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18 October 2025, Volume 29 Issue 29 Previous Issue    Next Issue

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Internal heat acupuncture inhibits osteoblast apoptosis and delays steroid-induced avascular necrosis of the femoral head in rabbits Tian Xinbao, Ma Liangchen, Tian Fubao, Liu Yuanyuan, Xu Jianfeng, Lin Ruizhu, Zhu Ning 2025, 29 (29):  6161-6166.  doi: 10.12307/2025.635 Abstract ( 172 )   PDF (2127KB) ( 100 )   Save BACKGROUND: Steroid-induced avascular necrosis of the femoral head is a common progressive, crippling and high incidence of non-traumatic osteonecrosis of the femoral head, but its exact pathogenesis is not clear. Internal heat acupuncture therapy has a good clinical effect in the treatment of steroid-induced avascular necrosis of the femoral head, but its specific mechanism is not clear. OBJECTIVE: To investigate the effect of internal heat acupuncture on osteoblast apoptosis and expression of Bcl-2-associated X protein (Bax) and B lymphocytoma-2 (Bcl-2 ) in steroid-induced avascular necrosis of the femoral head in rabbits.  METHODS: Totally 24 male New Zealand rabbits were randomly divided into blank group, model group, and internal heat acupuncture group (n=8). The rabbit model of steroid-induced avascular necrosis of the femoral head was made in the last two groups by methylprednisolone sodium succinate combined with Escherichia coli endotoxin. After successful model establishment for 4 weeks, the rabbits in the internal heat acupuncture group received internal heat acupuncture intervention on the buttocks of rabbits, once a week for 20 minutes each time, while the other two groups did not receive any intervention. After 4 weeks of treatment, samples were harvested. Morphological changes of femoral head and osteoblast apoptosis were observed by hematoxylin-eosin staining and TUNEL assay. Protein expression of Bcl-2 and Bax in rabbit femoral head tissue was detected by immunohistochemistry and western blot assay. RESULTS AND CONCLUSION: (1) In the blank group, there were abundant hematopoietic cells in the bone marrow cavity, clear and orderly trabecular structure, few adipocytes and few empty bone lacunae. In the model group, the number of adipocytes in the bone marrow cavity increased significantly, accompanied by hyperplasia, steatosis of some osteocytes and more empty bone lacunae. After the intervention of internal heat acupuncture, the number of adipocytes and hollow bone lacunae was less than that in the model group, but more obvious than that in the blank group. (2) Compared with the blank group, the apoptosis of osteoblasts in the model group was significantly increased, the expression of Bax was significantly increased (P < 0.001), and the expression of Bcl-2 was significantly decreased (P < 0.001). After the intervention of internal heat acupuncture, the apoptosis of osteoblasts was significantly decreased, the expression of Bax was significantly decreased (P < 0.001), and the expression of Bcl-2 was significantly increased (P < 0.001). (3) The results show that internal heat acupuncture can alleviate steroid-induced avascular necrosis of the femoral head by inhibiting osteoblast apoptosis in the femoral head. Figures and Tables | References | Related Articles | Metrics

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Three-dimensional model of swallowing musculoskeletal system based on CT image data and biomechanical characteristics analysis Fang Dandan, Ma Ruijie, Huang Yi, He Kelin, Wu Lei 2025, 29 (29):  6167-6163.  doi: 10.12307/2025.796 Abstract ( 138 )   PDF (1808KB) ( 357 )   Save BACKGROUND: At present, there are many clinical studies on dysphagia, but little is known about the stress of bones and hyoid muscles caused by dysphagia.  OBJECTIVE: To establish a three-dimensional model of swallowing musculoskeletal system to investigate the stress changes of hyoid and suprahyoid muscles during swallowing. METHODS: A healthy adult male was selected for head and neck CT scanning. A three-dimensional model was constructed by image extraction method. According to hyoid motion, the lowest and highest positions of hyoid were set, and the muscle strength of suprahyoid muscles was successively loaded to observe the stress influence of suprahyoid muscles on hyoid under physiological state. By changing the material properties of muscles, we simulated different degrees of dysphagia and observed the stress changes of suprahyoid muscle group under the condition of dysphagia. RESULTS AND CONCLUSION: (1) The finite element models including C2-C4 vertebrae, partial temporal bone, mandible, hyoid, and mylohyoid-geniohyoid muscle were established, which could reflect the displacement of hyoid and stress changes during swallowing. (2) Under physiological conditions, among suprahyoid muscles, mylohyoid muscle had the greatest influence on hyoid stress, followed by digastric muscle, geniohyoid muscle, and stylohyoid muscle. (3) By simulating different degrees of dysphagia, it was found that with the increase of the severity of dysphagia, the stress of suprahyoid muscles gradually increased. (4) These findings conclude that among suprahyoid muscles, mylohyoid muscle and digastric muscle have the greatest influence on hyoid stress, which suggests the importance of specific muscle stimulation. The aggravation of dysphagia was positively correlated with the stress change of suprahyoid muscles, which could provide a biomechanical reference for the mechanism study and clinical diagnosis and treatment of dysphagia. Figures and Tables | References | Related Articles | Metrics

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Analysis of risk factors for lumbar fascial edema in patients with osteoporotic vertebral compression fractures Chen Hao, Wu Pigen, Teng Jiaqi, Zhang Liang, Feng Xinmin 2025, 29 (29):  6174-6179.  doi: 10.12307/2025.789 Abstract ( 173 )   PDF (1244KB) ( 46 )   Save BACKGROUND: Related studies have shown that bone density, postoperative infection, adjacent vertebral fracture, and lumbar fascial edema may be risk factors for lingering pain after vertebroplasty. OBJECTIVE: To scrutinize the risk factors for lumbar fascia edema in osteoporotic vertebral compression fractures patients and investigate its influence on lingering pain after vertebroplasty. METHODS: A retrospective analysis was conducted on 204 osteoporotic vertebral compression fractures patients who underwent percutaneous vertebroplasty at the Clinical Medical College of Yangzhou University from February to October 2022. Patients were categorized based on MRI findings into two groups: without lumbar fascia edema (84 cases) and with lumbar fascia edema (120 cases). Preoperative data, encompassing age, gender, height, weight, body mass index, bone density, serum total protein, serum albumin, inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), degree of fracture compression, presence of prior compression fractures, fracture count, lumbar instability, and Japanese senile independence score were gathered. Postoperative follow-up recorded data such as the number of new vertebral fractures and visual analog scale scores were recorded. Logistic regression method was used to analyze the risk factors of lumbar fascial edema, and the receiver operating characteristic curve was used to determine whether the risk factors had relevant diagnostic significance. RESULTS AND CONCLUSION: (1) Age, prior vertebral compression fractures, Japanese senile independence score score, and lumbar instability presence emerged as autonomous risk factors for lumbar fascia edema in osteoporotic vertebral compression fractures patients, with corresponding odds ratios of 2.76, 1.70, 2.56, and 4.74, respectively. (2) Employing a visual analog scale score of 4 at 1 month postoperatively to distinguish residual pain revealed 31 cases with residual pain in the lumbar fascia edema group, in contrast to only 8 cases in the non-fascia edema group (P < 0.01). (3) The fascia edema group exhibited a significantly higher visual analog scale score at 1 month postoperatively (2.12±1.35) compared to the group without fascia edema (1.67±1.08) (P < 0.01). (4) It is indicated that age, Japanese senile independence score, prior compression fractures, and lumbar instability presence independently contribute to lumbar fascia edema in osteoporotic vertebral compression fractures patients. Lumbar fascia edema emerges as a determinant of persistent pain in the lumbar region following percutaneous vertebroplasty in these patients. Figures and Tables | References | Related Articles | Metrics

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Buqi Huoxue Compounds intervene in neurological function, p-Akt and serum exosome expression in a rat model of cerebral ischemia-reperfusion injury Liu Tong, , Huang Zhibin, Chen Yuning, Jiang Ying, Liao Xiangyu, Chen Qiongjun, Xiong Liang, Liu Yue, 2025, 29 (29):  6180-6186.  doi: 10.12307/2025.762 Abstract ( 189 )   PDF (2003KB) ( 210 )   Save BACKGROUND: Buqi Huoxue Compounds have shown significant clinical effects on the treatment of ischemic stroke due to qi deficiency and phlegm stasis, but its specific mechanism of action needs to be further clarified. OBJECTIVE: To observe the effects of Buqi Huoxue Compounds on the neurological function, p-Akt and serum exosome expression in a rat model of cerebral ischemia-reperfusion injury.  METHODS: Forty adult male SPF Sprague-Dawley rats, 6 weeks old, were randomly divided into sham operation group, model group, Buqi Huoxue Compounds group, Buqi Huoxue Compounds+GW4869 group, with 10 rats in each group. In the latter three groups, a rat model of cerebral ischemia-reperfusion injury was established using thread technique. The sham operation group was given incision and separation without inserting a suture. The Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds (6.49 g/kg, administered three times a day) 2 hours after reperfusion; the GW4869+Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds (6.49 g/kg, administered three times a day) 2 hours after reperfusion and intraperitoneally given GW4869 [2.5 mg/(kg•d)] 2 hours before gavage with 3 days after modeling. Both the sham operation group and model group received equal amounts of saline via gavage, three times a day, for 7 consecutive days. Neurological function, cerebral infarct volume, brain tissue morphology, characterization of serum exosome, p-Akt in the cortical area and CD63 and TSG101 in serum exosome were detected after 7 days of administration. RESULTS AND CONCLUSION: (1) After modeling, compared with the sham operation group, the neurological function scores of the model group, Buqi Huoxue Compounds group, and Buqi Huoxue Compounds+GW4869 group were significantly increased (P < 0.01 or P < 0.05). After 7 days of intervention, the neurological function scores of the Buqi Huoxue Compounds group were significantly lower than those of the model group and Buqi Huoxue Compounds+ GW4869 group (all P < 0.01). (2) The results of 2,3,5-triphenyltetrazolium chloride staining showed that cerebral infarct foci were observed in the model group, Buqi Huoxue Compounds group, and Buqi Huoxue Compounds+GW4869 group, and the cerebral infarct volume in the Buqi Huoxue Compounds group was smaller than that in the model group and the Buqi Huoxue Compounds+GW4869 group (P < 0.01). (3) The results of hematoxylin-eosin staining showed that the morphological and structural abnormalities of nerve cells in the Buqi Huoxue Compounds group and Buqi Huoxue Compounds+GW4869 group were less severe than those in the model group, but some cells still exhibited cytoplasmic agglutination and pyknosis in the Buqi Huoxue Compounds group and Buqi Huoxue Compounds+GW4869 group. (4) NanoSight analysis showed that the diameters of the isolated particles ranged from 60 nm to 300 nm, consistent with the characteristic size of exosomes. (5) Western blot results showed that the expression of p-Akt in the infarct zone and expression of CD63 and TSG101 in serum exosomes were significantly lower in the model group compared with the sham operation group (P < 0.05 or P < 0.01). Compared with the model group, the expression of p-Akt in the infarct zone and expression of CD63 and TSG101 in serum exosomes were significantly higher in the Buqi Huoxue Compounds group than in the model group (P < 0.05 or P < 0.01). However, the p-Akt expression in the infarct zone and CD63 expression in serum exosomes decreased significantly in the Buqi Huoxue Compounds+GW4869 group (P < 0.05), while TSG101 expression decreased without significant difference after the addition of GW4869. (6) To conclude, Buqi Huoxue Compounds attenuate cerebral ischemia-reperfusion injury and increase the expression of p-Akt in rats by promoting exosome secretion. Figures and Tables | References | Related Articles | Metrics

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Therapeutic effect of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rat models: fecal metabolomics analysis Chai Jinlian, Sun Tiefeng, Li Wei, Zhang Bochun, Li Guangzheng, Zhou Zhongqi, Liang Xuezhen, Wang Ping 2025, 29 (29):  6187-6197.  doi: 10.12307/2025.772 Abstract ( 161 )   PDF (2832KB) ( 304 )   Save BACKGROUND: Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Colla can enter the bone, promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells, and has a good repair effect on steroid-induced osteonecrosis of the femoral head. OBJECTIVE: To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics.  METHODS: Thirty SD rats were randomly divided into three groups using a random number table method: the control group (n=10) was injected with normal saline into the right gluteal muscle (injected on the first 3 days of each week for 3 consecutive weeks), and was given pure water gavage (once a day for 6 consecutive weeks). The model group (n=10) was injected with methylprednisolone sodium succinate into the right gluteal muscle (injected on the first 3 days of each week for 3 consecutive weeks) to establish a steroid-induced osteonecrosis of the femoral head model, and was given pure water gavage (once a day for 6 consecutive weeks). The Cornus Cervi Colla group (n=10) was also established with a steroid-induced osteonecrosis of the femoral head model, and was given Cornus Cervi Colla gavage (once a day for 6 consecutive weeks). After gavage, cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining, respectively. RESULTS AND CONCLUSION: (1) Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Colla and model groups, with 65 significantly differing and clearly annotated metabolites. Lipid and amino acid metabolites were significantly increased, with bile acids, sulfated steroids, ephedrine, hypoxanthine, betaine, L-carnitine, B-mouse bile acid, cytidine, 4-pyridoxic acid, taurine, N-acetyl-d-glucosamine, and butyric acid being the most impacted (variable weight value VIP > 5). The metabolic pathways of taurine and hypotaurine were crucial in the metabolic regulatory network (pathway impact=0.428 57). (2) Micro-CT scanning results of bone tissue showed that the femoral heads of rats in the model group and the Cornus Cervi Colla group had different degrees of damage; the femoral head contour was irregular; the trabeculae in the subchondral bone of the femoral head were missing and disordered, and some cystic structures were visible. Compared with the model group, the degree of trabecular damage in the rats of the Cornus Cervi Colla group was milder. Hematoxylin-eosin staining results showed that the trabeculae in the subchondral bone of the femoral heads of rats in the model group and the Cornus Cervi Colla group were sparse or interrupted, and the empty bone lacuna rate and adipocyte invasion were increased. Compared with the model group, the empty bone lacuna rate and adipocyte invasion in the subchondral bone of the femoral heads of rats in the Cornus Cervi Colla group were reduced. (3) These results conclude that Cornus Cervi Colla potentially mitigates steroid-induced osteonecrosis of the femoral head through the metabolic processes involving taurine and associated pathways. Figures and Tables | References | Related Articles | Metrics

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Protective mechanism of tanshinone IIA in mouse ovarian cryopreservation Wu Xiaochou, Wang Huiying, Wang Jie, Zhang Caifeng, Hou Yanyun, Jin Bo 2025, 29 (29):  6198-6204.  doi: 10.12307/2025.776 Abstract ( 217 )   PDF (2894KB) ( 185 )   Save BACKGROUND: Ovarian tissue vitrification cryopreservation is one of the important methods for preserving fertility. Tanshinone IIA has various pharmacological activities, including anti-oxidation, inhibition of inflammatory response, and reduction of apoptosis, but its role as an additive for vitrification cryoprotection of ovarian tissue is still unclear. OBJECTIVE: To explore the protective effect of tanshinone IIA on vitrification cryopreservation of mouse ovarian tissue.  METHODS: Twenty-five 6-week-old female KM mice were randomly selected and their ovarian tissues were randomly divided into five groups, with 10 ovaries per group. The fresh group was not cryopreserved. The frozen control group used vitrification cryoprotectant. The 0.5, 2.5, and 5 µmol/L tanshinone IIA groups used vitrification cryoprotectant containing 0.5, 2.5, and 5 µmol/L tanshinone IIA, respectively, and were cryopreserved in liquid nitrogen. After 3 days of storage, the cryopreserved tubes were taken out and thawed. The ovarian tissue and follicle morphology of each group were observed by hematoxylin-eosin staining, and the normal follicle morphology and survival rate were analyzed. The levels of superoxide dismutase, catalase, malondialdehyde, tumor necrosis factor-α, interleukin-1β, and interleukin-17 in the ovary were detected by enzyme-linked immunosorbent assay. RT-qPCR and western blot assay were used to detect the mRNA and protein expressions of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the mouse ovary.  RESULTS AND CONCLUSION: (1) Compared with the fresh group, the frozen control group had abnormal morphology of follicles at all levels in the ovary, decreased follicle survival rate (P < 0.05), decreased superoxide dismutase and catalase activities (P < 0.05); the levels of malondialdehyde, and tumor necrosis factor α, interleukin 1β, and interleukin 17 were all increased (P < 0.05), and the mRNA and protein expressions of Nrf2 and HO-1 were decreased (P < 0.05). (2) Compared with the frozen control group, different concentrations of tanshinone IIA could improve the morphology of follicles at all levels in the ovary, increase the survival rate of follicles, enhance the activities of superoxide dismutase and catalase, and reduce the levels of malondialdehyde, tumor necrosis factor α, interleukin 1β, and interleukin 17, increased the mRNA and protein expression of Nrf2 and HO-1 in a concentration-dependent manner, with 5 µmol/L tanshinone IIA having the most significant effect. (3) The results show that tanshinone IIA may reduce the oxidative stress level and inflammatory response of mouse ovarian tissue by mediating the Nrf2/HO-1 signaling pathway, thereby alleviating the reproductive damage caused by vitrification cryopreservation of mouse ovaries. Figures and Tables | References | Related Articles | Metrics

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Transcriptome sequencing analysis of the mechanism by which cold water swimming regulates inflammatory response in rats Si Juncheng, Peng Lina, Sun Lili, Wang Yu, Shi Lei, Shen Wenhui, Li Mengqi, Zang Wanli 2025, 29 (29):  6205-6211.  doi: 10.12307/2025.777 Abstract ( 198 )   PDF (1963KB) ( 143 )   Save BACKGROUND: When exercising in a cold environment, the body’s inflammatory response is affected by both low temperature and exercise intervention, and its impact and mechanism remain to be explored. OBJECTIVE: To explore the effects and mechanisms of cold water swimming on inflammatory response of rats based on transcriptome sequencing technology. METHODS: 40 male SD rats were randomly divided into room temperature control group, room temperature swimming group, cold water control group, and cold water swimming group, with 10 rats in each group. The room temperature control group had no intervention and was free to eat. The room temperature swimming group received swimming at 30 min/time, 6 times/week, for 5 weeks; the water temperature was (28±2) °C, and the water depth was 35 cm. In the cold water control group, the rats were placed in a water tank with a depth of 3 cm; the water temperature was (18±2) °C, and they were free to move. The cold water swimming group received swimming at 30 min/time, 6 times/week, for 5 weeks; the water temperature was (18±2) °C, and the water depth was 35 cm. Enzyme-linked immunosorbent assay was used to detect the levels of serum interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein. Based on the transcriptome sequencing results, differentially expressed genes were screened to draw Venn diagrams and heat maps, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed. The protein-protein interaction network was used to screen core genes. RT-qPCR was used to detect the mRNA expression of IRF7, OAS2, and OASL in rat spleen tissue. RESULTS AND CONCLUSION: (1) The ELISA results showed that compared with the room temperature control group, the levels of various inflammatory indicators in the room temperature swimming group and the cold water swimming group were significantly increased (P < 0.05), and there was no significant difference in the cold water control group. Compared with the room temperature swimming group, there was no significant difference in the expression of inflammatory indicators in the cold water swimming group. Compared with the cold water control group, the expressions of interleukin-6 and tumor necrosis factor-α in the cold water swimming group showed an upward trend, and high-sensitivity C-reactive protein increased significantly (P < 0.05). (2) Transcriptome analysis: Venn diagram showed that there were 39 differentially expressed genes affected by the dual factors of temperature and exercise intervention. Cluster heat map analysis results showed that the overall gene expression trends of the room temperature swimming group and the cold water swimming group were similar, and the cold water control group showed an opposite trend. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis results showed that differentially expressed genes were enriched in the immune system, locomotion, nucleic acid-binding transcription factor activity, NOD-like receptor signaling pathways and other pathways. The number of genes enriched in the NOD-like receptor signaling pathway was relatively large, and the q value was small, which may be a key pathway. The protein-protein interaction network screened out IRF7, OAS2, OASL, IFIT2, IFIT3 and other core genes. (3) RT-qPCR verification results showed that compared with the room temperature control group, the expressions of IRF7, OAS2 and OASL were significantly increased in the room temperature swimming group and the cold water swimming group (P < 0.01), and there was no significant difference in the cold water control group. Compared with the cold water control group, the expression of each gene was significantly increased in the cold water swimming group (P < 0.01). (4) It is concluded that cold water swimming can promote inflammatory response, and its mechanism may be regulated through the NOD-like receptor signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Effects of myocardial extracellular matrix remodeling on connexin 43 and its Ser368 phosphorylation and electrical conduction Song Yuting, Wen Chunlei, Li Yi, Bai Xue, Gao Hong, Hu Tingju, Wang Zijun, Yan Xu 2025, 29 (29):  6212-6218.  doi: 10.12307/2025.775 Abstract ( 172 )   PDF (2044KB) ( 199 )   Save BACKGROUND: Our previous studies found that decreased expression of connexin 43 and its Ser368 phosphorylation after myocardial hypothermic ischemia-reperfusion was closely associated with decreased cardiac conduction velocity and reperfusion arrhythmia.  OBJECTIVE: To observe the effect of changes in membrane-type matrix metalloproteinase 2, matrix metalloproteinase 2 and collagen type IV on the expression of connexin 43 and its Ser368 phosphorylation and electrical conduction in the myocardial extracellular matrix after hypothermic ischemia-reperfusion. METHODS: Sixteen Langendorff extracorporeal cardiac perfusion models were successfully established from SD rats and randomly divided into a control group (n=8) and a hypothermic ischemia-reperfusion group (n=8). The control group was balanced perfused with 37 °C Krebs-Henseleit solution for 15 minutes and then continued to be perfused with 37 °C Krebs-Henseleit solution for 90 minutes. The hypothermic ischemia-reperfusion group was balanced perfused with 37 °C Krebs-Henseleit solution for 15 minutes, and then the heart was arrested for 60 minutes by injection of 4 °C Thomas solution. During the cardiac arrest, the periphery was protected by 4 °C Krebs-Henseleit solution. Half-volume 4 °C Thomas solution was reperfused 30 minutes after the arrest. After stopping the arrest, the heart was reperfused with 37 °C Krebs-Henseleit solution for 30 minutes. The occurrence of arrhythmias, rebeating time, and the duration of arrhythmias were recorded from the immediate time point to the end of the reperfusion period. Conduction velocity, absolute inhomogeneity, and inhomogeneity index were measured using the Mapping Lab multi-channel electrophysiological mapping system at the time of balanced perfusion for 15 minutes (T1), reperfusion for 15 minutes/continuous perfusion for 90 minutes (T2), and reperfusion for 30 minutes/continuous perfusion for 105 minutes (T3). The relative expression levels of membrane-type matrix metalloproteinase 2, matrix metalloproteinase 2, collagen type IV, connexin 43, and its Ser368 phosphorylation in ventricular tissue were detected by western blot assay.  RESULTS AND CONCLUSION: (1) No arrhythmia occurred in the control group. There were six cases of arrhythmia in the hypothermic ischemia-reperfusion group during reperfusion. Rebeating time and duration of arrhythmias were (25.38±12.02) and (158.67±67.68) seconds, respectively. (2) The conduction isochronal diagrams at T1, T2, and T3 in the control group were uniform and regular in direction, and the conduction velocity at T2 and T3 was not different from that at T1 (P > 0.05). The conduction isochronal diagrams at T2 and T3 in the hypothermic ischemia-reperfusion group were uneven and irregular in direction, and the conduction velocity was slower than that at T1 (P < 0.01). The conduction velocity at T2 and T3 in the hypothermic ischemia-reperfusion group was slower than that in the control group (P < 0.01).  Conduction dispersion was greater in the hypothermic ischemia-reperfusion group than that in the control group at T2 and T3 (P < 0.05). (3) Compared with the control group, the protein expressions of membrane-type matrix metalloproteinase 2 and matrix metalloproteinase 2 in the hypothermic ischemia-reperfusion group were increased (P < 0.05 or P < 0.01), and the protein expression levels of type IV collagen, connexin 43 and its Ser368 phosphorylation were decreased (P < 0.05 or P < 0.01). (4) The results indicate that after hypothermic ischemia-reperfusion, myocardial extracellular matrix remodeling may mediate the downregulation of myocardial connexin 43 and its Ser368 phosphorylation, slowed conduction velocity and increased conduction dispersion, thereby increasing the risk of arrhythmia. Figures and Tables | References | Related Articles | Metrics

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Ginsenoside Rb1 alleviates cerebral ischemic injury in mice by regulating microglial polarization Liu Ruojing, Zhao Xue, Zhu Yizhen, Fu Lingling, Zhu Junde 2025, 29 (29):  6219-6227.  doi: 10.12307/2025.774 Abstract ( 136 )   PDF (2691KB) ( 150 )   Save BACKGROUND: Previous studies by the research team have shown that the neuroprotective effect of ginsenoside Rb1 on improving cerebral ischemia-reperfusion injury may be related to the Wnt/β-catenin signaling pathway, but the specific mechanism of action remains unclear. OBJECTIVE: To explore the molecular mechanism of ginsenoside Rb1 in alleviating cerebral ischemia-reperfusion injury in mice. METHODS: 100 C57BL/6 mice were randomly divided into four groups. The sham operation group (n=25) did not undergo model establishment. In the cerebral ischemia-reperfusion injury group (n=25), the middle cerebral artery occlusion model was established by thread embolism. In the ginsenoside Rb1 group (n=25), the middle cerebral artery occlusion model was established by thread embolism and ginsenoside Rb1 was intraperitoneally injected every day for 3 days before the establishment. In ginsenoside Rb1+inhibitor group (n=25), the middle cerebral artery occlusion model was established by thread embolism and ginsenoside Rb1 and Wnt/β-catenin signaling pathway inhibitor XAV939 were intraperitoneally injected every day for 3 days before the establishment. Three days after modeling, Zea Longa score and balance beam test were used to evaluate the neurological deficits of mice. TTC staining was used to observe the volume of cerebral infarction. The dry-wet mass method was used to detect the degree of brain edema in mice. The activities of superoxide dismutase and glutathione peroxidase and the concentration of malondialdehyde in the parietal lobe of the ischemic side were detected by colorimetry. The co-expression of microglial marker Iba1 and inducible nitric oxide synthase (or arginase 1) was detected by immunofluorescence. The levels of aquaporin AQP4, inflammatory-related factors, and phosphorylation of Wnt/β-catenin pathway proteins glycogen synthase kinase 3β and β-catenin were detected by western blot assay. The mRNA expression of inflammatory factors was detected by q-PCR. RESULTS AND CONCLUSION: (1) Compared with cerebral ischemia-reperfusion injury group, the neurological deficit symptoms, cerebral infarction foci and brain tissue edema, oxidative stress and inflammatory response of the mice were alleviated; the number of M1 microglia (Iba1 and inducible nitric oxide synthase co-expressed) decreased; the number of M2 microglia (Iba1 and arginase 1 co-expressed) increased; the expression of phosphorylated glycogen synthase kinase 3β and phosphorylated β-catenin protein decreased in ginsenoside Rb1 group. Compared with ginsenoside Rb1 group, the neurological deficit symptoms, cerebral infarction foci and brain tissue edema, oxidative stress and inflammatory response of the mice were aggravated; the number of M1 microglia increased; the number of M2 microglia decreased; the expression of phosphorylated glycogen synthase kinase 3β and phosphorylated β-catenin protein increased in ginsenoside Rb1+inhibitor group. (2) The results indicate that ginsenoside Rb1 can regulate the polarization of microglia to M2 type and alleviate oxidative stress damage and inflammatory response after cerebral ischemia-reperfusion injury. Its mechanism may be related to the nuclear translocation of β-catenin mediated by the Wnt/β-catenin signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Du Meridian electroacupuncture inhibits ferroptosis and promotes neurorepair in rats with acute cervical spinal cord injury  Sun Rongyan, Xu Luchun, Jiang Guozheng, Song Jiawei, Ma Yukun, Fan Jiaojiao, Wang Guanlong, Yang Yongdong, Yu Xing 2025, 29 (29):  6228-6238.  doi: 10.12307/2025.767 Abstract ( 168 )   PDF (3678KB) ( 166 )   Save BACKGROUND: Recent studies have shown that Du Meridian electroacupuncture has a unique effect on alleviating spinal cord injury, but the underlying mechanisms require further clarification. OBJECTIVE: To investigate the regulatory effects and the associated action mechanisms of Du Meridian electroacupuncture on ferroptosis after cervical spinal cord injury in rats.  METHODS: One hundred SD rats were randomly divided into sham, model, Du Meridian electroacupuncture, RSL3, and Du Meridian electroacupuncture + RSL3 groups. The sham group underwent only laminectomy. The other four groups were subjected to cervical spinal cord injury by the Allen method. The Du Meridian electroacupuncture group received electroacupuncture after cervical spinal cord injury. The RSL3 group received intraperitoneal injections of glutathione peroxidase 4 inhibitor RSL3 after cervical spinal cord injury. The Du Meridian electroacupuncture + RSL3 group received both electroacupuncture and RSL3 intervention after cervical spinal cord injury. Samples were collected on postoperative days 7 and 28 to assess motor function, histological morphology, neuronal survival, glial scar formation, oxidative stress levels, Fe2+ content, glutathione peroxidase 4, and long-chain acyl-CoA synthetase 4 expression.  RESULTS AND CONCLUSION: (1) Finally, 90 rats completed the follow-up experiment, with 18 rats in each group. (2) FLS and BBB scores were significantly higher in the Du Meridian electroacupuncture group compared with the model and Du Meridian electroacupuncture + RSL3 groups (P < 0.05). (3) Compared with the model group, Du Meridian electroacupuncture improved cervical spinal cord tissue morphology and mitochondrial ultrastructure, while these effects were inhibited by RSL3. (4) Du Meridian electroacupuncture increased the expression of microtubule-associated protein 2, glutathione peroxidase 4, glutathione, and superoxide dismutase (P < 0.05) and reduced the expression of glial fibrillary acidic protein, long-chain acyl-CoA synthetase 4, reactive oxygen species, malondialdehyde, and Fe2+ compared with the model group (P < 0.05). However, RSL3 reversed the inhibitory effects of Du Meridian electroacupuncture on ferroptosis, lipid peroxidation and oxidative stress. (5) The results suggest that Du Meridian electroacupuncture inhibits ferroptosis by regulating the glutathione peroxidase 4/long-chain acyl-CoA synthetase 4 axis, thereby reducing secondary neuronal damage and glial scar formation after cervical spinal cord injury and improving neurological function. Figures and Tables | References | Related Articles | Metrics

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Construction and evaluation of spleen-deficiency hyperlipidemia mouse models Chen Lijuan, Gao Xinxue, Wu Jin, Du Ying, Lyu Meijun, Sui Guoyuan, Jia Lianqun, Pan Guowei 2025, 29 (29):  6237-6242.  doi: 10.12307/2025.799 Abstract ( 202 )   PDF (1431KB) ( 103 )   Save BACKGROUND: Traditional Chinese medicine has unique advantages in preventing and treating spleen-deficiency and hyperlipidemia. In basic studies, models of spleen-deficiency and hyperlipidemia are commonly found in rats, pigs, and other animals. This has limitations for medical research that can only use mouse models. It is urgent to establish and evaluate mouse models of spleen-deficiency and hyperlipidemia to support basic research on traditional Chinese medicine in preventing and treating spleen-deficiency and hyperlipidemia. OBJECTIVE: To establish a mouse model of spleen-deficiency hyperlipidemia. METHODS: Totally 24 C57BL/6J mice were randomly divided into normal group (n=12) and spleen-deficiency hyperlipemia group (n=12). Mice in normal group were fed basic diet. Mice in the spleen-deficiency hyperlipemia group were prepared with a diet disorder+fatigue internal injury+high-fat feeding method to establish a spleen-deficiency high-fat model. In the first 2 weeks, the mice were forced to swim to their endurance limit on a single day and were only fed cabbage, with free access to water. They were also gavaged with refined lard + high-fat feed on two-day intervals. After 2 weeks, the mice were fed a high-fat diet every day and the diet continued until 12 weeks. The mice were fed with a high-fat diet for 4 and 12 weeks, and their body weight, food intake, gripping strength, fecal water content, small intestinal charcoal propulsion rate, serum D-xylose and gastrin levels, spleen index and thymus index, blood lipid level, total body fat mass, body fat percentage, and liver lipid deposition were tested.   RESULTS AND CONCLUSION: (1) Compared with the normal group, the body weight, fecal water content, total body fat mass, body fat percentage, triglyceride and total cholesterol levels of the mice in the spleen-deficiency hyperlipemia group fed with high-fat diet for 4 and 12 weeks were increased (P < 0.05); the daily food intake, gripping force, and D-xylose level of the mice fed with high-fat diet for 4 and 12 weeks were decreased (P < 0.05); the spleen index of the mice fed with high-fat diet for 4 weeks was increased (P < 0.05); the small intestinal carbon propulsion rate, gastrin level, spleen index, and thymus index of the mice fed with high-fat diet for 12 weeks were decreased (P < 0.05); the low-density lipoprotein cholesterol level of the mice fed with high-fat diet for 12 weeks was increased (P < 0.05). (2) The results of liver oil red O staining showed that the lipid deposition in the spleen-deficiency hyperlipemia group after 4 weeks of high-fat diet feeding was slightly more than that in the normal group, and the lipid deposition in the high-fat diet feeding for 12 weeks was significantly more than that in the normal group. (3) The results show that a stable spleen deficiency and hyperlipidemia mouse model can be prepared by the compound method of eating disorders, exhaustion, and high-fat feeding.  Figures and Tables | References | Related Articles | Metrics

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Effects of exercise on activation of microglia and astrocytes and neuronal apoptosis in depressed rats Du Juan, Zhang Yi, Hao Quanshui 2025, 29 (29):  6243-6248.  doi: 10.12307/2025.779 Abstract ( 160 )   PDF (1415KB) ( 85 )   Save BACKGROUND: Cyclooxygenase-2 can significantly enhance depressive-like behavior in rats, and cyclooxygenase-2 inhibitors have antidepressant effects. Exercise can significantly reduce depressive-like behaviors in depressed patients. However, it is currently unclear whether exercise exerts an antidepressant effect by inhibiting cyclooxygenase-2. OBJECTIVE: To reveal the effects of exercise on cyclooxygenase-2 expression, microglia and astrocyte activation, oxidative stress and neuronal apoptosis in depressed rats, as well as the possible molecular mechanisms.  METHODS: The rat model of depression was induced by chronic unpredictable mild stimulation. After modeling, the chronic unpredictable mild stimulation rats were randomly divided into stimulation group and wheel running group, with 10 rats in each group. In addition, 10 normal rats were selected as the control group. The rats in the control group and stimulation group did not exercise. The rats in the wheel running group performed forced wheel running for a total of 4 weeks. Depressive-like behavior was evaluated by sucrose preference test. Hippocampal cyclooxygenase-2 expression was detected by immunofluorescence staining. The expression of cyclooxygenase-2, Iba-1, CD11b, CD45, glial fibrillary acid protein, Bcl-2, Bax, and cleaved caspase-3 proteins in the hippocampus was detected by western blot analysis. The cyclooxygenase-2 mRNA level in the hippocampus was detected by RT-PCR. The activities of antioxidant enzymes in hippocampal tissue homogenates were determined using kits.   RESULTS AND CONCLUSION: Compared with stimulation group, sucrose consumption was increased; cyclooxygenase-2 expression in hippocampus was decreased; superoxide dismutase, catalase, and glutathione peroxidase levels in hippocampus were increased; malonaldehyde level was decreased; Iba1, CD11b, and CD45 protein expression levels in hippocampus were decreased, and glial fibrillary acid protein level in hippocampus was decreased. Bcl-2 protein expression levels in the hippocampus were increased, while Bax and cleaved caspase-3 levels were decreased in wheel running group (P < 0.05). This study showed that wheel running could reduce depressive-like behavior by inhibiting the expression of cyclooxygenase-2 in the hippocampus of chronic unpredictable mild stimulation rats. In addition, wheel running can exert antidepressant effects by inhibiting microglia and astrocyte activation, oxidative stress, and neuronal apoptosis in the hippocampus. Figures and Tables | References | Related Articles | Metrics

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Acute effects of blood flow restriction resistance exercise on serum metabolites in obese young men Liu Haowei, Tian Haodong, Huang Li, Yu Hanglin, Peng Li 2025, 29 (29):  6249-6259.  doi: 10.12307/2025.746 Abstract ( 151 )   PDF (3153KB) ( 138 )   Save BACKGROUND: Blood flow restriction resistance exercise is an emerging mode of resistance exercise that restricts blood flow at lower loads, achieving effects similar to or even better than high-load exercises. Current research on its specific mechanisms and applications in obesity improvement is still limited. Exploring the potential mechanisms of blood flow restriction resistance exercise and its application in obese populations could provide a novel exercise prescription option for this group. OBJECTIVE: To explore the potential mechanisms of blood flow restriction resistance exercise on obesity-related metabolism by comparing the effect of a single session of traditional resistance exercise and blood flow restriction resistance exercise on serum metabolites in obese young men. METHODS: Twenty-five obese young men underwent a single session of traditional resistance exercise (n=13) or blood flow restriction resistance exercise (n=12). Venous blood samples were collected before exercise, immediately post-exercise, 1 hour post-exercise, and 24 hours post-exercise. High-performance liquid chromatography-tandem mass spectrometry was used to analyze the serum metabolome, focusing on the metabolites of the three major energy substances (carbohydrates, lipids, and amino acids) and related metabolic pathways. RESULTS AND CONCLUSION: (1) Both resistance exercise and blood flow restriction resistance exercise induced acute changes in the serum metabolomic profile. (2) In the traditional resistance exercise group, two carbohydrate differential metabolites, four lipid differential metabolites, and three amino acid differential metabolites were identified. In the blood flow restriction resistance exercise group, 10 lipid differential metabolites and 3 amino acid differential metabolites were discovered. (3) Both traditional resistance exercise and blood flow restriction resistance exercise significantly affected the serum metabolites in obese young men, with the greatest impact observed 1 hour post-exercise. Comparatively, blood flow restriction resistance exercise had a broader and more prolonged effect on the metabolites. (4) Traditional resistance exercise showed a more pronounced regulation of carbohydrate metabolites, particularly in the consumption of D-galactose and glycerol, while blood flow restriction resistance exercise exhibited unique advantages in the regulation of lipid and amino acid metabolites, such as an increase in phospholipids and the potential promotion of fatty acid oxidation via aspartic acid. These differences may be related to inflammation regulation and insulin sensitivity, but further research is needed to verify their clinical significance. Figures and Tables | References | Related Articles | Metrics

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Mechanisms by which traumatic brain injury promotes bone callus formation and fracture healing Liu Hanfei, Cai Zhencun, Zhou Xueting, Wen Hang, Chen Zhenjun 2025, 29 (29):  6260-6268.  doi: 10.12307/2025.742 Abstract ( 246 )   PDF (1183KB) ( 138 )   Save BACKGROUND: Delayed healing and nonunion of fractures are common clinical issues. Clinical observations have shown that patients with limb fractures combined with traumatic brain injury experience significantly faster fracture healing compared with those without brain injury. The potential mechanisms behind this phenomenon have become a crucial focus of current research. Recent studies indicate that traumatic brain injury significantly accelerates callus formation and fracture healing processes by regulating cytokines, hormones, neural signals, and stem cell mechanisms. OBJECTIVE: To summarize the latest research progress in the mechanisms by which traumatic brain injury promotes callus formation and fracture healing, thereby providing a theoretical basis for clinical applications. METHODS: The first author conducted a search of CNKI, WanFang, VIP, PubMed, Embase, Web of Science, and Cochrane Library databases for literature published from January 2013 to October 2024, with some references traced back up to 20 years. The search terms used were “traumatic brain injury, callus, fracture healing, inflammatory response, cytokines, hormones, neuropeptides, genes, stem cells” in Chinese and English. A total of 83 articles meeting the inclusion criteria were ultimately selected. RESULTS AND CONCLUSION: The mechanism by which traumatic brain injury promotes callus formation and fracture healing is highly complex, involving multiple regulatory pathways such as cytokines, hormones, the nervous system, and stem cells. However, the precise mechanisms are still not fully understood and require further investigation. Current research suggests that traumatic brain injury accelerates bone callus formation and bone tissue regeneration by promoting the release of cytokines (e.g., insulin-like growth factor-1) and hormones (e.g., growth hormone and leptin), regulating the nervous system, and promoting stem cell proliferation and differentiation. Additionally, traumatic brain injury triggers a series of immune responses, including the release of inflammatory factors and activation of immune cells, which modulate fracture healing. These responses improve local blood flow, cell migration, and fibroblast activation, supporting various stages of bone healing. Stem cell activation induced by traumatic brain injury is also crucial, as activated stem cells differentiate into osteoblasts, chondrocytes, and adipocytes, facilitating bone tissue regeneration and repair. Therefore, traumatic brain injury-induced immune responses and stem cell activation work together to accelerate fracture healing, providing essential support for the process. These mechanisms significantly shorten the healing time and improve patient outcomes. In conclusion, traumatic brain injury promotes callus formation and fracture healing through multiple mechanisms, highlighting its importance in bone repair. Future research should focus on the signaling pathways and regulatory factors influenced by traumatic brain injury to further understand its mechanisms. These findings will provide a foundation for developing targeted therapies, stem cell treatments, and neural regulation therapies, with potential clinical value in shortening healing time, optimizing recovery protocols, and improving prognosis. Exploring traumatic brain injury-induced biological effects will open new avenues for fracture treatment. Figures and Tables | References | Related Articles | Metrics

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Application of artificial intelligence in the diagnosis and treatment of lumbar disc herniation: evolution towards standardization, efficiency, and precision of diagnosis and treatment methods Zhang Ziyu, Chen Longhao, Sheng Wei, Lyu Hanzhe, Shen Ying, Wang Binghao, Lyu Zhizhen, Lyu Lijiang 2025, 29 (29):  6269-6276.  doi: 10.12307/2025.759 Abstract ( 171 )   PDF (1492KB) ( 279 )   Save BACKGROUND: In recent years, artificial intelligence has been increasingly integrated into the diagnosis and treatment of lumbar disc herniation, enhancing the accuracy and efficiency of diagnostic procedures and diversifying therapeutic approaches. This integration has positioned artificial intelligence as a burgeoning focal point within the field. OBJECTIVE: To provide a comprehensive overview of the current applications of artificial intelligence in the diagnosis and treatment of lumbar disc herniation, to analyze the limitations of the relevant technologies. METHODS: A systematic computer-assisted literature search was performed in PubMed, CNKI, WanFang Database, and VIP Database for relevant publications regarding the application of artificial intelligence in the diagnosis and treatment of lumbar disc herniation from database inception up to August 2024. The search keywords included “lumbar disc herniation, artificial intelligence, machine learning, deep learning, big data, robot, neural network, model, algorithm.” A total of 101 articles were selected based on predefined inclusion criteria and were reviewed. RESULTS AND CONCLUSION: Different artificial intelligence technologies have propelled the intelligent treatment of lumbar disc herniation, showing great potential for future development. Deep learning technology, based on advanced algorithms, constructs corresponding learning models to optimize the processing of X-ray, CT, and MRI images, achieving precise localization, identification, and analysis of degenerated intervertebral discs, and improving the accuracy of automated diagnosis. Big data technology utilizes data platforms to analyze vast medical data, simulate disease development trends, and provide a new perspective for disease assessment and prediction. Surgical robots, combined with robotic arms, 3D high-definition vision systems, and 5G communication technology, support remote precise surgical operations, demonstrating significant technological advantages. In the future, the diagnosis and treatment of lumbar disc herniation by artificial intelligence will evolve towards standardization, efficiency, and precision through continuous optimization of algorithms and the professional development of data platforms. Figures and Tables | References | Related Articles | Metrics

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Regularity of prescriptions for ischemic stroke based on latent structure combined with association rules Ping Xingfeng, Huang Zongxuan, Li Kai, Xie Guangmin, Lyu Junying 2025, 29 (29):  6277-6284.  doi: 10.12307/2025.905 Abstract ( 154 )   PDF (2345KB) ( 147 )   Save BACKGROUND: Currently, traditional Chinese medicine has accumulated extensive experience in the treatment and management of ischemic stroke. The application of latent structure combined with association rule analysis to deeply explore and summarize the “medicine-prescription-syndrome” rules is conducive to promoting the optimization of ischemic stroke prevention and treatment strategies.  OBJECTIVE: To explore the rules of Chinese medicine in the treatment of ischemic stroke, and provide a reference for the clinical treatment of ischemic stroke based on syndrome differentiation METHODS: A systematic search was conducted for clinical research literature on traditional Chinese medicine treatment of ischemic stroke from China National Knowledge Infrastructure (CNKI), WanFang, VIP, and SinoMed databases, covering the period from January 1, 1990, to August 15, 2024. The relevant studies were selected and the data were extracted into an Excel 2019 database for analysis. The frequency of use of Chinese herbs, their properties, meridional tropism, therapeutic effects and associated syndromes were analyzed. High-frequency herbs (≥ 4%) were subjected to latent structure modeling, comprehensive clustering, and association rule analysis using Lantern 5.0 and RStudio software, followed by summary of medication patterns and potential traditional Chinese medicine syndromes for ischemic stroke. RESULTS AND CONCLUSION: (1) A total of 231 articles were included, involving 203 kinds of traditional Chinese medicine, and the frequency of use was 2 524 times. (2) The high-frequency Chinese herbs were Chuanxiong, Earthworm, Angelica, Astragalus, Salviorrhiza, red peony root, safflower, leech, peach kernel, and pinellia. These herbs had predominantly warm, cold, or neutral properties, with bitter, sweet, and pungent flavors. Primary meridional tropism targets the liver, spleen and heart. Drug for invigorating blood circulation and eliminating stasis, deficiency tonifying drug, calming liver wind drug, expectorant cough suppressant and anti-asthmatic drug were used more frequently. (3) The latent structure model analysis identified 7 latent variables, 14 latent classes, 6 comprehensive clustering models, and 19 core prescriptions. It is hypothesized that the main traditional Chinese medicine syndromes for ischemic stroke are qi deficiency and blood stasis syndrome, wind-phlegm obstructing the channels syndrome, phlegm and blood stasis obstructing the channels syndrome, and phlegm-heat obstructing the viscera syndrome. (4) The association rule analysis revealed 29 strongly associative rules, including 2 two-item rules and 27 three-item rules. The highest degree of support was Angelica-Chuanxiong, and the highest degree of confidence was Angelica + licorice-Chuanxiong. The results show that ischemic stroke is a syndrome with qi and blood deficiency, liver and kidney Yin deficiency as the root causes, and wind, phlegm, blood stasis, and fire as the manifestations. The treatment is mainly to benefit qi and strengthen health, promote blood circulation and remove blood stasis, combined with pathological factors such as “phlegm and heat,” “qi stagnation,” “Yin deficiency,” and “liver fire,” supplemented by clearing heat and phlegm, promoting qi stagnation, nourishing liver and kidney, clearing liver and reducing fire.  Figures and Tables | References | Related Articles | Metrics

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Role and mechanism of resveratrol in delaying exercise-induced fatigue Chen Jun, Jia Shaohui, Guo Chenggen, Xue Xinxuan, Dong Kunwei 2025, 29 (29):  6285-6294.  doi: 10.12307/2025.798 Abstract ( 273 )   PDF (1582KB) ( 182 )   Save BACKGROUND: Resveratrol is a naturally occurring polyphenolic compound in plants, recognized for its anti-inflammatory, antioxidant, and antiproliferative properties. Its role in preventing and treating various chronic diseases has been extensively documented. Recent evidence suggests that resveratrol may help delay exercise-induced fatigue, although the underlying mechanisms remain to be systematically elucidated. OBJECTIVE: To explore the possible role and mechanism of resveratrol in delaying exercise-induced fatigue, based on the mechanism of exercise-induced fatigue, in order to provide a theoretical basis for the research and application of resveratrol in the field of sports nutrition. METHODS: Chinese and English search terms were “resveratrol, exercise-induced fatigue, oxidative stress, inflammation, energy substance, muscle injury, mitochondrial quality, neurotransmitter.” CNKI, WanFang Data, and PubMed were searched for relevant research literature published from January, 1992 to August 2024. A total of 73 core related articles were obtained according to inclusion and exclusion criteria. RESULTS AND CONCLUSION: (1) Resveratrol is a naturally occurring polyphenolic compound commonly found in plants such as grape skins, berries, and peanuts. It exhibits multiple biological activities, including antioxidant, anti-aging, anticancer, and anti-inflammatory properties. Resveratrol shows potential for preventing and treating various chronic diseases and is also thought to delay the onset of exercise-induced fatigue. (2) Exercise-induced fatigue is a non-pathological fatigue phenomenon with a complex mechanism. It is related to peripheral mechanisms such as the depletion of energy substrates, the accumulation of metabolic by-products, inflammation, and oxidative stress, as well as central mechanisms, including protective inhibition by the central nervous system and neurotransmitter imbalances. (3) Resveratrol activates the kelch-like epichlorohydrin-associated protein 1/nuclear factor erythroid 2-related factor 2 pathway, upregulating antioxidant-related genes such as catalase and superoxide dismutase while downregulating genes such as malondialdehyde and 4-hydroxy-2-nonenal, ultimately reducing oxidative stress. Resveratrol also activates silent information regulator 1, inhibits the nuclear factor-kappaB and nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 inflammasome pathways, and downregulates pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β, alleviating inflammation. Additionally, resveratrol increases short-chain fatty acid production by the gut microbiota, elevates the lactate/pyruvate ratio in the liver to promote gluconeogenesis, and enhances fatty acid oxidation, thereby improving energy substrate utilization. Furthermore, through silent information regulator 1/peroxisome proliferator-activated receptor-γ coactivator-1α/nuclear respiratory factor 1 activation, resveratrol enhances mitochondrial biogenesis in skeletal muscle, promotes mitochondrial fusion and fission for optimal dynamics, and activates mitophagy, improving mitochondrial quality. It also diminishes plasma tryptophan levels, decreases excessive serotonin secretion in the brain, increases dopamine release, and reduces glutamate toxicity, helping regulate neurotransmitter imbalances. Moreover, resveratrol lowers plasma lactate and ammonia levels, promoting metabolic by-product clearance, thereby delaying the onset of exercise-induced fatigue. (4) While current evidence indicates that resveratrol is effective in delaying exercise-induced fatigue, the optimal dose, timing, and duration of supplementation remain uncertain. Moreover, the interactions between resveratrol and other supplements, such as caffeine and vitamins, remain underexplored. Thus, future research should focus on optimizing supplementation strategies for resveratrol. Figures and Tables | References | Related Articles | Metrics

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Meta-analysis of dose-effect of exercise on improving muscle health in community-dwelling older adults with sarcopenia Jiang Siqi, Huang Huanhuan, Yu Xinyu, Peng Ying, Zhou Wei, Zhao Qinghua 2025, 29 (29):  6295-6304.  doi: 10.12307/2025.791 Abstract ( 320 )   PDF (3709KB) ( 178 )   Save OBJECTIIVE: The positive role of exercise intervention in the prevention and treatment of sarcopenia has received widespread attention, but the optimal exercise dose for elderly sarcopenic patients still needs to be further determined. The article explored the dose-effect relationship between various elements of exercise prescription and the improvement of muscle mass, muscle strength and physical function in community-dwelling elderly patients with sarcopenia, aiming to provide scientific support for the development of exercise prescription for community-dwelling elderly patients with sarcopenia. METHODS: Literature published from the inception to October 9, 2024 in PubMed, EMBASE, Scopus, Web of Science, CNKI, WanFang, VIP, and CBMdisc databases was systematically searched. Meta-analysis was performed using RevMan 5.3 software. Standardized mean difference (SMD) and its 95%CI were used as effect statistics.  RESULTS: (1) A total of 11 randomized controlled trials were included, with 348 in the trial group and 304 in the control group. (2) Meta-analysis results showed that exercise improved appendicular skeletal muscle mass index, grip strength, and walking speed in elderly patients with sarcopenia (SMDs 0.46, 0.63, 0.67, P < 0.05). (3) When the frequency of exercise was 2-3 days/week, appendicular skeletal muscle mass index (SMD=0.57, 95%CI: 0.28-0.86, P < 0.001), grip strength (SMD=0.70, 95%CI: 0.37-1.02, P < 0.001), and walking speed (SMD=0.69, 95%CI: 0.20-1.18, P=0.006) were effectively improved in elderly patients with sarcopenia. (4) When the duration of exercise was 25-60 minutes per session, appendicular skeletal muscle mass index (SMD=0.28, 95%CI: 0.07-0.50, P=0.01), grip strength (SMD=0.37, 95%CI: 0.16-0.59, P < 0.001), and walking speed (SMD=0.39, 95%CI: 0.06-0.73, P=0.02) were effectively improved in elderly patients with sarcopenia. (5) When the exercise intensity was moderate, appendicular skeletal muscle mass index (SMD=0.69, 95%CI: 0.35-1.03, P < 0.001), and grip strength (SMD=0.36, 95%CI: 0.09-0.64, P=0.009), and walking speed (SMD=0.91, 95%CI: 0.34-1.47, P=0.002) were effectively improved in elderly patients with sarcopenia. (6) When the dose of exercise cycle was 8-12 weeks, appendicular skeletal muscle mass index (SMD=0.42, 95%CI: 0.20-0.64, P < 0.001), grip strength (SMD=0.45, 95%CI: 0.26-0.64, P < 0.001), and walking speed (SMD=0.76, 95%CI: 0.27-1.25, P=0.002) were effectively improved in elderly patients with sarcopenia. CONCLUSION: Active, regular exercise can improve muscle health in older adults with sarcopenia. It is recommended that older patients with sarcopenia exercise at least 2 to 3 days per week, 25 to 60 minutes each time, lasting for 8 to 12 weeks of moderate intensity exercise to improve muscle health. Figures and Tables | References | Related Articles | Metrics

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Acupuncture for treatment of postmenopausal osteoporosis: meta-analysis, systematic evaluation and trial sequential analysis Yu Bingbing, Wang Tingting, Fang Junlin, Guo Yun, Huang Yingru 2025, 29 (29):  6305-6316.  doi: 10.12307/2025.763 Abstract ( 182 )   PDF (4981KB) ( 107 )   Save OBJECTIVE: To assess the efficacy and safety of acupuncture in treating postmenopausal osteoporosis. METHODS: Clinical randomized controlled trials on acupuncture for postmenopausal osteoporosis were retrieved from databases including CNKI, VIP, WanFang, China Biomedical Literature Service System, Web of Science, PubMed, Embase, and Cochrane Library. The search period was from the inception of the database to July 23, 2024. The quality of evidence and risk of bias of the included studies were assessed using the GRADEprofiler and the revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0). Meta-analysis was performed using StataSE 15 and TSA 0.9.5, along with heterogeneity analysis, sensitivity analysis, subgroup analysis, publication bias analysis, trim-and-fill analysis, and trial sequential analysis.  RESULTS: The study included 19 randomized controlled trials involving a total of 1 464 patients. (1) The meta-analysis revealed that compared with conventional therapies, acupuncture significantly increased the total effective rate (RR=1.25, 95% confidence interval [1.19, 1.32], P < 0.001), lumbar spine  L2-L4 bone mineral density (mean difference=0.08, 95% confidence interval [0.05, 0.11], P < 0.001), and estrogen levels (standard mean difference=0.55, 95% confidence interval [0.30, 0.81], P < 0.001). Additionally, acupuncture increased bone mineral density and gonadotropin levels in the femoral neck, greater trochanter, and Ward’s triangle, reduced visual analogue scale scores, and improved bone metabolism without significantly increasing the incidence of adverse events. (2) Subgroup analysis of the main outcome indicators showed no significant difference between the treatment and control groups when the body mass index was greater than 23.9 kg/m² and the total treatment duration was 6 months. All other treatment subgroups were significantly superior to the control group. (3) Publication bias analysis indicated a significant risk of publication bias in the overall efficacy; however, a trim-and-fill analysis showed that this risk did not significantly impact the reliability of the conclusions. Publication bias analysis showed no significant risk of publication bias in the bone mineral density values of lumbar spine L2-L4 and estradiol levels. (4) The sequential analysis of the trial further confirmed that acupuncture significantly increased the overall effective rate, bone mineral density values at the lumbar spine L1-L4, and estradiol levels.  CONCLUSION: Acupuncture is an effective and safe treatment for postmenopausal osteoporosis. More rigorously designed and high-quality studies are needed in the future to verify this conclusion. Figures and Tables | References | Related Articles | Metrics

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Systematic review of machine learning models for predicting functional recovery and prognosis in stroke Wang Jiaru, Zhang Ying, Yang Yong, Qi Wen, Xiao Huaye, Ma Qiuping, Yang Lianzhao, Luo Ziwei, He Yaqing, Zhang Jiangyin, Wei Jiawen, Meng Yuan, Tan Silian 2025, 29 (29):  6317-6325.  doi: 10.12307/2025.793 Abstract ( 482 )   PDF (2034KB) ( 186 )   Save OBJECTIVE: Nowadays, machine learning algorithms are gradually being applied to predict stroke and cardiovascular disease. Compared with traditional regression models, machine learning can learn from data to achieve high prediction accuracy by exploring the flexible relationship between a large number of predictive features and outcome variables, providing a new method for the formulation of individualized treatment and rehabilitation programs. This study aims to systematically evaluate stroke functional recovery and prognosis prediction models based on machine learning, comprehensively assessing their predictive performance and clinical application potential to provide references for the development, application, and promotion of related predictive models.  METHODS: This review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Relevant literature on stroke prognosis prediction using machine learning methods was selected by searching PubMed, EMbase, Web of Science Core Collection, CNKI, WanFang, and the China Biomedical Literature Database, with the search period from January 1, 2014, to July 1, 2024. Two researchers independently screened the literature and extracted data based on inclusion and exclusion criteria, using the Prediction model Risk Of Bias ASsessment Tool (PROBAST) to assess model quality.  RESULTS: (1) A total of 3 126 articles were obtained in the preliminary search. After screening and exclusion, 18 articles were finally included. 150 prediction models were constructed using 13 machine learning methods. The three most frequently used methods are Logistic Regression, Random Forest, and Extreme Gradient Boosting (XGBoost). Only one study was externally validated. Eight studies reported how the missing data were handled. (2) In terms of outcome indicators, 8 studies used the combination of clinical data and imaging data to build models, 9 studies only used clinical data to build models, and 1 study only used imaging data to build models. (3) Each of the 18 studies gave the most important characteristics of the study, with the most mentioned being the National Institute of Health Stroke Scale and age. All studies reported area under curve values ranging from 0.74 to 0.96, with the highest area under curve being 0.96. The overall risk of bias in all models was high. The high risk of bias in the field of model analysis was the main reason for the high risk of overall bias in all models. (4) The results of meta-analysis showed that age and National Institute of Health Stroke Scale score had significant influence on stroke prognosis, with age [MD=8.49, 95%CI(6.24, 10.75), P < 0.01] and National Institute of Health Stroke Scale score [MD=4.78, 95%CI(2.56, 7.00), P < 0.01].   CONCLUSION: This study systematically evaluated the predictive model of functional recovery and prognosis of stroke based on machine learning, and all the models have good predictive potential. However, future studies should increase the sample size of the included model, adopt prospective studies, and add external validation of the model to improve the stability and prediction accuracy of the model, control the risk of bias, and contribute to the validation and promotion of the model in practical clinical applications. At the same time, the interpolation of missing values is more transparent and accurate. Although existing machine learning models show good predictive performance, it is also important to focus on the functionality and usability of the model, and the inclusion of features will reduce ease of use. We should develop easy to use model interfaces and user-friendly clinical tools to enable medical staff to better apply the model for clinical decision.  Figures and Tables | References | Related Articles | Metrics

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Causal relationship between immune cells and bone metabolic diseases: a Mendelian randomization analysis of European populations in international databases Chen Tianxin, , Zhang Zhilong, Zhang Shuai, Gao Yun, Zhu Yuqi, Yang Shengping 2025, 29 (29):  6326-6332.  doi: 10.12307/2025.760 Abstract ( 174 )   PDF (1768KB) ( 77 )   Save BACKGROUND: Immune cells are correlated with various metabolic bone diseases, yet the specific immunological mechanisms and causal relationships remain elusive. OBJECTIVE: To investigate the causal relationship between immune cells and the risk of metabolic bone diseases through two-sample Mendelian randomization.  METHODS: Genome-wide association study (GWAS) data on 731 immune cells and metabolic bone diseases (osteonecrosis, osteomalacia, osteoporosis, and osteoporosis combined with pathological fracture) were obtained from publicly available databases. Genetic variants related to immune cells were employed as instrumental variables. The inverse variance weighting method was utilized as the primary analytical approach, while MR-Egger and weighted median methods were applied to assess the causal relationships between immune cells and the risk of metabolic bone diseases. In addition, MR-PRESSO, MR-Egger regression, Cochran’s Q test, and the leave-one-out method were implemented to evaluate genetic polymorphisms and the heterogeneity of instrumental variables, and MR Steiger method was used to exclude reverse causality. RESULTS AND CONCLUSION: (1) The analysis revealed that IgD- CD38dim%B cells, HLA DR on CD14+ CD16- monocytes, and HLA DR on CD14+ monocytes were significantly and causally associated with an increased risk of osteoporosis (P < 6.8×10-5). Sensitivity analyses confirmed the reliability and stability of these results. Furthermore, among the immune cell types studied, 28 demonstrated potential causal associations with osteonecrosis, 23 with osteomalacia, 46 with osteoporosis, and 45 with the combined condition of osteoporosis and pathologic fracture (P < 0.05). (2) This study provides a comprehensive assessment of the causal influence of immune cells on metabolic bone diseases, highlighting the significant role of immune factors in the pathogenesis of these conditions, particularly osteoporosis. The findings contribute valuable insights into the relationship between immune traits and bone metabolism, laying a foundation for future research in this domain. This study utilized an international database to analyze the European population, which offers a reference for Chinese biomedical research in the realm of metabolic bone diseases, and facilitates the conduction of relevant studies for the Chinese population, thereby promoting the enhancement of the prevention and treatment of metabolic bone diseases. Figures and Tables | References | Related Articles | Metrics

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Association between dietary preferences and the risk of osteoarthritis in Europeans: analysis of human genome-wide association study data Pang Jiahui, Wang Bo, Hu Yingxuan, Hu Ziwei, Wu Wen 2025, 29 (29):  6333-6342.  doi: 10.12307/2025.790 Abstract ( 237 )   PDF (1519KB) ( 100 )   Save BACKGROUND: Some studies have shown a potential relationship between dietary intake and osteoarthritis, but whether there is a causal relationship between food preferences and osteoarthritis is still unknown. There is currently no large-scale genome-wide association study on dietary preferences and osteoarthritis in China. OBJECTIVE: To explore the causal association between dietary preferences and osteoarthritis in European populations, in order to provide a theoretical basis for the prevention of osteoarthritis and to provide reference data for the identification of high-risk groups for hip and knee osteoarthritis in China. METHODS: A total of 20 dietary preference genetic statistics datasets were selected to screen for exposure factor-related instrumental variables. The dataset for osteoarthritis was selected for the ending. After exclusion of the instrumental variables related to confounders, the two-sample Mendelian randomized causal association analysis was conducted mainly by inverse variance weighted analysis, and other four statistical methods were used as supplements. Sensitivity test was performed for the results. RESULTS AND CONCLUSION: (1) The results of the inverse variance weighted analysis showed that preference for barbecue (OR=1.204, 95%CI: 1.058-1.370, P=0.005), beef (OR=1.167, 95%CI: 1.034-1.317, P=0.012), chicken (OR=1.399, 95%CI: 1.119-1.749, P=0.003), pork chops (OR=1.218, 95%CI:1.039-1.427, P=0.015) and coffee (OR=1.133, 95%CI: 1.037-1.238, P=0.006) were risk factors for osteoarthritis of the knee and hip joints, vegetables (OR=0.893, 95%CI: 0.827-0.964, P=0.004), and vinegar (OR=0.897, 95%CI: 0.812-0.991, P=0.032) were protective factors for knee-hip osteoarthritis. (2) The results of the sensitivity analysis showed that the instrumental variables included in the analysis without horizontal pleiotropy and bias, and the corresponding inverse variance weighted analysis of effects model was used according to the results of the heterogeneity analysis. (3) The results of this study provide certain reference value in the research on the relationship between dietary preferences and hip and knee osteoarthritis, but only included human whole genome association study data from European populations, and the validity of the research results in other races remains to be tested. Moreover, no stratification was performed on gender, age and other health status. It is difficult to completely rule out the bias from population stratification in the research results. In the future, larger-scale and more finely classified sample data are still needed to carry out relevant causal relationship research. Figures and Tables | References | Related Articles | Metrics

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Bioinformatic analysis on expression of Foxp3 in tumor microenvironment of ovarian cancer and its relationship with survival prognosis Lin Rongqin, Pan Xiuxie, Bian Lihong 2025, 29 (29):  6343-6350.  doi: 10.12307/2025.794 Abstract ( 163 )   PDF (2295KB) ( 167 )   Save BACKGROUND: The immune cell composition and functional states within the tumor microenvironment of epithelial ovarian cancer directly influence patient prognosis and therapeutic response. Recent studies indicate that CD4+ T cells not only support anti-tumor immunity but can also exert direct anti-tumor effects under specific conditions. High infiltration of CD8+ T cells is considered a positive prognostic marker. FOXP3+ regulatory T cells play a crucial role in maintaining immune tolerance and modulating immune responses.  OBJECTIVE: The data from 416 epithelial ovarian cancer patients along with clinical pathology samples from 21 patients were comprehensively analyzed utilizing bioinformatics algorithms to investigate the relationship between the expression of CD4+ T cells, CD8+ T cells, and FOXP3+ T cells in the tumor microenvironment and survival outcomes in ovarian cancer patients. METHODS: (1) The study categorized 416 cases of epithelial ovarian cancer from the Ovarian Cancer subset of The Cancer Genome Atlas using the Non-negative Matrix Factorization algorithm. The CIBERSORT algorithm (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts) was employed to examine differences in immune cell infiltration between patients with high and low survival rates. (2) Multiplex immunohistochemistry was used to assess the expression of CD4, CD8, and FOXP3 in pathological tissue samples from 21 patients from Chinese People’s Liberation Army General Hospital, and their association with patient prognosis was analyzed.  RESULTS AND CONCLUSION: The high survival rate group exhibited significantly greater infiltration of immune cells, including CD4+ T cells, CD8+ T cells, and FOXP3+ regulatory T cells, compared with the low survival rate group (P < 0.01). Results from the multiplex immunohistochemistry experiments revealed that high expression of FOXP3 was significantly correlated with better prognosis in ovarian cancer patients (P < 0.05). It is indicated that the expression of FOXP3 in the tumor microenvironment is associated with survival outcomes in epithelial ovarian cancer patients, suggesting that the infiltration of FOXP3+ regulatory T cells in the tumor microenvironment is a key factor influencing patient prognosis. Figures and Tables | References | Related Articles | Metrics

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Growth factors promote knee cartilage regeneration: a bibliometric analysis of research hotspots Liu Jian, Liu Qing, Huang Ye, Cao Guanglei, Liu Yuan, Song Qingpeng 2025, 29 (29):  6351-6359.  doi: 10.12307/2025.788 Abstract ( 261 )   PDF (1708KB) ( 118 )   Save BACKGROUND: The reduction of contact area, edge load, and stress increase of adjacent cartilage caused by knee cartilage defect are considered to easily cause degenerative changes in this tissue, which may develop into knee osteoarthritis. Growth factors are considered to be a treatment method to promote the healing of damaged cartilage and delay the progression of degenerative arthritis. OBJECTIVE: To analyze the hotspots and prospects of growth factor-promoted knee cartilage regeneration research by bibliometric methods. METHODS: The first author retrieved 321 articles related to growth factor-promoted knee cartilage regeneration research from the Web of Science core set database. VOSviewer 1.6.19 software was used to analyze the publication volume, country, institution, keyword, and literature citation status of the articles, and investigate the research hotspots. RESULTS AND CONCLUSION: (1) From 2000 to 2024, the annual number of publications in the field of growth factor-promoted knee cartilage regeneration showed an overall upward trend, with the highest number of publications in 2021. Harvard University in the United States published the most papers. (2) Keyword analysis showed that the frequency of keywords such as growth factor, cartilage, cartilage repair, platelet-rich plasma, and cartilage regeneration was high. In addition, the keyword co-occurrence network diagram showed that growth factor was closely related to keywords such as cartilage repair and cartilage regeneration, indicating that growth factor research plays an important role in the field of cartilage regeneration. (3) The results of literature citation analysis showed that the combination of platelet-rich plasma and muscle-derived stem cells may provide a new and effective treatment strategy for patients with osteoarthritis, which can deepen the understanding of cartilage repair mechanisms by promoting stem cell proliferation and cartilage formation. Fibroblast growth factor 2, fibroblast growth factor 18, and insulin growth factor 1 play a key role in cartilage repair and can promote chondrocyte proliferation and matrix synthesis. In particular, fibroblast growth factor 18 can promote the repair of damaged cartilage, thereby alleviating patients’ pain and dysfunction, which deserves further in-depth study in the future. The latest research has developed a new Polyhedrin Delivery System (PODS) that can continuously release growth factors such as bone morphogenetic protein 2 and 7, significantly promoting chondrocyte proliferation and cartilage repair. This system provides a new perspective and potential therapy for the treatment of osteoarthritis. (4) Therefore, bone morphogenetic protein 2, 7, insulin growth factor 1, and recombinant human fibroblast growth factor 18 are promising growth factor therapies for promoting cartilage regeneration. In the future, further in-depth research on the mechanism of action of growth factors, optimization of treatment strategies, and strengthening of long-term efficacy and safety evaluation are needed. Figures and Tables | References | Related Articles | Metrics

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Long noncoding RNAs related to osteoporosis: current research status and developmental trends Wu Wangxiang, Ran Dongcheng, Xu Jiamu, Xu Jiafu, Chen Jingjing, Wang Chunqing 2025, 29 (29):  6360-6368.  doi: 10.12307/2025.764 Abstract ( 68 )   PDF (3131KB) ( 151 )   Save BACKGROUND: Studies have indicated that long noncoding RNAs play a crucial role in the pathogenesis and progression of osteoporosis. Thus, it is essential to comprehend the current research status, hotspots, and developmental trajectories of long noncoding RNAs in the field of osteoporosis research. OBJECTIVE: To explore the research status, development trends, and hotspots in the field of osteoporosis-related long noncoding RNAs by conducting bibliometric statistics and visualization analysis of the relevant literature. METHODS: Using the search string “(TS=(Osteoporosis OR Osteoporoses) AND TS=(Long non coding RNA OR LncRNA OR Lnc RNA OR Long noncoding RNA)) ,” a subject term search was conducted in the Web of Science Core Collection database for articles published from January 2015 to September 2024. After manual filtering of the obtained raw data, visualization analysis of authors, institutions, countries, and keywords was performed using Cite Space 6.2.R4 software and Microsoft 365 (Office).  RESULTS AND CONCLUSION: A total of 265 articles were included from the Web of Science Core Collection database. Since 2015, there has been an overall upward trend in the number of publications in this field, with China being the leading country in terms of publication volume and research centrality, while Beihang University holds the highest institutional centrality. After keywords directly related to the article’s theme were excluded, the terms “osteogenic differentiation,” “expression,” “bone formation,” and “mesenchymal stem cells” emerged as core topics based on co-occurrence frequency and centrality. A comprehensive analysis of the keyword cluster map, keyword burst map, and keyword timeline map reveals that investigating the mechanisms by which long non-coding RNAs influence the formation and differentiation of osteoblasts, as well as the differentiation of osteoclasts and bone resorption, constitutes both a current research hotspot and a future research trend in this field. Figures and Tables | References | Related Articles | Metrics

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Causal association between metabolites and sarcopenia: a big data analysis of genome-wide association studies in the European population Chen Jiayong, Tang Meiling, Lu Jianqi, Pang Yan, Yang Shangbing, Mao Meiling, Luo Wenkuan, Lu Wei 2025, 29 (29):  6369-6380.  doi: 10.12307/2025.715 Abstract ( 141 )   PDF (20022KB) ( 8 )   Save BACKGROUND: Studies at home and abroad have shown that sarcopenia is closely related to metabolites. At present, the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown.  OBJECTIVE: To analyze the causal relationship between 1 400 metabolites and sarcopenia and its relevance with cardiovascular disease using Mendelian randomization. METHODS: Genome-wide association study (GWAS) data of sarcopenia-related characteristics (grip strength, limb muscle lean body mass, and walking speed) were obtained from the OPEN GWAS website as outcome data. A GWAS containing 1 400 metabolites was used as an exposure factor, and single nucleotide polymorphisms significantly associated with exposure factors were selected as instrumental variables. The causal association between 1 400 metabolites and sarcopenia was analyzed by “TwoSampleMR” and “gwasglue” packages of R software (V4.3.2). The research methods included inverse variance weighting, MR-Eggeer regression intercept, weighted median method, and simple mode. Heterogeneity, pleiotropic, sensitivity and other verification analysis were performed. Finally, reverse Mendelian randomization analysis was performed. RESULTS AND CONCLUSION: (1) The causal relationship between 1 400 serum metabolites and sarcopenia was analyzed by inverse variance weighting. The results showed that 1-linoleoyl-2-linoleoyl-GPC (18:2/18:3) and glycodeoxycholate 3-sulfate were protective factors, and the risk of disease decreased with the increase of metabolites (P < 0.01). (2) Two unknown metabolites (X-12822 and X-15486) and trans-3,4-methyleneheptanoate were risk factors. With the increase of two unknown metabolites (X-12822 and X-15486), the degree of low grip strength of male hands increased. Similarly, with the increase of trans-3,4-methylene heptanoate, the risk of disease also increased (P < 0.01 ). (3) To conclude, 1-linoleoyl-2-linoleoyl-GPC (18:2/18:3) and glycodeoxycholate 3-sulfate have inhibitory effects on sarcopenia. Two unknown metabolites (X-12822 and X-15486) and trans-3,4-methyleneheptanoate can promote sarcopenia. This may be a new idea and new basis for sarcopenia research and treatment in the future. This study will also provide a reference for the study of the role of related metabolites in the Chinese population. Figures and Tables | References | Related Articles | Metrics