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18 November 2025, Volume 29 Issue 32 Previous Issue    Next Issue

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Deferoxamine alleviates the inhibitory effect of glucocorticoids on osteogenic differentiation Tang Haoxu, Liang Yingjie, Li Ce, Ding Penglin, Qian Minlong, Yuan Lingli 2025, 29 (32):  6821-6827.  doi: 10.12307/2026.525 Abstract ( 142 )   PDF (2077KB) ( 48 )   Save BACKGROUND: Deferoxamine exhibits multiple functions such as stem cell modulation, immune regulation, and promotion of angiogenesis and osteogenesis, but its role in the osteoinhibition induced by dexamethasone in osteoblasts remains unclear. OBJECTIVE: To investigate the effects of deferoxamine on osteoblasts treated with dexamethasone through the hypoxia-inducible factor 1α/vascular endothelial growth factor signaling pathway and to explore its potential mechanisms of action.  METHODS: The proliferation of MC3T3-E1 cells treated with various concentrations of deferoxamine for 24, 48, and 72 hours was assessed using the cell counting kit-8 assay to determine the optimal intervention concentration. There were control, dexamethasone, dexamethasone plus deferoxamine 10 μmol/L, and dexamethasone plus deferoxamine 20 μmol/L groups in the experiment. Cell counting kit-8 assay and flow cytometry were employed to evaluate the effect of deferoxamine on dexamethasone-induced cell proliferation and apoptosis. Alkaline phosphatase staining and activity assays were conducted to assess alkaline phosphatase levels in MC3T3-E1 cells. Alizarin red staining was used to observe the formation of mineralized nodules. Western blot was employed to detect the expression of osteogenic and signaling proteins. RESULTS AND CONCLUSION: (1) Deferoxamine showed no significant cytotoxicity to MC3T3-E1 cells within the range of 5-20 μmol/L and could ameliorate the inhibitory effects of dexamethasone on MC3T3-E1 cell proliferation and apoptosis. (2) Compared with the dexamethasone group, deferoxamine groups increased alkaline phosphatase activity and cell mineralization, and also significantly increased the protein expression of osteopontin, runt-related transcription factor 2, and alkaline phosphatase in MC3T3-E1 cells. (3) Deferoxamine also activated the hypoxia-inducible factor 1α/vascular endothelial growth factor pathway in dexamethasone-treated MC3T3-E1 cells. To conclude, deferoxamine can alleviate apoptosis in osteoblasts induced by dexamethasone treatment, maintain the vitality of osteoblasts by activating the hypoxia-inducible factor 1α/vascular endothelial growth factor signaling pathway, and promote their proliferation, which may help delay the progression of steroid-induced osteonecrosis of the femoral head.  Figures and Tables | References | Related Articles | Metrics

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Mechanism of Jiangu Formula in treating osteoporosis based on osteoclast-osteoblast coupling Lu Xiuli, Xu Huazhen, Chen Yuxing, Yao Nan, Hu Zixuan, Huang Dane 2025, 29 (32):  6828-6835.  doi: 10.12307/2025.970 Abstract ( 120 )   PDF (1707KB) ( 53 )   Save BACKGROUND: Previous studies have found that Jiangu Formula can play a dual role in anti-osteoporosis therapy by inhibiting bone resorption and promoting bone formation, but its mechanism of action has not been elucidated.  OBJECTIVE: To investigate the effect of Jiangu Formula on the coupling mechanism between bone resorption and bone formation at the cellular and molecular levels.  METHODS: Serum containing Jiangu Formula was prepared and its toxicity to bone marrow derived macrophages was determined using MTT assay. The cell proliferation ability of MC3T3-E1 cells that treated Jiangu Formula medicated serum was measured by using cell counting kit-8 method. Tartrate resistant acid phosphatase staining was used to determine the bone resorption inhibition effect of serum containing Jiangu Formula on osteoclast differentiation. The Jiangu Fang conditional culture medium was prepared and the promoting effect of the conditional culture medium on bone formation of MC3T3-E1 was determined through alkaline phosphatase staining. The effect of serum containing Jiangu Formula on the mRNA levels of osteoclast associated sphingosine kinase 2, collagen triple helix repeat containing 1, and slit homolog 3 coupled genes, as well as the effect of conditioned culture medium on the mRNA levels of bone formation related secreted phosphoprotein 1, alkaline phosphatase, Sp7 transcription factor, and secreted protein acidic and rich in cysteine genes, were determined by RT-qPCR method.  RESULTS AND CONCLUSION: (1) The MTT and cell counting kit-8 methods showed that serum containing Jiangu Formula had no significant cytotoxic effects at a concentration of < 5%. (2) Tartrate resistant acid phosphatase staining results indicated that serum containing Jiangu Formula dose-dependently inhibited osteoclast differentiation at 2.5%, 1.25%, and 0.63% concentrations. (3) The alkaline phosphatase staining results showed that the osteoclast conditioned medium of Jiangu Formula promoted osteoblast differentiation in a dose-dependent manner. (4) In addition, RT-qPCR results showed that serum containing 0.63% Jiangu Formula could increase the mRNA levels of osteoclast derived slit homolog 3 and sphingosine kinase 2 coupling factors, and the conditional culture medium could increase the mRNA expression levels of bone formation related secreted phosphoprotein 1, Sp7 transcription factor, and secreted protein acidic and rich in cysteine. To conclude, the serum containing Jiangu Formula can promote bone formation while inhibiting bone resorption, and its mechanism may be related to the mRNA expression of the coupling factors osteoclast derived slit homolog 3 and sphingosine kinase 2 that promote bone resorption and bone formation. Figures and Tables | References | Related Articles | Metrics

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Spermidine/spermine N1-acetyltransferase 1 participates in vascular smooth muscle cell calcification Wang Kairu, Fu Shizhe, Li Jiahui, Yan Ru, Ma Yuru, Shi Bo, Ye Congyan , Yan Rui, Cong Guangzhi, Jia Shaobin 2025, 29 (32):  6836-6842.  doi: 10.12307/2025.941 Abstract ( 138 )   PDF (2730KB) ( 144 )   Save BACKGROUND: Polyamines play a crucial role in tissue calcification. Spermidine/spermine N1-acetyltransferase 1(SAT1), as a key rate-limiting enzyme regulating intracellular polyamine metabolism, has been associated with various pathological processes. However, its role in vascular calcification remains unclear. OBJECTIVE: To investigate the role of SAT1 in rat vascular smooth muscle cell calcification.  METHODS: (1) Bioinformatics analysis: Differential expression of SAT1 in human carotid atherosclerotic plaques and their surrounding healthy carotid artery tissues were using GEO datasets. PanglaoDB database was used to analyze SAT1 expression abundance and localization across different cell types through single-cell sequencing. (2) Rat vascular smooth muscle cells were divided into three groups: a control group cultured in DMEM medium, a calcification group induced by DMEM medium containing 10 mmol/L β-glycerophosphate sodium and 3 mmol/L calcium chloride, and the 50, 100 μmol/L diacetylaminotriazamidine groups treated with the SAT1 inhibitor, diacetylaminotriazamidine, in addition to the calcification medium. After 7-10 days of culture, alizarin red S staining was performed, and cellular calcium content and alkaline phosphatase activity were assessed. Western blot was used to detect the protein expression of Runt-related transcription factor 2, bone morphogenetic protein 2, alpha-smooth muscle actin, and SAT1. Immunofluorescence staining was conducted to examine the expression of Runt-related transcription factor 2 and SAT1.    RESULTS AND CONCLUSION: (1) Bioinformatics analysis revealed significantly upregulated expression of SAT1 and Runt-related transcription factor 2 (P < 0.05) in carotid atherosclerotic plaques compared with healthy carotid tissues (P < 0.05). Single-cell sequencing database analysis confirmed SAT1 expression in vascular smooth muscle cells. (2) Compared with the control group, the calcification group showed significantly increased Runt-related transcription factor 2, bone morphogenetic protein 2, SAT1, calcium content, and alkaline phosphatase activity, while alpha-smooth muscle actin expression was significantly decreased (all P < 0.05). Compared with the calcification group, the 50 and 100 μmol/L diacetylaminotriazamidine groups showed significantly decreased Runt-related transcription factor 2, bone morphogenetic protein 2, calcium content, and alkaline phosphatase activity, while alpha-smooth muscle actin expression was significantly increased (all P < 0.05). (3) Immunofluorescence experiments demonstrated that compared with the calcification group, the expression intensity of Runt-related transcription factor 2 was significantly reduced in the 50 and 100 μmol/L diacetylaminotriazamidine groups. Overall, SAT1 may promote vascular smooth muscle cell calcification by upregulating Runt-related transcription factor 2 expression.   Figures and Tables | References | Related Articles | Metrics

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Effect of dihydroquercetin on the expression of inflammatory response markers in rats with spinal cord injury Xu Biao, Dong Yuzhen, Lu Tan 2025, 29 (32):  6843-6850.  doi: 10.12307/2025.932 Abstract ( 150 )   PDF (2036KB) ( 103 )   Save BACKGROUND: The “inflammatory storm” induced by microglia is an important pathological factor causing the death of neuronal cells after spinal cord injury, which is extremely unfavorable for the recovery after spinal cord injury. Dihydroquercetin belongs to the vitamin P group and has excellent biological activity. It has good anti-inflammatory, anti-lipid peroxidation and neuroprotective effects on spinal cord injury. The mechanism by which it promotes the repair of spinal cord injury needs to be further clarified. OBJECTIVE: To investigate whether dihydroquercetin can ameliorate the inflammatory state induced after spinal cord injury through its anti-inflammatory and antioxidant properties for the purpose of protection against spinal cord injury. METHODS: Forty-eight Sprague-Dawley rats were divided into sham operation group, spinal cord injury group, low-dose dihydroquercetin group, and high-dose dihydroquercetin group according to the random number table method. The sham operation group only underwent laminectomy and was given intraperitoneal injection of normal saline after the operation. Animal models of spinal cord injury were made in the latter three groups. After the operation, normal saline, 30 mg/kg, and 50 mg/kg dihydroquercetin were given by intraperitoneal injection respectively, and samples were collected 4 weeks after the operation. The Basso-Beattie-Bresnahan (BBB) limb motor function score and mechanical paw withdrawal threshold were used to evaluate the limb motor function and pain recovery of rats. Hematoxylin-eosin staining was used to observe the pathological changes of spinal cord tissue; Nissl staining was used to observe the number of Nissl bodies and the morphology of neurons. The activity of superoxide dismutase in spinal cord tissue was detected. Immunofluorescence was used to detect the expression of reactive oxygen species and microglia Iba1. Western blot was used to detect the protein expression of Iba1 and interleukin-1β, interleukin-6, interleukin-10, tumor necrosis factor-α, and p38 mitogen-activated protein kinase in the spinal cord. RESULTS AND CONCLUSION: (1) In the behavioral test, the BBB limb motor function score showed that since 14 days after the operation, the BBB limb motor function score of the high-dose dihydroquercetin group was significantly better than that of the spinal cord injury group (P < 0.01); the mechanical paw withdrawal threshold was significantly lower in the high-dose dihydroquercetin than the spinal cord injury group at 21 days after the operation (P < 0.05), and the former group showed better motor function. (2) Hematoxylin-eosin staining and Nissl staining showed that compared with the spinal cord injury group, the high-dose dihydroquercetin group showed slightly swollen but structurally intact and clearer neuron morphology in the spinal cord tissue, and the number of Nissl bodies increased. (3) Superoxide dismutase detection: Compared with the spinal cord injury group, the activity of superoxide dismutase in the spinal cord tissue of the high-dose dihydroquercetin increased significantly (P < 0.05). (4) Reactive oxygen species immunofluorescence detection: Compared with the spinal cord injury group, the high-dose dihydroquercetin could significantly reduce the accumulation of reactive oxygen species after spinal cord injury (P < 0.05). (5) Detection of microglial marker Iba1: Compared with the spinal cord injury group, the high-dose dihydroquercetin could significantly reduce the expression of microglial marker Iba1 after spinal cord injury (P < 0.01). (6) Western blot detection results showed that compared with the spinal cord injury group, the expressions of inflammatory factors (interleukin-1β, interleukin-6, and tumor necrosis factor-α) and phosphorylated p38 mitogen-activated protein kinase in the high-dose dihydroquercetin group decreased significantly (P < 0.01), while the expression of anti-inflammatory factor interleukin-10 increased significantly (P < 0.01). These findings indicate that dihydroquercetin can effectively reverse the expression changes of multiple inflammatory markers induced after spinal cord injury in rats, thereby exerting neuroprotective effects and improving motor function. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which Tongdu Huoxue Decoction inhibits macrophage inflammation to delay intervertebral disc degeneration in rats Yan Laijun, Ge Haiya, Wang Zhengming, Yang Zongrui, Niu Lifeng, Zhan Hongsheng 2025, 29 (32):  6851-6857.  doi: 10.12307/2025.943 Abstract ( 122 )   PDF (1725KB) ( 127 )   Save BACKGROUND: Intervertebral disc degeneration is the main pathological factor causing low back pain, which is closely related to macrophage-mediated immune inflammation. Tongdu Huoxue Decoction is a proven prescription for the treatment of intervertebral disc degeneration, but it is still unclear whether it can treat intervertebral disc degeneration by regulating the polarization phenotype of macrophages to inhibit inflammation in intervertebral disc tissue. OBJECTIVE: To investigate the regulatory effects of Tongdu Huoxue Decoction on the expression of macrophage-related inflammatory factors in intervertebral disc tissues of rats, as well as its mechanisms for the treatment of intervertebral disc degeneration.  METHODS: Twenty-four Sprague-Dawley rats were randomly divided into sham operation group, model group, and Tongdu Huoxue Decoction group, with eight rats in each group. An intervertebral disc degeneration model was established using the annulus fibrosus puncture method in the latter two groups. On the 1st postoperative day, 10.8 g/kg Tongdu Huoxue Decoction was given by gavage in the Tongdu Huoxue Decoction group, and the same dose of saline was given by gavage in the sham operation group and the model group, once a day. After 4 weeks of intervention, histopathological changes in the intervertebral disc tissues were assessed using hematoxylin-eosin. Immunohistochemistry and quantitative real-time PCR were performed to detect the relative expression levels of CD68, CD206, interleukin 1β, interleukin 10, type II collagen, and matrix metalloproteinase 13 proteins or mRNA in the intervertebral disc tissues.  RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining results revealed that the model group exhibited a significant decrease in intervertebral disc height, disorganized annulus fibrosus structure with fissures, and unclear demarcation between the nucleus pulposus and the annulus fibrosus. The Tongdu Huoxue Decoction group showed organized arrangement of the annulus fibrosus with pyknosis. (2) Immunohistochemical results demonstrated that, compared with the model group, the Tongdu Huoxue Decoction group had significantly lower expressions of CD68, interleukin 1β, and matrix metalloproteinase 13, and significantly higher expressions of CD206, type II collagen and interleukin 10 (P < 0.05 or P < 0.01). (3) qPCR results showed that there were significant differences in the mRNA expression of CD68, CD206, interleukin 1β, matrix metalloproteinase 13, type II collagen, and interleukin 10 between the three groups (P < 0.001). To conclude, Tongdu Huoxue Decoction can improve intervertebral disc degeneration in the rat model of intervertebral disc degeneration, and its mechanism is associated with the inhibition of macrophage-related inflammatory responses in the intervertebral discs. Figures and Tables | References | Related Articles | Metrics

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tert-Butyl hydroperoxide can induce ferroptosis in nucleus pulposus cells Chen Chao, Hu Yaoquan, Lyu Zhengpin, He Qicong, Yangyang Zijiu, Luo Haoyan, Wu Guishuai, Zuo Qianlin, Wang Xuenan, Zhang Fan 2025, 29 (32):  6858-6865.  doi: 10.12307/2025.934 Abstract ( 164 )   PDF (2542KB) ( 86 )   Save BACKGROUND: Degeneration of nucleus pulposus cells is a key component of intervertebral disc degeneration.  Ferroptosis, a novel form of programmed cell death, is closely associated with the onset and progression of intervertebral disc degeneration; however, its precise mechanisms remain unclear.  OBJECTIVE: To establish an oxidative stress model in vitro by inducing ferroptosis in nucleus pulposus cells using tert-butyl hydroperoxide and to investigate the mechanisms of tert-butyl hydroperoxide-induced ferroptosis in nucleus pulposus cells, thereby elucidating the role of ferroptosis in the pathogenesis of intervertebral disc degeneration. METHODS: Nucleus pulposus cells were treated with varying concentrations of tert-butyl hydroperoxide (0, 25, 50, 100, and 200 μmol/L), and cell morphology and viability were assessed using fluorescence microscopy and the cell counting kit-8 assay. Interventions with 100 μmol/L tert-butyl hydroperoxide, 10 μmol/L  RSL3, or dimethylsulfoxide were applied to nucleus pulposus cells, and cell proliferation was evaluated using the EdU assay. The expression levels of ferroptosis-related proteins (glutathione peroxidase 4, ferritin heavy chain 1, PTGS2, and ACSL4) and intervertebral disc degeneration marker proteins (matrix metalloproteinase 13 and Col2A) were analyzed via western blot and immunofluorescence. Additionally, reactive oxygen species and lipid peroxidation levels were quantified using the reactive oxygen species detection kit and C11-BODIPY probe. Mitochondrial morphological changes were observed under transmission electron microscopy. RESULTS AND CONCLUSION: (1) tert-Butyl hydroperoxide treatment significantly reduced the viability and proliferation of nucleus pulposus cells. (2) tert-Butyl hydroperoxide induced typical ferroptosis-related morphological changes in nucleus pulposus cells. (3) tert-Butyl hydroperoxide exposure led to a decrease in the expression of ferroptosis-suppressing proteins glutathione peroxidase 4 and ferritin heavy chain 1, while increasing the expression of ferroptosis-promoting factors ACSL4 and PTGS2. (4) tert-Butyl hydroperoxide elevated intracellular reactive oxygen species production and lipid peroxidation levels in nucleus pulposus cells. (5) Transmission electron microscopy revealed ferroptosis-specific mitochondrial changes in nucleus pulposus cells treated with tert-butyl hydroperoxide, including contraction, reduced cristae, and increased membrane density. (6) tert-Butyl hydroperoxide treatment also resulted in the increased expression of matrix metalloproteinase 13 and decreased expression of Col2A in nucleus pulposus cells. In conclusion, tert-butyl hydroperoxide induces ferroptosis in nucleus pulposus cells, contributing to the development of intervertebral disc degeneration. This process may represent a key pathological mechanism in intervertebral disc degeneration and offers potential targets for developing novel therapeutic strategies. Figures and Tables | References | Related Articles | Metrics

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Difference of energy metabolism and skeletal muscle oxygenation in athletes under high temperature, high humidity and low oxygen environment Geng Zhizhong, Wang Jinhao, Cao Guohuan, Tan Chenhao, Li Longji, Qiu Jun 2025, 29 (32):  6866-6876.  doi: 10.12307/2025.783 Abstract ( 147 )   PDF (2711KB) ( 131 )   Save BACKGROUND: Competitive athletes exercising in high-temperature, high-humidity, or low-oxygen environments experience intensified skeletal muscle deoxygenation and reduced fat oxidation, which can impair athletic performance. OBJECTIVE: To evaluate the impact of high-temperature, high-humidity, and low-oxygen environments on the fat oxidation rates of athletes during incremental load exercise, and to analyze the differences in deoxyhemoglobin kinetic parameters in skeletal muscle, thereby clarifying the relationship between fat oxidation capacity and skeletal muscle oxygenation under varying environmental conditions. METHODS: Twelve male modern pentathlon athletes were recruited for tests under three environmental conditions: normal (23 °C, RH45%, FiO2=21.0%), high temperature and high humidity (35 °C, RH70%, FiO2=21.0%), and low oxygen (23 °C, RH45%, FiO2=15.6%). Resting metabolism and incremental load exercise were tested. Gas exchange data during and post-exercise were collected to calculate fat oxidation rate, carbohydrate oxidation rate, energy expenditure, and excess post-exercise oxygen consumption. Simultaneous measurements of SmO2 and total hemoglobin in the vastus lateralis muscle were used to calculate deoxyhemoglobin (HHb) levels. Deoxyhemoglobin change parameters-linear fitting slope (ΔEHHb), slope before the inflection point (ΔEHHB-1), and slope after the inflection point (ΔEHHB-2)-were determined using a bilinear function model. Fat oxidation curves were fitted using a SIN function model to identify the intensity (FATmax) that induced maximal fat oxidation (MFO), along with the curve’s expansion, symmetry, and translation. RESULTS AND CONCLUSION: (1) Energy metabolism: No significant differences in maximal fat oxidation were observed across environments in each group  (P > 0.05). Compared with the normal environment group, both high temperature and high humidity group and low oxygen group showed significantly decreased time to maximal fat oxidation and FATmax (P < 0.05). The percentage of maximal fat oxidation corresponding to peak oxygen uptake was lower in the low oxygen environment group (P < 0.05). Fat oxidation was consistently low in the low oxygen environment group during exercise, while in the high temperature and high humidity environment group, it decreased only at higher exercise loads. Additionally, the expansion parameter was significantly reduced in both high temperature and high humidity and low oxygen environment groups (P < 0.05). (2) Deoxyhemoglobin dynamics: The ΔEHHb was significantly higher in the high temperature and high humidity environment group, and ΔEHHB-1 was significantly increased in both high temperature and high humidity and low oxygen environment groups (P < 0.05). (3) Correlation analysis: ΔEHHb was significantly negatively correlated with symmetry; ΔEHHB-1 was negatively correlated with FATmax and maximal fat oxidation; ΔEHHB-2 was positively correlated with maximal fat oxidation, and V̇O2@BP was positively correlated with symmetry, expansion, and FATmax. (4) These findings indicate that incremental load exercise in high temperature, high humidity, and low oxygen environments accelerates skeletal muscle deoxygenation, thereby inhibiting fat oxidation capacity. Compared with high temperature and high humidity, low oxygen environments may more rapidly disrupt the balance between oxygen delivery and utilization in athletes’ skeletal muscle, leading to a greater reliance on anaerobic glycolysis and a consequent reduction in fat oxidation capacity during exercise. Figures and Tables | References | Related Articles | Metrics

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Expression of mitochondrial creatine kinase 2 in a rat model of temporomandibular joint osteoarthritis and its role in inflammation progression Nigeayi · Aihemaiti, Yilidanna · Dilixiati, An Wei, Maimaitituxun · Tuerdi 2025, 29 (32):  6877-6884.  doi: 10.12307/2025.921 Abstract ( 109 )   PDF (2182KB) ( 197 )   Save BACKGROUND: Due to its unknown etiology and the lack of definitive curative treatments, management of temporomandibular joint osteoarthritis primarily focuses on symptom relief. Therefore, the identification of effective early molecular diagnostic biomarkers or potential therapeutic targets holds great significance. OBJECTIVE: To investigate the expression of mitochondrial creatine kinase 2 in temporomandibular joint osteoarthritis in rats and its role in the progression of inflammation.  METHODS: (1) Animal experiment: Twenty Sprague-Dawley rats were randomly divided into control and unilateral anterior crossbite groups (n=10). A rat model of temporomandibular joint osteoarthritis was made in the unilateral anterior crossbite group. Four weeks after modeling, histological evaluations, including hematoxylin-eosin and Safranin O-fast green staining, were performed to assess pathological changes in the cartilage and subchondral bone of the mandibular condyle. Quantitative real-time PCR and immunohistochemical staining were utilized to detect the mRNA and protein expression levels of interleukin-1β, matrix metalloproteinase 13, type II collagen, aggrecan, and mitochondrial creatine kinase 2 in condylar cartilage. (2) Cell experiment: Passage 3 condylar cartilage cells from Sprague-Dawley rats were divided into control group and model group. Cells in the control group were routinely cultured, while an inflammation model of condylar cartilage cells was established with interleukin 1β in the model group were treated with interleukin-1β to induce inflammatory cell models. After 24 hours of interleukin-1β treatment, western blot was used to evaluate the expression of matrix metalloproteinase 13, type II collagen proteins in chondrocytes. Western blot was also used to detect the protein expression of mitochondrial creatine kinase 2 in the model group at 0, 12, 24, 48, and 72 hours after treatment with interleukin-1β.  RESULTS AND CONCLUSION: (1) Animal experiment: The results of hematoxylin-eosin staining showed that the unilateral anterior crossbite group exhibited disintegration of the fibrous layer in the cartilage of the mandibular condyle, disorganization of chondrocyte hierarchy, dense cellularity of the proliferative layer, obvious cell clustering, and infiltration of inflammatory cells in the subchondral bone. The results of Safranin O-fast green staining showed that in the cartilage matrix in the unilateral anterior crossbite group, the red stain became less extensive and lighter in color, and the tidal line was discontinuous. The mRNA and protein expression levels of interleukin-1β and matrix metalloproteinase 13 were elevated in the unilateral anterior crossbite group compared with the control group (P < 0.05). Conversely, the relative expression of type II collagen, aggrecan, and mitochondrial creatine kinase 2 mRNA and protein decreased (P < 0.05). (2) Cell experiment: Compared with the control group, the protein expression of matrix metalloproteinase 13 in the experimental group was significantly increased (P < 0.05), while the protein expression of type II collagen was decreased (P < 0.05). With prolonged interleukin-1β treatment, the protein expression of mitochondrial creatine kinase 2 in condylar chondrocytes of the model group gradually decreased. All the results indicate that the relative expression level of mitochondrial creatine kinase 2 was negatively correlated with the degree of chondrocyte inflammation in the rat model of temporomandibular joint osteoarthritis. Therefore, it is reasonable to infer that mitochondrial creatine kinase 2 is an important indicator for assessing the progression of inflammation in temporomandibular joint osteoarthritis. Figures and Tables | References | Related Articles | Metrics

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Effects of different concentrations of hypertonic glucose in the repair of tendon injury in rats Zhou Lina, , Li Yun, , Liu Xixia, 2025, 29 (32):  6885-6892.  doi: 10.12307/2025.942 Abstract ( 118 )   PDF (1772KB) ( 63 )   Save BACKGROUND: Numerous clinical trials have demonstrated that hypertonic glucose prolotherapy promotes tendon injury healing, yet the underlying mechanisms remain unclear. OBJECTIVE: To investigate the effects of different concentrations of hypertonic glucose on rat behavior, cellular morphology, tendon extracellular matrix components, and growth factors. METHODS: Fifty male Sprague-Dawley rats were randomly assigned into five groups: control blank, model, 5% glucose, 15% glucose, and 25% glucose groups, with 10 rats in each group. (1) Modeling: Except for the control blank group, all groups received an Achilles tendon injection of type I collagenase. (2) Intervention: The control blank and model groups received no treatment. The 5%, 15%, and 25% glucose groups received injections of 30 µL of 5%, 15%, and 25% glucose, respectively, into the right Achilles tendon once a week for 3 weeks. (3) Assessments: Behavioral assessments, hematoxylin-eosin staining, western blot, and RT-qPCR were conducted to assess type I collagen, type III collagen, transforming growth factor β1, vascular endothelial growth factor, and SCX expression levels in tendon tissue.  RESULTS AND CONCLUSION: (1) Behavioral analysis: Compared with the control blank group, the model group showed a significant reduction in 5-minute running distance (P < 0.05). Compared with the model group, the 25% glucose group exhibited a significant increase in 5-minute running distance (P < 0.05). (2) Compared with the control blank group, tendon tissue in the other groups showed varying degrees of collagen disarray, increased number of blood vessels, and increased number of cells. However, glucose-treated groups exhibited more orderly collagen alignment than the model group. (3) Compared with the control blank group, the mRNA expression of type I collagen α1 was reduced, and the mRNA expression of type III collagen was increased in the model group (P < 0.05). Compared with the model group, the 25% glucose group exhibited increased mRNA expression of type I collagen α1, while both the 15% and 25% glucose groups showed significantly decreased mRNA expression of type III collagen and increased SCX mRNA expression (P < 0.05). (4) Compared with the control group, the model group displayed reduced protein expression of type I collagen and increased protein expression of type III collagen and vascular endothelial growth factor (P < 0.05). Compared with the model group, the glucose intervention groups had decreased protein expression of type III collagen, with the 25% glucose group showing increased protein expression of type I collagen and the 15% glucose group exhibiting elevated protein expression of vascular endothelial growth factor and transforming growth factor β1 (P < 0.05). To conclude, hypertonic glucose promotes vascular endothelial growth factor and transforming growth factor β1 expression, modulates collagen synthesis, increases the content of type I collagen, and accelerates tendon healing. Furthermore, 25% hypertonic glucose concentration has the optimal intervention effect. Figures and Tables | References | Related Articles | Metrics

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Oxidative stress-related genes and molecular mechanisms after spinal cord injury: data analysis and verification based on GEO database Wang Ziheng, Wu Shuang 2025, 29 (32):  6893-6904.  doi: 10.12307/2025.912 Abstract ( 184 )   PDF (9445KB) ( 66 )   Save BACKGROUND: The biological significance of oxidative stress in spinal cord injury has not been systematically investigated.  OBJECTIVE: To investigate the role of oxidative stress-related genes in the development of spinal cord injury and to elucidate the related molecular mechanisms.  METHODS: The GSE151371 dataset was obtained from the Gene Expression Omnibus (GEO) database and selected a gene set highly relevant to oxidative stress from the GeneCards database (including 899 genes with relevance scores of no less than 7). Firstly, we performed differential expression gene analysis on samples from spinal cord injury patients and healthy controls. Subsequently, we cross-referenced these 899 oxidative stress genes with the differential expression genes to identify oxidative stress-related genes closely associated with spinal cord injury (spinal cord injury-reactive oxygen species-related genes). Then, the Least Absolute Shrinkage and Selection Operator and Support Vector Machine-Recursive Feature Elimination algorithms were used to derive potential biomarkers based on the spinal cord injury-reactive oxygen species-related genes. Following this, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses on these biomarkers were conducted to explore their roles in biological processes and the signaling pathways they participate in. Additionally, we constructed a competing endogenous RNA network and performed an in-depth analysis of the immune microenvironment. We predicted transcription factors related to these biomarkers and explored potential therapeutic drugs. Finally, fifteen blood samples from eight patients with acute spinal cord injury and seven controls were collected from Affiliated Hospital of Guizhou Medical University for reverse transcription quantitative polymerase chain reaction analysis to evaluate the expression of biomarkers between spinal cord injury and control samples.  RESULTS AND CONCLUSION: (1) There were 2 511 differential expression genes between spinal cord injury and control samples. Cross-analysis of oxidative stress genes and differential expression gene resulted in 151 spinal cord injury-reactive oxygen species-related genes. Least Absolute Shrinkage and Selection Operator and Support Vector Machine-Recursive Feature Elimination identified six biomarkers-S100A9, PLAU, CASP4, GAPDH, CYP1B1, and HSPA1B-involved in activities such as nicotinamide adenine dinucleotide phosphate oxidoreductase activity and oxidative phosphorylation. (2) Six messenger RNAs (mRNAs), eight microRNAs (miRNAs), and 50 long noncoding RNAs (lncRNAs) formed the mRNA-miRNA-lncRNA network, including relationships such as S100A9-hsa-mir-16-5p-HCG18 and CYP1B1-hsa-mir-429-KCNQ1OT1. (3) Infiltration levels of nine immune cells, including plasma cells, resting natural killer cells, and M0 macrophages, showed significant differences between spinal cord injury and control samples. (4) The top five predicted transcription factors were FOSB, ZNF581, SP110, NFIL3, and BATF2, with ZNF581 and NFIL3 showing significant expression differences between spinal cord injury and control samples. (5) The study predicted a variety of drugs based on the six biomarkers, and the molecular docking results showed that β-naphthoflavone had good binding activity to the target protein of CYP1B1. The interaction pairs they formed included DB01373-S100A9 and DB01065-CYP1B1. (6) In reverse transcription quantitative polymerase chain reaction verification, S100A9, GAPDH, CYP1B1, and HSPA1B showed significant differences between spinal cord injury and control groups, while PLAU and CASP4 showed an increasing trend in spinal cord injury group. (7) This study identified six key biomarkers, including S100A9, PLAU, CASP4, GAPDH, CYP1B1, and HSPA1B, and subsequently predicted 100 small-molecule drugs based on these biomarkers. These findings provide valuable insights for health management and disease prevention among the Chinese population, offering new perspectives for spinal cord injury treatment options. Figures and Tables | References | Related Articles | Metrics

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Influenza A virus recombinant hemagglutinin 1 induces the production of beta-defensin and interferon-gamma in mouse tracheal epithelial cells Lei Qi, Zhao Bingbing, Luo Hong, Chen Qiang, Jiang Yan 2025, 29 (32):  6905-6912.  doi: 10.12307/2025.922 Abstract ( 96 )   PDF (1828KB) ( 70 )   Save BACKGROUND: β-defensin has the ability against influenza A virus and inhibits a series of inflammatory responses induced by influenza A virus infection within cells. There have been no reports on whether hemagglutinin 1 from influenza A virus can induce the secretion of mouse β-defensin and interferon-γ when acting in mouse tracheal epithelial cells. OBJECTIVE: To investigate the effect of recombinant hemagglutinin 1 on the production levels of mouse β-defensin and interferon-γ in mouse tracheal epithelial cells. METHODS: Primary mouse tracheal epithelial cell were divided into six groups: blank control group (Control), recombinant hemagglutinin 1 group (200 ng/mL), recombinant hemagglutinin 1 + influenza A virus group, influenza A virus group (2×TCID50), recombinant hemagglutinin 1 + inactivated influenza A virus group, and inactivated influenza A virus (I) group. After the mouse tracheal epithelial cells in each group were treated for 4, 8, or 24 hours, hematoxylin-eosin staining was used for pathological observation. The mRNA levels of mouse β-defensin 2, 3, and 4, and interferon-γ were detected by qRT-PCR. The protein levels of mouse β-defensin 2, 3, and 4 were measured by enzyme-linked immunosorbent assay, and the protein expression of interferon-γ was detected by western blot. RESULTS AND CONCLUSION: (1) The recombinant hemagglutinin 1 acting alone or in combination with influenza A virus could cause different pathological changes in tracheal epithelial cells. Phenomena such as vacuolation, nuclear pyknosis and cell fusion could be observed in the cells. (2) Compared with the control group, recombinant hemagglutinin 1 alone or in combination with influenza A virus or inactivated influenza A virus significantly induced the production of mouse β-defensin 2, 3, and 4 (P < 0.05) and interferon-γ in mouse tracheal epithelial cells (P < 0.05). These results indicate that recombinant hemagglutinin 1 alone or in combination with influenza A virus can induce the production of mouse β-defensin 2, 3, and 4 and interferon-γ in mouse tracheal epithelial cells. Figures and Tables | References | Related Articles | Metrics

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Lower extremity biomechanical characterization during step-down test in patients with patellofemoral pain Gao Yuan, Xiong Zheyu, Zheng Wei, Chen Haonan, Chen Fangyuqing 2025, 29 (32):  6913-6919.  doi: 10.12307/2025.925 Abstract ( 112 )   PDF (1458KB) ( 97 )   Save BACKGROUND: The pathogenesis of patellofemoral pain is complex, and poor movement patterns and incorrect muscle activation patterns have been suggested to increase patellofemoral joint stress and cause injury, but the results of current studies are not uniform. Current biomechanical studies of step-down test in patients with patellofemoral pain have focused on kinematic characteristics, and there is a lack of research on surface electromyographic characteristics. In addition, there are no studies that analyze the differences in biomechanical performance between the healthy and affected sides of patellofemoral pain patients compared with healthy subjects during the downward step test. OBJECTIVE: To investigate the kinematic and surface electromyographic characteristics of patients with patellofemoral pain during bilateral lower extremity step-downs. METHODS: Twenty-one men with patellofemoral pain and 21 healthy men were recruited, and both groups of subjects underwent a step-down test. Kinematic, kinetic and surface electromyographic data were synchronously collected using a three-dimensional dynamic capture system, a force platform and a surface electromyographic tester.   RESULTS AND CONCLUSION: (1) Kinematics: Compared with the healthy control group, the affected and healthy sides of the patellofemoral pain group showed a smaller hip flexion angle (P=0.005, P=0.011), a larger hip internal rotation angle (P=0.033, P=0.039), and a larger knee valgus angle (P=0.001, P=0.001), and the affected side of the patellofemoral pain group exhibited a larger hip internal rotation angle (P=0.013), a smaller knee flexion angle (P=0.043), and a smaller ankle dorsiflexion angle (P=0.002); and compared with the healthy side, the affected side exhibited a smaller ankle dorsiflexion angle (P=0.002). (2) Surface electromyography: Compared with the healthy control group, the patellofemoral pain group showed reduced activation of the vastus medialis oblique (P=0.002), reduced activation of the gluteus medius (P=0.015), and a decreased vastus medialis oblique / vastus lateralis ratio (P=0.010) on the affected side; and compared with the healthy side, there was a reduced activation of the gluteus medius on the affected side (P=0.008). (3) The results indicate that patients with patellofemoral pain have abnormal lower limb biomechanical characteristics during step-down test, which are mainly manifested as changes in kinematic and indexes of the lower limb joints in the sagittal and frontal planes as well as changes in activation levels of the medial femoral and gluteus medius muscles. These changes reflect the fact that patients with patellofemoral pain adopt a stiff landing pattern during step-downs and show pronation of other joints of the lower extremity. In addition, abnormal lower extremity biomechanical characteristics are also present in the healthy limbs of patients with patellofemoral pain, and bilateral lower extremity asymmetry exists in such patients. Figures and Tables | References | Related Articles | Metrics

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Bilateral lower limb biomechanical abnormalities in patients with unilateral chronic ankle instability Guo Ping, Wang Juan 2025, 29 (32):  6920-6926.  doi: 10.12307/2025.974 Abstract ( 130 )   PDF (1093KB) ( 70 )   Save BACKGROUND: Recent studies have shown that patients with unilateral chronic ankle instability have bilateral sensorimotor impairment. However, it is still unknown how bilateral sensorimotor impairment affects the biomechanical characteristics of the affected and unaffected sides.  OBJECTIVE: To investigate the kinematic and kinetic characteristics of the bilateral lower limbs in patients with unilateral chronic ankle instability during lateral cutting maneuver. METHODS: Eighteen patients with unilateral chronic ankle instability and eighteen healthy subjects were recruited. The patients with chronic ankle instability completed 90° cutting on the affected and healthy sides. The healthy subjects completed 90° cutting on the dominant side. The kinematic parameters of the lower limbs during lateral incision were collected using an infrared high-speed motion capture system, and the kinetic parameters of the lower limbs were collected using a three-dimensional force platform. Paired and independent sample t-tests were used to compare differences in various biomechanical variables. RESULTS AND CONCLUSION: (1) Compared with healthy subjects, patients with chronic ankle instability showed higher ankle inversion (P=0.047) and internal rotation (P=0.046) angles on the affected side, and higher ankle inversion angles (P=0.049) on the unaffected side. Compared with the affected side, the knee valgus (P < 0.001) and hip adduction (P=0.046) angles of patients with chronic ankle instability were significantly increased on the unaffected side. (2) Compared with healthy subjects, patients with chronic ankle instability showed higher knee extension moment on the affected side (P=0.029). Compared with the affected side, the plantar flexion moment of the ankle on the unaffected side of patients with chronic ankle instability was significantly increased (P=0.027), and the extension moment of the knee was significantly reduced (P=0.048). To conclude, patients with unilateral chronic ankle instability have abnormal biomechanical characteristics of the lower limbs not only on the affected side but also on the unaffected side, and there are potential risks of “giving way” or recurrence ankle sprains on both sides. Furthermore, patients with unilateral chronic ankle instability also exhibit changes in the biomechanical characteristics of the proximal joints in the coronal plane on the affected side. Figures and Tables | References | Related Articles | Metrics

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Exploration of biomarkers for moyamoya disease and analysis of traditional Chinese medicine targets#br# #br# Zhou Rulin, Hu Yuanzheng, Wang Zongqing, Zhou Guoping, Zhang Baochao, Xu Qian, Bai Fanghui 2025, 29 (32):  6927-6938.  doi: 10.12307/2025.936 Abstract ( 118 )   PDF (6869KB) ( 268 )   Save BACKGROUND: The pathogenesis of moyamoya disease is unclear, and there is a lack of early diagnostic methods and effective medical treatments. OBJECTIVE: To identify biomarkers of moyamoya disease through machine learning, and analyze the therapeutic mechanism of Bu Huang Si Wu Tang in moyamoya disease. METHODS: Moyamoya disease gene dataset from gene expression omnibus database was retrieved. R language was used to screen differentially expressed genes and perform enrichment analysis on differentially expressed genes. Moyamoya disease biomarkers were screened using least absolute shrinkage and selection operator and support vector machine-recursive feature elimination machine learning algorithms. A diagnostic model was constructed by establishing a column chart, and its clinical utility and diagnostic value were evaluated and further validated through detecting clinical serum markers of patients with moyamoya disease. In vitro experiments were performed to observe the effect of Bu Huang Si Wu Tang on umbilical vein endothelial cells under oxygen glucose deprivation, and the main components of Bu Huang Si Wu Tang were selected for molecular docking and molecular dynamics simulation with the screened targets to explore its potential mechanism. RESULTS AND CONCLUSION: This study identified 76 differentially expressed genes, mainly enriched in immune and metabolic related pathways. Two potential biomarkers, complement factor D (CFD) and DKFZp434L192, were obtained through machine learning. The calibration curve, decision curve analysis, and clinical impact curve showed that the column chart had good predictive ability. qRT-PCR analysis showed that CFD and DKFZp434L192 expression levels were significantly upregulated in patients with moyamoya disease (P < 0.001). In vitro experiments showed that Bu Huang Si Wu Tang significantly enhanced the activity and migration ability (P < 0.01) of umbilical vein endothelial cells under oxygen glucose deprivation. Molecular docking results showed that all four active ingredients of Bu Huang Si Wu Tang could bind to the target site, and the dynamic simulation results further verified its binding stability. To conclude, CFD and DKFZp434L192 exhibit good diagnostic efficacy for moyamoya disease and can serve as potential diagnostic biomarkers and therapeutic targets for moyamoya disease. Bu Huang Si Wu Tang has a certain protective effect on vascular endothelial cells under ischemic conditions, which may be related to CFD. Figures and Tables | References | Related Articles | Metrics

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Effects of Agiophyllum Oligo Saccharides on inflammation and apoptosis of mouse synovial cells Zhao Xuemei, Wang Rui, Ao · Wuliji, Bao Shuyin, Jiang Xiaohua 2025, 29 (32):  6939-6946.  doi: 10.12307/2025.939 Abstract ( 118 )   PDF (2266KB) ( 34 )   Save BACKGROUND: For knee osteoarthritis, synovium inflammation and abnormal proliferation and activation of fibroblast-like synoviocytes caused by insufficient apoptosis are important driving factors for disease progression. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway plays a key role in regulating inflammatory response and apoptosis of synovial cells. As a traditional Mongolian medicine component, Agiophyllum Oligo Saccharides has anti-inflammatory and immunomodulatory functions, but its specific molecular mechanism has not been fully revealed. OBJECTIVE: To explore the effects and mechanism of Agiophyllum Oligo Saccharides on lipopolysaccharide-induced inflammation and apoptosis of mouse synovial cells. METHODS: The mouse synovial cells were randomly divided into a control group, a model group, an Agiophyllum Oligo Saccharides group and a Bay 11-7082 group. Osteoarthritic synoviocyte model was prepared using 1.0 µg/mL lipopolysaccharide intervention for 36 hour. The Agiophyllum Oligo Saccharides group was treated with 1.0 µg/mL lipopolysaccharide and 32 µg/mL Agiophyllum Oligo Saccharides for 36 hours; and the Bay 11-7082 group was firstly incubated for 4 hours with 1 μmol/L NF-κB pathway inhibitor Bay 11-7082, and then 1.0 µg/mL lipopolysaccharide and 32 µg/mL Agiophyllum Oligo Saccharides for 36 hours. Western blot was used to detect TLR4, MyD88, NF-κBp65, p-NF-κBp65, and IκBα protein expression. The level of tumor necrosis factor-α and interleukin-1β in the supernatant were analyzed by ELISA. To detect the expressions of Bax and Bcl-2, western blot and immunofluorescence analysis were performed. The intracellular reactive oxygen species level was detected by DCFH-DA. RESULTS AND CONCLUSION: (1) Compared with the control group, the levels of tumor necrosis factor-α, interleukin-1β and reactive oxygen species, the protein expressions of TLR4, MyD88, Bcl-2, and p-NF-κBp65/ NF-κBp65 increased (P < 0.05), whereas the protein expressions of IκBα and Bax decreased (P < 0.05) in the model group. (2) Compared with the model group, the levels of tumor necrosis factor-α, interleukin-1β and reactive oxygen species, the protein expressions of TLR4, MyD88, Bcl-2, and p-NF-κBp65/NF-κBp65 decreased (P < 0.05), while the expressions of IκBα and BAX increased (P < 0.05) in the Agiophyllum Oligo Saccharides group. (3) The levels of tumor necrosis factor-α, interleukin-1β and reactive oxygen species and the protein expression of Bcl-2 in the Bay 11-7082 group were higher than those in the Agiophyllum Oligo Saccharides group (P < 0.05), but still lower than those in the model group (P < 0.05), whereas the expression of Bax protein was lower than that in the Agiophyllum Oligo Saccharides group (P < 0.05), but still higher than that in the model group  (P < 0.05). (4) Compared with the model group and the Agiophyllum Oligo Saccharides group, the protein expressions of TLR4, MyD88 and p-NF-κBp65/NF-κBp65 decreased (P < 0.05), whereas the protein expressions of IκBα increased (P < 0.05) in the Bay 11-7082 group. To conclude, Agiophyllum Oligo Saccharides could inhibit inflammation of mouse synovial cells and promote apoptosis of synovial cells with inflammation, and the mechanisms may be correlated with regulating the TLR4/NF-κB signaling pathway.  Figures and Tables | References | Related Articles | Metrics

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Integration of pathways for interaction mechanism between exercise and proteins Wei Huqiang, Wu Hebin, Hou Yali, Zhang Xiangyong, Wang Zixuan, Wang Wenxuan, Bai Caiqin 2025, 29 (32):  6947-6954.  doi: 10.12307/2025.989 Abstract ( 158 )   PDF (1319KB) ( 147 )   Save BACKGROUND: Protein is one of the essential nutrients for the human body and is a key component of human cell tissue. Protein supplementation can promote the synthesis of myofibrillar protein and play a key role in strength training. However, the interaction mechanism and signaling pathway between protein and exercise are still unclear.  OBJECTIVE: To explore the mechanism of interaction between exercise and protein, and to optimize the benefits of protein supplementation on exercise performance. METHODS: Using “sports, proteins, amino acids, polypeptide, interaction mechanisms, signaling pathway” as Chinese and English search terms, we searched WanFang Data, CNKI, VIP, and PubMed databases respectively. Articles were screened according to the inclusion criteria, and finally 73 articles were included in the review. RESULTS AND CONCLUSION: Current research on protein supplementation promoting exercise performance mainly focuses on promoting muscle growth, endurance improvement, and body recovery through protein supplementation, but there are differences in the existing experimental results. The interaction mechanism between protein molecules and proteins in the body is not yet clear. The research on the interaction mechanism between exercise and peptides is still in its infancy. Exercise can stimulate the full absorption of external protein intake, which can affect the mechanism of protein molecules in the body. Supplementing peptide nutrition can more accurately affect the body’s state, thus better eliminating the phenomena of “sub-health” and “modern diseases.” Therefore, studying the interaction mechanism between exercise and proteins is particularly important, delving into the specific mechanisms by which amino acids act on the body, and further exploring the interaction mechanism between exercise and peptides. Figures and Tables | References | Related Articles | Metrics

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Monomeric traditional Chinese medicine in the treatment of rheumatoid arthritis: regulation of T cell balance Zhu Jiaping, Gao Bo, Lou Chunbiao, Yang Fengyong, Yang Kun 2025, 29 (32):  6955-6962.  doi: 10.12307/2025.965 Abstract ( 160 )   PDF (2130KB) ( 68 )   Save BACKGROUND: Rheumatoid arthritis is a complex autoimmune disease characterized by joint swelling, pain, and progressive damage. The basic pathological changes include synovitis and pannus formation, with T lymphocyte infiltration being the key to its pathogenesis. In recent years, the application of traditional Chinese medicine (TCM) monomers in the treatment of rheumatoid arthritis has attracted increasing attention. They have shown long-lasting efficacy and fewer side effects by regulating the T helper cell 17 (Th17)/regulatory T cells (Treg) balance in the treatment of rheumatoid arthritis.   OBJECTIVE: To discuss the mechanisms by which TCM monomers regulate the Th17/Treg balance to treat rheumatoid arthritis, based on the latest basic research, providing a solid theoretical basis for future applications of TCM in the treatment of rheumatoid arthritis.   METHODS: Using keywords such as “rheumatoid arthritis, Th17/Treg, traditional Chinese medicine, Chinese herbal monomer,” and their Chinese equivalents, literature searches were conducted in PubMed, Web of Science, Embase, Cochrane, VIP, CBM, CNKI, and WanFang databases for relevant studies from their inception to August 2024. Inclusion and exclusion criteria were established, and the articles were screened by reading the titles, abstracts, and full texts. Finally, 57 relevant articles were included.   RESULTS AND CONCLUSION: (1) TCM monomers have immunoregulatory effects in the treatment of rheumatoid arthritis. They exert therapeutic effects by maintaining the Th17/Treg balance through the regulation of transcription factors, cytokines, signaling pathways, and miRNAs. (2) There may be synergistic effects among some TCM monomers, but the specific mechanisms and enhancement effects in regulating the Th17/Treg balance require further exploration. (3) Regulating the Th17/Treg balance using TCM monomers may become a key clinical therapy for the treatment of rheumatoid arthritis. Figures and Tables | References | Related Articles | Metrics

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Blood flow restriction training intervention in the elderly with sarcopenic obesity Liu Chenchen, Liu Ruize, Bao Mengmeng, Fang Li, Cao Liquan, Wu Jiangbo 2025, 29 (32):  6963-6970.  doi: 10.12307/2025.997 Abstract ( 111 )   PDF (1405KB) ( 102 )   Save BACKGROUND: Sarcopenic obesity is a syndrome characterized by the loss of muscle mass and an increase in body fat, which increases the risk of metabolic diseases and physical disabilities in the elderly. Blood flow restriction training involves applying pressure to a body part during exercise to reduce blood flow, achieving the effects of high-intensity training with low-intensity exercise, making it suitable for the elderly and those with limited mobility. OBJECTIVE: To review and discuss the biological mechanisms, effectiveness, and limitations of blood flow restriction training in addressing sarcopenic obesity in the elderly, and to provide exercise prescription recommendations based on current evidence.  METHODS: Literature published up to September 2024 was retrieved from major databases. English and Chinese search terms included “blood flow restriction training, KAATSU, elderly, sarcopenia, sarcopenic obesity, muscle, fat.” A total of 66 articles were selected, organized, and analyzed. RESULTS AND CONCLUSION: This study explored the biological mechanisms of blood flow restriction training, including creating an ischemic-hypoxic environment, accumulating metabolites, activating potential signaling pathways, and promoting satellite cell proliferation. The effectiveness of blood flow restriction training in improving muscle strength, mass, and reducing body fat was evaluated, and its potential advantages and risks in the elderly population were discussed. It is recommended that elderly patients with sarcopenic obesity undergo blood flow restriction training combined with 20%-40% 1 RM resistance training for three to four times per week. Starting from the first week, there are three sets of training with 30, 15, and 15 repetitions respectively. From the second week, there are four sets with 30, 15, 15, and 15 repetitions respectively. The rest interval between each set is 30-60 seconds. The cuff width is 3-5 cm. The pressure of each set increases incrementally by 40%, 60%, and 80% of the arterial occlusion pressure. The airbag pressure ranges from 80 to 240 mmHg. Future research is needed to further verify the long-term effects of blood flow restriction training, optimize the training protocol, and explore its application possibilities in different disease contexts. Figures and Tables | References | Related Articles | Metrics

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Application of concentrated growth factor in treatment of chronic wounds Zuo Chaoqi, Zhang Zhiqiang, Cao Nan, Guo Xuan, Xie Kai, Wang Haixia, Zhang Guangliang 2025, 29 (32):  6971-6978.  doi: 10.12307/2025.996 Abstract ( 113 )   PDF (1099KB) ( 96 )   Save BACKGROUND: Current treatment strategies for chronic non-healing wounds have shown unsatisfactory results, necessitating the exploration of novel therapeutic approaches. Concentrated growth factors, rich in high-concentration growth factors and possessing a stable natural three-dimensional structure, have demonstrated significant application value in the treatment of chronic non-healing wounds. OBJECTIVE: To review the current status of concentrated growth factor application in chronic non-healing wounds, analyze the shortcomings of concentrated growth factor in clinical applications, and propose constructive suggestions and prospects.  METHODS: CNKI, WanFang, and VIP databases were searched with the key words of “concentrated growth factor, platelet concentrate products, chronic wound, chronic ulcer, wound healing, platelet-rich plasma, platelet-rich fibrin” in Chinese. PubMed was searched with the key words of “CGF, concentrated growth factor, platelet concentrate products, chronic wound, chronic ulcer, wound healing, PRP, PRF, platelet-rich plasma, platelet-rich fibrin” in English. The  articles published from 2000 to 2024 were searched and further analyzed and summarized after screening.  RESULTS AND CONCLUSION: Concentrated growth factor, with its diverse application forms, high concentration of growth factors, natural three-dimensional structure, compatibility with various material technologies, relatively low cost, and ease of operation, has demonstrated significant clinical value in the treatment of chronic wounds. Numerous researchers have validated its positive effects in chronic wound therapy through clinical applications. However, there is currently no clear consensus on standardized concentrated growth factor application protocols, and certain deficiencies have been revealed in practical applications, including issues with dosage, centrifugation settings, identification schemes, and preparation methods for different forms of concentrated growth factor. There is substantial room for research on concentrated growth factor, and it is believed that with a clear consensus on its application in the future, concentrated growth factor could play a significant role in clinical practice.  Figures and Tables | References | Related Articles | Metrics

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Neural physiological basis and exercise-induced mechanism of central fatigue Wang Qifei, Du Xingbin, Kong Jianda 2025, 29 (32):  6979-6988.  doi: 10.12307/2025.940 Abstract ( 178 )   PDF (1382KB) ( 84 )   Save BACKGROUND: Central fatigue refers to the phenomenon where changes in the functions of the central nervous system lead to a decline in an individual’s exercise capacity and an increase in the sense of fatigue. With the continuous development of sports science, the mechanisms of exercise-induced central fatigue have gradually become a research hotspot. Although a large number of studies have explored the roles of biological mechanisms such as neurotransmitters, energy metabolism, and neuroinflammation in central fatigue, the interactions of these mechanisms and their manifestations in different exercise scenarios are still not fully understood. OBJECTIVE: To explore various biological mechanisms of exercise-induced central fatigue, clarify the interactions of neurotransmitters, energy metabolism, neural network activities, neuroinflammation, and oxidative stress in the formation of fatigue, and thereby provide a new perspective for understanding central fatigue. METHODS: Web of Science, PubMed, CNKI, WanFang, and VIP databases were searched with search terms “central fatigue, neurophysiological basis, exercise, physical activity, neurotransmitters, serotonin, dopamine, glutamate, GABA, energy metabolism, astrocytes, neuroinflammation, oxidative stress, cortical activity, neural network activity, sport” in Chinese and English. Relevant literature published from the establishment of each database to August 2024 was retrieved, and finally 74 articles were included for review. RESULTS AND CONCLUSION: Exercise-induced central fatigue involves multiple complex biological mechanisms. The imbalance of neurotransmitters (such as serotonin, dopamine, glutamate, and γ-aminobutyric acid) is a key factor in central fatigue. In particular, the increase in serotonin is closely related to the enhancement of the sense of fatigue. The disorder of energy metabolism, especially the glycogen metabolism of astrocytes and the supply of lactic acid, plays an important role in the formation of fatigue during long-term exercise. Neuroinflammation and oxidative stress exacerbate the manifestations of central fatigue by affecting the release of neurotransmitters and the functions of neural networks. In addition, changes in the activities of neural networks, such as the decrease in the excitability of the cerebral cortex, directly affect exercise performance. Future studies should strengthen the comprehensive exploration of neurotransmitter, metabolic, and inflammatory pathways, conduct more human studies to verify the findings of animal experiments, explore the differences in the mechanisms of central fatigue under different exercise conditions (such as intensity, time, and environment), and study the potential of drug interventions or nutritional supplements based on neurotransmitter regulation in alleviating central fatigue. Figures and Tables | References | Related Articles | Metrics

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Meta-analysis of the effectiveness of dry needling at myofascial trigger points in the treatment of knee disorders Yao Tingfeng, Liu Lin, Liu Shixuan, Lu Xinyue 2025, 29 (32):  6989-6996.  doi: 10.12307/2025.920 Abstract ( 102 )   PDF (3448KB) ( 65 )   Save OBJECTIVE: Dry needling therapy is widely used in various myofascial pain syndromes. The purpose of this study was to systematically evaluate the clinical effect of dry needling in the treatment of knee joint diseases. METHODS: PubMed, EBSCO, ScienceDirect, Web of Science, CINAHL, Cochrane Library, CNKI and other databases were searched for relevant literature. Randomized controlled trials with dry needling as the main treatment method and patients diagnosed with knee joint disease were selected. Two evaluators independently screened the articles, scored the methodological quality, and extracted the data. The main indicators were visual analog scale score, and the secondary indicators were the Western Ontario McMaster Universities (WOMAC) score, pressure pain threshold, knee mobility and Kujala score ( knee function score scale). RESULTS: A total of 15 randomized controlled trials involving 698 patients were included in the Meta-analysis. The results showed that compared with non-dry needling, dry needling at myofascial trigger points had a significant advantage in visual analog scale score, the WOMAC pain score and WOMAC stiffness score [MD=-0.63, 95% confidence interval (CI): -1.06 to -0.19, P=0.005; MD=-0.74, 95% CI: -1.32 to -0.17, P=0.01; MD=-0.43, 95% CI: -0.77 to -0.09, P=0.01). However, there was no significant advantage in WOMAC total score, WOMAC functional score, pressure pain threshold, knee mobility, and Kujala score. CONCLUSION: Dry needling can effectively treat knee pain and stiffness; however, the clinical advantages of dry needling in improving other knee joint dysfunction and its follow-up effect are not well documented. Therefore, in some older patients with chronic knee pain or joint stiffness, the use of dry needling can be carefully considered. Figures and Tables | References | Related Articles | Metrics

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Visual analysis of dynamic evolution of research topics in the field of physical activity and hippocampal tissue Deng Qing, Wang Qingjun, Zhang Yeting 2025, 29 (32):  6997-7003.  doi: 10.12307/2025.948 Abstract ( 96 )   PDF (1572KB) ( 89 )   Save BACKGROUND: Numerous studies have explored the effects of physical activity on the hippocampus, but the relationship between physical activity and the human hippocampus remains controversial and confusing. Therefore, it is necessary to sort out the relevant research in the field of physical activity and hippocampal tissue.  OBJECTIVE: To explore the dynamic evolution process of research topics in the field of physical activity and hippocampus, clarify the development status and changes in knowledge structure, and provide directions for further research through bibliometrics.  METHODS: The Web of Science database was searched by the search formula: TS=(“physical exercise” AND hippocampus) OR TS=(“physical activity” AND hippocampus) OR TS=(“exercise” AND hippocampus). According to the inclusion and exclusion criteria, 3 225 relevant documents were selected as content. SciMAT software was used for visual analysis. RESULTS AND CONCLUSION: (1) The field of physical activity and hippocampal tissue is booming, with more and more in-depth research and more room for future development. (2) This field can be divided into four directions: “messenger RNA,” behavior,” “environment” and “cognitive function,” and forms 7 main evolutionary paths. (3) Topics such as “neurotrophic factors,” “aerobic exercise” and “cognitive impairment” are likely to be the focus of future research. (4) This research field focuses on the elderly population, and the use of different model mice to explore the mechanism of physical activity on the hippocampus has promoted further research in this field. Figures and Tables | References | Related Articles | Metrics

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Relationship between seven serum lipid traits and osteoarthritis: a large sample analysis of European population in IEU OPEN GWAS database Wu Zhenhua, Zhang Xiwei, Wang Yipin, Li Qianqian 2025, 29 (32):  7004-7014.  doi: 10.12307/2025.916 Abstract ( 82 )   PDF (4312KB) ( 105 )   Save BACKGROUND: Osteoarthritis is a complex disease closely related to metabolic abnormalities. However, previous studies only involved limited blood lipid indicators and did not conduct more comprehensive blood lipid profile analysis. An in-depth exploration of the causal relationship between the seven items of blood lipids and osteoarthritis will not only help understand the pathogenesis of osteoarthritis, but also provide new research directions and clinical basis for its prevention and treatment. OBJECTIVE: To explore the causal relationship between blood lipids and osteoarthritis. METHODS: The genome-wide association analysis statistical data of 7 items of blood lipids and osteoarthritis from the IEU OPEN GWAS database were used to summarize, and significant single nucleotide polymorphisms were used as instrumental variables. The causal relationship between seven items (serum total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, apolipoprotein AI and apolipoprotein A1) of blood lipids and osteoarthritis (osteoarthritis, knee or hip osteoarthritis, knee osteoarthritis and hip osteoarthritis) was determined through two-sample Mendelian randomization analysis. The inverse variance weighting was the main effect, and the MR-Egger regression method and the weighted median method were the supplementary effects. Bonferroni correction and reverse Mendelian randomization analysis could ensure validity. Multivariable Mendelian randomization analysis was used to further eliminate confounding factors. A significant causal relationship between seven items of blood lipids and osteoarthritis was obtained to ensure the robustness of the analysis. Co-localization analysis was used to once again ensure the robustness of the causal relationship and identify significantly influencing gene loci, making the evidence of causality more complete. RESULTS AND CONCLUSION: (1) In the two sample Mendelian randomization analysis, the results from inverse variance weighting indicated negative correlations between osteoarthritis and the following serum lipids: total cholesterol (OR=0.937 2, 95%CI=0.885 6-0.991 9, P=0.025), low-density lipoprotein cholesterol (OR=0.959 4, 95%CI=0.923 6-0.996 6, P=0.033), high-density lipoprotein cholesterol (OR=0.911 2, 95%CI=0.833 5-0.996 2, P=0.04), apolipoprotein B (OR=0.926 7, 95%CI=0.887 7-0.967 4, P=0.000 5), and apolipoprotein AI (OR=0.951 2, 95%CI=0.911 0-0.993 1, P=0.023). Additionally, total cholesterol (OR=0.892 3, 95%CI=0.843 1-0.944 3, P=0.000 08), triglycerides (OR=0.938 5, 95%CI=0.884 7-0.995 6, P=0.035), and apolipoprotein B (OR=0.911 6, 95%CI= 0.865 9-0.959 7, P=0.000 4) were negatively associated with knee or hip osteoarthritis. For knee osteoarthritis specifically, total cholesterol (OR=0.898 3, 95%CI=0.841 2-0.959 3, P=0.001), high-density lipoprotein cholesterol (OR=0.881 2, 95%CI=0.794 7-0.977 0, P=0.016), and apolipoprotein B (OR=0.919 0, 95%CI=0.869 8-0.971 0, P=0.002) also showed negative correlations. Lastly, with respect to hip osteoarthritis, total cholesterol (OR=0.864 5, 95%CI=0.797 5- 0.937 3, P=0.000 4), low-density lipoprotein cholesterol (OR=0.925 6, 95%CI=0.879 5-0.974 1, P=0.003), and apolipoprotein B (OR=0.888 8, 95%CI=0.817 6- 0.966 3, P=0.005) exhibited negative correlations. No statistically significant differences were found in the reverse Mendelian randomization analysis. (2) In the multivariable Mendelian randomization analysis, the results from inverse variance weighting indicated a negative correlation between high-density lipoprotein cholesterol and osteoarthritis (OR=0.942 7, 95%CI=0.896 1-0.991 8, P=0.022). Additionally, total cholesterol (OR=0.799 8, 95%CI=0.647 8-0.987 6,  P=0.037) and high-density lipoprotein cholesterol (OR=0.865 1, 95%CI=0.7781-0.961 9, P=0.007) were also negatively associated with knee osteoarthritis. (3) Colocalization analysis revealed that total cholesterol and low-density lipoprotein were significantly associated with osteoarthritis at single nucleotide polymorphisms rs13107325 (H4 posterior probability=99.9%). (4) These findings, using international databases and non-Asian populations, provide valuable insights for early clinical diagnosis, understanding the pathogenesis, and researching prevention and treatment of osteoarthritis in Chinese biomedicine and the Chinese population. Figures and Tables | References | Related Articles | Metrics

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Antioxidants from different sources and osteoarthritis: a genome-wide association analysis in European populations Liu Xiaowu, Liu Jinping, Wu Ting, He Xian, Cai Jianxiong 2025, 29 (32):  7015-7027.  doi: 10.12307/2025.797 Abstract ( 99 )   PDF (4926KB) ( 124 )   Save BACKGROUND: Currently, numerous observational studies have frequently associated dietary antioxidant intake and circulating antioxidant levels with osteoarthritis. Nevertheless, the underlying causal mechanisms remain unclear. Therefore, this study employs publicly available genome-wide association data to investigate the causal associations between antioxidant intake, circulating levels, and osteoarthritis, offering evidence for the prevention and treatment of osteoarthritis. OBJECTIVE: To assess the potential causal associations between dietary antioxidants (including vitamins A, C, E, and carotenoids) and circulating antioxidants (such as Glutathione S-transferase, glutathione peroxidase, catalase, superoxide dismutase, ascorbic acid, α-tocopherol, γ-tocopherol, albumin, uric acid, bilirubin, zinc, and selenium) with osteoarthritis through Mendelian randomization.  METHODS: Data from genome-wide association studies on four dietary antioxidants and twelve circulating antioxidants were employed as exposure variables. The outcome variable was the osteoarthritis consortium dataset, which comprised 77 052 osteoarthritis cases and 378 169 healthy controls. Causal effects were evaluated using the inverse variance-weighted method, MR-Egger regression, and the weighted median approach. Stability and reliability of the findings were assessed through horizontal pleiotropy tests and sensitivity analyses. RESULTS AND CONCLUSION: (1) These results demonstrated that dietary vitamin C intake was inversely associated with knee osteoarthritis risk (OR=0.83, 95%CI: 0.71-0.96, P=0.015). Conversely, vitamin E intake was positively associated with knee osteoarthritis (OR=1.20, 95%CI: 1.05-1.34, P=0.004) and both knee and hip osteoarthritis (OR=1.15, 95%CI: 1.03-1.27, P=0.008). (2) Circulating antioxidant albumin levels were negatively associated with knee (OR=0.94, 95%CI: 0.91-0.97, P=0.001), hip (OR=0.95, 95%CI: 0.91-0.99, P=0.03), and knee or hip osteoarthritis (OR=0.95, 95%CI: 0.92-0.98, P=0.01). Uric acid levels were positively associated with knee osteoarthritis (OR=1.10, 95%CI: 1.03-1.17, P=0.003). (3) Sensitivity analyses yielded consistent results without evidence of horizontal pleiotropy. (4) European genome-wide data indicated that vitamin C intake was associated with a decreased risk of knee osteoarthritis, and lower serum albumin levels were associated with reduced risks of knee and hip osteoarthritis. In contrast, vitamin E intake and higher serum uric acid were associated with an increased risk of knee osteoarthritis. These findings support public health education and osteoarthritis interventions, indicating that serum albumin could be a potential biomarker for risk assessment. (5) The study underscores the role of certain antioxidants in osteoarthritis prevention and provides evidence to inform nutritional guidelines and public health strategies for the Chinese population. Furthermore, it contributes to biomarker research in arthritis, facilitating the development of early diagnostic tools and risk assessment strategies for the Chinese population. Figures and Tables | References | Related Articles | Metrics

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Screening of target genes for bile acid metabolism in Crohn’s disease and its value in disease diagnosis and therapeutic monitoring Chen Hui, Zhang Lu, Chen Jing, Wang Nanzhang, Wang Ruochun, Lu Cuihua, Ji Yifei 2025, 29 (32):  7028-7040.  doi: 10.12307/2025.937 Abstract ( 119 )   PDF (9460KB) ( 6 )   Save BACKGROUND: Bile acid metabolism plays a crucial role in the development and progression of Crohn’s disease. There is no research on changes in bile acid metabolism and key target genes following treatment with biological agents. OBJECTIVE: To investigate the expression characteristics of bile acid metabolism-related genes in patients with Crohn’s disease, identify key genes associated with response to biological agents. METHODS: Transcriptome data were obtained through the GEO database to analyze differentially expressed genes between inflammation-control groups and inflammation-treatment groups. GO, KEGG, and GSEA enrichment analyses were used to evaluate the effects of biological agent therapy on bile acid metabolism. Protein-protein interaction network and WGCNA algorithm were employed to analyze differentially expressed genes, identifying modules closely related to biological agent treatment response, which led to the determination of UGT2A3 as a key gene in bile acid metabolism. In the inflammation group of the GSE186582 dataset, samples were divided into high and low expression groups based on UGT2A3 levels to study its relationship with immune infiltration and explore the interaction between UGT2A3 and the immune microenvironment. Clinical characteristics and intestinal manifestations were compared between high and low expression groups, and correlations between UGT2A3 and clinical indicators (C-reactive protein, erythrocyte sedimentation rate, Crohn’s disease activity index, and Crohn’s disease endoscopic activity score) were investigated. The competing endogenous RNA regulatory network of UGT2A3 was constructed, and its upstream miRNA was functionally enriched to explore the molecular mechanism of UGT2A3 in bile acid metabolism. Single-cell analysis and clustering were performed using high-throughput sequencing data of GSE134809 to observe the expression of UGT2A3 in different samples and cell populations. Colon tissue samples from untreated and biologic-treated Crohn’s disease patients and healthy colon tissue samples from patients with intestinal polyps were collected, and UGT2A3 expression was detected by immunohistochemistry, qRT-PCR, and western blot assay. Fresh feces from Crohn’s disease patients and healthy controls were collected to detect bile acid levels, and the relationship between UGT2A3 and fecal bile acid levels was analyzed. RESULTS AND CONCLUSION: A total of 11 bile acid metabolism-related genes were screened, showing significant changes in gene expression after biological agent therapy. GO and KEGG enrichment analyses revealed that intestinal nutrient absorption and metabolic processes normalized after treatment, while leukocyte chemotaxis and inflammatory response pathway activity decreased. GSEA analysis revealed significant enrichment of bile acid metabolism-related pathways after treatment. Protein-protein interaction network construction and WGCNA analysis identified UGT2A3 as a key gene closely associated with treatment response. UGT2A3 expression was significantly decreased in inflamed tissues of Crohn’s disease patients and returned to normal levels after biological agent therapy. This result was confirmed in clinical specimens. UGT2A3 expression levels showed significant negative correlations with C-reactive protein, erythrocyte sedimentation rate, Crohn’s Disease Activity Index, and Crohn’s Disease Endoscopic Index of Severity. Receiver Operating Characteristic curve analysis demonstrated that UGT2A3 has good diagnostic value (Area Under Curve AUC=0.801 0) and effectively reflects treatment outcomes. Immune infiltration analysis showed significantly increased infiltration of various immune cells in samples with low UGT2A3 expression, and its expression levels negatively correlated with immune scores, microenvironment scores, and stromal scores. Compared with the low UGT2A3 expression group, patients with high expression showed less fecal occult blood and penetrating inflammation, with milder intestinal strictures and general condition severity. Fecal bile acid analysis revealed that UGT2A3 expression strongly negatively correlated with primary bile acid content and strongly positively correlated with secondary bile acid content. Figures and Tables | References | Related Articles | Metrics