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18 June 2025, Volume 29 Issue 17 Previous Issue    Next Issue

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Mechanism by which programmed cell death protein 1 influences osteoblast differentiation under high-glucose conditions Zhang Wanli, Bai Tao, Han Nianrong, Akram·Osman, Liu Yanlu, Huang Yifei, Hu Wei 2025, 29 (17):  3521-3528.  doi: 10.12307/2025.665 Abstract ( 395 )   PDF (1787KB) ( 122 )   Save BACKGROUND: Programmed cell death protein 1 belongs to the immunoglobulin gene superfamily and can regulate the differentiation of osteoblasts and affect bone homeostasis. However, there are few studies on the regulatory role and mechanism of programmed cell death protein 1 in diabetic osteoporosis. OBJECTIVE: To investigate the regulatory role and mechanism of programmed cell death protein 1 on osteogenic differentiation of rat bone marrow mesenchymal stem cells under high-glucose environment.  METHODS: (1) Animal experiment: A total of 12 Sprageu-Dawley rats were randomized into a control group (n=6) and a model group (n=6). The control group was fed routinely, whereas the model group was injected intraperitoneally with streptozotocin to establish a model of type 1 diabetes mellitus, and the high-fat feed was fed for 8 weeks to establish a model of type 1 diabetic osteoporosis. After 8 weeks of feeding, the femurs of rats in the two groups were taken and subjected to hematoxylin-eosin staining and micro-CT assay. The mRNA expression of programmed cell death protein 1 and programmed death ligand 1 was detected. (2) Cell experiment: Passage 3 rat bone marrow mesenchymal stem cells were randomly divided into four groups: normal control group, high-glucose model group cultured in low glucose medium, programmed cell death protein 1-silenced group transfected with programmed cell death protein 1 siRNA, and programmed cell death protein 1-silenced null group transfected with siRNA-NC. After 48 hours of transfection, the normal control group was cultured in a new low-glucose medium, and the other three groups were cultured in a high-glucose medium for another 48 hours of culture followed by osteogenic induction. After 21 days of osteogenic induction, alizarin red staining, and qRT-PCR (programmed cell death protein 1 and RUNX2 mRNA expression) and western blot (β-catenin, GSK-3β, p-GSK-3β and Axin2 protein expression) were performed. RESULTS AND CONCLUSION: In the animal experiment, hematoxylin-eosin staining and micro-CT assay showed successful modeling of type 1 diabetic osteoporosis in the model group. qRT-PCR assay showed that the mRNA expression of programmed cell death protein 1 and programmed cell death ligand 1 was higher in the model group than the control group (P < 0.05). In the cell experiment, the results of alizarin red staining showed that the ability of mineralized nodule formation was lower in the high-glucose model group and the programmed cell death protein 1-silenced null group than in the control group and the programmed cell death protein 1-silenced group. Compared with the normal control group, the programmed cell death protein 1 mRNA expression and GSK3β and Axin2 protein expression were elevated in the high-glucose model group and the programmed cell death protein 1-silenced null group (P < 0.05), and the RUNX2 mRNA expression and p-GSK3β and β-catenin protein expression were decreased (P < 0.05). Compared with the high-glucose model group and the programmed cell death protein 1-silenced null group, programmed cell death protein 1 mRNA expression and GSK3β and Axin2 protein expression were decreased in the programmed cell death protein 1-silenced group (P < 0.05), and RUNX2 mRNA expression and p-GSK3β and β-catenin protein expression were elevated (P < 0.05). To conclude, programmed cell death protein 1 silencing can activate the Wnt/β-catenin and improve the osteogenic differentiation of rat bone marrow mesenchymal stem cells under high-glucose conditions. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Astragaloside IV alleviates oxidative stress injury and promotes osteogenesis in MC3T3-E1 cells Zhang Jiahao, Li Jiacheng, Wen Mingtao, Guo Yanbo, Luo Di, Li Gang 2025, 29 (17):  3529-3536.  doi: 10.12307/2025.706 Abstract ( 339 )   PDF (1968KB) ( 99 )   Save BACKGROUND: Oxidative stress is one of the main causes of osteoporosis, and reducing the level of oxidative stress with increasing antioxidant defense is an important research direction for the treatment of osteoporosis. Studies have confirmed that astragaloside IV has anti-osteoporosis effects, but its mechanism of action is not clear. OBJECTIVE: To investigate the osteogenic effect of astragaloside IV in MC3T3-E1 cells under oxidative stress conditions.  METHODS: MC3T3-E1 cells were randomly divided into four groups: the control group was cultured in a complete medium; the model group was cultured in the complete medium containing hydrogen peroxide which was replaced with another complete medium after 24 hours of intervention; the astragaloside IV group was cultured with the complete medium containing hydrogen peroxide and astragaloside IV which was replaced with another complete medium containing astragaloside IV after 24 hours of intervention; and the inhibitor group was cultured in the complete medium containing hydrogen peroxide, astragaloside IV, and extracellular signal-regulated kinases (ERK) inhibitor which was replaced with complete medium containing hydrogen peroxide, astragaloside IV, and ERK inhibitor after 24 hours of intervention. After 48 hours of intervention with hydrogen peroxide, malondialdehyde content was detected to evaluate the mitigating effect of astragaloside IV on the oxidative stress in MC3T3-E1 cells. Osteogenic induction was performed after 48 hours of intervention with hydrogen peroxide, and the osteogenic and mineralizing ability of MC3T3-E1 cells was verified by alkaline phosphatase staining and alizarin red staining; the expression of osteogenesis-related genes was detected by RT-qPCR; and the expression of osteogenesis-related proteins and ERK/AMP-activated protein kinase (AMPK) signaling pathway proteins was detected by western blot.  RESULTS AND CONCLUSION: The intracellular alkaline phosphatase content and mineralized nodule formation were less in the model group than in the control group (P < 0.05), and were more in the astragaloside IV group than in the model group (P < 0.05). Compared with the control group, intracellular malondialdehyde content increased in the model group (P < 0.05), mRNA and protein expression of osteocalcin, RUNX2, and type I collagen decreased (P < 0.05), and AMPK mRNA and p-AMPK protein expressions were elevated (P < 0.05); compared with the model group, intracellular malondialdehyde content in the astragaloside IV group decreased (P < 0.05), the mRNA and protein expressions of osteocalcin, RUNX2, and type I collagen were elevated (P < 0.05), the mRNA expressions of ERK1/2 and AMPK were elevated (P < 0.05), and the protein expressions of p-AMPK and p-ERK1/2 were elevated (P < 0.05). Additionally, ERK inhibitors partially inhibited the above effects of astragaloside IV. To conclude, astragaloside IV can promote osteogenic differentiation of MC3T3-E1 cells by activating the ERK/AMPK pathway. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration Yu Yangyi , Song Zhuoyue, Lian Qiang, Ding Kang, Li Guangheng 2025, 29 (17):  3537-3547.  doi: 10.12307/2025.708 Abstract ( 246 )   PDF (3215KB) ( 75 )   Save BACKGROUND: Adeno-associated virus (AAV) gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years. However, given the complexity of osteoarthritis pathogenesis, single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results. Previous studies have shown that nuclear factor κB could promote the inflammatory pathway in osteoarthritic chondrocytes, and bone morphogenetic protein 4 (BMP4) could promote cartilage regeneration.  OBJECTIVE: To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment. METHODS: Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared. Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells. The experiments were divided into five groups: PBS group; osteoarthritis group; AAV-BMP4 group; AAV-p65shRNA group; and BMP4-p65shRNA 1:1 group. Samples were collected at 4, 12, and 24 weeks postoperatively. Tissue staining, including safranin O and Alcian blue, was applied after collecting articular tissue. Then, the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.  RESULTS AND CONCLUSION: The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment. Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis (P < 0.05). In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage (P < 0.05). In the present study, we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions. Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis. This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment. These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.  中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Personalized GYROID condylar prosthesis: design and finite element analysis Liu Danyu, Jiang Tingting, Jiang Zhixiu, Ji Yuchen, Cao Yilin, Wang Lei, Su Yucheng, Wang Xinyu 2025, 29 (17):  3548-3556.  doi: 10.12307/2025.428 Abstract ( 286 )   PDF (4144KB) ( 128 )   Save BACKGROUND: Currently, the mandibular joint prosthesis manufactured at home and abroad needs to rely on screws to fix the condylar part of the prosthesis during the replacement process, and the retention hole is reserved to facilitate the operation during the operation. However, due to the lack of personalized jaw design, the reattachment plate may not fit the jaw, resulting in screw loosening and dislocation. Therefore, personalized condylar prosthesis replacement is of great value in the repair of the temporomandibular joint. OBJECTIVE: To design a personalized condylar prosthesis with an internal GYROID for mandibular condylar repair and reconstruction. METHODS: The GYROID structure was selected in the Rhinoceros 7 software with the single cell size of 6 mm and the wall thickness of 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 mm. The mechanical properties of the GYROID structure were analyzed by finite element method. 3D printing of GYROID structural test specimens with different wall thickness (0.2, 0.3, 0.4, 0.5, 0.6, 0.7, and 0.8 mm) was performed to test the mechanical properties of the specimens through room temperature compression experiments. A wall thickness value conforming to the range of mandibular mechanical properties was selected through finite element analysis and room temperature compression test results. An adult male mandibular CT data were used for inverse modeling to design a condylar prosthesis with an internal GYROID. Finite element analysis was used to simulate the movement of the apical staggered position and the opposite-blade jaw position after condylar prosthesis replacement. RESULTS AND CONCLUSION: (1) The results of finite element analysis and room temperature compression experiment showed that the elastic modulus of the GYROID structure increased with the increase of wall thickness. The elastic modulus of the GYROID structure with wall thickness of 0.5-0.7 mm was within the range of the elastic modulus of the mandible (1.5-4.0 GPa). Therefore, the 6 mm monocellular GYROID structural model with a wall thickness of 0.6 mm was selected for the design of the condylar prosthesis. (2) The results of finite element analysis showed that the stress distribution of mandibular model was symmetrical. The stress distribution of the two types of occlusion was roughly the same, and the stress peak was not significantly different. The stress concentrated in the neck of the condylar prosthesis, and the stress on the replacement side was slightly larger than that on the healthy side. The maximum equivalent stress of the whole internal fixation model was 269.34 MPa, and the maximum equivalent stress of the screw was 20.14 MPa. The equivalent stress and equivalent strain values of the prosthesis were greater than that of the opposite edge jaw position when the tooth tip was interlaced. The equivalent stress and equivalent strain values of the screw were smaller than that of the opposite edge jaw position when the tooth tip was interlaced. (3) The results showed that the design and retention of the personalized GYROID condylar prosthesis were good, which was consistent with the mechanical conduction of the mandible. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Reactive soft tissue preservation combined with demineralized dentin matrix for extraction site preservation Dai Jieting, Ren Bihui, Xu Yehao, Guo Shuigen, Wei Hongwu 2025, 29 (17):  3557-3565.  doi: 10.12307/2025.643 Abstract ( 184 )   PDF (1490KB) ( 83 )   Save BACKGROUND: Stem cell mesenchyme within reactive soft tissues has the potential to promote tissue regeneration. Demineralized dentin matrix, which has good biocompatibility, can be used as a scaffold material for the site preservation surgery to promote the attachment, proliferation, and differentiation of osteoblasts. OBJECTIVE: To evaluate the changes in alveolar bone height and width after 6 months of site preservation with demineralized dentin matrix after 1 month of extraction of affected teeth with preservation of reactive soft tissues. METHODS: A total of 38 patients with 62 extraction sites were included. One month after the extraction of the affected teeth with preservation of reactive soft tissues, demineralized dentin matrix was used to perform site-preservation surgery. Cone-beam CT was taken preoperatively, immediately postoperatively, and 6 months postoperatively to measure the proximal-medial bone height, central bone height, distal-medial bone height, buccal bone height, lingual bone height, and alveolar bone height, and alveolar bone width. Extraction defects were categorized as one-, two-, three-, or four-wall defects based on the number of alveolar fossa bone walls remaining after tooth extraction. Changes in bone volume were compared preoperatively, immediately postoperatively, and 6 months postoperatively. RESULTS AND CONCLUSION: No wound infection occurred at any site during bone healing. Compared with preoperative data, there was a significant increase in alveolar bone height and bone immediately postoperatively (P < 0.05); there was also an increase in alveolar bone height but no change in alveolar bone width 6 months postoperatively (P > 0.05). Compared with the immediate postoperative period, alveolar bone width was increased by (1.253±2.896) mm 6 months postoperatively, but there was no change in alveolar bone height (P > 0.05). The bone height of the four bone defect types was significantly increased immediately and 6 months postoperatively (P < 0.05), and no changes in the bone width were observed (P > 0.05). Compared with the preoperative data, there was the least increase in proximal-medial bone volume in one-wall bone defects at 6 months postoperatively (P < 0.05) and the most increase in proximal-medial bone volume in two-wall bone defects (P < 0.05). These findings indicate that demineralized dentin matrix applied to site preservation can effectively prevent and slow down alveolar bone resorption after tooth extraction, and can rebuild the alveolar bone contour where resorption has occurred to a certain extent; preservation of reactive tissues applied to demineralized dentin matrix site preservation after tooth extraction can achieve wound closure with good clinical efficacy; demineralized dentin matrix applied to the alveolar socket site preservation with one-, two-, three-, and four-wall defects shares similar effects. However, demineralized dentin matrix is more effective for site preservation when applied to extraction sockets with intact bone walls. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Sedentary behavior and lower-limb muscle strength in community-dwelling older adults: the mediating and moderating effects of fear of falling and age Hong Jintao, Wang Jingjing, Li Yansong, Wang Chen, Mi Shouling 2025, 29 (17):  3566-3571.  doi: 10.12307/2025.662 Abstract ( 240 )   PDF (1136KB) ( 128 )   Save BACKGROUND: The lower-limb muscle strength shows a significant physiological decline with aging. There may be a certain correlation between sedentary behavior, fear of falling, age and lower-limb muscle strength, but the influence path and effect relationship among them are not yet clear. OBJECTIVE: To examine the relationship between sedentary behavior and lower-limb muscle strength, and to explore the influences of fear of falling and age in such an association among community-dwelling older adults.  METHODS: This cross-sectional study recruited 331 community-dwelling older adults (aged ≥ 60 years) in Shanghai. A questionnaire survey was conducted to collect basic information, demographic data, etc. The Short Form of the International Physical Activity Questionnaire was applied to measure sedentary time. Lower-limb muscle strength was assessed by the 30-second chair-stand test. Fear of falling was measured by the Chinese version of Fall Efficacy Scale-International. Descriptive statistics analysis, correlation analysis, regression-based path analysis and mediation analyses were performed on the data.  RESULTS AND CONCLUSION: Valid data from 318 community-dwelling older adults [78.9% females, mean age (67.8±5.5) years old] were finally included in the analysis. There were 185 with sedentary time ≥ 3 hours and 133 with sedentary time < 3 hours. (1) There was a positive correlation between sedentary behavior and fear of falling (P < 0.01), and there were negative correlations between lower-limb muscle strength and sedentary behavior (P < 0.01) and between lower-limb muscle strength and fear of falling (P < 0.001). (2) Sedentary behavior negatively predicted lower-limb muscle strength (β=−0.125, P < 0.05), and positively predicted fear of falling (β=0.182, P < 0.01). Fear of falling negatively predicted lower-limb muscle strength (β=−0.293, P < 0.001). (3) Fear of falling mediated the relationship between sedentary behavior and lower-limb muscle strength (β =−0.053, 95% confidence interval: −0.100 to −0.018). (4) Sedentary behavior had a statistically significant predictive effect on fear of falling (β=0.164, P < 0.01), indicating that age moderates the effect of sedentary behavior on fear of falling. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Unilateral chronic ankle instability affects bilateral postural stability, proprioception, plantar tactile sensation and muscle strength Liu Yanhao, Dong Shiyu, Liu Ziyin, Song Qipeng, Shen Peixin 2025, 29 (17):  3572-3578.  doi: 10.12307/2025.663 Abstract ( 271 )   PDF (1903KB) ( 171 )   Save BACKGROUND: Unilateral chronic ankle instability has adverse effects on the affected limb, and evidence has shown that the nonaffected side may be similarly involved, but direct evidence is currently lacking. OBJECTIVE: To investigate the effects of unilateral chronic ankle instability on bilateral postural stability, proprioception, plantar tactile sensation, and muscle strength. METHODS: A total of 122 participants were recruited in this study, including 67 individuals with unilateral chronic ankle instability and 55 individuals without chronic ankle instability. Postural stability, proprioception, plantar tactile sensation and muscle strength were tested bilaterally in individuals with unilateral chronic ankle instability, as well as in those without chronic ankle instability. One-way analysis of variance or Kruskal-Wallis test was used for intergroup comparisons. RESULTS AND CONCLUSION: (1) Compared with individuals without chronic ankle instability, individuals with chronic ankle instability had longer time to stability in the anterior-posterior direction bilaterally (P=0.001-0.012), and longer time to stability in the medial-lateral direction on the affected side (P=0.012-0.025); had higher proprioception thresholds of plantarflexion, dorsiflexion, inversion, and eversion of the bilateral ankles (P=0.000-0.035); showed lower tactile sensation sensitivities of the bilateral great toe, first metatarsal head, fifth metatarsal head, arch, and heel (P=0.000-0.008); and had weaker muscle strength for inversion and eversion of the bilateral ankles (P=0.000-0.019). (2) Individuals with unilateral chronic ankle instability have bilateral deficits in postural stability, proprioception, plantar tactile sensation, and muscle strength. Therefore, the rehabilitation needs of both limbs should be fully considered when treating chronic ankle instability. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Central nervous mechanisms underlying effects of cognitive impairment on dual-task stance: #br# functional near-infrared spectroscopy analysis Dong Zhiwen, Yu Cong, Chen Yan, Ding Jianjun 2025, 29 (17):  3579-3587.  doi: 10.12307/2025.632 Abstract ( 210 )   PDF (1569KB) ( 345 )   Save BACKGROUND: Elderly people with mild cognitive impairment experience a decline in postural control ability due to cognitive function decline, making them more prone to falls. The dual-task paradigm, which more closely mirrors daily life, is often used to assess postural control ability. However, previous dual-task studies on cognition and postural control in elderly people with mild cognitive impairment have mainly focused on the external manifestations of postural control, with direct evidence of central nervous mechanisms still lacking.  OBJECTIVE: To investigate the activation characteristics of the cerebral somatic sensorimotor cortex in the elderly people with mild cognitive impairment while performing the dual task of stance postural control and spatial working memory.  METHODS: Participants were screened using the Montreal Cognitive Assessment, enrolling 16 elderly people with mild cognitive impairment and 17 healthy older people. They performed five task tests: spatial working memory, dual-feet balance stance, Romberg stance, dual task of dual-feet balance stance and spatial working memory, and dual task of Romberg stance and spatial working memory. Functional near-infrared spectroscopy and a three-dimentional force platform were used simultaneously to collect data on cerebral cortex (20 channels) hemodynamics and center of pressure swing trajectory.  RESULTS AND CONCLUSION: In Romberg stance, dual task of dual-feet balance stance and spatial working memory, and dual task of Romberg stance and spatial working memory tasks, center of pressure displacements in anterior-posterior and medial-lateral directions were significantly greater in mild cognitive impairment elderly people than that in normal elder people (P < 0.05). In dual task of dual-feet balance stance and spatial working memory task, ΔHbO2 at channel 15 (right pre-motor cortex and supplementary motor area) was significantly greater in mild cognitive impairment elderly people than that in normal elder people (P < 0.05). In dual task of Romberg stance and spatial working memory task, ΔHbO2 at channels 15 and 17 (right pre-motor cortex and supplementary motor area) was significantly greater in the elderly people with mild cognitive impairment compared with the healthy older people (P < 0.05). In dual task of Romberg stance and spatial working memory task, a significantly positive correlation in the elderly people with mild cognitive impairment (r=0.659, P < 0.05) and a strong positive correlation in the healthy older people were observed between center of pressure displacement in medial-lateral direction and ΔHbO2 at channel 15 (r=0.840, P < 0.05). The results indicate that compared with the cognitively normal healthy older people, the elderly people with mild cognitive impairment showed weaker stance postural control capability during the dual task of stance postural control and spatial working memory, with higher activation levels in the right pre-motor cortex and supplementary motor area. The increased brain resource allocation for lateral postural control may represent the brain compensation mechanism in the elderly people with mild cognitive impairment due to cognitive decline leading to weakened stance postural control ability. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Effects of pressor stimulation at different times on rat skeletal muscle morphology and tumor necrosis factor alpha and nuclear factor kappaB Shi Peili, Lin Sen, Zhao Wenteng, Peng Yali, Hu Yazhe 2025, 29 (17):  3588-3595.  doi: 10.12307/2025.650 Abstract ( 206 )   PDF (1377KB) ( 75 )   Save BACKGROUND: Studies have shown that different durations of pressure application on normal muscles can produce varying physiological responses. OBJECTIVE: To explore the expression levels of inflammatory factors tumor necrosis factor α and nuclear κB in skeletal muscle under different pressure durations. METHODS: Twenty healthy male SPF-grade Sprague-Dawley rats were randomly divided into four groups: control group, 10-second pressure group, 20-second pressure group, and 30-second pressure group. The right leg of each rat was used for the experiment. The control group received no intervention, while rats in each pressure group were anesthetized by intraperitoneal injection of 2% pentobarbital sodium (35 mg/kg), and the thin femoral muscle of the rats was pressed continuously at a constant pressure of 200 kPa using a homemade mechanical pressure device for 10, 20, and 30 seconds, respectively. Muscle tissue at the pressing site of the right hind limb was collected immediately after pressure. Hematoxylin-eosin staining was used to observe the morphological changes of skeletal muscle tissues and changes in the cross-sectional area of muscle fibers, and immunohistochemistry was used to detect the expression levels of tumor necrosis factor α and nuclear factor κB in rat skeletal muscle. RESULTS AND CONCLUSION: Hematoxylin-eosin staining results revealed that the pressure groups showed loosely arranged skeletal muscle fibers, reduced cross-sectional area and diameter, and enlarged intermuscular spaces. Compared with the control group, the cross-sectional area of muscle fibers was significantly reduced in the pressure groups (P < 0.05), but there was no significant difference between the three pressure groups (P > 0.05). The 10-second pressure group showed no significant presence of red blood cells in the interstitial spaces, while the 20-second pressure group exhibited a small amount of red blood cells, and the 30-second pressure group showed capillary dilation with red blood cells in the interstitial spaces. The expression level of tumor necrosis factor α in the 30-second pressure group was significantly higher than that in the control group (P < 0.05). The expression level of nuclear factor κB in skeletal muscle showed no significant difference among groups (P > 0.05). To conclude, skeletal muscle undergoes morphological changes and reduced cross-sectional area after pressure at 200 kPa, but there is no significant difference among the 10-, 20-, and 30-second pressure groups. As the duration of pressure increases to 30 seconds, the inflammatory factor tumor necrosis factor α is activated, but nuclear factor κB remains unaffected, suggesting that inflammatory factors may express under short-term pressure, while transcription factors show no significant change. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Aerobic exercise promotes remodeling of the energy metabolism network in the skeletal muscle of mice with sarcopenic obesity Chen Cong, , , Wu Huijuan, , Hu Yue, , Zhou Huanghao, , Huang Chunxiu 2025, 29 (17):  3596-3604.  doi: 10.12307/2025.631 Abstract ( 245 )   PDF (2634KB) ( 163 )   Save BACKGROUND: Sarcopenia obesity is characterized by the coexistence of sarcopenia and obesity with a continuously increasing prevalence. Aerobic exercise can alleviate the progression of sarcopenic obesity, but the overall metabolic changes in skeletal muscle after exercise are still unclear. OBJECTIVE: To investigate the effects of exercise on various aspects of the energy metabolic pathways in the skeletal muscle of mice with sarcopenic obesity. METHODS: Male C57BL/6J mice were randomly divided into normal control (normal diet) and model (high-fat diet) groups. After 12 weeks of feeding, sarcopenic obesity model mice were screened by body mass and behavior assessments. The sarcopenia obesity mice were then divided into the sedentary and exercise groups. Mice in the exercise group were subjected to treadmill training on the basis of a high-fat diet. After 8 weeks of intervention, body mass, lipid metabolism, muscle volume of calf muscle group of the hind limb, skeletal muscle morphology, and expressions of energy metabolic pathway-related genes were detected. RESULTS AND CONCLUSION: Compared with the normal control group, the levels of triglycerides, total cholesterol, and free fatty acid in the sedentary group were significantly increased, along with significantly increased lipid droplets in skeletal muscle (P < 0.05). Compared with the sedentary group, all of the above indicators in the exercise group showed a significant decreasing trend (P < 0.05). Compared with the normal control group, grip strength and fatigue latency time, muscle volume, and fiber cross-sectional area were significantly decreased in the sedentary group, but the mRNA expression of Atrogin-1 and Murf-1  was elevated (P < 0.05). Compared with the sedentary group, grip strength and fatigue latency time, muscle volume, and fiber cross-sectional area were significantly improved in the exercise group (P < 0.05), while the mRNA expression of Atrogin-1 and Murf-1 was reduced (P < 0.05). Compared with the normal control group, the mRNA expression of intramuscular transcription factors Pparα and Pgc-1α was decreased in the sedentary group (P < 0.05), the mRNA expression of fatty acid synthesis-related enzymes Srebp1c and Fasn was elevated (P < 0.05), and the mRNA expression of the β-oxidation system Cpt1β, Acox1, Acox3 and fatty acid metabolism Arf1 and Plin3 was decreased (P < 0.05). Compared with the sedentary group, the abnormal expression of the above genes was significantly reversed in the exercise group (P < 0.05). To conclude, aerobic exercise can alleviate lipid deposition and improve muscle quality and strength of sarcopenic obesity mice by regulating the expression of genes in the intramuscular energy metabolism network. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Effects of 1,8-cineole on inflammatory response in a rat model of experimental periodontitis He Li, , Ren Lu, , Jiang Xiaoxi, , Liu Xuqian, , Li Chunhui, 2025, 29 (17):  3605-3613.  doi: 10.12307/2025.638 Abstract ( 196 )   PDF (2102KB) ( 147 )   Save BACKGROUND: Previous studies have shown that 1,8-cineole has anti-inflammatory, antioxidation, antibacterial and anti-tumor effects. It has good anti-inflammatory effects in many diseases.  OBJECTIVE: To investigate the effect of 1,8-cineole on inflammatory response in a rat model of experimental periodontitis. METHODS: Thirty Sprague-Dawley rats were assigned into normal control group, periodontitis control group and 1,8-cineole group with ten rats in each group according to the completely randomized digital table method. Except for the normal control group, rats in the other groups were induced into experimental periodontitis. The periodontitis model was constructed by the orthodontic ligature wire method. Eight weeks after modeling, in the 1,8-cineole group, 1,8-cineole was placed into periodontal pockets, twice per day for 4 weeks. In the normal control group and the periodontitis control group, the same amount of normal saline was placed into periodontal pockets, twice per day for 4 weeks. After administration, general observation and periodontal clinical indicators were performed. Hematoxylin-eosin staining was used for periodontal histological evaluation. The expressions of inflammatory factors in the serum and gingiva at mRNA and protein levels were detected. RESULTS AND CONCLUSION: (1) Compared with the normal control group, rats in the periodontitis control group showed increased gingival bleeding index and periodontal probing depth (P < 0.05), increased serum levels of interleukin 1β, tumor necrosis factor α, and interleukin 6 (P < 0.05), decreased serum level of interleukin 10 (P < 0.05), increased mRNA and protein levels of interleukin 1β, tumor necrosis factor α, and interleukin 6 in gingival tissue (P < 0.05), and decreased mRNA and protein level of interleukin 10 in gingival tissue (P < 0.05). Hematoxylin-eosin staining of periodontal tissues showed that compared with the normal control group, periodontal inflammation was obvious in the periodontitis control group. (2) Compared with the periodontitis control group, rats in the 1,8-cineole group showed decreased gingival bleeding index and periodontal probing depth (P < 0.05), decreased serum levels of interleukin 1β, tumor necrosis factor α, and interleukin 6 (P < 0.05), increased serum level of interleukin 10 (P < 0.05), decreased mRNA and protein levels of interleukin 1β, tumor necrosis factor α, and interleukin 6 in gingival tissue (P < 0.05), and increased mRNA and protein level of interleukin 10 in gingival tissue (P < 0.05). Hematoxylin-eosin staining of periodontal tissues showed that compared with the periodontitis control group, periodontal inflammation was remarkably alleviated in the 1,8-cineole group. To conclude, 1,8-cineole can attenuate the inflammatory response in the rat model of experimental periodontitis. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Mechanism of central analgesia in rats with myofascial pain syndrome by intervention of “trigger points” with stagnant moving needles Zhao Liping, Chen Yibo, Wang Yaqian, Li Zhitong, Zhang Qi, Gou Bo 2025, 29 (17):  3614-3623.  doi: 10.12307/2025.637 Abstract ( 214 )   PDF (2392KB) ( 257 )   Save BACKGROUND: The analgesic effect of stagnant moving needle on myofascial pain syndrome is remarkable, but the analgesic mechanism is still unclear.  OBJECTIVE: To investigate the analgesic mechanism of stagnant moving needle acupuncture in the treatment of myofascial pain syndrome.  METHODS:  Fifty-four SD rats were randomly divided into a blank group (n=16) and a modeling group (n=38). The models of left myofascial pain syndrome in the modeling group were prepared by using the method of “striking combined with centrifugal movement”. Twelve weeks after modeling, six mice were randomly selected to verify the success of the modeling. The rest of the 32 rats were randomly divided into the model group and the stagnant moving needle group, with 16 rats in each group. The stagnant needle moving group was treated by stagnant moving needle into the local excitation point nodule of the left medial vastus muscle fascia in rats, twice a week, for 4 weeks. The mechanical foot contraction reflex threshold of the left foot were measured weekly in the pre/post modeling and post-intervention groups of rats. At 4 weeks after treatment, hematoxylin-eosin staining was used to observe the morphological changes in the muscle tissue of the left medial femoral muscle of rats, ELISA was used to detect the levels of substance P and β-endorphin in the serum and the gray matter around the midbrain aqueduct. Immunohistochemistry was used to detect positive expression of microglia markers (Iba-1) and c-fos in the gray matter around the midbrain aqueduct. Western blot assay was used to detect the expression level of brain-derived neurotrophic factor protein in the periaqueductal gray. RESULTS AND CONCLUSION: Compared with the blank group, the mechanical pain threshold of the rats in the model group and the stagnant moving needle group decreased after modeling (P < 0.05). After 4 weeks of treatment, the mechanical pain threshold of the rats in the stagnant moving needle group was higher than that in the model group (P < 0.05). Hematoxylin-eosin staining results showed that in the model group, the muscle fibers of the left lower limb medial femoral muscle of rats were disorganized, unequal in thickness, myocytes were enlarged, with inward movement of the nucleus, rounded contracture nodules and tension bands; whereas in the stagnant moving needle group, the muscle fibers were arranged in a neat way, the myocytes were angular, and the contracture nodules were occasionally seen. Compared with the blank group, the expression of substance P in the serum of the model group was significantly higher (P < 0.05), while the levels of β-endorphin in serum and substance P and β-endorphin in brain were decreased (P < 0.01). Compared with the model group, the level of serum substance P in the stagnant moving needle group was decreased (P < 0.05), and the levels of serum β-endorphin and brain substance P and β-endorphin were increased (P < 0.05). Compared with the blank group, the positive expression of c-fos and Iba-1 and the protein of brain-derived neurotrophic factor in the model group were increased (P < 0.05). Compared with the model group, the positive expression of c-fos in the stagnant moving needle group was increased (P < 0.05), and the positive expression of Iba-1 and the protein of brain-derived neurotrophic factor were decreased (P < 0.05). These findings suggest that stagnant moving needle may indirectly promote the release of β-endorphin by microglia polarized to the M2 phenotype and increase the excitability of c-fos neurons by inhibiting the activity of microglia in the gray matter around the periaqueductal gray and downregulating the expression of brain-derived neurotrophic factor protein, thereby reducing the degree of central sensitization and effectively relieving myofascial pain syndrome.  中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Animal model of cervical spondylosis and its internal molecular mechanism Qian Jiaming, Wang Xiaole, Fang Ting, Zhou Maosheng, Liu Fushui, 2025, 29 (17):  3624-3631.  doi: 10.12307/2025.189 Abstract ( 241 )   PDF (1361KB) ( 85 )   Save BACKGROUND: There are many problems to completely transform clinical diseases into animal models, but the ideal animal model is the premise of the mechanism research of cervical spondylosis, and it is very important to select the appropriate animal model of cervical spondylosis. OBJECTIVE: To analyze the species, sex, age, type of cervical spondylosis model and its internal molecular mechanism of animal models of cervical spondylosis in detail so as to explore how to select suitable animal models for experimental research of cervical spondylosis. METHODS: PubMed, Medline, Embase, Web of Science, WanFang, VIP, and CNKI databases were searched with Chinese and English search terms “cervical spondylosis, cervical spondylotic myelopathy, cervical spondylotic radiculopathy, cervical spondylosis of vertebral artery type, neck type cervical spondylosis, unbalanced dynamic and static forces, joint injury, neck pain, animal model.” According to the inclusion and exclusion criteria, the literature was screened, and finally 61 articles were included for review and analysis.  RESULTS AND CONCLUSION: Rats are the most commonly used animals, and males seem to be more popular. It is recommended to use young adult animals. According to the characteristics of molding, cervical spondylosis models were divided into cervical spondylotic myelopath, cervical spondylotic radiculopathy, neck type cervical spondylosis, and other type cervical spondylosis. The advantages and disadvantages of various modeling methods were evaluated. Based on the studies of existing animal models, the molecular mechanism of cervical spondylosis was summarized. Therapeutic signals mediate nuclear factor-κB, phosphatidylinositol‐3 kinase/protein kinase B, mitogen-activated protein kinase, and other pathways to regulate the biological processes of inflammation, apoptosis and autophagy of spinal cord, nerve root, intervertebral disc, muscle and other tissues, and ultimately delay the progression of cervical spondylosis. The quality of some studies is poor, and the clinical compatibility is not high. In the future, it is necessary to further standardize the animal model of cervical spondylosis, formulate relevant guidelines, improve the credibility of the research results, and lay a solid foundation for further human clinical trials. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Diabetic nephropathy model: animal model, two-dimensional cell simulation and three-dimensional organoid model  Qian Zuping, Chen Yong, Ran Yan, Da Jingjing, Zha Yan 2025, 29 (17):  3632-3640.  doi: 10.12307/2025.634 Abstract ( 445 )   PDF (1575KB) ( 189 )   Save BACKGROUND: In recent years, human pluripotent stem cell derived kidney organoids and rodent models of diabetic kidney disease have also made some progress. However, because the pathogenesis of diabetic kidney disease is affected by environmental factors and genetic factors, the pathogenesis is complex, and the clinical treatment for diabetic kidney disease patients needs to vary from person to person. Therefore, more flexible and integrated approaches need to be developed, leading to the discovery of strong preclinical evidence to support more targeted interventions in patients with diabetic kidney disease. OBJECTIVE: To reviewthe research progress of diabetic kidney disease model from the aspects of diabetic kidney disease animal model, two-dimensional cell culture simulation diabetic kidney disease model, and three-dimensional organoid diabetic kidney disease model, to provide clues and ideas for further research. METHODS: China National Knowledge Network and PubMed databases were searched with“diabetes, diabetic nephropathy, diabetic kidney diseases, diabetic nephropathy models, diabetic nephropathy animal models, organoids, diabetic and organoids, diabetic and kidney organoids, kidney organoids, diabetic nephropathy cell models, diabetic nephropathy syndrome combined animal models” as Chinese and English search terms. Totally 101 articles were finally included for review and analysis. RESULTS AND CONCLUSION: Both in vivo and in vitro models of diabetic kidney disease are powerful tools to further study the pathogenesis of diabetic kidney disease. The interactions between multiple systems can be observed in animal models. Two-dimensional cell culture is easy to operate and low cost. The emerging kidney organoids fill the gap between two-dimensional and global levels, without species differences, and simulate the complexity of human kidney to a certain extent. With the continuous development of organoid technology, kidney organoids are expected to provide a new perspective for exploring the pathogenesis, pathophysiology, and drug screening of diabetic kidney disease. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Copper influences the occurrence and development of diabetic complications  Luo Yuncai, Meng Maohua, , Li Ying, , Wang Huan, Lu Jing, Shu Jiayu, Li Wenjie, Sun Jinyi, Dong Qiang, 2025, 29 (17):  3641-3649.  doi: 10.12307/2025.629 Abstract ( 194 )   PDF (1690KB) ( 138 )   Save BACKGROUND: As an essential trace element for body growth and development, copper participates in many processes such as redox process, energy generation, signal transduction and bone metabolism. The imbalance of copper homeostasis in diabetic patients will lead to the increase of oxidative stress and the impairment of antioxidant mechanism, which stimulate the production of inflammatory mediators and inflammatory factors, and thus lead to cytotoxicity and body damage. In recent years, the role of copper in diabetes has gradually attracted attention, and some studies have confirmed that copper plays a key regulatory role in the pathological process of diabetes.  OBJECTIVE: To summarize the current progress in the role of copper in systemic complications of diabetes and provide some theoretical reference for its future research and treatment. METHODS: The first author searched PubMed, Web of Science, CNKI and WanFang databases for literature related to the role of copper in systemic complications of diabetes. The search terms were “copper, Cu, diabetes, diabetic complications, diabetic cardiomyopathy, diabetic nephropathy, diabetic retinopathy, diabetic osteoporosis, diabetic periodontitis” in English and Chinese, respectively. After screening, 95 articles were included in the review. RESULTS AND CONCLUSION: (1) Copper is involved in the occurrence and development of diabetic complications and most of the damage caused by copper to the body is due to interference with the body’s redox level. (2) In diabetic cardiomyopathy, increased Cu2+ in the corpuscular circulation and impaired uptake of copper ions by cardiomyocytes, the accumulation of redox-active Cu2+ and ceruloplasmin outside the cardiomyocyte induces copper oxidative stress in cardiomyocytes, leading to acute cardiac impairment. (3) In diabetic nephropathy, the toxic effect of excessive copper leads cause granular degeneration and vacuolar degeneration of renal tubular epithelial cells and proximal tubular necrosis, eventually leading to chronic or acute renal failure. (4) Excessive copper in diabetic patients can produce reactive oxygen species and directly or indirectly affect the function of copper protein with antioxidant function, thus damaging retinal cells. (5) In patients with diabetic osteoporosis, accumulated copper induces lipid peroxidation and interferes with bone metabolism. Copper acts on osteoblasts mainly through inhibition of superoxide dismutase, glutathione peroxidase, and alkaline phosphatase activities. (6) Excessive copper exacerbates inflammatory changes in periodontal tissue by promoting inflammatory responses. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Evaluating the compensatory function of intelligent assistive devices for the blind in China based on the International Classification of Functioning, Disability and Health Bu Nan, Yang Yicheng, , Song Beibei, Bai Kaixiang, Du Yunyun, 2025, 29 (17):  3650-3656.  doi: 10.12307/2025.639 Abstract ( 252 )   PDF (1586KB) ( 266 )   Save BACKGROUND: The use of assistive devices and technologies for blindness is a common intervention for people with visual impairment today, improving participation in activities of daily living and work-learning abilities, and facilitating return to family and society. The forms, technologies and functions of assistive devices for blindness in the age of digital information and intelligence vary, and their classification has not yet been effectively discussed and evaluated in a uniform manner. OBJECTIVE: To classify and evaluate the compensation function of intelligent guide devices for the people with visual impairment in China based on the International Classification of Functioning, Disability and Health (ICF). METHODS: CNKI, CQVIP and WanFang databases were searched for relevant literature. The time frame for the search was from January 1, 2013 to December 31, 2023. Based on the ICF theoretical model and framework structure, the terminology structure and coding procedure were applied to summarize the relevant visual impairment assessment categories, collate and analyze the research and classification of the compensation function of intelligent assistive devices for the people with visual impairment in China. RESULTS AND CONCLUSION: (1) A total of 197 articles were finally included. There was 1 article on body function, containing b2 (b210); 1 article on body structure, containing s2 (s220); 119 articles addressing activity and participation, containing d1 (10 articles involving d110, d115, d120, d140, and d166,) d3 (4 articles involving d315, d325, d345, and d360), d4 (102 articles involving d465, d470), and d8 (3 articles involving d820, d825); 76 articles addressing environmental factors, including e1 (72 articles involving e115, e120, e125, e130, e140, e150, e155, e160) and e2 (4 articles involving e210 and e240). (2) The ICF-based research classification of the compensation function of intelligent guide devices for the people with visual impairment contains 4 parts, 8 classifications and 25 categories, with areas related to physical compensation, daily necessities, education and learning, traveling and blindness guidance, and layout planning.  中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Exercise intervention for sarcopenic obesity in older adults Zhao Yanan, Lu Donglei, Tan Sijie, 2025, 29 (17):  3657-3667.  doi: 10.12307/2025.623 Abstract ( 274 )   PDF (2477KB) ( 306 )   Save BACKGROUND: Exercise is an important strategy for the prevention and management of sarcopenic obesity in older adults, but there is a lack of exploration and research on accurate and personalized exercise prescription for sarcopenic obesity in older adults. OBJECTIVE: To review the tandem mechanism of sarcopenic obesity in older adults and the effects of different exercise interventions in older patients with sarcopenic obesity, in order to provide theoretical and practical guidance for the formulation of exercise prescriptions for sarcopenic obesity in older adults. METHODS: PubMed, Web of Science, CNKI, VIP, and WanFang databases were retrieved for relevant literature using the keywords of “sarcopenic obesity, sarcopenic adiposity, aging, sport, exercise, exercise intervention, exercise prescription, resistant training, aerobic training, combination training, muscle strength, muscle mass, physical activity” in Chinese and English, respectively. A total of 85 articles were included for review according to the inclusive and exclusive criteria. RESULTS AND CONCLUSION: (1) Resistance exercise is still an effective exercise method to prevent and alleviate sarcopenic obesity in older adults. Resistance exercise is more significant in improving and improving skeletal muscle mass, muscle strength and endurance, and physical function ability. However, in practice, it should be applied in a gradual manner, with a gradual increase in intensity to a medium-to-high level. (2) Aerobic exercise is also an important intervention to control and slow the progress of sarcopenic obesity, and it is more effective in improving cardiorespiratory endurance, decreasing percentage of body fat, and decreasing the area of visceral fat in older patients with sarcopenic obesity. (3) Combining the advantages of aerobic exercise and resistance exercise can better improve body composition and reduce cardiovascular disease risk factors. To some extent, combined exercise is better than single exercise. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Mechanism of alpha-synuclein in mitochondrial damage induced by Parkinson’s disease Wang Jingying, , Ren Binbin, Ma Suna, Yang Yueyue, , Wu Song, , Guan Mengya, 2025, 29 (17):  3668-3674.  doi: 10.12307/2025.626 Abstract ( 302 )   PDF (1650KB) ( 235 )   Save BACKGROUND: Currently, the pathogenesis of Parkinson’s disease is not clear. Relevant studies have shown that α-synuclein and mitochondria are closely related to the pathogenesis of Parkinson’s disease. It mainly involves oxidative stress, mitochondrial complex damage, calcium homeostasis, mitochondrial dynamics and mitochondrial quality control. OBJECTIVE: To review the association between α-synuclein and mitochondrial damage in Parkinson’s disease. METHODS: The first author searched more than 50 documents from CNKI and WanFang databases from 2010 to 2024 using the keywords of “Parkinson’s disease, mitochondrial damage and mechanism, α-synuclein” in Chinese as well as more than 750 documents from PubMed between 2010 and 2024 using the keywords of “Parkinson’s disease, alpha-synuclein, mitochondria, oxidative stress, calcium homeostasis, mitophagy, mitochondrial dynamics, mitochondrial protein introduction” in English. Finally, 70 documents were included for review.  RESULTS AND CONCLUSION: Recent studies have confirmed the important role of mitochondrial dysfunction in the pathophysiology of Parkinson’s disease, and the interaction between α-synuclein and mitochondria is a particularly significant factor in the pathogenesis of Parkinson’s disease. The cascade of events that begin with naturally unfolded α-synuclein and eventually form mature fibril is collectively known as α-synuclein aggregation. The toxicity of aggregation accumulates in dopaminergic neurons and then disrupts mitochondrial function, thereby triggering Parkinson’s disease. Therefore, the underlying mechanism of this bidirectional relationship between α-synuclein and mitochondrial dysfunction may provide new insights into the pathophysiology of Parkinson’s disease. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Role of ferroptosis in ischemic brain injury and the regulatory mechanism of traditional Chinese medicine Zhou Panpan, Yang Tong, Wang Shurui, Cui Yinglin 2025, 29 (17):  3675-3683.  doi: 10.12307/2025.630 Abstract ( 220 )   PDF (1512KB) ( 335 )   Save BACKGROUND: Ferroptosis is a programmed cell death mode regulated by iron dependent lipid peroxidation, closely related to the occurrence, development, and outcome of ischemic brain injury. With the continuous deepening of research on ferroptosis in recent years, it has been found that Chinese herbal compounds and monomers can regulate ferroptosis by reducing iron overload, reducing the production of reactive oxygen species, and regulating lipid synthesis, to alleviate cerebral ischemic injury and promote neurological function recovery.  OBJECTIVE: To explore the relationship between ferroptosis and ischemic brain injury, and the mechanism by which traditional Chinese medicine regulates ferroptosis in the treatment of ischemic brain injury.  METHODS: Literature on ferroptosis and ischemic brain injury and the regulatory mechanism of traditional Chinese medicine published from January 2018 to May 2024 was searched in CNKI and PubMed databases. The search terms were “iron death, ischemic stroke, brain injury, reactive oxygen species, lipid metabolism, traditional Chinese medicine formulas, terpenes, flavonoids, phenols, alkaloids, phthalides” in Chinese and English, respectively. Irrelevant, duplicated or outdated literature was excluded. A total of 1 526 relevant literature were retrieved, and 87 articles were ultimately included.  RESULTS AND CONCLUSION: Numerous experimental studies have confirmed that ferroptosis plays an important role in ischemic brain injury. Chinese medicine prescriptions can regulate ferroptosis through various approaches, for examples: total saponins of Panax notoginseng can regulate iron metabolism and inhibit lipid peroxidation; carvacrol inhibits neuronal ferroptosis by increasing glutathione peroxidase 4 expression; Chinese herbal compounds and monomeric active ingredients can regulate ferroptosis-related pathways , such as glutathione/glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor 2 (Nrf2)/hemoglobin oxygenase 1 (HO-1), ferric death inhibitory protein 1 (FSP1)/CoQ10 and guanosine triphosphate cyclohydrolase 1 (GCH1)/tetrahydrobiopterin (BH4), to reduce neuronal damage and death, and exert neuroprotective effects. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Acute effects and moderators of sedentary interruption on vascular function in adults: a Meta-analysis Yin Mingyue, Liu Qian, Xu Xiongzhuang, Ma Zhiying, Deng Shengji, Deng Jianfeng, Li Yongming 2025, 29 (17):  3684-3696.  doi: 10.12307/2025.627 Abstract ( 220 )   PDF (4162KB) ( 279 )   Save OBJECTIVE: Prolonged sedentary behavior can acutely reduce peripheral and central vascular function, thereby increasing the risk of cardiovascular disease. Interrupting sedentary behavior may be a potential practical strategy to prevent vascular dysfunction caused by prolonged sitting. However, current research findings on its acute effects are inconsistent, and specific application recommendations have not yet been established. This study aims to perform a Meta-analysis on the acute effects of interrupting sedentary behavior on peripheral and central vascular function in adults and to explore its regulatory factors. METHODS: Following PRISMA reporting guidelines, literature search was conducted in March 2024 using the keywords of “interrupting,” “sedentary,” and “vascular function” in the Web of Science Core Collection, PubMed, and China National Knowledge Infrastructure (CNKI) databases. Acute randomized crossover trials addressing the acute effects of interrupting sedentary behavior on peripheral and central vascular function in adults were included. Risk of Bias 2 developed by Cochrane was used to assess bias risk, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to evaluate the evidence level. The “meta” and “metaphor” packages in R (version 4.2.0) were used for main effect aggregation (Hedge’s g acted as the effect size indicator), publication bias testing, subgroup analysis, and regression analysis. RESULTS: Twenty-two randomized crossover trials involving 364 subjects (aged 21 to 70 years) were included. Meta-analysis results showed that compared with prolonged sitting, interrupting sedentary behavior acutely improved peripheral vascular blood flow volume (Hedge’s g=0.48, 95% confidence interval: 0.14-0.82, P < 0.01, I²=63%, low evidence level), shear stress (Hedge’s g=0.65, 95% confidence interval: 0.37-0.93], P < 0.01, I²=54%, moderate evidence level), and flow-mediated dilation (Hedge’s g=0.43, 95% confidence interval: 0.15-0.72, P < 0.01, I²=61%, moderate evidence level). Disease had a significant moderating effect on the main effect aggregation for blood flow volume (P=0.01 between subgroups), while the mode (P=0.01 between subgroups) and frequency (P=0.02 between subgroups) of interruptions had significant moderating effects on shear stress. Improvements in peripheral vascular shear stress from interrupting sedentary behavior were affected by age (β=-0.02, 95% confidence interval: -0.03-0.01, P=0.09) and body mass index (β=-0.10, 95% confidence interval: -0.18 to -0.02, P < 0.01). Improvements in flow-mediated dilation were influenced by the total number of interruptions (β=-0.09, 95% confidence interval: -0.17 to -0.01, P=0.03) and the duration of sitting during the control period (β=-0.21, 95% confidence interval: -0.34 to -0.09, P < 0.01). Each additional hour of sitting was associated with a 0.67% reduction in the acute improvement effect of flow-mediated dilation from interrupting sedentary behavior (P < 0.01), and acute benefits disappeared when sitting control time exceeded 6 hours. A qualitative systematic review found that interrupting sedentary behavior did not significantly affect pulse wave velocity in various populations but could effectively prevent central vascular function decline in older adults due to prolonged sitting. CONCLUSION: Interrupting sedentary behavior acutely improves peripheral vascular blood flow volume (low evidence level), shear stress (moderate evidence level), and flow-mediated dilation (moderate evidence level) in adults and may prevent or protect against central vascular function decline in older adults due to prolonged sitting (very low evidence level). Characteristics of subjects (disease factors, sex, age, and body mass index), interruption intervention schemes (mode, frequency, total number of interruptions), and duration of sitting control all influence the acute improvement effects of interrupting sedentary behavior on vascular function. It is recommended that adults interrupt sedentary behavior with exercises involving large muscle groups, such as stair climbing, at high frequencies (e.g., once every 40 minutes) with at least 5 minutes of moderate- to low-intensity activity each time, and limit the cumulative duration of prolonged sitting to no more than 6 hours per day. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Inflammation, metabolites and osteoporosis Lyu Hao, Zhang Ge, Hu Zhimu, Wang Yan, Chu Qingsong, Zhou Yao, Jiang Ting, Wang Jiuxiang 2025, 29 (17):  3697-3704.  doi: 10.12307/2025.651 Abstract ( 227 )   PDF (2533KB) ( 127 )   Save BACKGROUND: Multiple studies and observations have indicated a close relationship between inflammation, metabolites, and osteoporosis. However, it is still unclear whether there is a genetic causal effect between inflammation-related proteins and osteoporosis and whether metabolites play a mediating role in this process. OBJECTIVE: To investigate the causal relationships between inflammation-related proteins and osteoporosis using Mendelian randomization method as well as the mediating effect of plasma metabolites in this process. METHODS: Summary data from genome-wide association studies (GWAS) were used, with osteoporosis data sourced from the Fengenn database, and GWAS data on inflammation-related proteins and plasma metabolites obtained from published studies. The inverse-variance weighted method was primarily used to assess the exposure-outcome relationships. Bidirectional Mendelian randomization analyses were used to explore the causal relationships between inflammation-related proteins and osteoporosis, and two-step Mendelian randomization was used to discover potential mediating metabolites. Sensitivity analyses were then performed to further validate the robustness of the results. Cochran’s Q test was used to assess heterogeneity, and horizontal pleiotropy was evaluated using the MR-Egger intercept and MR-PRESSO methods.   RESULTS AND CONCLUSION: The initial bidirectional Mendelian randomization analysis identified five inflammation-related proteins that showed a positive causal relationship with osteoporosis and no reverse causal relationship. Artemin (odds ratio [OR]=0.895, 95% confidence interval [CI]: 0.819-0.979, P=0.015) was negatively associated with osteoporosis, whereas chemokine (C-X-C Motif) ligand 1 (OR=1.100, 95% CI: 1.002-1.209, P=0.046), chemokine (C-X-C Motif) ligand 11 (OR=1.150, 95% CI: 1.043-1.268, P=0.005), interleukin 17C (OR=1.087, 95% CI: 1.004-1.176, P=0.040), and tumor necrosis factor-like weak inducer of apoptosis (OR=1.108, 95% CI: 1.002-1.226, P=0.046) were positively associated with osteoporosis. Sensitivity analyses indicated no heterogeneity or pleiotropy in these causal effects. Subsequently, we conducted a two-step Mendelian randomization to discover potential mediating metabolites. This study showed that 1-palmitoyl-gpc (16:0) increased the negative effect of Artemin on osteoporosis. 5α-androstan-3α,17β-diol monosulfate increased the risk of osteoporosis mediated by chemokine (C-X-C Motif) ligand 1 and chemokine (C-X-C Motif) ligand 11. The ratio of α-ketoglutarate to succinate led to an increased risk of osteoporosis mediated by chemokine (C-X-C Motif) ligand 11 and interleukin-17C. Spermidine and the ratio of proline to trans-4-hydroxyproline contributed to an increased risk of osteoporosis mediated by chemokine (C-X-C Motif) ligand 11. 12,13-DiHOME contributed to an increased risk of osteoporosis mediated by interleukin-17C. The sulfate level of piperine metabolite C16H19NO3(3) and adenosine 3’,5’-cyclic monophosphate contributed to an increased risk of osteoporosis mediated by tumor necrosis factor-like weak inducer of apoptosis. In conclusion, the above data indicate that some inflammation-related proteins can influence the risk of osteoporosis, both positively and negatively, and some of these effects are mediated by plasma metabolites. This provides new insights for future investigations into the occurrence and development mechanisms of osteoporosis. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Association between obesity and diffuse idiopathic skeletal hyperostosis Kong Luming, Zhao Diqian, Bai Wenzhe, Li Nianhu 2025, 29 (17):  3705-3712.  doi: 10.12307/2025.648 Abstract ( 174 )   PDF (2280KB) ( 84 )   Save BACKGROUND: Diffuse idiopathic skeletal hyperostosis is a systemic, non-inflammatory disease characterized by calcification and ossification of ligaments, tendons, and their attachments, predominantly affecting men over the age of 50. Studies have shown a higher prevalence of diffuse idiopathic skeletal hyperostosis among obese individuals; however, the causal relationship between the two remains unclear. OBJECTIVE: To investigate the causal relationship between obesity and diffuse idiopathic skeletal hyperostosis using Mendelian randomization analysis. METHODS: The study utilized single nucleotide polymorphisms from the Genome Wide Association Study database as instrumental variables, incorporating data related to obesity and diffuse idiopathic skeletal hyperostosis. A bidirectional two-sample Mendelian randomization analysis was performed to assess the causal relationship between obesity and diffuse idiopathic skeletal hyperostosis, with evaluations for pleiotropy, heterogeneity, and sensitivity. RESULTS AND CONCLUSION: The Mendelian randomization analysis revealed a significant positive causal relationship between obesity and diffuse idiopathic skeletal hyperostosis. The inverse-variance weighted method indicated that “obesity” (odds ratio [OR]=1.111, 95% confidence interval [CI]: 1.068-1.156, P=1.598×10-7), “obesity due to excess calories” (OR=1.093, 95% CI: 1.042-1.146, P=0.000), and “obesity, other/unspecified” (OR=1.109, 95% CI: 1.069-1.152, P=4.908×10-8) were significantly associated with diffuse idiopathic skeletal hyperostosis. Conversely, the reverse Mendelian randomization analysis did not find a causal relationship between diffuse idiopathic skeletal hyperostosis and obesity. The robustness of the Mendelian randomization analysis results was confirmed by pleiotropy, heterogeneity and sensitivity tests, indicating that while obesity significantly increases the risk of diffuse idiopathic skeletal hyperostosis, but diffuse idiopathic skeletal hyperostosis does not pose a risk factor for obesity. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Medication pattern and mechanism of marine traditional Chinese medicine in the treatment of osteoporosis Lai Yue, Lin Xuan, Xu Miao, Liu Huan, Shen Jianlin, Huang Wenhua 2025, 29 (17):  3713-3723.  doi: 10.12307/2025.646 Abstract ( 202 )   PDF (5599KB) ( 17 )   Save BACKGROUND: Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis. OBJECTIVE: To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.  METHODS: Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis, and special attention was paid to the core Chinese medicine constituents of these prescriptions. The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry. RESULTS AND CONCLUSION: (1) We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1, 2024. Among these, 48 patent groups utilized marine traditional Chinese medicine. These prescriptions contained 183 Chinese herbal medicines, of which 13 marine traditional Chinese medicines were used 574 times in total, and the number of flavors used in a single patented formula ranged from 2 to 41. (2) Oyster was the most frequently used marine ingredient, while Dipsacus asper, epimedium, Rehmannia glutinosa, Eucommia ulmoides Oliv. were the most frequent non-marine components.  Association rule analysis identified oyster, Dipsacus asper, and epimedium as the core drug group. Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB, AKT1, TP53, PPARG, and SRC. Sitosterol, liquiritigenin, japonine, luteolin, and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions. (3) The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis. (4) The molecular docking verified the beneficial interactions between core components and core targets. (5) The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin, sitosterol, kaempferol, and other components, aligning with the drug components identified by network pharmacology. Quantitative analysis indicated that flavonoids, terpenes, and alkaloids constituted a significant proportion of the compound medicine’s components. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Types and contents of fatty acids and the risk of knee osteoarthritis Tang Xiran, Chen Weijian, Jiang Tao, Tan Xianyun, Liu Wengang 2025, 29 (17):  3724-3731.  doi: 10.12307/2025.645 Abstract ( 205 )   PDF (2629KB) ( 105 )   Save BACKGROUND: In recent years, epidemiological studies have shown that obesity is a risk factor for knee osteoarthritis, and fatty acid intake, metabolism and biosynthesis are closely related to the development of obesity. However, the causal relationship between fatty acids and osteoarthritis is still unknown. OBJECTIVE: Using the Mendelian randomization analysis to investigate the causal relationship between five fatty acid phenotypes and knee osteoarthritis. METHODS: The genome-wide association study data on fatty acid ratios from the UK Biobank (met-D) and genome-wide association study data on knee osteoarthritis from the EBI-A database were pooled together. Single nucleotide polymorphisms were used as instrumental variables and sensitive single nucleotide polymorphisms were selected for analysis. Two-sample Mendelian randomization analysis was conducted to evaluate the causal relationship between fatty acids and knee osteoarthritis outcome risk. We used inverse variance weighting method, MR-Egger regression method, weighted median method, weighted model method, and simple model method to study the causal relationship between fatty acids and knee osteoarthritis. Further inverse Mendelian randomization analysis was performed in the same way to ensure the validity of the results. RESULTS AND CONCLUSION: The forward analysis and inverse variance weighting method showed a causal relationship between three types of fatty acid phenotypes and knee osteoarthritis. Among them, the proportion of saturated fatty acids to total fatty acids was positively correlated with the risk of knee osteoarthritis (odds ratio [OR]=1.825, 95% confidence interval (CI): 1.230, 2.706, P=0.003), the proportion of omega 3 polyunsaturated fatty acids to total fatty acids was negatively correlated with the risk of knee osteoarthritis (OR=0.822, 95% CI: 0.688 8, 0.981, P=0.03), and the proportion of omega 6 polyunsaturated fatty acids to total fatty acids was positively correlated with the risk of knee osteoarthritis (OR=1.268, 95% CI: 1.079, 1.491, P=0.004). There were two types of fatty acid phenotypes that do not have a causal relationship with knee osteoarthritis, including total fatty acids (OR=0.925, 95% CI: 0.804-1.066, P=0.283) and the proportion of monounsaturated fatty acids to total fatty acids (OR=0.877, 95% CI: 0.756-1.018, P=0.084). The reverse analysis results indicated that when knee osteoarthritis was used as exposure data, there was no significant causal relationship with the phenotype of fatty acids. The sensitivity analysis results showed that the P-values of the bidirectional Mendelian randomization Cochran’s Q-test and MR Egger regression were both greater than 0.05, indicating that there was no significant heterogeneity or pleiotropy in the causal effect analysis between fatty acid phenotype and knee osteoarthritis. To conclude, reducing the content of saturated fatty acids and omega 6 polyunsaturated fatty acids and increasing the content of omega 3 polyunsaturated fatty acids can reduce the risk of knee osteoarthritis. This provides valuable clues for studying the biological mechanisms of knee osteoarthritis and exploring the early prevention and treatment of knee osteoarthritis, as well as providing new directions for the development of interventional drugs. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics

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Causal relationship between 91 inflammatory proteins and cervical disc degeneration Liu Shuaiyi, Zhao Xiaoxuan, Li Qi, Xing Zheng, Li Qingwen, Chu Xiaolei 2025, 29 (17):  3732-3740.  doi: 10.12307/2025.644 Abstract ( 185 )   PDF (2239KB) ( 124 )   Save BACKGROUND: Cervical disc degeneration is a common degenerative disease, and inflammatory proteins play an important role in cervical disc degeneration, but the specific mechanisms involved remain to be thoroughly investigated. OBJECTIVE: Using the Mendelian randomization method to assess the potential causal relationship between 91 inflammatory proteins and cervical disc degeneration. METHODS: Genome-wide association analysis statistics for 91 inflammatory proteins (from GCST90274758 to GCST90274848) were obtained from the Genome-Wide Association Analysis Catalog of publicly available genome-wide association analysis data and genome-wide association analysis data for cervical disc degeneration from the Finngen database (finngen_R10_M13_CERVICDISCV). Inverse variance weighting, MR-Egger regression, weighted median, weighted modeling, and simple modeling were used to investigate the causal relationship between inflammatory proteins and cervical disc degeneration. Sensitivity analyses were performed to test whether the results of the Mendelian randomization analysis were reliable, and then the inverse Mendelian randomization analysis was performed in the same way. RESULTS AND CONCLUSION: The results of the forward analysis showed that a total of six inflammatory proteins were significantly and causally associated with cervical disc degeneration, of which glial cell lineage-derived neurotrophic factor (odds ratio (OR)=1.095, 95% confidence interval (CI): 1.012-1.184, P=0.023), interleukin 4 (OR=1.094, 95% CI: 1.002-1.194, P=0.045) and monocyte chemotactic protein-1 levels (OR=1.062, 95% CI: 1.001-1.127, P=0.048) showed a direct positive causal association with the risk of cervical disc degeneration; interleukin 17C (OR=0.906, 95% CI: 0.839-0.979, P=0.013), interleukin 18 (OR=0.924, 95% CI: 0.866-0.986, P=0.017) and interleukin 2 levels (OR=0.894, 95% CI: 0.821-0.973, P=0.010) showed a direct negative causal association with the risk of cervical disc degeneration. The results of the inverse analysis showed that when cervical disc degeneration was used as exposure data, there was no significant causal relationship with any of the 91 inflammatory proteins. The results of the sensitivity analysis showed that the Cochran’s Q test for the two-way Mendelian randomization, the MR-Egger regression method, and the MR-PRESSO results had P values greater than 0.05, indicating that there was no significant heterogeneity or multiplicity in the analysis of the causal effect between inflammatory proteins and cervical disc degeneration. To conclude, there may be a relatively significant potential causal relationship between glial cell line-derived neurotrophic factor, interleukin 4, monocyte chemotactic protein-1, interleukin 17C levels, interleukin 18, and interleukin 2 levels and cervical disc degeneration, which provides valuable clues for research on the potential mechanisms of cervical disc degeneration as well as early prevention and drug treatment of cervical disc degeneration. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程 Figures and Tables | References | Related Articles | Metrics