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28 February 2025, Volume 29 Issue 6 Previous Issue    Next Issue

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Effects of artificial turf versus natural grass on biomechanical performance of the lower limbs in young females during jump-landing Lu Jieming, Li Yajing, Du Peijie, Xu Dongqing 2025, 29 (6):  1101-1107.  doi: 10.12307/2025.270 Abstract ( 529 )   PDF (960KB) ( 116 )   Save BACKGROUND: It has been found that internal factors such as anatomical structure, hormone level and neuromuscular function of athletes are closely related to the risk of anterior cruciate ligament injuries, and external factors such as the material of the playing field also become one of the risk factors affecting the occurrence of non-contact anterior cruciate ligament injuries, but they are relatively under-attended in the current studies. OBJECTIVE: To explore effects of artificial turf versus natural grass on the biomechanical performance of the lower limbs in young females during jump-landing. METHODS: According to the test needs, artificial turf and natural grass in accordance with the standards of GB/T 20033.3-2006 and GB/T 19995.1-2005 were leveled and fixed on two three-dimensional force measuring platforms. Twenty-one young females were voluntarily recruited and completed the jump-landing task on the artificial turf and natural grass. Subjects stood on the steps and then jumped forward, jumped down to the force measuring platform and immediately jumped with full force to the force measuring platform again. The two landings were required to fall to the two force measuring platforms, and the whole jumping action was considered successful without any pause. The kinematic, kinetic and electromyographic data of the lower limbs during the landing process were collected synchronously to compare and analyze the differences between the two. RESULTS AND CONCLUSION: In terms of kinetics, posterior and vertical ground reaction force at the initial landing moment during jump-landing on the natural grass were significantly lower than those on the artificial turf (P < 0.05, P < 0.01), as well as at the peak ground reaction force moment (P < 0.05, P < 0.05). Additionally, the knee flexion moment when jump-landing on the natural grass was higher than that on the artificial turf (P < 0.01). In terms of electromyography, within 100 ms after the initial landing moment, the electromyography activity levels of medial femoris muscle, lateral femoris muscle and anterior tibialis muscle when jump-landing on the natural grass were significantly lower than those on the artificial turf (P < 0.05, P < 0.01, P < 0.05). To conclude, compared with the natural grass, jump-landing on the artificial turf leads to an change in biomechanical performance that will cause an increase in anterior cruciate ligament tension. Figures and Tables | References | Related Articles | Metrics

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Effect of transcranial magneto-acousto-electrical stimulation on the plasticity of the prefrontal cortex network in mice  Zhang Shuai, Li Zichun, Xu Yihao, Xie Xiaofeng, Guo Zhongsheng, Zhao Qingyang 2025, 29 (6):  1108-1117.  doi: 10.12307/2025.306 Abstract ( 243 )   PDF (2819KB) ( 188 )   Save BACKGROUND: Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system. However, the mechanism by which it affects synaptic plasticity in the brain is still not enough. OBJECTIVE: To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice. METHODS: (1) Animal experiment: Twenty-four C57 mice were equally and randomly divided into four groups: the control group receiving pseudo-stimulation, the 6.35 W/cm2 stimulation group receiving coupled stimulation of 0.3 T, 6.35 W/cm2, the 17.36 W/cm2 stimulation group receiving coupled stimulation of 0.3 T, 17.36 W/cm2, and the 56.25 W/cm2 stimulation group receiving coupled stimulation of 0.3 T, 56.25 W/cm2. The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice. (2) Modeling and simulation experiments: A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities.  RESULTS AND CONCLUSION: Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time, improve the working memory ability of mice (P < 0.05), and continue to stimulate the frontal lobe of mice after learning behavior. There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups (P > 0.1). Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β and γ rhythms. As the stimulation intensity increased, there was an asynchronous decrease in β and γ rhythms. Through β-γ phase amplitude coupling, it was found that stimuli could enhance the neural network’s ability to adapt to new information and task requirements. Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network, increase the long-term synaptic weight level, and decrease the short-term synaptic weight level only when the stimulation intensity was high. To conclude, there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks. This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities. Figures and Tables | References | Related Articles | Metrics

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Wen-Shen-Tong-Du Decoction promoting spinal cord injury repair in mice  Zhao Ruihua, Chen Sixian, Guo Yang, Shi Lei, Wu Chengjie, Wu Mao, Yang Guanglu, Zhang Haoheng, Ma Yong 2025, 29 (6):  1118-1126.  doi: 10.12307/2025.302 Abstract ( 242 )   PDF (2157KB) ( 144 )   Save BACKGROUND: Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells, promoting the phagocytosis of myelin debris by microvascular endothelial cells, affecting the migration and infiltration of microglia, promoting the recovery of damaged neurons, and decreasing neuronal apoptosis after spinal cord injury, but the mechanism of this is still not clear. OBJECTIVE: To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2 (TREM2) and PI3K/Akt signaling pathways in mice following spinal cord injury.  METHODS: Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group, a model group and a Wen-Shen-Tong-Du Decoction group, with 12 mice in each group. In the model and Wen-Shen-Tong-Du Decoction groups, mouse models of T10 spinal cord injury were prepared by the modified Allen’s method. On the 1st day after modeling, the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage, and the sham-operation group and the model group were given saline by gavage once a day for 28 days. During the drug administration period, mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test. On the 7th and 28th days after modeling, hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice; immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and TREM2; and western blot assay was used to detect the expression of TREM2, PI3K, p-PI3K, Akt, p-Akt, Bcl2, Bax and Caspase3 in spinal cord tissue.  RESULTS AND CONCLUSION: Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury, and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury. Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group, manifesting as reduced degrees of dorsal white matter and neuronal atrophy, decreased cytoplasmic vacuolization, and reduced inflammatory cell infiltration. Immunofluorescence double staining results showed that on the 7th day after modeling, the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group (P < 0.05), and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group (P < 0.05); on the 28th day after modeling, the protein expression of TREM2 in the model group was lower than that in the sham-operation group (P < 0.05), and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group (P < 0.05). Western blot results analysis demonstrated that on the 7th day after modeling, compared with the sham-operation group, the model group exhibited a significant reduction in TREM2, PI3K, and Bcl2/Bax (P < 0.05), as well as a significant increase in p-Akt, Bax and p-Akt/Aktp-PI3K (P < 0.05); compared with the model group, the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2, PI3K, p-PI3K, Akt, p-Akt, Bcl2, p-PI3K/PI3K, p-Akt/Ak, and Bcl2/Bax (P < 0.05), as well as a significant decrease in Bax and Caspase3 protein expression (P < 0.05). On the 28th day after modeling, compared with the sham-operation group, the model group exhibited a significant reduction in TREM2, PI3K, p-PI3K, Akt, p-Akt, Bcl2 and Bcl2/Bax  (P < 0.05), as well as a significant increase in Bax protein expression (P < 0.05); compared with the model group, the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2, PI3K, Akt, p-Akt, Bcl2, and Bcl2/Bax (P < 0.05), as well as a significant decrease in Bax protein expression (P < 0.05). To conclude, Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia, and then inhibit neuronal apoptosis, thus exerting neuroprotective effects and promoting the repair of spinal cord injury. Figures and Tables | References | Related Articles | Metrics

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Effects of electroacupuncture on the expression of metabolic enzymes and autophagy genes in gastrocnemius muscle tissues of exercising rats Zheng Rongfa, Mo Weibin, Huang Peng, Chen Junji, Liang Ting, Zi Fangyu, Li Guofeng 2025, 29 (6):  1127-1136.  doi: 10.12307/2025.303 Abstract ( 206 )   PDF (1733KB) ( 199 )   Save BACKGROUND: Acute exercise tends to cause skeletal muscle tissue damage and lipid metabolism disorders in vivo, but the mechanism by which acute exercise combined with electroacupuncture modulates metabolic and autophagic pathways in vivo is unclear. OBJECTIVE: To observe the changes in metabolic enzymes and autophagy levels in skeletal muscle of rats subjected to acute exercise by electroacupuncture at the acupoints of “Zusanli” and “Huantiao.” METHODS: Fifty male Sprague-Dawley rats were randomly divided into three groups: quiet control group (n=10), model group (n=20), and reverse electroacupuncture group (n=20). The latter two groups were set up with two time points, i.e. immediate and 3 hours after exercise groups (n=10 per time point). The model group and the reverse electroacupuncture group underwent acute exercise training after adaptive treadmill training. The rats in the reverse electroacupuncture group underwent electroacupuncture treatment (parameters: electroacupuncture on both sides of the rats at the acupoints of “Zusanli” and “Huantiao,” continuous wave, frequency of 2 Hz, intensity of 2 mA, leaving the needle in the body for 30 minutes, once a day for 7 consecutive days) before treadmill training. Bilateral gastrocnemius muscle tissues were taken under anesthesia immediately after exercise and 3 hours after exercise, and hematoxylin-eosin staining was used to observe the histopathological changes of rat skeletal muscle. ELISA kit was used to detect the activities of hepatic lipase, fatty acid synthase, hormone-sensitive lipase, and carnitine palmitoyltransferase 1 in rat skeletal muscle tissues. Immunohistochemistry and western blot were used to detect the changes in the expression of autophagy genes. RESULTS AND CONCLUSION: After hematoxylin-eosin staining, the arrangement of gastrocnemius muscle fibers in the model group was disturbed, swollen and ruptured immediately after exercise and 3 hours after exercise. In the reverse electroacupuncture group, gastrocnemius muscle fibers were tightly arranged and the number of swollen and ruptured cells was greatly reduced immediately after exercise and 3 hours after exercise, and there was no significant difference when compared with the quiet control group. Compared with the quiet control group, the activities of hepatic lipase and fatty acid synthase were lower while the activities of lipoprotein lipase, hormone-sensitive lipase, and carnitine palmitoyltransferase 1 were higher in the model group and the reverse electroacupuncture group 3 hours after exercise (P < 0.05 or P < 0.01). Compared with the model group, the activities of lipoprotein lipase and carnitine palmitoyltransferase 1 were higher in the reverse electroacupuncture group immediately after exercise (P < 0.05), while the activity of lipoprotein lipase was higher and the activity of hormone-sensitive lipase was lower in the reverse electroacupuncture group 3 hours after exercise (P < 0.01). Immunohistochemical results showed that compared with the quiet control group, the expression of P62, autophagy-related gene 5 and autophagy-related gene 7 was higher in the model group immediately and 3 hours after exercise, as well as in the reverse electroacupuncture group immediately after exercise (P < 0.05 or P < 0.01); compared with the model group, the expression of P62 and autophagy-related gene 7 was lower in the reverse electroacupuncture group immediately and 3 hours after exercise (P < 0.05). Western blot results showed that the protein expression of P62 and autophagy-related gene 7 in the reverse electroacupuncture group was lower than that in the model group immediately after exercise (P < 0.05); the protein expression of Parkin in the model group was higher than that in the quiet control group immediately and 3 hours after exercise (P < 0.05); and the protein expression of Parkin in the reverse electroacupuncture group was lower than that in the model group immediately and 3 hours after exercise (P < 0.05). To conclude, acute exercise induces disorders, swelling and rupture of gastrocnemius muscle fibers in rats and electroacupuncture on both sides of the acupoints of “Zusanli” and “Huantiao” can improve the level of lipid metabolism and regulate autophagy cells in rat skeletal muscle, preventing the disorders of lipid metabolism and damage of gastrocnemius muscle tissues caused by acute exercise. The mechanism may be closely related to the regulation of autophagy-related factor P62, autophagy-related gene 5, autophagy-related gene 7, and Parkin protein expression to promote the occurrence of autophagy or regulate the autophagy pathway in rat skeletal muscle cells.  Figures and Tables | References | Related Articles | Metrics

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Troxerutin modulates nuclear factor-kappaB signaling pathway to inhibit brain injury and neuronal apoptosis in cerebral infarction rats  Liu Zhezhe, Yu Meiqing, Wang Tingting, Zhang Min, Li Baiyan 2025, 29 (6):  1137-1143.  doi: 10.12307/2025.319 Abstract ( 201 )   PDF (1334KB) ( 92 )   Save BACKGROUND: Troxerutin has been found to have a significant ameliorative effect on brain disorders, but there are fewer studies on the effects of troxerutin on the treatment of cerebral infarction and on neuronal cells. OBJECTIVE: To investigate the mechanism by which troxerutin regulates nuclear factor-κB signaling pathway to reduce brain injury and neuronal apoptosis in cerebral infarction rats. METHODS: Fifty clean grade rats were randomized into healthy group, model group, and troxerutin+nuclear factor-κB agonist group, troxerutin group, and nuclear factor-κB inhibitor group. Except for the healthy group, all other groups were used to establish a rat model of cerebral infarction by arterial ligation. The healthy and model groups were treated once a day with an equal amount of physiological saline by gavage. The troxerutin+nuclear factor-κB agonist group was intervened with 72 mg/kg troxerutin by gavage + 20 mg/kg RANK intraperitoneally. The troxerutin group was treated with 72 mg/kg troxerutin by gavage. The nuclear factor κB inhibitor group was intervened intraperitoneally with 120 mg/kg nuclear factor κB inhibitor pyrrolidine disulfiram. Administration in each group was given once a day for 30 continuous days. Zea-longa was used to detect neurological damage in rats, hematoxylin-eosin staining was used to observe pathological changes, TUNEL was used to detect neuronal apoptosis, and immunoblotting and PCR were used to detect the expression of nuclear factor-κB p65 and nuclear factor-κB p50 at protein and mRNA levels, respectively.  RESULTS AND CONCLUSION: Compared with the healthy group, the neurological function score, neuronal apoptosis rate, nuclear factor-κB p65, nuclear factor-κB p50 mRNA and protein expression levels were elevated in the model group (P < 0.05). Compared with the model group, the neurological function score, neuronal apoptosis rate, nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were decreased in the troxerutin+nuclear factor-κB agonist group (P < 0.05). Compared with the troxerutin+nuclear factor-κB agonist group, the neurological function score, neuronal apoptosis rate, nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were reduced in the troxerutin group and nuclear factor-κB inhibitor group (P < 0.05). In addition, there was no difference between the troxerutin group and the nuclear factor-κB inhibitor group (P > 0.05). In the model group, there was a large number of cytoplasmic vacuolation, obvious edema and necrosis, and a large number of inflammatory cell infiltrations. In the troxerutin+nuclear factor-κB agonist, the swelling of brain tissue was reduced, and reticulate structures and condensed cells were reduced, still with some edema. In the troxerutin group and nuclear factor-κB inhibitor group, brain tissue swelling, neuronal edema degeneration, cytoplasmic vacuolation and neuronal nucleus consolidation were reduced, and the inflammatory cell infiltration was significantly decreased. To conclude, troxrutin can reduce the expression of neurological impairment, inhibit neuronal apoptosis and improve the pathological injury of brain tissue in rats with cerebral infarction, and its mechanism of action may be related to the modulation of nuclear factor-κB expression and related signaling pathways. Figures and Tables | References | Related Articles | Metrics

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Cistanoside A mediates p38/MAPK pathway to inhibit osteoclast activity  Li Yueyao, Zhang Min, Yang Jiaju 2025, 29 (6):  1144-1151.  doi: 10.12307/2025.300 Abstract ( 299 )   PDF (2086KB) ( 166 )   Save BACKGROUND: Cistanoside A has the effects of anti-inflammation, antioxidation, antioxidation, reducing renal damage and anti-osteoporosis, but its effect on osteoclast differentiation, function and its underlying molecular mechanisms remain unclear. OBJECTIVE: To investigate the effect of Cistanoside A on osteoclast differentiation and bone resorption induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in vitro and its mechanism. METHODS: Bone marrow macrophages were obtained from the femur and tibia of 4-6-week-old C57BL/6 mice. The cytotoxic effect of Cistanoside A (5, 10, 20, 40, 80, and 160 μmol/L) on bone marrow macrophage viability was examined using the cell counting kit-8 assay kit. Tartrate-resistant acid phosphatase staining was performed to observe the effect of different concentrations of Cistanoside A on osteoblast differentiation and its effective intervention concentration was determined. There was positive control group, Cistanoside A low, medium, and high dose groups (40, 80, and 160 μmol/L). After cell attachment, 50 ng/mL RANKL was added to induce osteoblast differentiation, and the corresponding dose of Cistanoside A was added to the Cistanoside A low, medium, and high dose groups, respectively. F-actin ring and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride staining were performed to detect the effects of Cistanoside A on the formation of osteoclasts. Toluidine blue staining of bone abrasion slices was used to observe the effects of Cistanoside A on bone resorption function of osteoclasts. The expression of upstream and downstream proteins of the JNK/MAPK pathway was detected by Western blot. The expression of genes related to osteoclast differentiation and bone resorption function such as tartrate-resistant acid phosphatase, DC-STAMP, Nfatc-1, Ctsk and c-Fos was detected by RT-qPCR.  RESULTS AND CONCLUSION: Tartrate-resistant acid phosphatase staining, F-actin ring staining and resorption pit assay showed that Cistanoside A significantly inhibited RANKL-induced osteoclast differentiation and bone resorption in a dose-dependent manner compared with the positive control group. The results of RT-qPCR showed that compared with the positive control group, both high and low dose groups of Cistanoside A could significantly downregulate the mRNA expression of tartrate-resistant acid phosphatase, DC-STAMP, Nfatc-1, Ctsk and c-Fos in a dose‐dependent manner. The results of western blot assay showed that the high dose group of Cistanoside A significantly inhibited the expression of p-JNK protein at 10, 20, 30 and 60 minutes of intervention; compared with the positive control group, Cistanoside A significantly inhibited the expression of Nfatc1 and c-Fos proteins in a dose-dependent manner. To conclude, Cistanoside A could inhibit the formation and bone resorption of osteoclasts by reducing the level of p-JNK protein, inhibiting the activation of MAPK pathway and the expression of key genes in osteoclasts. Figures and Tables | References | Related Articles | Metrics

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Buqi Huoxue Compounds intervene with the expression of related factors and autophagy related proteins in a rat model of cerebral ischemia/reperfusion Chen Yuning, Jiang Ying, Liao Xiangyu, Chen Qiongjun, Xiong Liang, Liu Yue, Liu Tong 2025, 29 (6):  1152-1158.  doi: 10.12307/2025.297 Abstract ( 209 )   PDF (1378KB) ( 159 )   Save BACKGROUND: Buqi Huoxue Compounds have significant clinical efficacy in treating ischemic stroke with Qi deficiency and phlegm stasis; however, the exact mechanism of action is not clear. OBJECTIVE: To observe the effect of Buqi Huoxue Compounds on the expression of vascular endothelial growth factor, basic fibroblast growth factor, brain-derived neurotrophic factor and autophagy related protein Beclin1 and p62 in a rat model of cerebral ischemia/reperfusion. METHODS: Forty male Sprague-Dawley rats were randomly divided into sham operation group, model group, Buqi Huoxue Compounds group and autophagy inhibitor group, with 10 rats in each group. In the latter three groups, a rat model of cerebral ischemia/reperfusion injury was established. 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 autophagy inhibitor group was intragastrically given Buqi Huoxue Compounds (6.49 g/kg, administered three times a day) 2 hours after reperfusion and intraperitoneally given 3-methyladenine 2 hours before gavage and at days 1-3 of gavage. The sham operation group and model group were given equal amounts of saline by gavage for 7 consecutive days. Neurological function, cerebral infarct volume, brain tissue morphology and expression of vascular endothelial growth factor, basic fibroblast growth factor, brain-derived neurotrophic factor and autophagy-related proteins Beclin1 and p62 in the ischemic cortical region of rats were detected at 24 hours after the final administration. RESULTS AND CONCLUSION: Zea-Longa scoring results showed that the neurological function of rats was severely damaged after modeling and neurological deficit of rats in the Buqi Huoxue Compounds group was less than that in the model group and the autophagy inhibitor group (P < 0.05). TTC staining showed that cerebral infarct foci were observed in the model group, Buqi Huoxue Compounds group, and autophagy inhibitor group, and the cerebral infarct volume in the Buqi Huoxue Compounds group was lower than that in the model group and the autophagy inhibitor group (P < 0.05). The results of hematoxylin-eosin staining in ischemic brain tissues showed that there were large gaps between nerve cells in the model group and cell arrangement was not neat, and cytoplasmic agglutination and pyknosis were observed. Immunohistochemical staining results showed that vascular endothelial growth factor was mostly expressed in neuronal cells, glial cells and capillary endothelium; basic fibroblast growth factor and brain-derived neurotrophic factor were mostly expressed in neuronal cells and glial cells; and there was no significant difference in the expression of vascular endothelial growth factor, basic fibroblast growth factor, and brain-derived neurotrophic factor among the four groups (P > 0.05). The results of western blot assay showed that compared with the sham operation group, Beclin1 protein expression was decreased (P < 0.05) and p62 protein expression was elevated (P < 0.05) in the model group; compared with the model group, Beclin1 protein expression was increased (P < 0.05) and p62 protein expression was reduced (P < 0.05) in the Buqi Huoxue Compounds group; compared with the Buqi Huoxue Compounds group, Beclin1 protein expression was decreased (P < 0.05) and p62 protein expression was elevated (P < 0.05) in the autophagy inhibitor group. To conclude, Buqi Huoxue Compounds attenuate cerebral ischemia-reperfusion injury in rats by promoting autophagy. Figures and Tables | References | Related Articles | Metrics

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Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats  Zheng Lin, Jin Wenjun, Luo Shanshan, Huang Rui, Wang Jie, Cheng Yuting, An Zheqing, Xiong Yue, Gong Zipeng, Liao Jian 2025, 29 (6):  1159-1167.  doi: 10.12307/2025.304 Abstract ( 243 )   PDF (1948KB) ( 208 )   Save BACKGROUND: Eucommia ulmoides has a certain osteogenic effect, which can promote the proliferation and differentiation of osteoblasts. However, it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE: To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS: Sixty female Sprague-Dawley rats were selected and randomly divided into five groups: blank control group, sham-operation group, model group, low-dose group Eucommia ulmoides group, and high-dose Eucommia ulmoides group, with twelve rats in each group. Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups. The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries. Three months after surgery, the low- and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage, respectively. The sham-operation group and model group were given the same amount of physiological saline by gavage. After 12 weeks of drug intervention, the changes in alveolar bone mass of rats in each group were observed through Micro-CT; hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats; enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats; western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats; and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin, Runt-related transcription factor 2 (Runx2), alkaline phosphatase, β-catenin, and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION: Compared with the blank control group, bone volume fraction, trabecular number, trabecular thickness, and bone mineral density were reduced in the model group (P < 0.05), and trabecular separation was elevated (P < 0.05). Pathological observation showed that the arrangement of trabeculae was disordered and irregular, the trabeculae were thinned or broken, and the marrow cavity was enlarged in the model group, with a significant reduction in bone volume; the level of alkaline phosphatase in the serum was increased (P < 0.05), and the level of osteocalcin was decreased (P < 0.05); mRNA expression of alkaline phosphatase, osteocalcin, Runx2, β-catenin, and frizzled9 were decreased (P < 0.05); protein expression of β-Catenin and Frizzled9 was decreased (P < 0.05). Compared with the model group, the low- and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction, trabecular number, trabecular thickness, and bone mineral density (P < 0.05) and a decrease in trabecular separation (P < 0.05). In the low- and high-dose Eucommia ulmoides groups, bone trabeculae were slightly aligned and thickened, with a significant increase in bone mass. Compared with the model group, the serum level of alkaline phosphatase was reduced (P < 0.05) and the serum level of osteocalcin was elevated (P < 0.05) in the low- and high-dose Eucommia ulmoides groups. Compared with the model group, the mRNA expression of alkaline phosphatase, osteocalcin, Runx2, β-catenin, and frizzled9 were increased in the low- and high-dose Eucommia ulmoides groups (P < 0.05). Compared with the model group, the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group (P < 0.05), while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group (P < 0.05). Compared with the low-dose Eucommia ulmoides group, the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes. To conclude, Eucommia ulmoides can effectively promote the alveolar bone formation, and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Epidural fibrous scar formation in rabbits following autologous ligamentum flavum intervention  Zhang Debao, Wang Peng, Li Kun, Zhang Shaojie, Li Zhijun, Li Shuwen, Wu Yimin 2025, 29 (6):  1168-1175.  doi: 10.12307/2025.325 Abstract ( 191 )   PDF (1797KB) ( 138 )   Save BACKGROUND: It has been proved clinically that adhesion of fibrous scar with the dura mater or nerve root after lumbar operation is an important factor for postoperative symptoms, such as postoperative pain and numbness.  OBJECTIVE: To verify the inhibitory effect of autologous ligamentum flavum on the formation of epidural fibrous scar after lumbar surgery and explore the possible molecular biological mechanism. METHODS: Forty-eight Japanese white rabbits (6-8 months old) were randomly divided into three groups: a ligamentum flavum preservation group, a ligamentum flavum non-preservation group, and an autologous fat reposition group. A lumbar laminectomy model was established in all the three groups of rabbits, and rabbit epidural tissues were collected at 3 and 6 weeks after modeling. Hematoxylin-eosin staining was used to observe histological changes and the number and density of fibroblasts, VG staining was used to observe the percentage of collagen fiber area, and immunohistochemistry was used to observe the expression of transforming growth factor β1 and Smad3 proteins.  RESULTS AND CONCLUSION: Hematoxylin-eosin staining results revealed that fibroblasts in the ligamentum flavum preservation group were few and loosely arranged, while the cells in the ligamentum flavum non-preservation and autologous fat reposition groups were more numerous and closely arranged. The number density of fibroblasts in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery (P < 0.05); however, there was no significant difference between the latter two groups. VG staining results showed that the collagen fibers in the ligamentum flavum preservation group were sparse and distributed unevenly, while a lot of red collagen fibers were gathered in the ligamentum flavum non-preservation and autologous fat reposition groups. The area percentage of collagen fibers in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery (P < 0.05), but there was no significant difference between the latter two groups. The results of immunohistochemistry showed that the degree of positive staining of retained histone the ligamentum flavum preservation group was significantly lower than that of the other two groups. The absorbance value of transforming growth factor β1 and Smad3 in the ligamentum flavum preservation group was significantly lower than that in the other two groups at 3 and 6 weeks after surgery (P < 0.05), but there was no significant difference between the latter two groups. To conclude, there are different degrees of epidural fibrous scar formation after lumbar surgery. If the ligamentum flavum is preserved, it can help to reduce the number of epidural fibroblasts as well as the formation of collagen fibers, thus reducing the adhesion of the fibrous scar tissue to the dural sac and nerve root. The mechanism is not only a purely mechanical blockade, but also to reduce the formation of epidural fibrous scar by interfering with the transforming growth factor β1/Smad3 signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Mechanism of agomelatine alleviating anxiety- and depression-like behaviors in APP/PS1 transgenic mice #br# #br# Li Tian, Ren Yuhua, Gao Yanping, Su Qiang 2025, 29 (6):  1176-1182.  doi: 10.12307/2025.323 Abstract ( 247 )   PDF (1342KB) ( 118 )   Save BACKGROUND: Agomelatine is a clinically proven treatment for neuropsychiatric symptoms, such as anxiety and depression. Furthermore, our previous study has demonstrated that agomelatine ameliorates cognitive behaviors, hippocampal synaptic plasticity, and brain pathology in a mouse model of Alzheimer’s disease. However, it remains unclear whether agomelatine can improve anxiety and depression-like behaviors in Alzheimer’s disease model mice.  OBJECTIVE: To investigate the improving effects of agomelatine on anxiety- and depression-like behaviors in APP/PS1 transgenic mice and its underlying molecular mechanisms.  METHODS: (1) Eighteen APP/PS1 transgenic mice were randomly divided into model control group (n=9) and model intervention group (n=9). Another wild-type mice were randomized into control group (n=9) and intervention group (n=9). Model intervention group and intervention group were intraperitoneally injected with 10 mg/kg agomelatine per day for 31 continuous days. Behavioral experiments, including the elevated cross maze and forced swimming tests, and mRNA sequencing of the hippocampus were then performed. (2) Mouse hippocampal neuronal cell lines (HT22) and brain microvascular endothelial cell lines (bEnd.3) were cultured and divided into four groups: blank group without any drug, drug group with 20 µmol/L agomelatine, model group with 10 µmol/L β-amyloid 1-42, and experimental group with 10 µmol/L β-amyloid 1-42+20 µmol /L agomelatine. After 24 hours of incubation, protein expression of S416p-tau and S9p-GSK3β in HT22 cells was detected by immunoblotting, and protein expression of low-density lipoprotein receptor-related protein 1 and glycosylation end-product receptor in bEnd.3 cells was detected by immunoblotting. RESULTS AND CONCLUSION: In the elevated plus maze test, the time spent in the open arms (P < 0.01) and the entries into open arms (P < 0.05) in the mice of model control group were evidently lower than those in the control group, whereas those were obviously increased in the model intervention group compared with the model control group (P < 0.05). Forced swimming test results showed that the immobile time exhibited a marked increase in the model control group compared with the control group (P < 0.05), but it was significantly decreased in the model intervention group compared with the model control group (P < 0.05). Hippocampal tissue mRNA sequencing showed that agomelatine enhanced the expression of low-density lipoprotein receptor-related protein 1 in the hippocampus of APP/PS1 mice. Western blot analysis revealed that the level of S416p-tau in HT22 cells was higher in the model group than the blank group (P < 0.05), while it was markedly decreased in the experimental group compared with the model group (P < 0.05); the level of S9p-GSK3β in HT22 cells was higher in the drug group than the blank group (P < 0.05) as well as higher in the experimental group than the model group (P < 0.05). Moreover, the expression of low-density lipoprotein receptor-related protein 1 in bEnd.3 cells was higher in the experimental group than the model group (P < 0.05). To conclude, agomelatine can alleviate anxiety- and depression-like behaviors in Alzheimer’s disease mice by promoting the clearance of β-amyloid and phosphorylated tau. Figures and Tables | References | Related Articles | Metrics

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Hemin regulates mitochondrial pathway of oxidative stress in mouse chondrocytes He Guanghui, Yuan Jie, Ke Yanqin, Qiu Xiaoting, Zhang Xiaoling 2025, 29 (6):  1183-1191.  doi: 10.12307/2025.269 Abstract ( 240 )   PDF (3135KB) ( 102 )   Save BACKGROUND: Studies have shown that mitochondrial oxidative stress has an important role in the development of knee osteoarthritis, and Hemin can regulate the expression of mitochondria-related proteins. Objective: To study the regulatory effect of Hemin on oxidative stress in mouse chondrocytes and its interventional effect and mechanism in knee osteoarthritis. METHODS: (1) In vitro cell experiment: Primary chondrocytes from C57BL/6 mice were extracted and induced with 10 ng/mL interleukin-1β to construct an in vitro chondrocyte model of osteoarthritis. The optimal concentration of Hemin (0, 1, 10, 20, 40, 80, and 160 μmol/L) for the intervention in mouse chondrocytes was determined by cell counting kit-8 method. Chondrocytes were randomly divided into control group, model group (interleukin-1β) and Hemin group (interleukin-1β+Hemin). Reactive oxygen species, mitochondrial membrane potential and apoptosis of chondrocytes in each group were detected. (2) In vivo experiment: Adult C57BL/6 mice were randomly divided into normal group, model group (osteoarthritis) and Hemin group (osteoarthritis+Hemin), with eight mice in each group. After 4 weeks of Hemin treatment, the behavioral test and histopathological observation of the knee joint were performed in each group. Changes in extracellular matrix-related protein expression and apoptosis in chondrocytes and the expression level of Nrf2/HO-1 protein in cartilage tissue were detected. RESULTS AND CONCLUSION: In vitro experiment: the optimal concentration of Hemin on primary chondrocytes was 40 μmol/L. Compared with the model group, the level of reactive oxygen species was significantly reduced, the mitochondrial membrane potential was significantly improved, and the apoptosis of chondrocytes was reduced in the hemin-treated interleukin-1β-induced chondrocytes. In vivo experiment: After 4 weeks of treatment, compared with the model group, the lower limb function of mice in the Hemin group was significantly improved, the histopathological score was significantly improved, and the apoptosis of knee chondrocytes was significantly reduced. All these findings indicate that Hemin can alleviate oxidative stress, restore mitochondrial function and reduce apoptosis in mouse chondrocytes induced by interleukin-1β. Hemin can improve extracellular matrix degradation, promote chondrocyte anabolism, reduce catabolism and reduce chondrocyte apoptosis in knee osteoarthritis. It may act by activating the chondrocyte Nrf2/HO-1 signaling pathway in the inflammatory environment. Figures and Tables | References | Related Articles | Metrics

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Modified double-bundle arthroscopic repair of the anterior cruciate ligament after Sherman type I injury  Wang Changbing, Zhao Lilian, Fu Chuying, Li Yanjin 2025, 29 (6):  1192-1198.  doi: 10.12307/2025.320 Abstract ( 167 )   PDF (1853KB) ( 146 )   Save BACKGROUND: Impaired hamstring muscle strength, anterior patellar pain, high incidence of osteoarthritis, and loss of proprioception after anterior cruciate ligament reconstruction lead to poor functional recovery due to a higher incidence of osteoarthritis and loss of proprioception. Arthroscopic repair of the anterior cruciate ligament combined with dynamic or static internal brace repair preserves the original ligament structure and results in favorable short-term outcomes. OBJECTIVE: To prospectively observe the efficacy and imaging findings of modified double-bundle arthroscopic repair of the anterior cruciate ligament after Sherman type I injury. METHODS: From January 2020 to September 2022, a total of 60 patients with anterior cruciate ligament injury admitted at the Department of Sports Medicine, Foshan Hospital of Traditional Chinese Medicine were included and divided into two groups (n=30 per group) according to the treatment protocols. The functional repair group was treated with double bundle repair combined with internal brace fixation, and the reconstruction group was treated with single bundle anatomical reconstruction of autologous hamstring muscle. All cases were followed up for 12 months after surgery, and International Knee Documentation Committee score, Lysholm score and KT-1000 difference between the affected and healthy sides of the two groups were evaluated at 3, 6 and 12 months after surgery. RESULTS AND CONCLUSION: Three months after surgery, International Knee Documentation Committee scores, Lysholm scores and KT-1000 difference between the affected and healthy sides were significantly different between the two groups (P < 0.05), and the functional repair group was better than the reconstruction group. At 6 and 12 months after surgery, there was no significant difference in International Knee Documentation Committee score, Lysholm score and KT-1000 difference between the two groups (P > 0.05). To conclude, anterior cruciate ligament repair preserves the original ligament structure, avoids drilling larger marrow tracts and removing autologous tendons for reconstruction, reduces the damage to the original normal structure, and has fewer complications. Early postoperative efficacy is better than that of anterior cruciate ligament reconstruction with stumps, but there is no significant difference in the efficacy of the two groups 6 months after surgery. Figures and Tables | References | Related Articles | Metrics

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Impact of graft thickness on corneal endothelial decompensation following simple Descemet’s stripping endothelial keratoplasty  Ba Yanhong, Gao Minghong, Chen Yingxin 2025, 29 (6):  1199-1207.  doi: 10.12307/2025.318 Abstract ( 208 )   PDF (1558KB) ( 163 )   Save BACKGROUND: Studies have shown that vision recovery with thinner grafts is faster and the risk of rejection is lower. In China, there is a lack of clinical efficacy analysis of different graft thicknesses after endothelial transplantation. Therefore, determining the optimal graft thickness is crucial for improving surgical efficacy. OBJECTIVE: To evaluate the effects of different graft thickness on vision recovery and other prognostic indexes after simple Descemet’s stripping endothelial keratoplasty. METHODS: A total of 72 patients (72 eyes) with corneal endothelial decompensation who received simple Descemet’s stripping endothelial keratoplasty at the General Hospital of Northern Theater Command from January 2013 to February 2023 were selected. There were 32 cases (32 eyes) in the thin graft group (< 100 μm) and 40 cases (40 eyes) in the thick graft group (≥ 100 μm). The best corrected visual acuity, corneal endothelial cell count, corneal graft transparency, postoperative complications and graft survival were observed in both groups before and 1, 3, 6, and 12 months after surgery. RESULTS AND CONCLUSION: The visual acuity after surgery was significantly improved in both groups, and the best corrected visual acuity 3 months after surgery in the thin graft group was better than that in the thick graft group (P < 0.05). There was no significant difference in the number of corneal endothelial cells and graft transparency between the two groups 1 year after surgery (P > 0.05). There was no significant difference in the incidence of postoperative complications such as secondary glaucoma, graft immune rejection and graft displacement between the two groups (P > 0.05). There was no significant difference in the 1-year survival rate of grafts between the two groups (93.8% vs. 92.3%, P > 0.05). To conclude, simple Descemet’s stripping endothelial keratoplasty is a safe and effective surgical method for corneal endothelial transplantation, and its postoperative efficacy is similar to that of traditional Descemet’s stripping endothelial keratoplasty, and the graft implantation method is simpler. Thinner grafts can provide optimal corrected vision earlier and complete corneal remodeling sooner. Therefore, in the treatment of corneal endothelial decompensation, thinner grafts are preferred to improve recovery time. Figures and Tables | References | Related Articles | Metrics

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Characterization of postural stability in elderly patients with idiopathic normal pressure hydrocephalus #br# #br# Liang Xiaoxiao, Zheng Jiejiao, Duan Linru, Chen Xi, Zhang Tingyu 2025, 29 (6):  1208-1213.  doi: 10.12307/2025.321 Abstract ( 185 )   PDF (843KB) ( 80 )   Save BACKGROUND: Impaired postural control is an important risk factor for falls and secondary damage in patients with idiopathic normal pressure hydrocephalus. Most of the existing studies have analyzed the gait parameters of patients during straight-line walking, but few have analyzed the postural stability characteristics of patients during static and dynamic activities. OBJECTIVE: To analyze the characteristics of postural stability in elderly patients with idiopathic normal pressure hydrocephalus. METHODS: Twenty-two patients clinically diagnosed with idiopathic normal pressure hydrocephalus at the Department of Neurosurgery, Huadong Hospital Affiliated to Fudan University, Shanghai, China, from September 2022 to February 2023 were selected as the patient group, and 18 healthy accompanying family members were selected as the healthy control group. The postural stability characteristics of the subjects were assessed using the Timed Up-and-Go Test, Multi-Directional Reach Test, Berg Balance Scale, and Static Balance Function Test (reaction time, speed of movement, directional control, maximum offset distance, and endpoint travel). RESULTS AND CONCLUSION: The time required to complete the Timed Up-and-Go Test was significantly longer in the patient group than in the healthy control group (P < 0.05). The results of the stretching test in the four directions of anterior, posterior, left and right were significantly lower in the patient group than in the healthy control group (P < 0.05). The Berg Balance Scale scores in the patient group were lower than those in the healthy control group (P < 0.05). In the Static Balance Function Test, the results of reaction, movement speed, directional control, maximum offset distance and endpoint travel index were smaller in the patient group than the healthy control group (P < 0.05). To conclude, patients with idiopathic normal pressure hydrocephalus exhibit overall postural control deficits, and impaired reaction and execution abilities make these patients unable to make timely and accurate motor responses in the face of disturbances from internal or external sources, resulting in postural instability and increasing the risk of falls.  Figures and Tables | References | Related Articles | Metrics

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Mechanisms of different yin nourishing and kidney tonifying methods on osteoclastysis pathway in ovariectomized rats #br# #br# Huang Xiaobin, Ge Jirong, Li Shengqiang, Xie Lihua, Huang Jingwen, He Yanyan, Xue Lipeng 2025, 29 (6):  1214-1219.  doi: 10.12307/2025.284 Abstract ( 234 )   PDF (956KB) ( 112 )   Save BACKGROUND: Liuwei Dihuang Wan takes “three tonifying and three reducing effects” as its compatibility feature to nourish yin and tonify the kidneys, while Zuogui Wan takes “seeking yin in yang” as its compatibility feature to nourish yin and tonify the kidneys by promoting yang. Both of them belong to the same method of nourishing yin and tonifying the kidneys, and have better curative effects at the symptomatic and cellular molecular levels. OBJECTIVE: To observe the effects of Liuwei Dihuang Wan and Zuogui Wan in bone metabolism, and to explore their mechanism of action in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) osteoblastic pathway.  METHODS: Thirty-two Sprague-Dawley rats were randomized into model, Liuwei Dihuang Wan, Zuogui Wan, and sham operation group, with eight rats in each group. Osteoporosis models were prepared using removal of both ovaries in the first three groups. Starting at 30 days postoperatively, rats in the Liuwei Dihuang Wan group were gavaged with Liuwei Dihuang Wan 1.125 g/kg/d; rats in the Zuoqui Wan group were gavaged with Zuogui Wan 2.25 g/kg/d; and rats in the sham operation group and the model group were gavaged with saline 10 mL/kg/d. After 12 weeks of gavage, the rat tibia was taken to measure bone mineral density. The serum levels of estrogen, bone alkaline phosphatase, and cAMP/cGMP were measured using ELISA, and the expression of OPG/RANKL in the femur was detected using western blot.  RESULTS AND CONCLUSION: Compared with the sham operation group, the model group showed a decrease in bone mineral density and levels of estrogen and bone alkaline phosphatase (P < 0.05) and an increase in cAMP/cGMP level (P < 0.05). Compared with the model group, the Liuwei Dihuang Wan group and the Zuogui Wan group significantly increased bone mineral density (P < 0.05) and bone alkaline phosphatase levels (P < 0.05); the Zuogui Wan group significantly decreased cAMP/cGMP levels (P < 0.05) and upregulated OPG expression (P < 0.05); the Liuwei Dihuang Wan group upregulated OPG expression and downregulated RANKL expression (P < 0.05); and both groups were unable to significantly increase estrogen levels (P > 0.05). To conclude, Zuogui Wan, which seeks yin from yang, can effectively increase the expression of OPG but cannot downregulate the expression of RANKL. However, Liuwei Dihuang Wan, which has three tonifying and three reducing effects, can bidirectionally regulate the expression of OPG and RANKL. This result suggests that Liuwei Dihuang Wan can significantly inhibit osteoclastic function compared with Zuogui Wan, and further research is needed to verify this conclusion. Figures and Tables | References | Related Articles | Metrics

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SR9009 combined with indolepropionic acid alleviates inflammation in C2C12 myoblasts through the nuclear factor-kappa B signaling pathway Ji Huihui, Jiang Xu, Zhang Zhimin, Xing Yunhong, Wang Liangliang, Li Na, Song Yuting, Luo Xuguang, Cui Huilin, Cao Ximei 2025, 29 (6):  1220-1229.  doi: 10.12307/2025.283 Abstract ( 433 )   PDF (2377KB) ( 114 )   Save BACKGROUND: Rev-erbα is involved in the regulation of inflammation, but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases. To reduce the relevant risk, an exploration on SR9009, a Rev-erbα agonist, combined with other drugs to relieve inflammation in skeletal myoblasts was conducted, laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE: To investigate the relationship of SR9009, indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts.  METHODS: (1) C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide (1 μg/mL). RNA-seq and KEGG pathway analysis were used to study signaling pathways. (2) C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid. Subsequently, cells were categorized into control group, lipopolysaccharide (1 μg/mL) group, SR9009 (10 μmol/L)+lipopolysaccharide group, indolepropionic acid (80μmol/L)+lipopolysaccharide group, and SR9009+indolepropionic acid+lipopolysaccharide group. ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.  Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6, tumor necrosis factor α, TLR4 and CD14. Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65. (3) After Rev-erbα was knocked down by siRNA, knockdown efficiency was assessed by RT-qPCR. And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured.  RESULTS AND CONCLUSION: Compared with the blank control group, lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes, the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated, and the level of interleukin-6 in the cell supernatant was significantly increased. The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide. Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L. Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway, thereby played an anti-inflammatory role, and suppressed the mRNA expression levels of interleukin-6, tumor necrosis factor α, TLR4 and CD14. Compared with the lipopolysaccharide group, the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated. SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation, further downregulated the mRNA expression levels of interleukin-6, tumor necrosis factor α, TLR4 and CD14. The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group. Rev-erbα increases time-dependently with lipopolysaccharide induction. The knockdown efficiency of Rev-erbα by siRNA reached over 58%, and lipopolysaccharide was added after Rev-erbα was successfully knocked down. Compared with the lipopolysaccharide group, the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated. These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation. SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts. Moreover, the combined anti-inflammatory effect is superior to that of the intervention alone. Figures and Tables | References | Related Articles | Metrics

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Pathogenesis and treatment progress of flap ischemia-reperfusion injury  He Bo, Chen Wen, Ma Suilu, He Zhijun, Song Yuan, Li Jinpeng, Liu Tao, Wei Xiaotao, Wang Weiwei, Xie Jing 2025, 29 (6):  1230-1238.  doi: 10.12307/2025.298 Abstract ( 324 )   PDF (883KB) ( 164 )   Save BACKGROUND: Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects, but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury. Therefore, it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE: To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS: CNKI, WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024. The search terms used were “flap, ischemia-reperfusion injury, inflammatory response, oxidative stress, Ca2+ overload, apoptosis, mesenchymal stem cells, platelet-rich plasma, signaling pathways, shock wave, pretreatment” in Chinese and English. After elimination of irrelevant literature, poor quality and obsolete literature, 77 documents were finally included for review. RESULTS AND CONCLUSION: Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response, oxidative stress response, Ca2+ overload, and apoptosis, which can cause apoptosis of vascular endothelial cells, vascular damage and microcirculation disorders in the flap, and eventually lead to flap necrosis. Studies have found that mesenchymal stem cell transplantation, platelet-rich plasma, signaling pathway modulators, shock waves, and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees, and reduce the necrosis rate and necrosis area of the grafted flap. Although there are many therapeutic methods for skin flap ischemia/reperfusion injury, a unified and effective therapeutic method has not yet been developed in the clinic, and the advantages and disadvantages of various therapeutic methods have not yet been compared. Most of the studies remain in the stage of animal experiments, rarely involving clinical observations. Therefore, a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic. Figures and Tables | References | Related Articles | Metrics

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ACSL4 mediates ferroptosis and its potential role in atherosclerotic cardiovascular disease Gao Yang, Qin Hewei, Liu Dandan 2025, 29 (6):  1239-1247.  doi: 10.12307/2025.299 Abstract ( 551 )   PDF (1154KB) ( 410 )   Save BACKGROUND: Ferroptosis is an iron-dependent regulatory form of cell death characterized by iron-dependent lipid peroxidation. Long-chain acyl-coenzyme A synthase 4 (ACSL4) is involved in the formation of lipid peroxidation substrates, thereby resulting in ferroptosis. Recent studies have shown that ACSL4-mediated ferroptosis plays a key role in atherosclerotic cardiovascular disease. OBJECTIVE: To summarize the structural function and regulatory mechanism of ACSL4 and its potential molecular mechanism mediating ferroptosis, and to elaborate the application of ACSL4 driving ferroptosis in atherosclerosis, ischemic stroke and myocardial infarction, in order to provide a new therapeutic strategy for the treatment of atherosclerotic cardiovascular diseases. METHODS: Relevant literature was searched in PubMed database from database inception to August 2023 using the keywords of “atherosclerosis, ferroptosis, long-chain acyl-coenzyme A synthase 4, ACSL4, glutathione peroxidase 4, ischemic stroke, myocardial infarction, endothelial cell, smooth muscle cells, foam cell.” Finally, 76 documents were included for review and analysis. RESULTS AND CONCLUSION: ACSL4 participates in the formation of coenzyme derivatives of polyunsaturated fatty acids and inserts them into phospholipids to provide substrates for lipid peroxidation, the core mechanism of iron death. Among the regulatory factors of ACSL4 expression, integrin α6β4, intracellular vesicular transport factor p115, and zinc lipoprotein A20 negatively regulate its expression. Meanwhile, multiple miRs down-regulate its expression by binding to 3’-UTR. On the contrary, up-regulation of ACSL4 is mostly regulated by transcription factors. ACSL4-dependent production of phospholipids containing polyunsaturated fatty acids is an essential prerequisite for lipid peroxidation and ferroptosis. Moreover, ACSL4 and glutathione peroxidase 4 are mutually dependent as positive and negative regulators of ferroptosis, and their specific mechanisms remain to be further studied. ACSL4-mediated ferroptosis is involved in the pathological mechanism of atherosclerosis, ischemic stroke, and myocardial infarction. Endothelial cell injury in atherosclerosis is closely related to ACSL4-mediated ferroptosis, but there are no reports on the involvement of ACSL4 in foam cell formation, smooth muscle cell phenotype transformation, and calcification. ACSL4 has become a research hotspot as a biomarker and potential target of ferroptosis. Targeting ACSL4 to inhibit ferroptosis may become a new direction for the treatment of atherosclerotic cardiovascular diseases. However, there are few studies on drugs inhibiting ACSL4, and further studies are needed in the future. Figures and Tables | References | Related Articles | Metrics

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Different exercise modalities promote functional recovery after peripheral nerve injury Zhao Xiaoxuan, Liu Shuaiyi, Li Qi, Xing Zheng, Li Qingwen, Chu Xiaolei 2025, 29 (6):  1248-1256.  doi: 10.12307/2025.305 Abstract ( 381 )   PDF (1006KB) ( 427 )   Save BACKGROUND: Exercise as a form of active rehabilitation can improve the dysfunction caused by peripheral nerve injury, and different exercise modalities target different lesion sites and recovery mechanisms. OBJECTIVE: To comprehensively analyze the application and mechanisms of different exercise modalities in functional recovery from peripheral nerve injury. METHODS: A computerized search was conducted in PubMed and CNKI databases for relevant literature published before January 2024. The search terms used were “peripheral nerve injury, spinal cord, exercise, cerebral cortex, muscle atrophy, mirror therapy, blood flow restriction training” in both English and Chinese. Finally, 77 articles were included for review. RESULTS AND CONCLUSION: Peripheral nerve injury can cause systemic pathological changes such as skeletal muscle atrophy, corresponding spinal cord segmental lesions, and sensorimotor cortex remodeling. Aerobic exercise can improve dysfunction by enhancing the immune response, promoting glial cell polarization, and promoting the release of nerve growth factor. Blood flow restriction exercise can regulate the secretion of muscle growth factor, promote muscle growth and enhance muscle strength. Mirror movement has a good effect in activating the cerebral cortex and reducing cortical remodeling. Different exercise modalities have potential benefits in functional recovery after peripheral nerve injury; however, there are still some problems and challenges, such as the choice of exercise modalities, the control of exercise intensity and frequency, and the detailed analysis of mechanisms. Figures and Tables | Related Articles | Metrics

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General pattern of GSK3/Nrf2-regulated biological rhythms in organismal aging  Chen Yilin, Jiang Xiaobo, Qu Honglin, Liu Ruilian 2025, 29 (6):  1257-1264.  doi: 10.12307/2025.308 Abstract ( 249 )   PDF (1006KB) ( 187 )   Save BACKGROUND: Disruption of biological rhythms (circadian rhythms) is a typical problem associated with aging. Maintaining the normal function of biological rhythms may be a promising anti-aging strategy. Expression of nuclear factor erthroid 2-related factor 2 (Nrf2) is biologically regulated. The glycogen synthase kinase 3 (GSK3) system represents a “regulatory valve” that controls subtle oscillations in Nrf2 levels. Circadian changes in the transcript levels of antioxidant genes can influence the response of organisms to oxidative stress. However, the specific molecular mechanism of GSK3/Nrf2 in regulating organismal aging is still puzzling.  OBJECTIVE: To search for the general pattern of GSK3/Nrf2-regulated biological rhythms in organismal aging by reviewing the literature in this field.  METHODS: The bibliographic method was used to search, review and screen the relevant literature using the keywords of “glycogen synthase kinase 3, nuclear factor erthroid 2-related factor 2, biorhythms and aging” to lay a theoretical foundation for the analysis of the whole paper. Comparative analysis method, through reading and analyzing the obtained literature, was performed to compare the similarities and differences between the literature, thereby providing reasonable theoretical support for the argument. Further comparative analysis of the literature was conducted to clarify the relationship between the relevant indicators as well as the ideas for analysis throughout the text. RESULTS AND CONCLUSION: GSK3 can indirectly regulate Nrf2 expression through the regulation of rhythm genes. GSK3 and Nrf2 are components of anti-aging programs and are associated with biological rhythms. In addition, GSK3/Nrf2 is involved in several metabolic pathways, including those associated with age-related diseases (type 2 diabetes and cancer) and neurodegenerative diseases. Figures and Tables | References | Related Articles | Metrics

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Promoting myogenesis based on the SphK1/S1P/S1PR2 signaling pathway: a new perspective on improving skeletal muscle health through exercise Zhang Wenhua, Li Xun, Zhang Weichao, Li Xinying, Ma Guoao, Wang Xiaoqiang 2025, 29 (6):  1265-1275.  doi: 10.12307/2025.310 Abstract ( 299 )   PDF (1006KB) ( 226 )   Save BACKGROUND: In recent years, improving the health of skeletal muscles through exercise has become an important research concern for scholars. Appropriate exercise has a positive effect on skeletal muscles. Among them, how to activate the sphingosine kinase1 (SphK1)/sphingosine-1-phase (S1P)/sphingosine-1-phase receptor2 (S1PR2) signaling pathway during exercise so as to improve the health of skeletal muscles is receiving attention from researchers. OBJECTIVE: To investigate how exercise improves the health of skeletal muscles through the SphK1/S1P/S1PR2 signaling pathway, and to explore new methods for treating related muscle diseases in order to improve human skeletal muscle health. METHODS: The first author searched for relevant literature from the establishment of the database to the present in the Web of Science, PubMed, CNKI, WanFang, and VIP databases. The search terms were “signaling pathway, SphK1, S1P, S1PR2, skeletal muscle, satellite cell, myogenesis, exercise” in Chinese and English. Finally, 69 articles were included for review and analysis. RESULTS AND CONCLUSION: The SphK1/S1P/S1PR2 signaling pathway is a complex regulatory network that triggers downstream signal transduction processes by SphK1 to catalyze the interaction between S1P and receptors such as S1PR2, thereby regulating multiple biological functions of cells, tissues, organs, and systems. The SphK1/S1P/S1PR2 signaling pathway can regulate satellite cell proliferation and myoblast differentiation, improving myogenesis. The physiological basis of the SphK1/S1P/S1PR2 signaling pathway and the potential impact of exercise on it were analyzed through literature research. Acute aerobic exercise can increase the expression of SphK1 in skeletal muscle. Both human and animal studies have confirmed that acute and long-term exercise can increase the expression of S1P in skeletal muscle. In addition, studies have shown that long-term resistance exercise can increase the expression of S1PR2 in skeletal muscle. Some experimental results indicate that acute and long-term exercise have no significant effect on muscle or blood S1P levels, and the reason for different results may be due to different research subjects, methods, intensities, and frequencies selected, while the specific mechanism is not yet clear. Research suggests that exercise can promote the expression of the SphK1/S1P/S1PR2 signaling pathway in skeletal muscle and regulate downstream related signaling pathways. Research on this signaling pathway may provide new strategies and methods for the treatment of skeletal muscle diseases, thereby improving skeletal muscle health. In the future, we should deepen the research on the association between SphK1/S1P/S1PR2 signaling pathway and skeletal muscle health, further reveal its regulatory relationship with satellite cells and myoblasts as well as its interactions with the upstream and downstream pathways, explore its clinical application value, take into account the changes of this pathway when formulating the rehabilitation program, explore the specific mechanisms by which different types of exercise affect the SphK1/S1P/S1PR2 signaling pathway in skeletal muscles, and use the SphK1/S1P/S1PR2 signaling pathway as a potential therapeutic target for diseases. Further development and application of human muscle models should be developed to improve research depth and accuracy. Figures and Tables | References | Related Articles | Metrics

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Improvement of myocardial injury by traditional Chinese medicine: mitochondrial calcium homeostasis mediates macrophage autophagy and pyroptosis pathway  Liu Lingyun, He Guixin, Qin Weibin, Song Hui, Zhang Liwen, Tang Weizhi, Yang Feifei, Zhu Ziyi, Ou Yangbin 2025, 29 (6):  1276-1284.  doi: 10.12307/2025.307 Abstract ( 312 )   PDF (1082KB) ( 330 )   Save BACKGROUND: The repair process of myocardial injury involves complex cellular and molecular mechanisms, especially mitochondrial calcium homeostasis, macrophage autophagy and pyroptosis pathways. Traditional Chinese medicine (TCM) has shown significant clinical efficacy in improving myocardial injury, but its mechanism of action needs to be thoroughly investigated. OBJECTIVE: To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury, and to summarize the progress of TCM in this field. METHODS: A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science, PubMed and CNKI. The search terms were “mitochondrial calcium homeostasis, macrophage autophagy, macrophage pyroptosis, traditional Chinese medicine, myocardial injury, myocardial injury reperfusion” in Chinese and English. Through literature review, we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis, explored the mechanism of their roles in myocardial injury, and summarized the pathways of multi-targeted, multi-pathway effects of TCM. RESULTS AND CONCLUSION: The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes. Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways. Autophagy contributes to cell clearance and regulation of inflammatory response, while pyroptosis affects myocardial repair by releasing inflammatory factors. TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms. For example, astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C, and epimedium glycoside plays a role in reducing β-amyloid deposition. In addition, herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways, such as PI3K/AKT and nuclear factor-κB signaling pathways. Future studies should focus on the interactions between mitochondrial calcium homeostasis, autophagy and pyroptosis pathways, as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury. Figures and Tables | References | Related Articles | Metrics

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Endoplasmic reticulum stress in the occurrence and development of common degenerative bone diseases Qian Kun, Li Ziqing, Sun Shui 2025, 29 (6):  1285-1295.  doi: 10.12307/2025.316 Abstract ( 238 )   PDF (1057KB) ( 403 )   Save BACKGROUND: The specific molecular mechanisms underlying common degenerative bone diseases, such as osteoarthritis, osteoporosis, and intervertebral disc degeneration, are currently unclear and may involve endoplasmic reticulum stress. At present, research on the systematic role of endoplasmic reticulum stress in the pathogenesis of these common skeletal diseases and related therapeutic progress is relatively limited. OBJECTIVE: To review the role of endoplasmic reticulum stress in common degenerative bone diseases, explore the molecular mechanisms of these diseases in depth, and provide new ideas and perspectives for prevention and treatment of these diseases. METHODS: Relevant literature from 2000 to 2024 was searched in CNKI, WanFang, VIP, PubMed and Web of Science databases using the search terms of “endoplasmic reticulum stress, bone disease, unfolded protein response, osteoarthritis, osteoporosis, intervertebral disc degeneration, autophagy, apoptosis, ferroptosis, pyroptosis” in Chinese and English. After removal of duplicates and older literature, a total of 115 articles met the inclusion criteria.  RESULTS AND CONCLUSION: Endoplasmic reticulum stress has a dual effect in regulating cell physiology. Mild endoplasmic reticulum stress promotes osteogenic differentiation and extracellular matrix synthesis; however, persistent excessive endoplasmic reticulum stress leads to cell death. Endoplasmic reticulum stress-induced cell autophagy and apoptosis are closely related to osteoarthritis, osteoporosis, and intervertebral disc degeneration. Aging, drug side effects, metabolic disorders, calcium imbalance, poor lifestyle habits and other reasons may lead to long-term activation of endoplasmic reticulum stress, which causes bone remodeling disorders, cartilage damage, nucleus pulposus cell death and other pathological manifestations, ultimately leading to the occurrence of osteoarthritis, osteoporosis and intervertebral disc degeneration. Intervention in the relevant mechanisms triggering endoplasmic reticulum stress is expected to play a role in the prevention and treatment of common degenerative bone diseases, such as osteoarthritis, osteoporosis and intervertebral disc degeneration. Figures and Tables | References | Related Articles | Metrics

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Gut microbiota and osteoporotic fractures #br# #br# Zhao Wensheng, Li Xiaolin, Peng Changhua, Deng Jia, Sheng Hao, Chen Hongwei, Zhang Chaoju, He Chuan 2025, 29 (6):  1296-1304.  doi: 10.12307/2025.311 Abstract ( 282 )   PDF (3045KB) ( 187 )   Save BACKGROUND: Osteoporotic fracture is the most serious complication of osteoporosis. Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture, but the causal relationship between the two is unclear. OBJECTIVE: To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method.  METHODS: The genome-wide association study (GWAS) datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9, respectively. Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable, Mendelian randomization analyses with random-effects inverse variance weighted, MR-Egger regression, weighted median, simple model, and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture. Sensitivity analyses were performed to test the reliability and robustness of the results. Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION: The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture. Elevated abundance of Actinomycetales [odds ratio (OR)=1.562, 95% confidence interval (CI): 1.027-2.375, P=0.037), Actinomycetaceae (OR=1.561, 95% CI: 1.027-2.374, P=0.037), Actinomyces (OR =1.544, 95% CI: 1.130-2.110, P=0.006), Butyricicoccus (OR=1.781, 95% CI: 1.194-2.657, P=0.005), Coprococcus 2 (OR=1.550, 95% CI: 1.068-2.251, P=0.021), Family XIII UCG-001 (OR=1.473, 95% CI: 1.001-2.168, P=0.049), Methanobrevibacter (OR=1.274, 95% CI: 1.001-1.621, P=0.049), and Roseburia (OR=1.429, 95% CI: 1.015-2.013, P=0.041) would increase the risk of osteoporotic fractures in patients. Elevated abundance of Bacteroidia (OR=0.660, 95% CI: 0.455-0.959, P=0.029), Bacteroidales (OR=0.660, 95% CI: 0.455-0.959, P=0.029), Christensenellacea (OR=0.725, 95% CI: 0.529-0.995, P=0.047), Ruminococcaceae (OR=0.643, 95% CI: 0.443-0.933, P=0.020), Enterorhabdus (OR=0.558, 95% CI: 0.395-0.788, P=0.001), Eubacterium rectale group (OR=0.631, 95% CI: 0.435-0.916, P=0.016), Lachnospiraceae UCG008 (OR=0.738, 95% CI: 0.546-0.998, P=0.048), and Ruminiclostridium 9 (OR=0.492, 95% CI: 0.324-0.746, P=0.001) would reduce the risk of osteoporotic fractures in patients. We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method. That is, using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable, eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture. The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice, but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering. Figures and Tables | References | Related Articles | Metrics

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Causal effects of different exercise intensities on the risk of osteoarthritis  Ma Haoyu, Qiao Hongchao, Hao Qianqian, Shi Dongbo 2025, 29 (6):  1305-1311.  doi: 10.12307/2025.317 Abstract ( 237 )   PDF (4710KB) ( 124 )   Save BACKGROUND: Increasing evidence supports the association between different exercise intensities and the risk of osteoarthritis, but this may be affected by confounding and reverse causality, and the conclusions have not been unified. OBJECTIVE: To explore the causal association between different exercise intensities and osteoarthritis using Mendelian randomization method. METHODS: Data from genome-wide association studies associated with different exercise intensities were selected, and instrumental variables were screened with a threshold of P < 5×10-8. Causal associations between exposure and risk of outcome were assessed using five analysis methods of Mendelian randomization with inverse variance weighting as the primary analysis method. Selected instrumental variables were used to assess causal associations between different exercise intensities and osteoarthritis, and sensitivity analyses with inverse Mendelian randomization were performed. RESULTS AND CONCLUSION: In the analysis results of the inverse variance weighting method, low-intensity exercise showed a significant protective effect on knee osteoarthritis [odds ratio (OR)=0.14, 95% confidence interval (CI): 0.06-0.32, P < 0.001], while sedentary behavior without exercise intensity, such as watching TV, was confirmed to be a risk factor for knee osteoarthritis and hip osteoarthritis (OR=2.24, 95% CI: 1.74-2.88, P < 0.001; OR=1.34, 95% CI: 1.01-1.78, P=0.04). Through the reverse Mendelian randomization analysis of osteoarthritis to different exercise intensities, it was found that osteoarthritis was negatively correlated with low-intensity exercise and positively correlated with watching TV. The analysis results show that there is a two-way causal relationship between different exercise intensity and osteoarthritis risk. Figures and Tables | References | Related Articles | Metrics

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Association between thyroid function levels and phenotypes associated with sarcopenia Li Jiatong, Jin Yue, Liu Runjia, Song Bowen, Zhu Xiaoqian, Li Nianhu 2025, 29 (6):  1312-1320.  doi: 10.12307/2025.289 Abstract ( 243 )   PDF (3715KB) ( 125 )   Save BACKGROUND: Several observational studies have found a close relationship between thyroid function levels and sarcopenia, but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE: To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS: A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin, free triiodothyronine, free tetraiodothyronine, subclinical hyperthyroidism, subclinical hypothyroidism, and four related phenotypes of sarcopenia - left hand grip strength, right hand grip strength, limb lean mass, and gait speed. The inverse-variance weighted method, weighted median method, simple mode method, weighted median estimator method, and MR Egger regression method were used as analysis methods, while heterogeneity test, pleiotropy test, MR-PRESSO, leave-one-out method, funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION: Elevated levels of thyroid-stimulating hormone increased left- (β=0.02, SE=0.01, P=0.01) and right-handed grip strength (β=0.02, SE=0.01, P=0.01), an increase in free triiodothyronine decreased left- (β=-0.06, SE=0.02, P=9.5×10-5) and right-handed grip strength (β=-0.07, SE=0.02, P=9.3×10-5), and subclinical hyperthyroidism decreased gait speed (β=-4.4×10-3, SE=1.7×10-3, P=0.01). The sensitivity analysis results were basically consistent with the main analysis results. To conclude, an increase in thyroid-stimulating hormone is a protective factor for sarcopenia, and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia. Figures and Tables | References | Related Articles | Metrics