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28 June 2026, Volume 30 Issue 18 Previous Issue    Next Issue

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Matrix metalloproteinase 9 mediates mitophagy to regulate osteogenesis and myogenesis Wang Siwei, Yao Xiaosheng, Qi Xiaonan, Wang Yu, Cui Haijian, Zhao Jiaxuan 2026, 30 (18):  4557-4567.  doi: 10.12307/2026.678 Abstract ( 66 )   PDF (8129KB) ( 14 )   Save BACKGROUND: Matrix metalloproteinase 9 affects osteogenic and myogenic differentiation, but its specific regulatory mechanism is not well understood. OBJECTIVE: To investigate the effects of oxidative stress injury on mitophagy in mouse MC3T3-E1 and C2C12 cells, and to examine the role of matrix metalloproteinase 9 as a critical regulator in regulating mitophagy and affecting osteogenic and myogenic differentiation via the PTEN-induced kinase 1/Parkin signaling pathway. METHODS: Mouse C2C12 and MC3T3-E1 cells were selected for differentiation and culture. Each cell line was divided into four groups: control, model (hydrogen peroxide-induced oxidative damage), GM6001 (matrix metalloproteinase 9 inhibitor), and 3-methyladenine (PTEN-induced kinase 1/Parkin pathway inhibitor) groups, respectively. Cells in each group were treated for 24 hours. Flow cytometry was used to detect intracellular mitochondrial membrane potential and reactive oxygen species levels. Transmission electron microscopy was used to observe cellular mitochondrial damage and mitophagy. Western blot was used to detect matrix metalloproteinase 9 protein expression. Quantitative reverse transcription polymerase chain reaction and western blot were used to detect the mRNA and protein expressions of P62, microtubule-associated protein light chain 3, PTEN-induced kinase 1, and parkin in MC3T3-E1 cells. Western blot was used to detect the protein expressions of osteogenic proteins osteocalcin, osteopontin, and Runt-related transcription factor 2 in MC3T3-E1 cells. Quantitative reverse transcription polymerase chain reaction was used to detect the mRNA expressions of myogenic genes myogenic factor 5, myogenic factor 6, myogenic differentiation 1, and myogenin in C2C12 cells. RESULTS AND CONCLUSION: (1) In MC3T3-E1 and C2C12 cells, mitochondrial membrane potential was decreased and reactive oxygen species levels were increased in the model, GM6001, and 3-methyladenine groups compared with the control group. Reactive oxygen species levels were decreased in the GM6001 group compared with the model group, and reactive oxygen species levels were increased in the 3-methyladenine group compared with the GM6001 group. (2) Transmission electron microscopy showed that mitochondrial damage was more severe and mitophagy was formed in the model group. Mitochondrial damage was improved in the GM6001 group. Mitochondrial damage and mitophagy were weaker in the 3-methyladenine group compared with the model group. (3) Compared with the control group, matrix metalloproteinase 9 protein expression was increased in the model, GM6001, and 3-methyladenine groups. Compared with the model group, matrix metalloproteinase 9 protein expression was significantly decreased in the 3-methyladenine group. Compared with the 3-methyladenine group, matrix metalloproteinase 9 protein expression was significantly decreased in the GM6001 group. (4) Compared with the control group, the mRNA and protein expressions of P62 were decreased in the model group, further decreased in the GM6001 group, and increased in the 3-methyladenine group. Compared with the control group, the mRNA and protein expressions of microtubule-associated protein light chain 3 II, microtubule-associated protein light chain 3 I, PTEN-induced kinase 1, and Parkin were elevated in the model group, further elevated in the GM6001 group, and decreased in the 3-methyladenine group. (5) In the MC3T3-E1 cells, compared with the control group, the protein expressions of osteocalcin, osteopontin, and Runt-related transcription factor 2 were decreased in the model, GM6001, and 3-methyladenine groups. Compared with the model group, the protein expressions of osteocalcin, and osteopontin were increased in the GM6001 group. Compared with the GM6001 group, the protein expressions of osteocalcin and osteopontin were decreased in the 3-methyladenine group. (6) In the C2C12 cell line, compared with the control group, the mRNA expressions of myogenic factor 5, myogenic factor 6, myogenic differentiation 1, and myogenin were decreased in the model, GM6001, and 3-methyladenine groups. Compared with the model group, the expressions of the above myogenic genes were elevated in the GM6001 group, and compared with the GM6001 group, the above myogenic gene expressions were decreased in the 3-methyladenine group. The results showed that matrix metalloproteinase 9 exhibits high expression levels in oxidative injury models, and its inhibitors enhance mitophagy in the oxidative damage environment. This regulation was based on the activation of PTEN-induced kinase 1/Parkin pathway, thereby promoting osteogenic and myogenic differentiation. Figures and Tables | References | Related Articles | Metrics

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Mechanistic insights into how Cervi Cornus Colla regulates the intestinal flora-bile acid metabolic pathway to alleviate steroid-induced osteonecrosis of the femoral head in a rat model  Chai Jinlian, Liang Xuezhen, Sun Tiefeng, Li Shudong, Li Wei, Li Guangzheng, Yu Huayun, Wang Ping 2026, 30 (18):  4568-4581.  doi: 10.12307/2026.744 Abstract ( 75 )   PDF (4826KB) ( 16 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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Finite element analysis of digitally designed free fibula flaps for repairing unilateral maxillary defects Zhai Kun, Liu Dongyang, Ma Jian, Lin Zhiyu, Zheng Maosheng, Ma Xiaoqin, Jing Jie 2026, 30 (18):  4582-4593.  doi: 10.12307/2026.699 Abstract ( 75 )   PDF (4250KB) ( 96 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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Effect of raloxifene on alveolar bone resorption in ovariectomized rats Zan Bingxin, Zhao Yu, Dai Qinggang 2026, 30 (18):  4594-4601.  doi: 10.12307/2026.711 Abstract ( 49 )   PDF (3590KB) ( 13 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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Effects of different sequential combinations of strength and endurance training on skeletal muscle function and aerobic metabolic capacity in young people Wang Shuo, Li Zhongshan, Che Tongtong, Xing Xinyang, Chen Zitong, Shi Yan 2026, 30 (18):  4602-4610.  doi: 10.12307/2026.764 Abstract ( 121 )   PDF (1378KB) ( 18 )   Save BACKGROUND: Youth is a critical window for physical development in the human body. During this stage, optimization of skeletal muscle function—including muscle strength, power output, and muscular endurance—is not only essential for athletic performance but also serves as a frontline defense against muscle decline and metabolic disorders caused by modern lifestyles. Meanwhile, cardiorespiratory endurance reflects the overall function of the cardiovascular and respiratory systems, which is a key predictor of health risks. OBJECTIVE: To investigate the effects of different arrangement order of strength and endurance training (strength priority vs. endurance priority) on lower limb skeletal muscle function (maximum strength and strength endurance) and aerobic metabolic capacity (maximum oxygen uptake) in young people. METHODS: Thirty healthy young college students from Hebei Sport University were randomly divided into three groups: strength priority group (n=10), endurance priority group (n=10) and control group (n=10). The strength priority group received strength training followed by endurance training, the endurance priority group had the opposite order, and the control group maintained daily activities. The intervention in each group lasted for 8 weeks, twice a week. The one repetition maximum (1RM) in squat/deadlift of the lower limb (maximum strength), the maximum repetitions at 70% 1RM squat/deadlift (strength endurance), and maximal oxygen uptake (estimated by indirect methods) were measured before and after the intervention. RESULTS AND CONCLUSION: After 8 weeks of intervention, 1RM squat/deadlift were significantly increased in strength priority group (P < 0.05, P < 0.01), and the maximum repetitions at 70% 1RM squat/deadlift were significantly increased (P < 0.01). In the endurance priority group, the maximum repetitions at 70% 1RM squat/deadlift were significantly increased (P < 0.01), but there was no significant change in 1RM squat/deadlift. The maximum oxygen uptake increased significantly in the endurance priority group (P < 0.05), remained unchanged in the strength priority group, and decreased significantly in the control group (P < 0.05). There were significant differences in the maximum repetitions at 70% 1RM squat/deadlift and maximum oxygen uptake between groups (P < 0.01), and the maximum oxygen uptake in the endurance priority group was significantly higher than that in the strength priority group (P < 0.05) and control group (P < 0.01). The above results suggest that, during synchronic training, the priority of strength training is more conducive to improving the maximum strength of the lower limbs and maintaining aerobic capacity in young people, while the priority of endurance training is more conducive to improving the strength endurance and aerobic metabolic capacity. Figures and Tables | References | Related Articles | Metrics

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Balance function and its influencing factors in patients with post-stroke hemiplegia Leng Xiaoxuan, Yu Zifu, Cao Xinyan, Gao Shiai, Chen Jinhui, Liu Xihua 2026, 30 (18):  4611-4617.  doi: 10.12307/2026.692 Abstract ( 90 )   PDF (1402KB) ( 34 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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Secreted modular calcium binding protein regulates autophagy in the acetabular cartilage of rats with developmental dysplasia of the hip Zheng Wen, Zhu Dongsheng, Wang Xiaodong 2026, 30 (18):  4618-4626.  doi: 10.12307/2026.681 Abstract ( 66 )   PDF (2420KB) ( 18 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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High-intensity interval training improves the function of exosomes derived from endothelial progenitor cells in spontaneously hypertensive rats Lu Anran, Wang Chenyu, Zhang Yan, Huang Huasheng 2026, 30 (18):  4627-4637.  doi: 10.12307/2026.713 Abstract ( 66 )   PDF (3180KB) ( 66 )   Save 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.  Figures and Tables | References | Related Articles | Metrics

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Moderate-intensity exercise improves renal injury and inflammatory response in mice with hyperuricemia Yang Ling, Dai Jiahui, Zhou Han, Yang Lin, Bian Bogao, Liu Gang 2026, 30 (18):  4638-4648.  doi: 10.12307/2026.753 Abstract ( 94 )   PDF (4161KB) ( 137 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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Effects and molecular mechanisms of light exposure on neurotransmitter release in a rat model of heart failure Ruan Lin, Li Jia, Shi Linan, Zhu Hong, Wu Dongning, Zheng Di, Li Yupeng, Zhao Yan 2026, 30 (18):  4649-4662.  doi: 10.12307/2026.750 Abstract ( 74 )   PDF (6103KB) ( 17 )   Save BACKGROUND: The development and progression of heart failure are closely related to abnormal activation of the neuroendocrine system. Studies have demonstrated that light exposure decreases dopamine levels in the rat brain, increases the activity of dopaminergic neurons in the paraventricular nucleus of the hypothalamus, and stimulates the release of corticotropin releasing factor. However, there is currently no direct evidence proving that light exposure induces heart failure. Objective: To investigate the effect and molecular mechanism of light exposure on neurotransmitter release in heart failure model rats, and to conduct cytological verification. Methods: (1) Animal experiment: Sprague-Dawley rats with heart failure were divided into model, light exposure model, and light exposure treatment groups, while shamsurgery rats were divided into light exposure control and blank groups, with six rats in each group. After 8-week experiment, enzyme linked immunosorbent assay was used to detect the effects of light exposure on serum levels of neurotransmitter and hormone in heart failure rats. Hematoxylin-eosin staining was used to detect pathological changes in the heart. Western blot assay was used to detect the regulatory effects of nuclear factor E2 related factor 2/heme oxidase 1/NADPH quinineoxidoreductase-1 signaling pathway. (2) Cell experiment: Mouse cardiomyocytes (HL-1 cells) were divided into blank, high-dose 5-hydroxytryptamine control (5-hydroxytryptamine 500 mg/mL), low-dose lipopolysaccharide (lipopolysaccharide 1 μg/mL), lipopolysaccharide + high-dose 5-hydroxytryptamine (5-hydroxytryptamine 500 mg/mL + lipopolysaccharide 1 μg/mL), ML385 (lipopolysaccharide 1 μg/mL + 5-hydroxytryptamine 500 mg/mL + nuclear factor E2 related factor 2 inhibitor ML385 2.5 μg/mL), and resveratrol (lipopolysaccharide 1 μg/mL + 5-hydroxytryptamine 500 mg/mL +  nuclear factor E2 related factor 2 agonist resveratrol 30 μg/mL) groups. After 36-hour intervention, the effects of various intervention conditions on cell proliferation were investigated. Western blot assay was used to verify the effect of 5-hydroxytryptamine on nuclear factor E2 related factor 2/heme oxidase 1/NADPH quinineoxidoreductase-1 signaling axis in HL-1 cells. Results and conclusion: (1) Animal experiment: Light exposure increases the serum levels of norepinephrine and 5-hydroxytryptamine in heart failure model rats, thereby exacerbating heart damage. Both light exposure model and model groups showed significant pathological damage to the myocardial tissue, including swelling, nuclear shrinkage, and the formation of vacuoles. However, the damage to myocardial cells in the light exposure treatment group was significantly alleviated. In the light exposure control group, the level of angiotensin converting enzyme 2 protein expression was lower than that in the blank group (P < 0.05), but higher than that in the model group (P < 0.05). Although Mas, c-fos, and heme oxygenase-1 expression levels were downregulated compared to the blank group, but these differences were not statistically significant (P > 0.05). In the light-exposed model group, the protein expression levels of angiotensin converting enzyme 2, Mas, nuclear factor E2 related factor 2, and heme oxygenase-1 were significantly downregulated compared to the blank group (P < 0.05). Compared with the light exposure model group, the expression level of proteins related to the nuclear factor E2 related factor 2/heme oxygenase-1/NADPH quinineoxidoreductase-1 signaling pathway was significantly upregulated in the light exposure treatment group (P < 0.05). (2) Cell experiments: 5-Hydroxytryptamine increased lipopolysaccharide-induced myocardial cell damage. This damage was associated with the inhibition of the nuclear factor E2 related factor 2/heme oxidase 1/NADPH quinineoxidoreductase-1 signaling pathway. Conclusion: Excessive light exposure may accelerate the progression of heart failure by regulating neurotransmitter composition, mediating the nuclear factor E2 related factor 2/heme oxidase 1/NADPH quinineoxidoreductase-1 signaling pathway.   Figures and Tables | References | Related Articles | Metrics

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Electroacupuncture improves inflammatory pathology and intestinal integrity in mice with ulcerative colitis Zhang Jiahao, Liu Jidong, Qu Yi, Wang Jianbo, Li Yang, Xue Yanan 2026, 30 (18):  4663-4674.  doi: 10.12307/2026.772 Abstract ( 87 )   PDF (14436KB) ( 21 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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Changes in the expression of six microRNAs in ovarian tissue from animal models of premature ovarian failure and in peripheral blood of patients with premature ovarian failure Wang Xinyue, Li Hongli, Guo Chunhui, Chen Jibing, Yu Hua 2026, 30 (18):  4675-4684.  doi: 10.12307/2026.746 Abstract ( 60 )   PDF (2197KB) ( 11 )   Save BACKGROUND: Studies have demonstrated that specific microRNAs (miRNAs) exhibit significant downregulation in a rat model of premature ovarian failure, and their overexpression can effectively alleviate symptoms of premature ovarian failure. Therefore, investigating miRNAs as potential auxiliary biomarkers holds substantial academic and clinical significance, offering a more stable and reliable reference for the diagnosis of premature ovarian failure.  OBJECTIVE: To investigate whether the expression patterns of six miRNAs in ovarian tissue from animal models of premature ovarian failure and in peripheral blood from patients with premature ovarian failure are consistent, and to validate the clinical diagnostic potential of these six miRNAs. METHODS: (1) Twenty Wistar rats were randomly divided into a normal group (n=10) and a premature ovarian failure group (n=10). The model of premature ovarian failure was established in the premature ovarian failure group by intraperitoneal injection of cisplatin [1 mg/(kg·d)] for 14 continuous days. Following modeling, serum samples were collected from both groups. Levels of follicle-stimulating hormone, estradiol, and anti-Müllerian hormone were measured using ELISA. Ovarian tissue morphology was examined via hematoxylin-eosin staining. Q-PCR was used to detect the expression of miR-10a-5p, miR-21-5p, miR-22-3p, miR-126-3p, miR-144-3p, and miR-144-5p in ovarian tissue. (2) Ten patients with premature ovarian failure and ten healthy female controls, all aged < 40 years, were enrolled. Chemiluminescence assays measured the levels of follicle-stimulating hormone, estradiol, and anti-Müllerian hormone in peripheral blood from both groups. Q-PCR was used to detect the expression of miR-10a-5p, miR-21-5p, miR-22-3p, miR-126-3p, miR-144-3p, and miR-144-5p in peripheral blood. The effect size and diagnostic performance of these six miRNAs in human blood samples were systematically evaluated using receiver operating characteristic curves. RESULTS AND CONCLUSION: (1) Compared with the normal group, rats with premature ovarian failure showed significantly elevated follicle-stimulating hormone level and reduced estradiol and anti-Müllerian hormone levels. Hematoxylin-eosin staining revealed a significant decrease in the number of follicles in the ovaries of rats with premature ovarian failure compared with the normal group. The expression of miR-10a-5p, miR-21-5p, miR-22-3p, miR-126-3p, miR-144-3p, and miR-144-5p was markedly downregulated in the ovaries of rats with premature ovarian failure compared with the normal group (P < 0.05). (2) Compared with healthy controls, patients with premature ovarian failure exhibited elevated levels of follicle-stimulating hormone in peripheral blood (P < 0.05), along with decreased levels of estradiol and anti-Müllerian hormone (P < 0.05). Q-PCR assay revealed that, compared with healthy controls, patients with premature ovarian failure exhibited downregulated expression of miR-10a-5p, miR-21-5p, miR-22-3p, miR-126-3p, miR-144-3p, and miR-144-5p in peripheral blood (P < 0.05). The receiver operating characteristic curves demonstrated that all six miRNAs exhibited excellent diagnostic discrimination capabilities (sensitivity: 100%, specificity: 100%), indicating their clinical potential as highly specific molecular biomarkers for premature ovarian failure. These findings indicate that these six miRNAs may serve not only as promising biomarkers for premature ovarian failure but also as clinically valuable tools. Figures and Tables | References | Related Articles | Metrics

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Comparison and evaluation of three methods for preparing insomnia mouse models Li Feifan, Zhang Yibo, Wang Jing, Zhu Jinqiang, Zheng Wenke 2026, 30 (18):  4685-4693.  doi: 10.12307/2026.749 Abstract ( 119 )   PDF (2096KB) ( 25 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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A novel treadmill-based method for assessing learning and memory in mice Pei Xiaxia, Li Tian, Zhang Yanli, Gao Yanping, Su Qiang 2026, 30 (18):  4694-4701.  doi: 10.12307/2026.717 Abstract ( 63 )   PDF (2256KB) ( 51 )   Save BACKGROUND: Currently, behavioral tests for assessing learning and memory are important technical methods for the drug development and exploration of the pathogenesis of Alzheimer's disease. However, animal behavior is easily influenced by various factors, including external conditions, the function of internal organs and cells, and psychological states. Therefore, developing appropriate experimental methods that can effectively reflect animal cognitive behavior is an important prerequisite for exploring the pathogenic mechanism and prevention and treatment of Alzheimer’s disease. OBJECTIVE: To verify that the treadmill test is a new method using two different mouse models and to explore the advantages and disadvantages of the treadmill test in evaluating the learning and memory ability of mice in comparison with the Morris water maze. METHODS: The genotypes of APP/PS1 transgenic mice (Alzheimer’s disease group, n=8) and littermate wild-type mice (control group, n=8) and the pathological features of β-amyloid in the brain were identified using polymerase chain reaction and thioflavin S staining. Subsequently, 11-month-old APP/PS1 transgenic mice (Alzheimer’s disease group, n=8) and their littermates of wild-type mice (control group, n=8) were subjected to a treadmill test. At the same time, 8-month-old 3×Tg-AD mice (Alzheimer’s disease group, n=8) and wild-type control mice (control group, n=8) were subjected to treadmill and water maze tests sequentially. RESULTS AND CONCLUSION: (1) The polymerase chain reaction results showed that the expression of APP and PSEN1 genes in APP/PS1 transgenic mice was higher than that in the control group (P < 0.001), and thioflavin S staining showed that there were more β-amyloid plaques in the hippocampus of APP/PS1 transgenic mice than in the control group (P < 0.001). The results of the treadmill test showed that the total number and duration of electric shocks in APP/PS1 transgenic mice were higher than those in the control group (P < 0.05). (2) The results of the treadmill test showed that the total number and duration of electric shocks in 3×Tg AD mice were higher than those in the control group (P < 0.05). The results of the water maze test showed that the escape latency of 3×Tg AD mice was longer than that of the control group from the 4th day of the localization navigation phase (P < 0.05). To conclude, the treadmill test can effectively reflect the learning and memory function of mice, and may become an experimental method for measuring mouse cognitive behaviors.  Figures and Tables | References | Related Articles | Metrics

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microRNA-146a regulates bone metabolism and its application in bone tissue engineering Li Jiayin, Sui Lei, Li Yanjing 2026, 30 (18):  4702-4712.  doi: 10.12307/2026.752 Abstract ( 56 )   PDF (1842KB) ( 16 )   Save BACKGROUND: Normal bone metabolism relies on the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Disruption of this balance can lead to bone metabolism-related diseases. MicroRNA-146a is a non-coding small RNA molecule that plays a crucial role in bone metabolism. OBJECTIVE: To review the molecular mechanisms by which microRNA-146a regulates bone metabolism and its applications in bone tissue engineering. METHODS: In April 2025, the authors conducted a search of relevant literature published from January 2000 to April 2025 in the CNKI, PubMed, and Web of Science databases. The search terms used in Chinese included microRNA-146a, bone, bone metabolism, osteoblast, osteoclast, and bone tissue regeneration. The English search terms were microRNA-146a, bone metabolism, osteoblast, osteoclast, and bone regeneration. There is no restriction on  the type of retrieved liter ature. A total of 11 230 documents were retrieved, comprising 988 Chinese documents from CNKI, 5 952 English documents from PubMed, and 4 290 English documents from Web of Science. The included literature focused on the process of bone metabolism and its influential factors, the regulation of bone metabolism by microRNA-146a, the biological behavior of key cells involved in bone metabolism, and the application of microRNA-146a in maintaining bone homeostasis and promoting bone tissue repair and regeneration. Literature with low relevance to the topic, outdated content, inadequate experimental design, poor credibility of research results, and insufficient argumentation were excluded. Based on the eligibility criteria, 90 articles closely related to the theme of this review—characterized by novel research, authentic and reliable data, sufficient argumentation, and clinical application value—were included in the final analysis. RESULTS AND CONCLUSIONS: (1) MicroRNA-146a can inhibit the formation and activity of osteoblasts by suppressing the expression of genes such as Wnt, Smad4, and silencing information regulator 2-related enzyme 1. It can also inhibit the formation of osteoclasts by suppressing the expression of genes such as tumor necrosis factor receptor-associated factor 6 and interleukin-1 receptor-associated kinase 1. Additionally, it can regulate the interaction between osteoblasts and osteoclasts. (2) Abnormal expression of microRNA-146a can lead to dysfunction in osteoblasts and osteoclasts, disrupt the balance of bone metabolism, and induce osteoporosis, osteoarthritis, periodontitis, and other bone metabolism-related diseases. (3) MicroRNA-146a may serve as a potential target for the diagnosis and treatment of bone metabolism-related diseases, offering promising applications in the treatment of bone metabolism-related diseases and in bone tissue engineering. Figures and Tables | References | Related Articles | Metrics

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Molecular mechanisms underlying non-coding RNA regulation of ferroptosis in osteoarthritis Liao Xingzhuan, Li Guangdi, Wu Yabin, Liu Xingyu, Wan Jiajia 2026, 30 (18):  4713-4725.  doi: 10.12307/2026.767 Abstract ( 71 )   PDF (1753KB) ( 51 )   Save 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.  Figures and Tables | References | Related Articles | Metrics

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Neuro mechanism of the endocannabinoid system in regulating exercise motivation Zhang Qingtong, Chen Leqin, Liu Chang, Chen Yuting, Guo Ruiwu 2026, 30 (18):  4726-4736.  doi: 10.12307/2026.754 Abstract ( 55 )   PDF (1996KB) ( 14 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which exercise regulates autophagy in different physiological systems Zhang Shuli, Hou Chaowen, Yuan Shanshan, Ma Yuhua 2026, 30 (18):  4737-4748.  doi: 10.12307/2026.751 Abstract ( 86 )   PDF (1711KB) ( 19 )   Save BACKGROUND: Studies have shown that exercise can regulate autophagy through multiple signaling pathways, playing a crucial role in maintaining cellular homeostasis, improving metabolism, delaying aging, and preventing diseases. OBJECTIVE: To systematically review the molecular mechanism by which exercise regulates autophagy and to analyze its pathophysiological roles in different physiological systems.  METHODS: An online search of the Web of Science, PubMed, CNKI, Wanfang, and VIP databases was conducted to retrieve relevant literature. The Chinese search terms included “exercise, mitophagy, AMPK/mTOR pathway, oxidative stress, Nrf2/Beclin1 pathway, LC3, ULK1, Beclin1, p62,” while the English search terms included “exercise, autophagy, mitophagy, lipophagy, AMPK/mTOR pathway, oxidative stress, Nrf2/Beclin1 pathway, LC3, ULK1, Beclin1, p62.” Based on the inclusion and exclusion criteria, 92 high-quality documents focusing on molecular mechanisms and multi-system effects were included in this systematic review.  RESULTS AND CONCLUSION: Exercise phosphorylates Unc-51-like kinase 1 through AMP-activated protein kinase, inhibits the activation of mammalian target of rapamycin complex 1 involved in autophagy initiation. This process relies on Beclin1-III phosphatidylinositol 3-kinase complex to promote the nucleation of autophagosomes, regulate the lipidation of microtubule-associated protein light chain 3, and Atg5-Atg12 complex mediated extension of autophagosomes. Oxidative stress forms an “antioxidant-autophagy” regulatory network through the Nrf2 Beclin1 pathway, promoting mitophagy to eliminate damaged organelles. Exercise degrades excess lipids in the liver via autophagy, while mitophagy enhances insulin sensitivity, thereby alleviating the progression of non-alcoholic fatty liver disease and diabetes. Mitophagy removes dysfunctional mitochondria from ischemic myocardial injury, inhibiting cardiomyocyte apoptosis and improving pathological conditions such as heart failure and atherosclerosis. Autophagy also clears amyloid-β protein plaques associated with Alzheimer’s disease and α - synuclein associated with Parkinson’s disease, delaying the progression of neurodegenerative diseases by enhancing neuronal activity and synaptic plasticity. Resistance exercise balances protein degradation through the insulin-like growth factor 1/mammalian target of rapamycin pathway, promoting muscle repair. Furthermore, autophagy can enhance the differentiation capacity of osteoblasts by activating the Wnt/β-catenin signaling pathway, thereby maintaining skeletal homeostasis. Exercise regulates autophagy through a multi-layered molecular network and exerts adaptive remodeling effects in various physiological systems. Although numerous studies have revealed the relationship between exercise and autophagy, the spatiotemporal specificity and precise regulatory mechanisms of different exercise modalities still require further investigation. Figures and Tables | References | Related Articles | Metrics

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Effects of different non-invasive brain stimulation protocols on gait and balance function in patients with Parkinson’s disease: a network meta-analysis Cheng Xiaofei, Yang Yuanyuan, Li Sihui, Wang Dehua, Liang Chunting, Li Jiawei, Yao Mingyang, Yao Xiaoduo, Tang Jiqin 2026, 30 (18):  4749-4762.  doi: 10.12307/2026.739 Abstract ( 64 )   PDF (10834KB) ( 4 )   Save 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). Figures and Tables | References | Related Articles | Metrics

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Lipid types and knee osteoarthritis: a genome-wide association study in European populations Yu Yueyue, Zhang Xu, Liu Yiwei, Meng Zihan, Hao Xinyue, Tian Chunyu, Li Ji’an, Zhang Yixin 2026, 30 (18):  4763-4770.  doi: 10.12307/2026.741 Abstract ( 42 )   PDF (4793KB) ( 37 )   Save 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.  Figures and Tables | References | Related Articles | Metrics

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Research hotspots and thematic evolution in the field of exercise interventions for multiple sclerosis Yang Jiangxi, Li Huangyan, Zhang Yeting, Yu Zuoyin 2026, 30 (18):  4771-4781.  doi: 10.12307/2026.721 Abstract ( 78 )   PDF (7823KB) ( 15 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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Relationship between inflammatory factors, white blood cells, and lumbar disc herniation Gu Shan, Zhang Long, Li Zhigang 2026, 30 (18):  4782-4790.  doi: 10.12307/2026.756 Abstract ( 82 )   PDF (5849KB) ( 13 )   Save BACKGROUND:  Lumbar disc herniation is a clinically prevalent spinal disease. Existing evidence suggests that cytokines and white blood cells are closely associated with the occurrence and progression of lumbar disc herniation, but the specific mechanisms remain unclear. OBJECTIVE: To explore the causal relationship between cytokines, white blood cells, and lumbar disc herniation using Mendelian randomization analysis. METHODS: Using 91 cytokine datasets from the GWAS Catalog database and six types of white blood cell data from the Blood Cell Consortium as exposures, along with data on lumbar disc herniation from the latest R12 Finnish database as the outcome, bidirectional two-sample Mendelian randomization and genome-wide association study colocalization analyses were performed to investigate the causal relationships between cytokines, white blood cells, and lumbar disc herniation. Sensitivity tests, including the Steiger test, Cochran’s Q test, MR-Egger intercept assessment, and leave-one-out analysis, were conducted to verify the accuracy of the results. The inverse variance weighting method was primarily used for statistical analysis. RESULTS AND CONCLUSION: (1) Basophils and eosinophils showed causal relationships with lumbar disc herniation (OR=0.93, 95%CI: 0.87–0.99; OR=0.94, 95%CI: 0.88–1.00). (2) Levels of S100 calcium-binding protein A12 (OR=0.74, 95%CI: 0.55–1.00), fibroblast growth factor (OR=1.03, 95%CI: 1.00–1.07), interleukin-20 receptor α protein (OR=1.09, 95%CI: 1.04–1.15), interleukin-6 (OR=1.07, 95%CI: 1.00–1.13), interleukin-7 (OR=1.08, 95%CI: 1.01–1.16), stem cell factor (OR=1.05, 95%CI: 1.01–1.09), and interleukin-2 (OR=0.94, 95%CI: 0.89–0.99) were causally associated with lumbar disc herniation. (3) In the colocalization analysis, the level of stem cell factor was found to be H3+H4=0.80, with the most significant single nucleotide polymorphism being rs6073966. These findings suggest that basophils, eosinophils, S100 calcium-binding protein A12, fibroblast growth factor, interleukin-20 receptor α protein, interleukin-2, interleukin-6, interleukin-7, and stem cell factor exhibit unidirectional causal effects on lumbar disc herniation. A potential related pathway may exist between stem cell factor and lumbar disc herniation. Figures and Tables | References | Related Articles | Metrics

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Knowledge structure and evolutionary trends in the application of surface electromyography in musculoskeletal pain rehabilitation Chen Yuanyue, Shen Junfan, Yu Cui, Lu Jianxia, Hu Wenxuan, Zhu Jun, Guo Chuan 2026, 30 (18):  4791-4801.  doi: 10.12307/2026.770 Abstract ( 62 )   PDF (3745KB) ( 31 )   Save 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. Figures and Tables | References | Related Articles | Metrics

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Literature visualization analysis of brain-computer interface applications in stroke rehabilitation Meng Zhuo, Zhao Renghao, Zhang Anqi, Hua Haotian, Wang Zicheng, Xu Yingtian, Tong Peijian 2026, 30 (18):  4802-4813.  doi: 10.12307/2026.722 Abstract ( 103 )   PDF (3717KB) ( 78 )   Save BACKGROUND: Recent advancements in brain-computer interface technology have demonstrated its clinical efficacy in stroke rehabilitation, yielding substantial therapeutic outcomes. A comprehensive visual analysis is imperative to elucidate current research frontiers and identify emerging hotspots in this rapidly evolving field. OBJECTIVE: To systematically examine research frontiers and developmental trends in brain-computer interface applications for stroke rehabilitation using bibliometric visualization tools. METHODS: Based on the Web of Science Core Collection and China National Knowledge Infrastructure (CNKI) databases, Citespace 6.4.1, VOSviewer 1.6.20, and Excel 2021 were employed for visualized data analysis of retrieved Chinese and English literature focusing on the application of brain-computer interface technology in post-stroke functional recovery. Using scientometric methods, we conducted an in-depth analysis of the current research status, hot topics, and future trends regarding brain-computer interface technology in stroke rehabilitation. RESULTS AND CONCLUSION: (1) A total of 985 Chinese and English articles (879 in English and 106 in Chinese) published between 2003 and 2025 were included. Annual publication output in this field has shown a consistent growth trend both domestically and globally. (2) China, the United States, and Germany were the most productive countries. The University of Tübingen (Germany) ranked as the most influential institution, while Huashan Hospital, Fudan University, topped Chinese institutions in publication output. Frontiers in Neuroscience (Switzerland) was the leading English journal, and the Chinese Journal of Rehabilitation Medicine was the foremost Chinese journal. Birbaumer Niels (Germany) had the highest publication output in English, whereas Jia Jie was the most prolific author in Chinese literature. (3) International research focused on theoretical validation and clinical efficacy, with a particular emphasis on upper limb and neural recovery. Domestic studies prioritized technological and systemic optimization, with a focus on exploring broader applications in rehabilitation. (4) “Motor imagery” emerged as a common high-frequency keyword in both Chinese and English literature, with research hotspots focusing on electroencephalography-based and motor imagery-driven brain-computer interface systems. (5) Future trends are likely to include multimodal integration, artificial intelligence fusion, expanded rehabilitation approaches, and strengthened international collaboration. Figures and Tables | References | Related Articles | Metrics

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Limb lymphedema: network pharmacology and molecular docking analysis of core drug mechanisms in traditional Chinese medicine treatment  Mi Baolai, Liu Yufei, Yang Qiaoli, Kang Yanlan, Yuan Liang, Cao Jianchun 2026, 30 (18):  4814-4824.  doi: 10.12307/2026.740 Abstract ( 52 )   PDF (4058KB) ( 22 )   Save 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.  Figures and Tables | References | Related Articles | Metrics