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18 September 2025, Volume 29 Issue 26 Previous Issue    Next Issue

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Single-cell sequencing reveals heterogeneity of B cells in osteoporosis patients and their interactions with osteoblasts Tang Zhi, Shao Yang, Li Shaoshuo, Qi Shubin, Lu Hengyang, Wu Mao, Yang Junfeng, Wang Jianwei 2025, 29 (26):  5501-5510.  doi: 10.12307/2025.738 Abstract ( 213 )   PDF (2472KB) ( 202 )   Save BACKGROUND: The pathogenesis of osteoporosis is closely related to the immune system. A comprehensive and in-depth study of the relationship between immunity and osteoporosis is crucial for understanding and treating the disease.  OBJECTIVE: To investigate the role of immune cells in osteoporosis using single-cell sequencing technology. METHODS: Femoral head tissue samples from osteoporosis and non-osteoporosis patients were downloaded from GEO database and analyzed using single-cell sequencing. Data analysis, including cell clustering, functional enrichment, pseudotime trajectory, and cell interaction analyses, was performed using R4.3.0 and software packages such as Seurat v.4.3, monocle (2.28.0), and CellChat. The femoral head tissues of patients with femoral neck fracture who underwent artificial hip replacement surgery were obtained, including two cases of osteoporosis patients and two cases of non-osteoporosis patients. Immunohistochemical staining was used to detect the protein expression of CCL13 and CCL18. qPCR was used to detect the immunoglobulin heavy constant γ-4, immunoglobulin λ constant 3, human class II major histocompatibility complex DRβ1, and CD83 mRNA expression. Western blot was used to detect the protein expression of receptor-type tyrosine protein phosphatase C, CD22, and CD99. RESULTS AND CONCLUSION: Transcriptomic analysis identified 10 cell clusters, including osteoclasts, myeloid cells, T cells, osteoblasts, macrophages, monocytes, erythrocytes, B cells, bone marrow mesenchymal stem cells, and mast cells. There was an increase in the ratio of osteoclasts to T cells and a decrease in the ratio of osteoblasts to B cells in the femoral head tissue of the osteoporosis group. Among the B-cell subpopulations, the proportion of B-cells of taxa 1,3 (BC1, BC3) in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group, and the proportion of B-cells of taxa 2 (BC2) was less than that of the non-osteoporosis group. BC1 was enriched significantly for labels such as regulation of adaptive immune response, somatic recombination of immune receptors, and modulation of lymphocyte-mediated immunity, while BC3 was enriched significantly for labels such as regulation of immunoglobulin production, response to type II interferon, apoptotic processes involving cysteine endopeptidases, and cytotoxicity. The communication intensity between B-cell subtype BC1 and osteoblasts in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group, while the communication intensity between BC3 and BC1 was also increased. The communication between BC3 and BC1 was significantly enriched in the CD22-receptor-type tyrosine protein phosphatase C pathway; the communication between BC1 and osteoblasts was mainly enriched in the CD99-CD99 pathway; and the communication between BC3 and osteoblasts was also highly enriched in the CD99-CD99 pathway. Protein expression of CCL13, CCL18, receptor-type tyrosine protein phosphatase C, CD22, CD99, immunoglobulin heavy constant γ-4, immunoglobulin λ constant 3, human class II major histocompatibility complex DRβ1, and CD83 mRNA were higher in femoral tissues of the osteoporosis group than those of the non-osteoporosis group (P < 0.05). To conclude, specific B cell subpopulations can influence the differentiation and apoptosis of osteoblasts in the femoral tissue of osteoporosis patients. Figures and Tables | References | Related Articles | Metrics

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Artificial tiger bone meal improves degeneration of spinal facet joints and immune microenvironment of articular cartilage in rats with spine osteoarthritis Li Wen, Zhao Jingyi, Hu Wen, Xiong Bin, Tang Chao 2025, 29 (26):  5511-5519.  doi: 10.12307/2025.778 Abstract ( 231 )   PDF (2933KB) ( 231 )   Save BACKGROUND: Spine osteoarthritis is a chronic inflammatory disease of the spine, articular ligaments, and tendons, and is the main cause of chronic low back pain. Artificial tiger bone powder has anti-inflammatory and pain-relieving biological effects, so it is expected to provide a new strategy for targeted therapy of spinal osteoarthritis. OBJECTIVE: To investigate the mechanism of artificial tiger bone meal in regulating the expression level of interleukin-23/interleukin-17 immune axis in improving spine osteoarthritis in rats. METHODS: Sixty SD rats were randomly divided into blank control group, model group, artificial tiger bone meal low-, medium- and high-dose groups, with 12 rats in each group. Except for the blank control group, osteoarthritis models were established in the other groups by injecting 0.1 mL of iodoacetic acid into the joint cavity of the lumbar vertebral joint capsule of the rats. 15 days after modeling, the artificial tiger bone meal low, medium and high dose groups were treated by intragastric administration of 120, 240 and 480 mg/kg per day respectively. The blank control group and model group were given the same volume of normal saline by gavage. After 21 days of treatment, the expression levels of interleukin-17, interleukin-23, matrix metalloproteinase-3, and chemokine receptor-6 in rat spinal articular cartilage were measured by western blot assay. The expression levels of related inflammatory factors in rat serum were detected by ELISA. The degree of joint injury and degeneration in rats was observed by hematoxylin-eosin staining and safranin O-fast green staining.   RESULTS AND CONCLUSION: (1) The results of western blot assay showed that the expression levels of interleukin 17, interleukin 23, matrix metalloproteinase 3, and chemokine receptor 6 in the articular cartilage of rats in the artificial tiger bone meal high-dose group were significantly lower than those in the model group (P < 0.05). (2) ELISA results showed that compared with the model group, the artificial tiger bone meal medium- and high-dose groups had a significant down-regulating effect on the levels of serum interleukin 17, tumor necrosis factor α, interleukin 1β, and matrix metalloproteinase 3 (P < 0.05). (3) Hematoxylin-eosin staining and saffron O-solid green staining showed that the infiltration and proliferation of synovial inflammatory cells in each treatment group of artificial tiger bone meal were significantly improved compared with the model group, and the pathological inflammation Osteoarthritis Research Society International score and Mankin’s score in the medium- and high-dose groups of artificial tiger bone meal were significantly reduced (P < 0.05). (4) It is suggested that artificial tiger bone meal could significantly improve the inflammation and degeneration of spinal facet joints caused by iodoacetic acid chemical stimulation. Among them, the effect of the high-dose group was more significant. The mechanism may be to inhibit the expression of interleukin-23/interleukin-17 immune axis-related inflammatory factors and improve the immune microenvironment of articular cartilage. Figures and Tables | References | Related Articles | Metrics

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Protective mechanism of nitrooleic acid on submandibular gland cell radiation injury in rats Lin Peiqi, Luo Qinliang, Zhang Ligang, Huang Guilin, Tang Jianhong, Zhang Nini 2025, 29 (26):  5520-5527.  doi: 10.12307/2025.768 Abstract ( 155 )   PDF (1840KB) ( 92 )   Save BACKGROUND: Recent studies have found that Nrf2/ARE signaling pathway activators have the characteristics of low toxicity and control, and have a protective effect against radiation tissue damage. OBJECTIVE: To investigate whether nitrooleic acid can protect submandibular gland epithelial cells from radiation injury by regulating the Nrf2/ARE signaling pathway. METHODS: Rat submandibular gland epithelial cells were cultured in vitro and CCK-8 assay was used to screen the optimal concentration and time of nitrooleic acid administration. Submandibular gland epithelial cells were divided into non-radiation group, radiation control group, nitrooleic acid group, nitrooleic acid + ML385 (Nrf2/ARE signaling pathway specific inhibitor) group, and ML385 group. Submandibular gland cells were pretreated with nitrooleic acid and ML385 for 24 hous according to the experimental groups, and then irradiated with 5 Gy radiation to establish the models. At 48 hours after irradiation, CCK-8 assay was used to detect the cell proliferation rate. Real-time quantitative PCR was used to detect the expression of Nrf2, HO-1, and NQO1 mRNA in the cells. Real-time quantitative PCR and enzyme-linked immunosorbent assay were used to detect the cell secretion function and the expression of inflammatory factors. DCFH-DA fluorescent probe kit was used to detect the level of intracellular reactive oxygen species.  RESULTS AND CONCLUSION: (1) Compared with the radiation control group, the proliferation rate of submandibular gland epithelial cells and the expression levels of secretion function related factors aquaporin 5 and α-amylase in the nitrooleic acid group of rats increased (P < 0.05), and the expression levels of Nrf2, HO-1, and NQO1 mRNA increased (P < 0.05), while the expression levels of inflammatory factors interleukin-1β, interleukin-6, and tumor necrosis factor-α decreased (P < 0.05), and reactive oxygen species generation reduced (P < 0.01). (2) Compared with the nitrooleic acid group, the addition of nitrooleic acid and ML385 group resulted in a decrease in cell proliferation rate and expression levels of secretion function related factors aquaporin 5 and α-amylase (P < 0.05), and mRNA expressions of Nrf2, HO-1, and NQO1 were all decreased (P < 0.05), while the expression levels of inflammatory factors interleukin-1β, interleukin-6, and tumor necrosis factor-α increased (P < 0.05), and generation of reactive oxygen species increased (P < 0.05). (3) Results indicated that in the radiation environment, nitrooleic acid has a certain protective effect on the proliferation ability and secretion function of rat submandibular gland epithelial cells, reduces the expression of inflammatory factors, lowers intracellular reactive oxygen species levels, and alleviates the damage of rat submandibular gland epithelial cells caused by radiation. This function may be related to the activation of Nrf2/ARE signaling pathway.  Figures and Tables | References | Related Articles | Metrics

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Effects of aerobic or resistance exercise on hippocampal ras/Drebrin dendritic spine plasticity in a mouse model of Alzheimer’s disease He Ningjuan, Li Li, Wang Su, Yang Jianshe, Lei Siyun, Wang Yang 2025, 29 (26):  5528-5535.  doi: 10.12307/2025.761 Abstract ( 156 )   PDF (1489KB) ( 130 )   Save BACKGROUND: Studies have shown that there is a close relationship between dendritic spine plasticity and Alzheimer’s disease, and that resistance or aerobic exercise has some efficacy in improving cognitive dysfunction, but the mechanism of action is unclear.  OBJECTIVE: To investigate the effect of aerobic exercise or resistance exercise on dendritic spine plasticity in the hippocampal CA1 region of APP/PS1 transgenic mice.  METHODS: Thirty 3-month-old male APP/PS1 mice were selected and randomly divided into three groups: a model group, a resistance exercise group, and an aerobic exercise group. The same litter of 3-month-old C57BL/6J mice were selected as a blank group. Mice in the resistance exercise group were subjected to ladder-climbing exercise and those in the aerobic exercise group were subjected to treadmill exercise for 12 weeks. At the end of the exercise intervention, the water maze experiment and the new arm of the Y maze were used to assess behavioral changes in mice. Hematoxylin-eosin staining, Nissl staining, Golgi staining, and electron microscopy were performed to observe neuronal morphology, Nissl bodies, dendritic spines, and ultrastructural changes in the synapses of the hippocampal region of the mouse brain. The protein expression levels of hippocampal amyloid-beta1-42, Ras, and Drebrin were measured using Western blot analysis. RESULTS AND CONCLUSION: Mice in the model group exhibited a prolonged escape latency over 5 consecutive days (P < 0.05, P < 0.01) and significantly fewer entries into the new arm of the Y maze (P < 0.01). Dendritic spine density in the CA1 region of the hippocampus, as well as Ras and Drebrin expression in the hippocampal tissues of mice in the model group, were lower than those in the normal group (P < 0.01), and amyloid-beta1-42 expression in the hippocampal tissues was higher in the model group compared with the normal group (P < 0.01). Mice in the resistance exercise group and the aerobic exercise group displayed a shortened escape latency over the same 5-day period (P < 0.05, P < 0.01) and showed a significantly greater number of entries into the new arm of the Y maze compared with the normal group (P < 0.01). Dendritic spine density in the CA1 region of the hippocampus, as well as Ras and Drebrin expression in the hippocampal tissues, were higher in both the resistance exercise group and the aerobic exercise group compared with the model group (P < 0.01).Amyloid-beta1-42 expression in the hippocampal tissue was lower in both exercise groups than in the model group (P < 0.01). To conclude, long-term regular aerobic or resistance exercise interventions can increase dendritic spine density and synaptic plasticity in the CA1 region of the hippocampus, enhancing spatial learning and memory abilities in a mouse model of Alzheimer’s disease. These effects may be associated with increased expression of Ras and Drebrin proteins in the hippocampus. Figures and Tables | References | Related Articles | Metrics

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Effect of high glucose on blood-brain barrier tight junctions in hCMEC/D3 human brain microvascular endothelial cells Yang Hongtao, Xu Yongjie, Zhou Yongjun, , Wang Shuang, Huang Changyudong, Zhu Liying, Pan Wei, 2025, 29 (26):  5536-5542.  doi: 10.12307/2025.769 Abstract ( 113 )   PDF (1723KB) ( 333 )   Save BACKGROUND: The blood-brain barrier is an important structure that protects the central nervous system, and the study of the effects of high glucose on the blood-brain barrier is important for the prevention of high glucose-induced damage to the central nervous system.  OBJECTIVE: To investigate the potential effect of high glucose on the blood-brain barrier function of hCMEC/D3 human brain microvascular endothelial cells. METHODS: hCMEC/D3 cells were cultured in regular sugar medium (glucose concentration of 25 mmol/L) and high-sugar medium (glucose concentration of 55 mmol/L). The morphology of cells in each group was observed by light microscopy. CCK-8 assay was used to detect changes in cell viability. A monolayer blood-brain barrier model was established using hCMEC/D3 cell line with Transwell chamber device. Changes in cell transmembrane resistance were monitored daily. The permeability of cell monolayers was detected by phenol red permeability. Flow cytometry was used to detect the apoptosis rate of the cells. Western blot assay was used to detect the expression of Bcl-2, Bax, Caspase-3, ZO-1, Occludin, Claudin-1, and histone deacetylase 4. The levels of histone deacetylase in cell supernatant were detected by ELISA. The expression of histone deacetylase 4 in cells was detected by immunofluorescence.  RESULTS AND CONCLUSION: (1) The cell viability of high sugar group was significantly lower than that of control group (P < 0.000 1). (2) The cells of the control group were in a good growth state, interwoven into a dense mesh, with interconnections between synapses. The cell growth of high glucose group was suppressed, and the connection of inter-cellular synapses was reduced. (3) Compared with the control group, the transmembrane resistance value of the high glucose group was reduced (P < 0.05); phenol-red permeability of the monolayer cell membrane was increased (P < 0.05); cell apoptosis rate was increased (P < 0.01); the expression of Bax protein was increased (P < 0.000 1); the expression of Caspase-3 protein had no significant change (P > 0.05); the expression of Bcl-2, ZO-1, Occludin, Claudin-1, and histone deacetylase 4 proteins was decreased (P < 0.01, P < 0.001, P < 0.01, P < 0.000 1, P < 0.01); the fluorescence expression of histone deacetylase 4 was decreased (P < 0.001) in the high glucose group. (4) The level of histone deacetylase 4 in the cell supernatant of the high glucose group was lower than that of the control group (P < 0.05). The results show that high glucose induces the increased apoptosis and enhances permeability of hCEMCE/D3 cells, and its mechanism may be related to the decreased expression level of histone deacetylase 4. Figures and Tables | References | Related Articles | Metrics

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An experimental method for simultaneously extracting the dura mater and deep cervical lymph nodes Shen Zilong, Wu Mingjie, Chen Xiaojing, Zhou Xibin, Zhou Chunxiang 2025, 29 (26):  5543-5548.  doi: 10.12307/2025.732 Abstract ( 146 )   PDF (1699KB) ( 176 )   Save BACKGROUND: Meningeal lymphatic vessels can drain cerebral spinal fluid and amyloid β-protein, promoting T lymphocyte to transport and home to deep cervical lymph nodes. A simple, quick and definite method of dural separation and accurate localization of deep cervical lymph nodes can provide strong support for the study of neurodegenerative diseases. OBJECTIVE: To establish a convenient and practical method for exfoliating dural and deep cervical lymph nodes. METHODS: ICR mice, 3 months old, were taken, anesthetized and injected with Evans blue and tracer in the occipital pool for localizing deep cervical lymph nodes. A midline incision of about 3 cm in length was made about 5 mm above the clavicle, the superficial fat and fascia were bluntly separated, and the lateral sternocleidomastoid muscle was pulled to expose the deep cervical lymph nodes, which were removed under a stereomicroscope and frozen at -80°C. Subsequently, the mouse head was cut and the skin and muscles of the head were separated to expose the entire skull structure. The skull and brain tissue were separated from the foramen magnum along the lower parietal bone with scissors, and the complete skull top was obtained. The skull was sequentially fixed in 40 g/L paraformaldehyde solution for 24 hours, 120 g/L paraformaldehyde for 24 hours, and 120 g/L paraformaldehyde for 10, 20, 30, and 40 minutes, and the dural structure was stripped. The drainage capacity of meningeal lymphatic vessels and deep cervical lymphatic vessels was verified by tracer, and the meningeal lymphatic vessels were identified by the lymphatic vessel endothelial hyaluronan receptor 1 using the immunofluorescence method. RESULTS AND CONCLUSION: (1) Obvious blue staining was observed in deep cervical lymph nodes 15 minutes after Evans blue staining. (2) The skull was sampled and fixed in 120 g/L paraformaldehyde for 24 hours, resulting in a less tight connection between the dura mater and the skull, and easier stripping of the dural structures with an intact shape. The dura mater fixed at 120 g/L concentration was more resilient and remained more intact during peeling compared with the conventional 40 g/L concentration; 120 g/L paraformaldehyde fixed meninges for a short time, and 30-40 minutes was preferred. (3) The frozen section of deep cervical lymph nodes showed the presence of the tracer, complete meningeal lymphatic vessels were visible in the dura mater, and the tracer was observed at the tail of lymphatic vessels. Immunofluorescence staining for endothelial hyaluronan receptor 1 was positive in the deep cervical lymph nodes and dural lymphatics. In summary, the best peeling concentration and time is 120 g/L paraformaldehyde fixed for 24 hours. At this concentration, the dura mater has a stretched morphology, a better toughness, and is more intact after peeling, which is conducive to later use. Verified by Evans blue, tracers and immunofluorescence, deep cervical lymph nodes are located accurately, which can be used as a basis for the study of various neurodegenerative diseases. Figures and Tables | References | Related Articles | Metrics

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Effect of massage on extracellular matrix collagen deposition in skeletal muscle of type 2 diabetic rats Sun Yahui, Wang Yufeng, Guo Chao, Yao Junjie, Ji Yuanyuan, Li Zhongxu, Lou Huijuan, Jiang Jinglei, Sun Yiping, Xu Jing, Cong Deyu 2025, 29 (26):  5549-5555.  doi: 10.12307/2025.784 Abstract ( 149 )   PDF (1452KB) ( 219 )   Save BACKGROUND: Studies have found that massage can reduce blood sugar, promote myogenic factor expression, and increase skeletal muscle content. The extracellular matrix is an important component of skeletal muscle, and association between massage and extracellular matrix and their mechanism of action are still unclear. OBJECTIVE: To explore the effect of massage on extracellular matrix collagen deposition in type 2 diabetic sarcopenia rats. METHODS: Totally 24 Wistar male rats were randomly divided into blank group, model group, and massage group. High-fat diet combined with the streptozotocin method was used to establish a type 2 diabetes mellitus and sarcopenia model. After successful model establishment, the massage group used abdominal massage combined with hind limbs. After 8 weeks of treatment, the fasting blood glucose and serum insulin levels of the rats were measured. The skeletal muscle mass was detected by dual-energy X-ray. The exhaustion time was measured by small animal treadmill. The sliding angle was measured by inclined board test. The pathological changes of skeletal muscle tissue were observed by hematoxylin-eosin staining. The skeletal muscle collagen deposition was observed by Masson staining. The mRNA and protein expressions of type I and type III collagen in skeletal muscle were detected by qPCR and western blot assay. RESULTS AND CONCLUSION: (1) Compared with the model group, the blood glucose (P < 0.05) and serum insulin (P < 0.01) decreased in the massage group. (2) Compared with the model group, the skeletal muscle mass, running exhaustion time, and the angle of inclined plate experiment were increased in massage group (P < 0.05). (3) Compared with the model group, the skeletal muscles of the massage group were arranged neatly, muscle atrophy was improved, and collagen fiber deposition was reduced. (4) Compared with the model group, the expression levels of type I and type III collagen mRNA and protein in skeletal muscle were decreased in the massage group (P < 0.05). (5) The results suggest that massage can enhance insulin sensitivity, lower blood sugar, improve skeletal muscle mass, strength and function, and diminish collagen deposition in rats with type 2 diabetes, and may be a potential target for massage to exert its therapeutic effects. Figures and Tables | References | Related Articles | Metrics

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Influence of neuromuscular function on the risk of biomechanical injury in landing manoeuvres in patients undergoing anterior cruciate ligament reconstruction Wang Xia, Xue Boshi, Yang Chen, Zhou Zhipeng, Zheng Liangliang 2025, 29 (26):  5556-5562.  doi: 10.12307/2025.782 Abstract ( 171 )   PDF (1333KB) ( 99 )   Save BACKGROUND: The re-injury rate of the anterior cruciate ligament continues to be high and the unclear relationship between neuromuscular function and biomechanical risk factors may be one of the reasons for poor injury prevention and rehabilitation. OBJECTIVE: To evaluate the biomechanics and neuromuscular function characteristics of the knee joint during landing movements after anterior cruciate ligament reconstruction, and to further explore the effects of muscle strength, proprioception, and dynamic postural control on the risk indicators of anterior cruciate ligament injury during landing maneuver. METHODS: Twenty-six male anterior cruciate ligament reconstruction patients and 26 healthy control males at the age of 18-35 years were recruited and randomized to undergo joint kinesthesia test, Y-balance test, and isometric muscle strength tests. Kinematic and kinetic data of the knee joints during single-legged jump landing tasks were collected using an infrared motion capture system and force plates. RESULTS AND CONCLUSION: (1) Compared with the healthy control group, patients after anterior cruciate ligament reconstruction demonstrated higher knee valgus angle (P=0.021), lower hamstring muscle strength (P < 0.001), lower quadriceps muscle strength (P < 0.001) and Y-balance anterior reach distance  (P < 0.001), and worse knee flexion kinesthesia (P < 0.001) and extension kinesthesia (P=0.001). (2) The predictor variables of knee extension moment were quadriceps strength and knee flexion kinesthesia (R2=0.298, P=0.007). The predictor variable of knee varus and valgus angle was hamstring strength (R2=0.117, P=0.048). The predictor variable of knee internal and external rotation angle was the hamstring-to-quadriceps peak torque ratio (R2=0.134, P =0.037). (3) The results showed that after anterior cruciate ligament reconstruction, patients still had abnormal biomechanical action patterns and neuromuscular function defects in the frontal plane of the knee joint, and elevating the muscle strength of the hamstrings, avoiding excessive quadriceps muscle strength and enhancing the proprioception of the knee joint were helpful to improve the biomechanical patterns of the sagittal plane, frontal plane and horizontal plane of the knee joint and reduce the risk of anterior cruciate ligament injury during landing maneuvers. Figures and Tables | References | Related Articles | Metrics

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Regulatory mechanism of electroacupuncture on hypothalamic-pituitary-testicular axis in oligospermic rats Zhao Zhenning, , , Li Kaiying, , , Yang Nan, , , Sun Wenjing, , , Wei Xiaoge, , , Mu Jing, Ma Huisheng, , 2025, 29 (26):  5563-5571.  doi: 10.12307/2025.751 Abstract ( 146 )   PDF (3166KB) ( 97 )   Save BACKGROUND: Electroacupuncture can treat oligoasthenospermia by stimulating hormone synthesis and release in the hypothalamus, pituitary gland and testis, but its mechanism is complex, and the efficacy of electroacupuncture is closely related to the idea of acupoint compatibility.  OBJECTIVE: To explore whether electroacupuncture therapy can improve the function status of hypothalamic-pituitary-testicular axis by adjusting the level of serum related sex hormones in rats, so as to treat adenine-induced oligoasthenospermia in rats. METHODS: Fifty adult male Sprague-Dawley rats were randomly divided into blank, model, electroacupuncture, L-carnitine, and non-meridian and non-acupuncture point groups, with 10 rats in each group. Except for the blank group, the rats in the other four groups were given 200 mg/(kg·d) adenine via intragastric administration for 28 days to establish oligoasthenospermia models. After modeling, the rats in the electroacupuncture group were given electroacupuncture treatment at Zhongji, Guanyuan, Zusanli and Sanyinjiao acupoints, the non-acupoint group was selected for electroacupuncture treatment at three non-acupoint points, and the rats in the L-carnitine group were given oral infusion of L-carnitine, once daily, for 28 continuous days. After treatment, the kidney and testicular organ coefficients were calculated. Sperm count, survival rate and motility rate were determined. Pathological morphological changes of kidney and testicular tissues were observed. Serum sex hormones testosterone, gonadotropin releasing hormone, follicle stimulating hormone, luteinizing hormone, estradiol, statin B and prolactin levels were detected in rats of each group. RESULTS AND CONCLUSION: (1) The renal organ coefficient in the model group was higher than that in the blank, electroacupuncture and L-carnitine groups (p < 0.05), the renal organ coefficient in the non-acupoint group was higher than that in the electroacupuncture group (P < 0.05), and there was no significant difference in the testicular organ coefficient among all groups (P > 0.05). (2) Compared with the blank group, sperm count, survival rate and motility rate were decreased in the model group (P < 0.05); compared with the model group, sperm count, survival rate and motility rate were increased in the electroacupuncture group and L-carnitine group (P < 0.05); compared with the non-acupoint group, sperm count, survival rate and motility rate were higher in the electroacupuncture group (P < 0.05). (3) Hematoxylin-eosin staining results indicated that the kidney and testicular tissues of rats in the model group were severely damaged, while damage to kidney and testicular tissues was less in the electroacupuncture group and L-carnitine group compared with the model group, but severer in the non-acupoint group than the electroacupuncture group. (4) Compared with the blank group, the levels of testosterone, gonadotropin releasing hormone, and inhibin B in the serum of rats in the model group were decreased (P < 0.05), and the levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and prolactin were increased (P < 0.05). Compared with the model group, the levels of testosterone, gonadotropin-releasing hormone, and inhibin B in the serum of rats in the electroacupuncture group and L-carnitine group were increased (P < 0.05), and the levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and prolactin were decreased (P < 0.05). Compared with the non-acupoint group, the levels of testosterone, gonadotropin-releasing hormone, and inhibin B in the serum of the rats in electroacupuncture group were increased (P < 0.05), and the levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and prolactin were decreased (P < 0.05). To conclude, electroacupuncture at Zhongji, Guanyuan, Zusanli, and Sanyinjiao acupoints can effectively treat oligoasthenospermia by regulating the functional state of the hypothalamic-pituitary-testicular axis in rats. Figures and Tables | References | Related Articles | Metrics

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Emodin promotes autophagy to improve myocardial injury in septic model mice Tian Yong, Zhou Qing, Luo Chuanquan, Hu Hongmei, Ma Changlin, Yang Lei, Wei Lin 2025, 29 (26):  5572-5578.  doi: 10.12307/2025.771 Abstract ( 153 )   PDF (1671KB) ( 188 )   Save BACKGROUND: Emodin has a variety of pharmacological activities such as anti-inflammatory, anti-viral and anti-oxidative stress, and also has a certain protective effect on sepsis-induced myocardial injury, but its mechanism of action is still unclear. OBJECTIVE: To investigate whether emodin can improve myocardial injury in septic mice by promoting autophagy. METHODS: Thirty-two male Kunming mice were divided into sham operation group (n=4), sham operation+emodin group (n=4), model group (n=8), model+emodin group (n=8), and emodin+3-methyladenine group (n=8). The myocardial injury model of septic mice was constructed by cecal ligation and puncture. 3-methyladenine (10 mg/kg) was injected intraperitoneally 1 hour before modeling. Emodin (20 mg/kg) was injected intraperitoneally 30 minutes before modeling, and the other groups were injected with the same amount of normal saline at the same time point. Blood and myocardial samples were collected from all mice 24 hours after surgery. ELISA was used to detect the levels of brain natriuretic peptide and cardiac troponin I in serum. Western blot assay was used to detect the protein expression of LC3B, Beclin-1, and p62 in myocardial tissue. Hematoxylin-eosin staining was used to observe the pathological changes in myocardial tissue. Ultrasound was used to evaluate the cardiac function of mice. RESULTS AND CONCLUSION: (1) Compared with the sham operation group, there was no significant difference in the levels of serum brain natriuretic peptide, cardiac troponin I, and the protein expression of myocardial autophagy proteins LC3II/LC3I and p62 in the sham operation+emodin group (P > 0.05). (2) Compared with the sham operation+emodin group, the levels of serum brain natriuretic peptide and cardiac troponin I were significantly increased in the model group (P < 0.05). Compared with the model group, the levels of serum brain natriuretic peptide and cardiac troponin I were decreased in the model+emodin group (P < 0.05). (3) Compared with the model group, the expression of LC3II/LC3I and Beclin-1 protein was increased and the expression of p62 protein was decreased in the myocardial tissue of the model+emodin group (P < 0.05). Compared with the model+emodin group, the expression of LC3II/LC3I and Beclin-1 protein decreased and the expression of p62 protein increased in the emodin+3-methyladenine group (P < 0.05). (4) The myocardial fibers in the sham operation group were normal, the myocardial fibers in the model group were disordered with a large number of inflammatory cell infiltration, the myocardial fibers in the model+emodin group were slightly disordered, and some vacuolar changes were observed. The myocardial fibers were disordered, and more inflammatory cell infiltration was observed in the emodin+3-methyladenine group. (5) Compared with the sham operation group, the left ventricular short axis shortening rate and left ventricular ejection fraction were decreased in the model group (P < 0.05). Compared with the model group, the left ventricular short axis shortening rate and left ventricular ejection fraction were increased in the model+emodin group (P < 0.05). Compared with the model+emodin group, the left ventricular ejection fraction of emodin+3-methyladenine group was decreased (P < 0.05), and the left ventricular short axis shortening rate was reduced but not statistically significant (P > 0.05). (6) The above results indicate that emodin pretreatment can improve myocardial injury and myocardial dysfunction in septic mice by promoting autophagy. Figures and Tables | References | Related Articles | Metrics

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Protective effect of Huaizhen Yanggan Capsule on knee osteoarthritis induced by sodium iodoacetate in model mice Sun Hailiang, Pang Jian, Shi Wanzhong, Shi Ying 2025, 29 (26):  5579-5587.  doi: 10.12307/2025.770 Abstract ( 148 )   PDF (3055KB) ( 77 )   Save BACKGROUND: Previous studies have shown that Huaizhen Yanggan Capsule has anti-inflammatory, analgesic, and antioxidant effects, but the mechanism of drug efficacy and whether it has therapeutic effects on knee osteoarthritis have not been elaborated. OBJECTIVE: To evaluate the anti-inflammatory and analgesic effects of Huaizhen Yanggan Capsule and its protective effect on knee osteoarthritis model mice. METHODS: (1) Experiment 1: The anti-inflammatory effect of Huaizhen Yanggan Capsule on mice was evaluated by ear swelling induced by xylene. The levels of interleukin-6 and tumor necrosis factor-α in ear tissues were detected by ELISA. The morphology of ear tissues of anti-inflammatory mice was observed by hematoxylin-eosin staining. (2) Experiment 2: The analgesic effect of Huaizhen Yanggan Capsule on mice was evaluated by hot plate analgesia experiment. The levels of 5-hydroxytryptamine, prostaglandin E2, bradykinin, and β-endorphin in serum of mice were detected by ELISA. (3) Experiment 3: The therapeutic effect of Huaizhen Yanggan Capsule on knee osteoarthritis was studied by injecting sodium iodoacetate into knee osteoarthritis model mice. The analgesic effect was evaluated by step analysis. The total antioxidant capacity kit was used to detect the total antioxidant capacity in serum. Micro-CT scan was used to analyze bone structure and bone volume fraction. The tissue morphology of articular cartilage was observed by hematoxylin-eosin staining and safranin O-fast green staining. The injury degree of articular cartilage was evaluated by modified Mankin’s score. The expression of tumor necrosis factor α, interleukin 6, and type II collagen in articular cartilage was detected by immunohistochemical staining.  RESULTS AND CONCLUSION: (1) In experiment 1, compared with blank group, Huaizhen Yanggan Capsule group could significantly inhibit the degree of ear swelling (P < 0.05), and decrease the levels of tumor necrosis factor α and interleukin 6 in ear tissue (P < 0.05). (2) In experiment 2, compared with blank group, Huaizhen Yanggan Capsule medium and high dose groups could significantly increase the pain threshold (P < 0.05), decrease the levels of 5-hydroxytryptamine, prostaglandin E2, and bradykinin in serum (P < 0.05), and increase the level of β-endorphin (P < 0.05). (3) In experiment 3, compared with the model group, the stride length of mice was significantly increased (P < 0.05); the serum total antioxidant capacity was significantly increased (P < 0.05); the subchondral bone destruction was inhibited by Micro-CT scanning, and bone volume fraction was significantly increased (P < 0.05) in Huaizhen Yanggan Capsule group. The surface of articular cartilage was flat and the modified Mankin’s score was significantly decreased by hematoxylin-eosin and saffrane-O-solid green staining (P < 0.05). The expression of type II collagen was increased by immunohistochemical staining (P < 0.05), and the expression levels of interleukin 6 and tumor necrosis factor α were decreased (P < 0.05). (4) The results suggest that Huaizhen Yanggan Capsule may have anti-inflammatory, analgesic and joint protective effects. It can relieve the pain of knee osteoarthritis model mice, enhance the antioxidant capacity of the body, and improve the cartilage tissue morphology and the bone microstructure of subchondral bone, inhibiting the progression of osteoarthritis.  Figures and Tables | References | Related Articles | Metrics

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Effect of Bushen Jianpi Formula on bone metabolism and bone microarchitecture in ovariectomized rats Guo Sunlin, Hong Enda, Dai Xinhua, Lin Xi, Peng Zhiyi, Cheng Yingxiong, Fan Linyan 2025, 29 (26):  5588-5594.  doi: 10.12307/2025.773 Abstract ( 159 )   PDF (6150KB) ( 102 )   Save BACKGROUND: Previous studies have found that for postmenopausal osteoporosis patients, the Bushen Jianpi Formula can help regulate serum osteoclast- and osteoblast-related factors and intestinal flora levels, improve clinical symptoms of patients and further improve efficacy. OBJECTIVE: To investigate the effect of Bushen Jianpi Formula on bone metabolism and bone microarchitecture in ovariectomized rats. METHODS: Twenty-four female SD rats were randomly divided into four groups by random number table method: sham operation group (n=6) was subjected to periovarian fat removal, and bilateral ovariectomy was performed in model group (n=6), alendronate group (n=6), and Bushen Jianpi Formula group (n=6). Five days after modeling, the Bushen Jianpi Formula group was given Bushen Jianpi Formula by intragastric administration (once a day). The alendronate sodium group was given alendronate by intragastric administration (once a week). The sham operation group and model group were given an equal volume of normal saline by intragastric administration (once a day) for 12 consecutive weeks. After intragastric administration, serum levels of procollagen I N-terminal peptide, β-isomerized C-terminal telopeptide of type I collagen degradation product, and tumor necrosis factor α were detected. The distal femur microstructure was detected by Micro-CT. The femoral tissue morphology was observed by hematoxylin-eosin staining. The expression of type I collagen and tumor necrosis factor α in the femur was detected by immunohistochemical staining.  RESULTS AND CONCLUSION: (1) The serum ELISA test showed that compared with the sham operation group, the level of procollagen I N-terminal peptide in the model group decreased (P < 0.05), and the levels of degradation products of β-isomerized C-terminal telopeptide of type I collagen and tumor necrosis factor α increased (P < 0.05). Compared with the model group, the levels of the procollagen I N-terminal peptide in the Bushen Jianpi Formula group and the alendronate sodium group increased (P < 0.05), and the levels of β-isomerized C-terminal telopeptide of type I collagen degradation products and tumor necrosis factor α decreased (P < 0.05). (2) Micro-CT three-dimensional reconstruction showed that compared with the sham operation group, the number of bone trabeculae in the model group was significantly reduced, the continuity was worsened, and the gaps were increased. Both alendronate sodium and Bushen Jianpi Formula had a positive improvement effect on this phenomenon. (3) Hematoxylin-eosin staining showed that compared with the sham operation group, the number of bone trabeculae in the model group was reduced and the shape became thinner, and the network structure was destroyed. Compared with the model group, the number of bone trabeculae in the Bushen Jianpi Formula group and the alendronate sodium group increased, the shape became thicker, and the reticular structure was restored. (4) Immunohistochemical staining showed that compared with the sham operation group, the expression of type I collagen was reduced and tumor necrosis factor α expression was increased in the model group. Compared with the model group, the expression of type I collagen increased and the expression of tumor necrosis factor α decreased in the Bushen Jianpi Formula group and the alendronate sodium group. The results show that the Bushen Jianpi Formula can effectively improve bone metabolism and bone microstructure in ovariectomized rats. Figures and Tables | References | Related Articles | Metrics

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Rheumatoid arthritis from the perspective of mitophagy: interaction analysis based on multiple machine learning algorithms Li Jiagen, Chen Yueping, Huang Keqi, Chen Shangtong, Huang Chuanhong 2025, 29 (26):  5595-5607.  doi: 10.12307/2025.745 Abstract ( 83 )   PDF (5706KB) ( 222 )   Save BACKGROUND: The pathogenesis of rheumatoid arthritis has not yet been fully clarified, and recent studies have shown that mitophagy is associated with rheumatoid arthritis, but the key mechanisms need to be explored in depth. OBJECTIVE: To identify and validate the core interaction genes of mitophagy in rheumatoid arthritis using multiple machine learning algorithms and to analyze its immunoregulatory process. METHODS: The rheumatoid arthritis transcriptome expression dataset GSE15573 was retrieved from the GEO database as an independent training set, with the GSE97779 and GSE55235 collections used as independent validation sets. The differentially expressed genes of rheumatoid arthritis were screened using the training set, and “WGCNA” analysis was also performed. Then we downloaded the mitophagy-related genes from the “MitoCarta3.0” database, and intersected them with the differentially expressed genes of rheumatoid arthritis and the genes in the “WGCNA” analysis module to obtain the rheumatoid arthritis-mitophagy-related genes, and then analyzed the related genes for functional enrichment to clarify the cellular pathways. Feature genes were initially identified using the “Random Forest” and “Lasso” algorithms. The overlapping genes from these two methods were further refined using the “GMM” algorithm to identify the core interaction genes between rheumatoid arthritis and mitophagy. A predictive model was then developed and validated using an external dataset. Finally, “CIBERSORT” was employed to analyze the proportions and interactions of immune cell subsets during immune infiltration, while “ssGSEA” was used to examine the associations between the rheumatoid arthritis-mitophagy core interaction genes and immune cell subsets. “ssGSEA” was also utilized to analyze the “GO” and “KEGG” biological pathways of the core interaction genes. RESULTS AND CONCLUSION: (1) Totally 807 differentially expressed genes in rheumatoid arthritis were obtained by differential analysis, 1 208 genes were selected from two feature modules by “WGCNA” analysis, 1 136 genes were sorted out from the MitoCarta 3.0 database, and 53 HUB genes were obtained from the intersection of the three genes as rheumatoid arthritis-mitophagy related genes. (2) The results of functional enrichment analysis of related genes showed that the cellular processes were mainly related to mitophagy, peroxisome metabolism, cellular senescence, and necroptosis. (3) The three machine learning algorithms identified four rheumatoid arthritis-mitophagy core interaction genes (DNAJA3, C12orf65, AKR7A2, and PDHB). The area under the curve of nomoscore was 0.989, and the area under the curve values of rheumatoid arthritis-mitophagy core interaction genes verified by the receiver operating characteristic curve of external patient samples were all greater than 0.7. (5) Immunoregulatory analysis showed that the mitophagy process in rheumatoid arthritis was closely associated with memory B cells, M0 macrophages, activated memory CD4 T cells, and resting memory CD4 T cells. (6) The biological pathway analysis revealed that the core interaction genes were strongly associated with 821 “GO” pathways (|cor| > 0.8, P < 0.001) and 48 “KEGG” pathways (|cor| > 0.8, P < 0.001). The key biological processes identified were related to mitochondrial DNA metabolic process, mitochondrial DNA repair, mitochondrial DNA replication, mitochondrial genome maintenance, positive regulation of mitochondrial depolarization, and positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway. To conclude, DNAJA3, C12orf65, AKR7A2, and PDHB are the core interaction genes of the mitophagy process in rheumatoid arthritis, which play key roles in disease progression by participating in specific immune processes and have precise and predictive effects on the diagnosis of rheumatoid arthritis. Figures and Tables | References | Related Articles | Metrics

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Bioinformatics identification and validation of aging key genes in hormonal osteonecrosis of the femoral head Qiu Boyuan, Liu Fei, Tong Siwen, Ou Zhixue, Wang Weiwei 2025, 29 (26):  5608-5620.  doi: 10.12307/2025.787 Abstract ( 181 )   PDF (3986KB) ( 358 )   Save BACKGROUND: Hormonal osteonecrosis of the femoral head is strongly associated with aging, but the regulatory targets and mechanisms are still unclear. Through bioinformatics combined with machine learning analysis and experimental verification, the key genes of hormonal osteonecrosis of the femoral head mediated by cell senescence will be identified, which will provide new ideas for the prevention and treatment of hormonal osteonecrosis of the femoral head. OBJECTIVE: To screen and validate the senescence core genes of hormonal osteonecrosis of the femoral head using bioinformatics analysis to explore its mechanism of action. METHODS: The GSE123568 dataset was obtained from the GPL15207 platform of the GEO database, which contained the gene expression profiles of peripheral serum samples of 30 hormonal osteonecrosis of the femoral head patients and 10 healthy controls. Data on 279 cellular senescence-related genes were obtained from the CellAge database. Differential analysis and weighted correlation network analysis (WGCNA) were performed on hormonal osteonecrosis of the femoral head gene profiles, and both were intersected with senescence-related genes and then concatenated to obtain hormonal osteonecrosis of the femoral head senescence potential genes, and GO and KEGG analyses were performed. The machine learning method screened out the pivotal genes, constructed nomogram model, and performed consensus clustering and immune infiltration analysis. Finally, clinical femoral samples were collected for validation by qPCR and western blot assay. RESULTS AND CONCLUSION: (1) 41 potential genes were obtained, which were mainly enriched in biological processes such as aging and oxidative stress response, as well as FoxO and tumor necrosis factor signaling pathways. (2) The pivotal genes catalase, connective tissue growth factor, forkhead box protein O3, insulin receptor substrate 2, and mitogen-activated protein kinase kinase 11 were obtained after machine learning identification, and the predictive ability of nomogram model was good. (3) The patients were classified into three groups, namely a, b and c, by the consensus clustering analysis. Catalase, forkhead box protein O3, insulin receptor substrate 2, and mitogen-activated protein kinase kinase 11 were differentially expressed among the three molecular subtypes (P < 0.05). Results of immune infiltration showed that the abundance of immune cells, such as activated CD4+ T cells, activated CD8+ T cells, and eosinophils, differed among the three molecular subclasses (P < 0.05). (4) The results of qPCR and western blot assay showed that the expression of catalase, connective tissue growth factor, forkhead box protein O3, and mitogen-activated protein kinase kinase 11 was lower in hormonal osteonecrosis of the femoral head group compared to the control group (P < 0.05), and the expression of insulin receptor substrate 2 was elevated (P < 0.05). (5) It is concluded that through in-depth analysis combined with bioinformatics and machine learning, and further experimental verification, five hormonal osteonecrosis of the femoral head age-related hub genes were finally identified. These genes are catalase, connective tissue growth factor, forkhead box o3, insulin receptor substrate 2, and serine/threonine kinase 11. These genes may provide potential molecular targets for the prevention and treatment of hormonal osteonecrosis of the femoral head in the future by regulating the cellular aging process. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which Tongan Decoction regulates synovial macrophage polarization in rats with knee osteoarthritis Chen Yixin, Lu Yan, Zhang Xuan, Chen Xiaoli, Tan Liangyuan, Xu Zhangjie, Chen Wanglong, Su Shaoting, Liang Jiyao, Zhou Honghai 2025, 29 (26):  5621-5631.  doi: 10.12307/2025.727 Abstract ( 184 )   PDF (3501KB) ( 377 )   Save BACKGROUND: Developed by the esteemed Chinese medicine master Wei Guikang, Tongan Decoction has proven highly effective in treating knee osteoarthritis. However, the mechanism of action is yet unclear.  OBJECTIVE: To elucidate how Tongan Decoction modulates synovial macrophage polarization as a therapeutic strategy for knee osteoarthritis in a rat model. METHODS: (1) We employed high-throughput microRNA sequencing and polymerase chain reaction to analyze the differentially expressed miRNA in synovial macrophages of normal and knee osteoarthritis rats. Predicted target genes of miR-27a were identified using bioinformatics databases, with subsequent validation through luciferase assays. A total of 68 Sprague-Dawley rats were randomly divided into normal control group (n=16), model group (n=16), miR-27a overexpression group (n=12), Tongan Decoction group (n=12), and Tongan Decoction+miR-27a inhibition group (n=12). The miR-27a overexpression group and the Tongan Decoction+miR-27a inhibition group were injected with miR-27a mimic and miR-27a inhibitor in the right knee joint cavity, respectively, once daily for 5 continuous days. On the 15th day after modeling, the Tongan Decoction group and the Tongan Decoction+miR-27a inhibition group were given Tongan Decoction by gastric lavage, and the other three groups were given saline by gastric lavage, once daily for 14 continuous days. After administration, behavioral tests, X-rays, hematoxylin-eosin staining of synovial and cartilage tissues of the knee joint and immunofluorescence staining of synovial tissues of the knee joint, RT-PCR, and Western blot were performed. RESULTS AND CONCLUSION: High-throughput sequencing of miRNA showed low expression of miR-27a in synovial tissues of rats with knee osteoarthritis. The target gene of miR-27a was nuclear factor κB, and luciferase assay showed that the two could bind to each other. Behavioral assays showed that miR-27a overexpression or Tongan Decoction alleviated joint dysfunction in rats with knee osteoarthritis, and miR-27a inhibition antagonized the effect of Tongan Decoction. X-ray films and hematoxylin-eosin staining showed that miR-27a overexpression or Tongan Decoction reduced the degree of knee osteoarthritis and miR-27a inhibition weakened the therapeutic effect of Tongan Decoction. The results of RT-PCR and western blot assay showed that compared with the normal control group, the expression of interleukin 10 was reduced in the model group (P < 0.05), and the expression of matrix metalloproteinase 13, interleukin 1β, and nuclear factor κB was elevated in the model group (P < 0.05). miR-27a overexpression or Tongan Decoction could differently reverse the changes in the above-mentioned indexes, while miR-27a inhibition weakened the effect of Tongan Decoction. Immunofluorescence staining results showed that CD86 protein expression in the model group was higher than that in the normal control group (P < 0.05), and CD206 protein expression was lower than that in the normal control group (P < 0.05); miR-27a overexpression group and Tongan Decoction had lower CD86 protein expression than that in the model group (P < 0.05), and higher CD206 protein expression than that in the model group (P < 0.05); in the Tongan Decoction+miR-27a inhibition group, CD86 protein expression was higher (P < 0.05) and CD206 protein expression was lower than that in the Tongan Decoction group (P < 0.05). Tongan Decoction mitigates knee osteoarthritis by upregulating miR-27a expression and suppressing nuclear factor κB activity, which improves knee joint function and further treats knee osteoarthritis. 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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Bioinformatics screening of key genes for endoplasmic reticulum stress in osteoarthritis and experimental validation Hao Maochen, Ma Chao, Liu Kai, Liu Kexin, Meng Lingting, Wang Xingru, Wang Jianzhong 2025, 29 (26):  5632-5641.  doi: 10.12307/2025.628 Abstract ( 173 )   PDF (3168KB) ( 267 )   Save BACKGROUND: Endoplasmic reticulum stress is closely associated with the occurrence and progression of osteoarthritis, but the key genes and regulatory mechanisms remain unclear.  OBJECTIVE: Utilizing bioinformatics to identify crucial endoplasmic reticulum stress-related genes in osteoarthritis, followed by experimental validation in cell models, aiming to offer new strategies for the prevention and treatment of osteoarthritis from the perspective of endoplasmic reticulum stress. METHODS: Osteoarthritis-related dataset GSE55235 was downloaded from the GEO database. Differential genes in synovial tissue of osteoarthritis were obtained through WGCNA machine learning algorithm and intersected with endoplasmic reticulum stress-related genes from the GeneCard database to acquire differential endoplasmic reticulum stress-related genes in osteoarthritis (ERSDEGs). These genes underwent GO and KEGG enrichment analysis, construction of a protein-protein interaction network, and validation of diagnostic efficiency in external datasets. Human primary synovioblast model of osteoarthritis was constructed. The control group was not treated, and the experimental group received 20 ng/mL lipopolysaccharide to simulate osteoarthritic synoviocyte modeling. Real-time fluorescence quantitative PCR was then performed to validate the expression level of each differential gene followed by immune infiltration analysis. RESULTS AND CONCLUSION: A total of 27 key endoplasmic reticulum stress-related genes in osteoarthritis were identified. GO enrichment analysis revealed that these genes were mainly enriched in collagen metabolism, chemokine, antigen binding, and immunoglobulin receptor binding processes. KEGG analysis indicated that they were mainly enriched in pathways such as rheumatoid arthritis and relaxin signaling pathways. The protein-protein interaction network was constructed, and the top five genes with the highest scores were identified using the Degree algorithm in Cytoscape software, including matrix metallopeptidase 1, tumor necrosis factor ligand superfamily member 11, matrix metallopeptidase 9, collagen type I alpha 1, and chemokine C-X-C motif ligand 12. Immune infiltration analysis showed that immune cells were mainly distributed in M2 macrophages, chemokine C-X-C motif ligand 12 showed a significant positive correlation with resting mast cells (r=0.70, P < 0.001) and a significant negative correlation with resting memory CD4+ T cells (r=-0.72, P < 0.001). Matrix metallopeptidase 9 showed a significant positive correlation with M0 macrophages (r=0.94, P < 0.001). Collagen type I alpha 1 was significantly positively correlated with resting NK cells (r=0.77, P < 0.001) and M0 macrophages (r=0.76, P < 0.001). Receiver operator characteristic curve analysis in external datasets GSE77298 and GSE1919 showed that the five key genes had good disease prediction value. In vitro cell experiments demonstrated significant differences in the expression levels of matrix metallopeptidase 1, tumor necrosis factor ligand superfamily member 11, matrix metallopeptidase 9, and chemokine C-X-C motif ligand 12 in the osteoarthritic cell model compared to the control group. These results showed that the key genes related to endoplasmic reticulum stress in osteoarthritis, including matrix metallopeptidase 1, tumor necrosis factor ligand superfamily member 11, matrix metallopeptidase 9, and chemokine C-X-C motif ligand 12, influence the occurrence and development of osteoarthritis through the links of collagen degradation and immune regulation, which are expected to provide new insights into the targeted treatment of osteoarthritis. Figures and Tables | References | Related Articles | Metrics

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Mitochondrial dysfunction and brain aging: a bibliometrics analysis based on the Web of Science Core Collection database Nan Songhua, Peng Chaojie, Cui Yinglin 2025, 29 (26):  5642-5651.  doi: 10.12307/2025.688 Abstract ( 187 )   PDF (3800KB) ( 296 )   Save BACKGROUND: With the rapid development of the biomedical field in recent years, research on brain aging and mitochondrial dysfunction has gradually become an academic hotspot. However, there has yet to be a systematic bibliometric analysis in this field. OBJECTIVE: To comprehensively analyze the research progress in the field of brain aging and mitochondrial dysfunction, and review and summarize relevant literature in the past 20 years, aiming to reveal the current research status, hotspots, and development trends in this field. METHODS: Using the Web of Science Core Collection database as a literature search platform, all documents related to brain aging and mitochondrial dysfunction published from the database inception to May 7, 2024 were collected. The CiteSpace 6.3.R1 visualization analysis tool was used to conduct a multi-dimensional in-depth analysis of the collected literature data, including country, institution, author, keywords, and co-cited literature, in order to reveal the research dynamics and cutting-edge hotspots in this field. RESULTS AND CONCLUSION: This study included 2 534 relevant documents and the number of publications in this field has been yearly increasing both domestically and internationally. The country with the highest number of publications is the United States (974 articles), followed by China (362 articles). At the institutional level, the University of California in the United States ranks first in terms of publication volume (117 articles). In terms of personal contributions, Professor Reddy P. Hemachandra from the Texas Tech Center for Health Sciences is the most prolific scholar in the field, while Professor Mattson MP from the National Institute on Aging in the United States is the most cited scholar. INT J MOL SCI is the most prolific journal in this field. High-frequency keywords include “oxidative stress,” “mitochondrial dysfunction,” “Alzheimer’s disease,” and “Parkinson’s disease.” By analyzing the cutting-edge hotspots in this field, it was found that the focus of research has gradually shifted from the exploration of molecular mechanisms to the search for biomarkers that can be used for the early identification and diagnosis of neurodegenerative diseases. In addition, mitochondrial dysfunction is expected to serve as a clinical interventional target for brain aging-related neurodegenerative diseases. Figures and Tables | References | Related Articles | Metrics

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Intestinal flora regulates bone metabolism: a visual analysis of literature from the Web of Science Core Collection Zeng Hao, Zou Shunyi, Li Zhengpeng, Chai Yuan, Huang Yourong, Zhang Xiaoyun 2025, 29 (26):  5652-5661.  doi: 10.12307/2025.725 Abstract ( 171 )   PDF (3685KB) ( 190 )   Save BACKGROUND: In recent years, a number of studies have confirmed that gut microbiome regulates bone metabolism through multiple pathways, and this field has become a research hotspot in orthopedics and microbiology. However, there is still no literature metrology and visual analysis on this field. OBJECTIVE: To explore the research status, hot spots and development trends in the field of gut microbiome regulation of bone metabolism, and to provide certain data support and reference for subsequent studies. METHODS: The Web of Science core collection database was used as the retrieval platform to retrieve the related literature in the field of intestinal flora regulating bone metabolism from 2004 to 2024. Citespace software was used to visually analyze the included literature and generate a visual atlas. RESULTS AND CONCLUSION: (1)  A total of 1,035 papers were included in this study. In the past 20 years, the number of publications in the field of gut microbiome regulation of bone metabolism has shown a significant growth trend, with the United States and China dominating research and publication activities in this field. Harvard University and the University of California system are the research institutions with the highest number of published papers and research centrality in this area, and Professor Pacifici R of Emory University is the most prolific author. (2) Inflammatory bowel disease, chain fatty acids, bone marrow are the core keywords in this field. Postmenopausal osteoporosis, rheumatoid arthritis, oxidative stress, mitochondrial dysfunction are the latest research frontiers in this field. (3) Among the top 10 cited papers, 4 discussed the mechanism of short-chain fatty acids affecting bone metabolism; 3 investigated the pathogenesis and therapeutic potential of intestinal flora in postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, and senile osteoporosis; 1 discussed the relationship between intestinal inflammation, intestinal flora, parathyroid hormone, and bone metabolism; and 1 examined the effects of Lactobacillus rhamnosus and T cells on the gut microbiome and bone metabolism. (4) NUTRIENTS has the most papers, while ENDOCRINOLOGY & METABOLISM has the most citations. (5) Based on literature co-citation analysis and keywords, further exploration is needed on the specific pathogenesis and treatment strategies of gut microbiome in postmenopausal osteoporosis and rheumatoid arthritis, revealing the molecular mechanism of regulating gut microbiota to inhibit oxidative stress and improve mitochondrial dysfunction affecting bone metabolism, and translating mechanism research into clinical application, which all constitute the future research directions and trends in this field. Figures and Tables | References | Related Articles | Metrics

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Effectiveness of different exercise regimens to reduce fall risks in older adults: a Meta-analysis Zhu Tianrui, Shi Jipeng, Sun Jiahe, Wang Luyi, Zhang Chen, Xu Hongqi, Quan Helong 2025, 29 (26):  5662-5672.  doi: 10.12307/2025.740 Abstract ( 384 )   PDF (2730KB) ( 251 )   Save OBJECTIVE: To explore the efficacy of different exercise regimens to reduce fall risks in older adults.  METHODS: PubMed, Embase, Web of Science, The Cochrane Library, WanFang, and CNKI were searched for studies about exercise interventions on fall risk in healthy older adult individuals at the age of 60 years and above. The search timeframe should cover from the inception of each database to July 2023. Quality assessment and risk-of-bias were assessed using the Cochrane risk of bias tool. Meta-analysis, subgroup analysis, sensitivity analysis, and publication bias were conducted using Review Manager 5.3 and Stata 16.0.  RESULTS: A total of 45 papers containing 54 studies with 3 074 participants were included in the analysis. Overall, exercise intervention can improve the interventional effects on balance (the unipedal stance test with eyes open, functional reach, Timed “Up & Go”, and Berg balance scale), lower limb muscle strength (30-second chair-stand test, Five-Times Sit-To-Stand Test, and Short Physical Performance Battery), and fall-efficacy (Falls Efficacy Scale-International), leading to reduced fall risk (P < 0.05). The Meta-analysis results revealed a dosage effect of different exercise regimens to reduce fall risk in the elderly. Mind-body exercise could efficiently increase scores of the unipedal stance test [mean difference (MD)=6.81, 95% confidence interval (CI) (2.17, 11.44), P < 0.01]; resistance exercise could efficiently increase the scores of the Timed “Up & Go” [MD=-3.12, 95%CI (-5.72, -0.52), P < 0.05] and the 30-second chair-stand test [MD=1.22, 95%CI (0.37, 2.08), P < 0.01]; and multicomponent physical activity could efficiently increase the scores of functional reach [MD=4.50, 95%CI (2.58, 6.42), P < 0.01], Berg Balance Scale [MD=1.05, 95%CI (0.39, 1.71), P < 0.01], Five-Times Sit-To-stand Test [MD=-3.15, 95%CI (-4.80, -1.50), P < 0.01], Short Physical Performance Battery [MD=0.55, 95%CI (0.37, 0.74), P < 0.01], and Falls Efficacy Scale-International [MD=-0.41, 95%CI (0.69, -0.13), P < 0.01].  Conclusion: Exercise interventions can effectively improve balance, enhance limb strength and functional ability, and reduce fear of falling, and lower the risk of falls in older adults. The components of different intervention programs (such as type of exercise, duration, frequency, and session length) have varying dose-response relationships with the results of fall risk screening tests in older adults. Figures and Tables | References | Related Articles | Metrics

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Mechanism of Notch signaling pathway regulating condylar cartilage development and temporomandibular joint inflammation An Xingqi, Li Wenjin 2025, 29 (26):  5673-5679.  doi: 10.12307/2025.741 Abstract ( 185 )   PDF (1525KB) ( 68 )   Save BACKGROUND: The condyle is the most important anatomical structure of the maxillofacial region, and it plays an important role in mastication and articulation of the human body, and its developmental process is quite different from that of the general bone tissues. Abnormal development of the condylar cartilage can lead to various temporomandibular joint disorders to varying degrees, which affects the patient’s quality of life. Abnormal conduction of Notch signaling not only influences the developmental process of the condylar cartilage, but also leads to a series of related diseases such as temporomandibular joint disorders. Aberrant Notch signaling not only affects condylar cartilage development and formation, but also leads to a series of related diseases such as temporomandibular joint disorders. However, the role of Notch signaling pathway in condylar cartilage development and temporomandibular joint disorders has not been fully elucidated.  OBJECTIVE: To deeply investigate the mechanism of Notch and condylar cartilage growth and development, and discuss the core of Notch as a therapeutic target for temporomandibular joint arthritis. METHODS: We retrieved, searched and screened relevant literature in CNKI and PubMed with the keywords “Notch signaling pathway, condylar chondrocyte, condylar cartilage, temporomandibular arthritis” in Chinese and English respectively to provide a theoretical basis for the full text. Using comparative analysis method, we compared the retrieved literature, excluded the literature with similar content, compared the differences between the screened literature, and selected the content needed for this article, providing the theoretical basis for the writing of the article. By further studying and analyzing the screened literature, the mechanism of action between the factors was clarified to provide a clear idea for the article. A total of 1 848 relevant papers were retrieved and 53 papers were finally included for review. RESULTS AND CONCLUSION: (1) The condylar cartilage grows and develops in a more complex manner than other bones, and it undergoes an endochondral osteogenesis. Condylar chondrocyte differentiation is susceptible to a variety of factors, which ultimately affects the formation of cartilage and osteoblasts. (2) The Notch signaling pathway has attracted much attention in recent years, and plays a very important role in condylar growth and development. (3) The Notch signaling pathway consists of four components: four Notch receptors (Notch 1-4), five Notch ligands (JAG 1/2 and DLL 1/3/4), intracellular transcription factors (CSL-binding proteins), and multiple target genes such as Hes and Hey. The Notch signaling pathway is divided into two main pathways: typical pathway and atypical pathway. (4) The Notch signaling pathway is interfered with by factors such as γ-secretase inhibitors or parathyroid hormone-related proteins in vivo, and common factors such as receptors and ligands are expressed abnormally, thus affecting condylar cartilage growth and development. (5) In addition to the various factors in the body, abnormal masticatory stress and excessive loading of the temporomandibular joint can also affect the normal transmission of the Notch signaling pathway, resulting in the abnormal development of the condylar cartilage. (6) The Notch signaling pathway also affects temporomandibular joint arthritis, and the abnormal signaling can affect the pathogenesis of temporomandibular joint arthritis. Figures and Tables | References | Related Articles | Metrics

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Role and mechanism of hypoxia-inducible factor 1 alpha regulating bone homeostasis in oral and maxillofacial diseases Li Zeming, Zhang Yuntao, Wang Maolin, Hou Yudong 2025, 29 (26):  5680-5687.  doi: 10.12307/2025.737 Abstract ( 201 )   PDF (1491KB) ( 188 )   Save BACKGROUND: More and more scholars are investigating the mechanism of hypoxia-inducible factor-1α in regulating bone homeostasis and oral and maxillofacial diseases to provide new targets and strategies for the treatment of related disorders, but there is no relevant review. OBJECTIVE: To summarize the regulatory potential of hypoxia-inducible factor-1α in a variety of oral and maxillofacial diseases and bone homeostasis with the aim of providing a new research direction for oral and maxillofacial bone tissue engineering. METHODS: A literature review was conducted in databases such as PubMed, Web of Science and CNKI, for articles Published from 2003 to 2024. The keywords were “hypoxia inducible factor-1α, oral cavity, bone formation, osteoclast, angiogenesis, oxidative stress, tissue engineering, periodontitis, pulpitis, temporomandibular joint osteoarthritis” in Chinese and English. Finally, 84 articles were included for review. RESULTS AND CONCLUSION: (1) Hypoxia-inducible factor-1α is essential in promoting bone tissue regeneration, facilitating osteogenic-angiogenic coupling, and mitigating damage from oxidative stress in bone tissue. (2) Increasing levels of hypoxia-inducible factor-1α in tissue cells reduces inflammation in periodontitis and promotes periodontal tissue remodeling, pulp regeneration, and involves in joint remodeling after temporomandibular joint osteoarthritis. (3) By stabilizing the level of hypoxia-inducible factor-1α in tissue cells, the micronutrient-carrying biomaterial promotes bone marrow mesenchymal stem cells to migrate and attach to the bone defect area, coupling angiogenesis and osteogenesis to achieve bone regeneration. (4) How to increase the level of hypoxia-inducible factor-1α in oral and maxillofacial tissues using bioactive materials to achieve bone regeneration at maxillofacial bone defects remains to be investigated. Figures and Tables | References | Related Articles | Metrics

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Cellular biomechanisms of Wallerian degeneration in peripheral nerve axon injury Shalayiding·Aierxiding, Aikebaierjiang·Aisaiti, Kutiluke·Shoukeer, Gulimire·Yilihamu, Aikeremujiang·Muheremu 2025, 29 (26):  5688-5694.  doi: 10.12307/2025.709 Abstract ( 158 )   PDF (1280KB) ( 5 )   Save BACKGROUND: Successful regeneration of the peripheral nervous system relies on the damaged neuronal axons and non-neuronal cells, including Schwann cells and immune cells. The cellular processes that promote or limit axonal regeneration will be instructive in improving prognosis after peripheral nerve injury. OBJECTIVE: To review the mechanisms and recent therapeutic advances in peripheral nerve axonal degeneration and regeneration during Wallerian degeneration. METHODS: Utilizing computer-based searches, relevant articles published between 2004 and 2024 were retrieved from the Web of Science Core Collection, WanFang Database, and CNKI Database. The search terms included “peripheral nerve injury, axon injury, axon degeneration, Wallerian degeneration, cells, mechanism” in English and Chinese. Finally, 108 articles were included for review. RESULTS AND CONCLUSION: Wallerian degeneration is a dynamic cellular process that is tightly regulated at the cellular and molecular levels. By unravelling the major roles and cellular molecular biological basis of Wallerian degeneration, it provides a useful framework for understanding Wallerian and Wallerian-like degeneration and lays the foundation for developing new therapeutic strategies to treat peripheral nerve injuries and neurodegenerative diseases. Figures and Tables | References | Related Articles | Metrics

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Role and molecular mechanism of pyroptosis in motor system diseases Geng Longyu, Sheng Li, Bai Shuo, Gao Beiyao, Ge Ruidong, Jiang Shan 2025, 29 (26):  5695-5703.  doi: 10.12307/2025.716 Abstract ( 166 )   PDF (1389KB) ( 144 )   Save BACKGROUND: A large number of studies have found that pyroptosis is closely related to the occurrence and development of motor system diseases, but there are few studies and reviews on pyroptosis in motor system diseases. OBJECTIVE: To review the current clinical and preclinical studies, summarize the role of pyroptosis in motor system diseases and related molecular mechanisms, and provide reference for the pyroptosis-targeted treatment for motor system diseases in the future. METHODS: The relevant literatures in PubMed and CNKI database were searched by computer from January 2000 to January 2024. The English search terms were “pyroptosis, tendons, ligaments, cartilage, muscles, bones” and the Chinese search terms were “pyroptosis, tendon, ligament, cartilage, skeletal muscle, bone” in Chinese. A combination of subject terms and free search terms was used. There were a total of 422 documents, including 334 in English and 88 in Chinese. After excluding duplicate literature and irrelevant literature, the literature without inclusion value was further excluded by reading the whole paper, and finally 78 documents were included for review and analysis. RESULTS AND CONCLUSION: Different pathways of pyroptosis and subsequent inflammatory responses can affect the progression of motor system diseases and the repair process of injuries. Excessive pyroptosis can not only cause a large number of tissue cells to die, but also aggravate tissue inflammation and degrade the extracellular matrix through substances such as inflammatory factors released after cell lysis, and damaging related molecular patterns can act as upstream signals to further aggravate pyroptosis. Current methods for preventing and treating motor system diseases mainly include NOD-like receptor thermal protein domain-associated protein 3 inhibitors, Chinese herbal extracts, exosome therapy, mesenchymal stem cell therapy, and exercise therapy. The review suggests that targeted intervention of some key factors in the process of pyroptosis may be a new direction for the treatment and prevention of motor system diseases. Figures and Tables | References | Related Articles | Metrics

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Role of O-linked N-acetylglucosamine glycosylation in neurodegenerative diseases and its clinical application prospects Jiang Qianping, Yang Dan, , , Wan Shilei, Xu Dandan, , , , Cao Lu, , Zhou Jing, , , 2025, 29 (26):  5704-5712.  doi: 10.12307/2025.699 Abstract ( 248 )   PDF (1711KB) ( 217 )   Save BACKGROUND: The abnormal aggregation of proteins and the loss of neurons are typical pathological changes observed in neurodegenerative diseases. Changes in the levels of O-linked N-acetylglucosamine glycosylation are closely related to relevant pathological changes and are promising potential therapeutic targets. OBJECTIVE: To review the role of O-linked N-acetylglucosamine glycosylation in neurodegenerative diseases and the current advancements in its clinical applications, aiming to provide new insights for the treatment of neurodegenerative disorders. METHODS: The first author conducted a literature search in the CNKI, VIP, WanFang Database, ChiCTR, Web of Science, PubMed, Cochrane Library, Clinical Trials and Alzforum, using the search terms “O-GlcNAcylation, Neurodegenerative diseases, Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington’s disease, OGA inhibitors, Clinical trial” in Chinese and English. A total of 66 relevant articles were included for review. RESULTS AND CONCLUSION: O-linked N-acetylglucosamine glycosylation is involved in the development and functional regulation of neurons, and its levels gradually decrease as neuronal development matures. In neurodegenerative diseases, the pathological proteins involved are regulated by O-linked N-acetylglucosamine glycosylation. Most evidence suggests that using O-GlcNAcase inhibitors to enhance O-linked N-acetylglucosamine glycosylation levels can significantly alleviate related pathological changes, making it a potential therapeutic strategy for neurodegenerative diseases. Some O-GlcNAcase inhibitors have completed Phase I clinical trials, demonstrating good safety and tolerability. Figures and Tables | References | Related Articles | Metrics

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Immune-associated peripheral ulcerative keratitis: feasibility of systemic immunomodulation combined with surgical treatment Liu Xiaohan, Chen Yingxin, Gao Minghong 2025, 29 (26):  5713-5720.  doi: 10.12307/2025.718 Abstract ( 169 )   PDF (1122KB) ( 251 )   Save BACKGROUND: If not detected and treated in a timely manner, immune-associated peripheral ulcerative keratitis can lead to corneal thinning, ulcers and even perforation, thereby causing visual loss and affecting the patient’s quality of life.  OBJECTIVE: To discuss the pathogenesis of immune-associated peripheral ulcerative keratitis and summarize the diagnosis and treatment ideas and the latest treatment methods for this disease. METHODS: Search terms were “peripheral ulcerative keratitis, immunity, immune system disease, pathogenesis, immunomodulatory therapy, surgical treatment, keratoplasty” in English and Chinese. Relevant literature on peripheral ulcerative keratitis published from database inception to October 2024 was searched by computer in CNKI, WanFang, PubMed, and EI databases. A total of 68 papers were ultimately selected to comprehensively describe the new research progress in the research on immune-associated peripheral ulcerative keratitis. RESULTS AND CONCLUSION: Immune-associated peripheral ulcerative keratitis includes Mooren’s ulcer, blepharokeratoconjunctivitis, superior limbic keratoconjunctivitis, and autoimmune related peripheral ulcerative keratitis. Due to the physiology of the corneal limbus, peripheral ulcerative keratitis is usually associated with an immune response, and the pathophysiologic mechanism is usually related to the deposition of immune complexes in the blood vessels at the limbus and the production of microangiitis. Systemic immunomodulatory therapy should be used whether or not an autoimmune disease is diagnosed prior to the onset of immune-associated peripheral ulcerative keratitis, which can help to reduce ocular complications associated with systemic inflammation. Nonsurgical treatment, such as immunomodulatory therapy, is beneficial for relieving ocular symptoms, but when nonsurgical treatment is ineffective or the lesion infiltrates the Descemet membrane, it can cause corneal perforation. Combined surgical treatment can help maintain the structural integrity of the eyeball. However, there is no clear evidence for the combination of immunomodulatory therapy and surgical treatment in the development of immune-associated Peripheral ulcerative keratitis. This article reviews the literature on the diagnosis and treatment of immune-associated peripheral ulcerative keratitiss. Figures and Tables | References | Related Articles | Metrics