,both the bone cement-augmented cortical bone trajectory screw group and the modified cortical bone trajectory screw group showed less vertebral mobility compared with the standard cortical bone trajectory screw group.(4)There were no statistically significant differences between the bone cement-augmented cortical bone trajectory screw group and the modified cortical bone trajectory screw group in terms of load-displacement ratio and lumbar mobility(P>0.05).(5)This suggests that the bone cement-augmented cortical bone trajectory screw technique offers superior biomechanical performance compared with the novel variable-diameter full-cortical bone screw.Additionally,the bone cement-augmented cortical bone trajectory screw technique may be a more suitable choice for internal fixation surgery in clinical patients with osteoporosis.

Abstract:BACKGROUND:Hyperuricemia can induce kidney damage and activate inflammatory signaling pathways,leading to glomerular hypertrophy and the deterioration of renal function.Exercise,as a non-pharmacological treatment method,can regulate the expression of proteins related to uric acid excretion.However,the regulatory mechanism of exercise on hyperuricemia remains unclear. OBJECTIVE:To explore the potential effect and molecular mechanism of moderate-intensity exercise on hyperuricemia. METHODS:(1)Using the Mendelian randomization analysis method,the moderate-intensity exercise datasets(ukb-a-508,ukb-b-4710)from the database developed by the MRC Integrative Epidemiology Unit at the University of Bristol were used as the exposure factors,and the serum uric acid level dataset(ebi-a-GCST90018977)was used as the outcome indicator.Meanwhile,the gout datasets(finn-b-GOUT,finn-b-M13GOUT)from the FinnGen,a genomics and personalized medicine research project in Finland,were included as another outcome indicator to explore the potential associations among moderate-intensity exercise,gout,and uric acid levels.(2)An animal experiment was conducted to explore the specific mechanism between moderate-intensity exercise and hyperuricemia.Four groups were set up:blank control group,moderate-intensity exercise+blank group,hyperuricemia model group,and moderate-intensity exercise+hyperuricemia model group.After 8 weeks of moderate-intensity treadmill training in the experimental C57BL/6 mice,biochemical indicators such as serum uric acid,creatinine,and blood urea nitrogen were detected.Hematoxylin-eosin staining was used to observe the pathological changes in kidney tissues.Additionally,qRT-PCR and western blot techniques were employed to analyze the gene and protein expression levels of Nod-like receptor family pyrin domain containing-3,Caspase-1,interleukin-1β,interleukin-6,and interleukin-11. RESULTS AND CONCLUSION:(1)The results of Mendelian randomization showed that there was a significant negative correlation between moderate-intensity exercise and both gout and serum uric acid level(P<0.05).(2)Compared with the blank control group,the levels of serum uric acid,creatinine,and blood urea nitrogen in the hyperuricemia model group increased significantly(P<0.05).(3)Compared with the blank control group,the hyperuricemia model group had pathological changes such as glomerular hypertrophy,vacuolar degeneration of renal tubular epithelial cells,and infiltration of inflammatory cells.(4)Compared with the blank control group,the mRNA expression levels of Nod-like receptor family pyrin domain containing-3,interleukin-1β,and interleukin-18 and the expression levels of Nod-like receptor family pyrin domain containing-3,Caspase-1,interleukin-1β,interleukin-6,and interleukin-11 in the hyperuricemia model group were significantly upregulated(P<0.05).(5)After moderate-intensity exercise intervention,the above detection indices in the moderate-intensity exercise+hyperuricemia model group decreased significantly(P<0.05),and the morphology of the renal tissue was improved.These findings suggest that moderate-intensity exercise can reduce the uric acid level and renal injury in hyperuricemia mice.In addition,moderate-intensity exercise can inhibit the activation of the Nod-like receptor family pyrin domain containing-3 signaling pathway and alleviate kidney inflammation.

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.