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18 November 2024, Volume 28 Issue 32 Previous Issue   

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Metabolomics analysis of serum and urine in patients with traumatic spinal cord injury Song Jiating, Chen Jianmin, Wang Kewen, Huang Lanying, Xu Senming, Gui Yuchang, Xu Jianwen 2024, 28 (32):  5085-5090.  doi: 10.12307/2024.426 Abstract ( 144 )   PDF (1901KB) ( 64 )   Save BACKGROUND: Traumatic spinal cord injury primarily relies on scale assessment and imaging examinations in clinical practice. However, there are limitations in predicting the prognosis of the injury. Therefore, the use of metabolomics technology for biomarker screening is significant for estimating the extent of damage, injury and recovery, as well as developing new therapies. OBJECTIVE: To characterize the metabolic features of patients with traumatic spinal cord injury using metabolomics technology and explore potential biomarkers and disrupted metabolic pathways.  METHODS: Serum and urine samples were collected from 20 patients with traumatic spinal cord injury (observation group) and 10 healthy subjects (control group). Metabolites were analyzed and multivariate statistical analysis was then performed for data processing to screen differential metabolites. Metabolic pathway enrichment was performed using MetaboAnalyst software. Logistic regression was applied to construct a biomarker combination model, and its relationship with the American Spinal Injury Association grading was analyzed.  RESULTS AND CONCLUSION: Significant differences in 160 and 73 metabolites were detected in the serum and urine samples of the two groups, respectively. Pathway enrichment analysis showed evident disturbances in lipid metabolism after traumatic spinal cord injury, including sphingolipid, arachidonic acid, α-linolenic acid, and arachidonic acid metabolism, as well as glycerophospholipid and inositol phosphate biosynthesis. The combination of two identified biomarkers, telmisartan and quercetin glycoside, showed a correlation with the American Spinal Injury Association grading in both serum and urine levels. Thus, metabolomics technology provides assistance in further understanding the pathological mechanisms of traumatic spinal cord injury and screening therapeutic targets. The identified metabolic biomarker combination may serve as a reference for assessing the severity of traumatic spinal cord injury. Figures and Tables | References | Related Articles | Metrics

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Correlation between intervertebral disc degeneration and hyperuricemia Li Yang, Ma Fei, Leng Yebo, Xu Shicai, He Baoqiang, Zhou Jiajun, Liao Yehui, Tang Qiang, Tang Chao, Wang Qing, Zhong Dejun 2024, 28 (32):  5091-5096.  doi: 10.12307/2024.505 Abstract ( 112 )   PDF (936KB) ( 47 )   Save BACKGROUND: Hyperuricemia is a common metabolic disease, and the main clinical manifestation of patients with hyperuricemia is the formation of uric acid crystals leading to gout. Previous studies have only reported that uric acid crystals lead to intervertebral disc degeneration, but there are fewer studies on the correlation between hyperuricemia and intervertebral disc degeneration. OBJECTIVE: To retrospectively analyze the characteristics of intervertebral disc degeneration in patients with hyperuricemia and the correlation between serum uric acid level and intervertebral disc degeneration.  METHODS: A retrospective analysis was performed in all patients diagnosed with intervertebral disc degeneration admitted at the Department of Orthopedics, the Affiliated Hospital of Southwest Medical University from January 2021 to December 2022. There were 97 hyperuricemia patients in the hyperuricemia group and 194 non-hyperuricemia patients in the control group according to sex and age in a ratio of 1:2. Blood uric acid test results were collected, and Pfirrmann scoring was performed for the degree of disc degeneration in patients based on the whole spinal MRI images. The difference in the degree of disc degeneration between the two groups was compared, and the correlation between the serum uric acid level and the degree of intervertebral disc degeneration was analyzed.  RESULTS AND CONCLUSION: The Pfirrmann score in the hyperuricemia group was higher than that in the control group, and the total number of disc degeneration in the hyperuricemia group was also significantly higher than that in the control group (P < 0.05). Spearman correlation analysis showed that the degree of disc degeneration in male patients was positively correlated with serum uric acid level at many spinal segments in the hyperuricemia group (C3/4: r=0.317, C4/5: r=0.333, C5/6: r=0.309, L2/3: r=0.443, P < 0.05); the degree of disc degeneration in female patients was also positively correlated with serum uric acid level (C3/4: r=0.354, C4/5: r=0.388, C6/7: r=0.312, T7/8: r=0.282, T9/10: r=0.305, T11/12: r=0.277, L4/5: r=0.319, L5-S1: r=0.367, P < 0.05). In the control group, there was no significant correlation between the degree of disc degeneration and serum uric acid level in male and female patients (P > 0.05). To conclude, in patients with hyperuricemia, the higher serum uric acid level indicates the more serious intervertebral disc degeneration. Therefore, hyperuricemia is one of the risk factors for intervertebral disc degeneration. Figures and Tables | References | Related Articles | Metrics

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Effect and mechanism of low intensity pulsed ultrasound on early angiogenesis in rats with acute tendon injury Liu Xueli, Shen Li, Bi Wenguang, Mou Yang, Li Sen 2024, 28 (32):  5097-5103.  doi: 10.12307/2024.496 Abstract ( 85 )   PDF (1498KB) ( 32 )   Save BACKGROUND: In recent years, increasing studies have shown that low-intensity pulsed ultrasound can promote the healing of acute tendon injuries, but the specific mechanism is still unclear.  OBJECTIVE: To observe the effect of low-intensity pulsed ultrasound on early angiogenesis after acute tendon injury, and to detect the regulatory relationship of low-intensity pulsed ultrasound with vascular endothelial growth factor-related signaling pathways, so as to reveal its potential mechanism of action.  METHODS: Animal models of acute Achilles tendon injury were established using local injection of type I collagenase for 3 days in SPF male Sprague-Dawley rats aged 8-12 weeks, and were then randomly divided into ultrasound group and control group. In the ultrasound group, low-intensity pulsed ultrasound was treated daily with a small ultrasonic probe with an effective radiation area of 1 cm2 perpendicular to the Achilles tendon. No intervention was performed in the control group. Ultrasound imaging examination was performed 2 weeks later to observe the early healing of the tendon. Hematoxylin-eosin staining and CD31 immunohistochemical staining were performed to observe the changes in the number of blood vessels in the tissues after 1 and 2 weeks of treatment. The expression of vascular endothelial growth factor-related signaling pathway molecules in Achilles tendon tissues was detected by western blot or qRT-PCR.  RESULTS AND CONCLUSION: Compared with the control group, the Achilles tendon in the ultrasound group was more continuous, the echo intensity was lower and more uniform, and the tendon thickness was significantly reduced (P < 0.05). Hematoxylin-eosin staining and CD31 immunohistochemical staining results showed that after 2 weeks of treatment, the number of new vessels in the ultrasound group was significantly increased compared with the control group (P < 0.05). Western blot and qRT-PCR results showed that after 2 weeks of continuous ultrasound intervention, the protein or mRNA expressions of vascular endothelial growth factor, Yes-associated protein, angiopoietin-2 and cysteine-rich angiogenic inducer 61 in the Achilles tendon of the ultrasound group were significantly higher than those of the control group (P < 0.05). These finding indicate that low-intensity pulsed ultrasound significantly increases the number of blood vessels in the early stage of acute tendon injury and accelerate tendon healing by up-regulating vascular endothelial growth factor expression. Figures and Tables | References | Related Articles | Metrics

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Syringin inhibits intervertebral disc degeneration in rats Zhang Yunxin, Zhang Cunxin, Wang Qian, Xu Xinliang, Lyu Chaoliang, Ni Yong 2024, 28 (32):  5104-5109.  doi: 10.12307/2024.506 Abstract ( 81 )   PDF (1479KB) ( 70 )   Save BACKGROUND: Intervertebral disc degeneration is caused by damage and degeneration of the nucleus pulposus and annulus fibrosus tissues inside the intervertebral disc, resulting in structural and functional changes of the intervertebral disc. However, there is yet no effective drug treatment for intervertebral disc degeneration. OBJECTIVE: To investigate the inhibitory effect of syringin on intervertebral disc degeneration. METHODS: A total of 10 male Sprague-Dawley rats were selected, and the coccygeal intervertebral disc (Co4/Co5) of each rat was set as model group, Co5/Co6 intervertebral disc as syringin group, and Co6/Co7 intervertebral disc as control group. The control group did not receive any treatment. In the model group and syringin group, a miniature puncture needle was used to puncture the annulus fibrosus to establish an intervertebral disc degeneration model. Immediately after modeling, 2.5 μL of normal saline and syringin solution (5 μmol/L) were given in the model and syringin groups, respectively. Four weeks after injection, the samples were taken. The  degree of intervertebral disc degeneration in rats was observed by hematoxylin-eosin and safranine O-fast green staining. The expressions of type II collagen, aggrecan and matrix metalloproteinases 3 and 13 in intervertebral disc tissue were analyzed by immunohistochemical staining. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that in the model group, the height of intervertebral disc decreased, the cartilage endplate became thinner and cracked, the fibrous ring structure was disordered and cracked, and the nucleus pulposus disappeared; in the syringin group, the height of intervertebral disc was normal or slightly lower than that in the control group, the degree of cartilage endplate degeneration was lighter than that in the model group, the fiber circle permutation was relatively regular with no cracks, and the nucleus pulposus was partially shrunk. Safranine O-fast green staining showed that in the model group, the cartilage endplate of the intervertebral disc was defective and the calcified layer of cartilage became thinner, showing obvious degeneration. The structure and morphology of intervertebral disc cartilage endplate in the syringin group recovered to some extent. Immunohistochemical staining showed that, compared with the control group, the expressions of type II collagen and aggrecan in the intervertebral disc cartilage were decreased in the model group (P < 0.000 1), while the expressions of matrix metalloproteinases 3 and 13 increased (P < 0.000 1). Compared with the model group, the expressions of type II collagen and aggrecan in the intervertebral disc cartilage tissue were increased in the syringin group (P < 0.001, P < 0.000 1), while the expressions of matrix metalloproteinases 3 and 13 decreased (P < 0.001, P < 0.000 1). These results showed that syringin could improve the structure and function of intervertebral disc by inhibiting the expression of matrix metalloproteinases 3 and 13 and increasing the expression of type II collagen and aggrecan, thus preventing and slowing down the procession of intervertebral disc degeneration. Figures and Tables | References | Related Articles | Metrics

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Visual analysis of high-definition transcranial direct current stimulation research Yan Jie, Zhou Jing, Zhao Jingpu, Zhang Qingfang, Zhou Mingchao, Wang Yulong 2024, 28 (32):  5110-5115.  doi: 10.12307/2024.500 Abstract ( 73 )   PDF (2777KB) ( 69 )   Save BACKGROUND: In recent years, High-definition transcranial direct current stimulation (HD-tDCS) has garnered significant attention due to its potential non-invasive modulation of brain function. However, there is still a lack of visual analysis in the literature regarding this technique. OBJECTIVE: To perform a visual analysis of HD-tDCS-related research so as to explore the current status and trends in this field. METHODS: English literature related to HD-tDCS was retrieved from the Web of Science Core Collection database covering the period from January 1, 2010 to May 6, 2023. The VOSviewer software was used to visualize and analyze the source journals, countries/regions, authors, institutions, cited references, and keywords of the included literature, creating a knowledge map to uncover the research landscape and hotspots. RESULTS AND CONCLUSION: A total of 336 articles were included, showing a consistent increase in the annual publication count of HD-tDCS research. Among these, the United States contributed the highest number of publications (141 articles) with 4 221 citations, followed by China with 70 articles and 401 citations. Brain Stimulation was the most prolific journal (28 articles), Marom Bikson was the most productive author (37 articles), and The City College of New York was the most active institution (35 articles). The most frequently mentioned keywords in the field included motor cortex, regulation, working memory, excitability, and dorsolateral prefrontal cortex. Notable recent keywords in the last 5 years include attention-deficit/hyperactivity disorder, brain networks, and stimulation intensity. Currently, the volume of HD-tDCS research is relatively limited, but is on an upward trajectory, indicating substantial research potential. It is expected that future studies in this domain will continue to focus on the application of HD-tDCS in cognitive and neuropsychiatric disorders, while also exploring its therapeutic mechanisms targeting the motor cortex and dorsolateral prefrontal cortex based on brain network analysis. Figures and Tables | References | Related Articles | Metrics

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Bioinformatics identification and validation of genes related to fatty acid metabolism in rheumatoid arthritis Lu Xiaoling, Liu Bin, Xu Bin 2024, 28 (32):  5116-5121.  doi: 10.12307/2024.544 Abstract ( 72 )   PDF (2902KB) ( 18 )   Save BACKGROUND: Research has shown that fatty acid metabolism genes are closely related to the development of rheumatoid arthritis. Therefore, exploring the progression of rheumatoid arthritis based on fatty acid metabolism genes is of clinical significance. OBJECTIVE: To investigate whether fatty acid metabolism genes can serve as reliable biomarkers for predicting the progression of rheumatoid arthritis. METHODS: Gene data related to synovial tissue were downloaded from the Gene Expression Comprehensive Database (GEO). STRING was used to construct the protein-protein interaction network analysis. Cytoscape was utilized for biological annotation (gene ontology) and signaling pathway enrichment analysis (Kyoto Encyclopedia of Genes and Genomes). Fatty acid metabolism related genes were screened from the molecular feature database (MSigDB). Least absolute shrinkage and selection operator and support vector machine recursive feature elimination feature were used to screen for potential biomarkers. Immune cell infiltration levels in normal individuals and rheumatoid arthritis patients were assessed using the CIBERSORT algorithm. Finally, the expression levels of fatty acid metabolism related genes were verified using the receiver operating characteristic curve in GSE77298. RESULTS AND CONCLUSION: 361 differentially expressed genes in rheumatoid arthritis were identified, of which 13 overlapped with the reported fatty acid metabolism related genes. Based on machine learning algorithms, five genes were selected, and the receiver operating characteristic curve showed that five genes (PCK1, PDK1, PTGS2, PLA2G2D, and DPEP2) could predict the development of rheumatoid arthritis. The CIBERSORT algorithm results showed that five genes were associated with activated mast cells, neutrophils, resting mast cells, and memory resting CD4+ T cells. The receiver operating characteristic curve showed that PLA2G2D and PCK1 have high diagnostic value. To conclude, the expression characteristics of fatty acid metabolism related genes can serve as potential biomarkers for predicting clinical outcomes, which can further improve the accuracy of prediction in RA patients. Figures and Tables | References | Related Articles | Metrics

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Autophagy, ferroptosis-related targets and renal function progression in patients with chronic kidney disease: bioinformatics analysis and experimental verification Chen Guanting, Zhang Linqi, Wang Xixi, Chen Xu 2024, 28 (32):  5122-5129.  doi: 10.12307/2024.510 Abstract ( 105 )   PDF (6017KB) ( 176 )   Save BACKGROUND: Autophagy and ferroptosis play important roles in the development of chronic kidney disease, but the molecular mechanisms and gene targets related to autophagy and ferroptosis in renal tissue of chronic kidney disease are still unclear.  OBJECTIVE: To screen differentially expressed genes in chronic kidney disease-related datasets based on bioinformatics, and to explore potential key biomarkers suitable for screening renal function progression in patients with chronic kidney disease.  METHODS: (1) The GSE137570 dataset was obtained from GEO database to screen the differentially expressed genes by Networkanalyst database analysis. Ferroptosis and autophagy related targets were obtained by OMIM, GENECARD, FerrDb and HAMdb databases. The respective data were intersected to obtain autophagy-ferroptosis related differentially expressed genes in chronic kidney disease for parallel enrichment analysis. The STRING website was used to construct the protein-protein interaction network of differentially expressed genes, which was imported into Cytoscape software and analyzed by MCODE and Cytohubba plug-in to screen potential core targets. Enrichment analysis was performed to obtain the functions of these potential core targets. (2) In the in vitro experiment, mouse renal tubular epithelial cells were divided into two groups: the control group received no intervention, while the model group was stimulated with 5 ng/mL transforming growth factor β1 for 24 hours to induce mesenchymal transformation of renal tubular epithelial cells. Flow cytometry was used to measure the levels of reactive oxygen species and changes in mitochondrial membrane potential in the cells. RT-PCR was employed to assess ferroptosis, autophagy-related markers, and the mRNA expression of potential core targets in the cells.  RESULTS AND CONCLUSION: After screening the GSE137570 dataset, a total of 480 differentially expressed genes were obtained, including 104 upregulated genes and 376 downregulated genes (log2| (FC) | > 1, P < 0.05). There were 562 ferroptosis-related targets and 1 266 autophagy-related targets obtained from the OMIM, GENECARD, FerrDb, and HAMdb databases. Intersection of differentially expressed genes with ferroptosis- and autophagy-related targets yielded 15 ferroptosis-related targets and 18 autophagy-related targets, respectively. The enrichment analysis results indicate that ferroptosis-related differentially expressed genes are primarily involved in biological processes such as sulfur amino acid metabolism, neutrophil degranulation, and ferroptosis signaling pathways. Autophagy-related differentially expressed genes are mainly enriched in biological processes such as platelet degranulation, extracellular matrix degradation, and receptor tyrosine kinase signaling. After screened by MCODE and CytoHubba, key genes were identified in the protein-protein interaction network, including CD44, ALB, TIMP1, PLG, CCL2, and DPP4. Immune infiltration analysis results indicate that immune cells such as B cells, CD4+ T cells, NK cells, and monocytes show significant differential expression in renal tissue after chronic kidney disease, and the core targets are also significantly correlated with these immune cells (P < 0.05). The results of receiver operator characteristic curve analysis further demonstrate that the pathological progression of chronic kidney disease can be effectively diagnosed by CD44, ALB, TIMP1, PLG, CCL2, and DPP4. Single-cell sequencing results show that, except for PLG, the expression of target genes in the renal tissue of mice in each model group is generally consistent with the results of this experiment. RT-PCR results demonstrate that, for the validation of autophagy and ferroptosis phenotypes, compared with the control group, the model group shows a significant decrease in mRNA expression of LC3B, Nrf2, and SLC7A11 (P < 0.05), and a significant increase in P62 mRNA expression (P < 0.05). Regarding the validation of potential core targets, compared with the control group, the model group exhibits a significant decrease in mRNA expression of ALB and PLG (P < 0.05), and a significant increase in TIMP1 and CCL2 mRNA expression (P < 0.05). Overall, these findings indicate that, through bioinformatics analysis and experimental validation, CD44, ALB, TIMP1, PLG, and CCL2 are abnormally expressed in the renal tissue of patients with chronic kidney disease, closely correlated with estimated glomerular filtration rate and tubulointerstitial fibrosis, and maybe play a predictive role in the progression of chronic kidney disease.  Figures and Tables | References | Related Articles | Metrics

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Bone remodeling in the Masquelet-induced membrane model of rat femur by modulation of H-type vessels by total flavonoids of rhizome drynariae Zeng Zhikui, Xiong Wei, Liang Weidong, Qian Guowen, Liang Chaoyi, Pan Bin, Guo Ling, Wei Wenqiang, Qiu Xunxiang, Deng Wenfang, Yuan Lingmei 2024, 28 (32):  5130-5135.  doi: 10.12307/2024.502 Abstract ( 52 )   PDF (1718KB) ( 33 )   Save BACKGROUND: Several studies have found that the total flavonoids of rhizome drynariae can promote neovascularization in the induced membrane, improve the biological properties of the induced membrane, and accelerate bone remodeling in the induced membrane, but the related molecular mechanisms still need to be further explored. OBJECTIVE: To explore the effect of total flavonoids of rhizome drynariae on bone remodeling in rat femoral Masquelet-induced membrane model by regulating H-type blood vessels.  METHODS: Thirty-six male Sprague-Dawley rats were stratified by body mass and then randomly divided into blank group, model group and traditional Chinese medicine group, with 12 rats in each group. A 4-mm femoral bone defect model was established in all the rats. Bone defects in the model group and traditional Chinese medicine group were filled with polymethylmethacrylate bone cement. At 6 weeks after modeling, the tail bone of the rats was implanted in the blank group, as well as in the other two groups after removal of bone cement. The traditional Chinese medicine group was given 157.5 mg/kg per day of total flavonoids of rhizome drynariae at 3 days after bone implantation, while the model and blank groups were given the same amount of saline by gavage until the 8th week after bone implantation. Bone graft samples were taken for relevant testing at 8 weeks after implantation.   RESULTS AND CONCLUSION: X-ray films showed that in the blank group, the fracture line in the defect area was clear, and only a small amount of bone callus formed; in the model group, the bone defect area still existed, where discontinuous cortical bone was visible; in the traditional Chinese medicine group, the defect area was filled with newborn bone tissues, the bone marrow cavity and part of the cortical bone formed, and the fracture line disappeared. Micro-CT scans showed that the amount of new bone in the defect area was low in the blank group, the number of bone trabeculae in the defect area was significantly increased in the model group, and a large amount of new bone tissue was filled in the bone defect area in the traditional Chinese medicine group. Hematoxylin-eosin staining results showed that in the blank group, only a small amount of new bone formed in the defect area and the quality of osteogenesis was poor; in the model group, there was more new bone tissue in the defect area, but some fibrous connective tissues were interspersed within the bone tissue; and in the traditional Chinese medicine group, a large amount of new bone formed in the defect area and the quality of osteogenesis was the best. CD31/Emcn immunofluorescence double-labeling staining results showed that the number of H-type blood vessels in the newborn bone tissue in the bone defect area of the blank group was sparse and sparsely distributed; compared with the blank group, there were more H-type blood vessels in the bone tissue in the bone defect area of the model group, and the blood vessels were distributed in relatively regular strips; the number of H-type blood vessels in the bone defect area of the traditional Chinese medicine group was the highest and the blood vessels were densely distributed. To conclude, the total flavonoids of rhizoma drynariae can upregulate the expression of H-type blood vessels to enhance the angiogenic-osteogenic effect, improve the osteogenic efficiency of the rat femoral Masquelet induced membrane model, and promote bone remodeling. Figures and Tables | References | Related Articles | Metrics

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Effect of ginsenoside Rg1 on muscle degeneration after massive rotator cuff injury in mice He Rongzhen, Ying Lyufang, He Xingwen, Chen Chuanshun, Yin Yuesong, Zhang Kexiang, Wang Zili 2024, 28 (32):  5136-5140.  doi: 10.12307/2024.504 Abstract ( 67 )   PDF (1231KB) ( 20 )   Save BACKGROUND: Rotator cuff muscle degeneration (muscle atrophy, fibrosis and fatty infiltration) is a common condition after rotator cuff tears, which seriously affects shoulder function and surgical outcomes. Ginsenoside Rg1 has biological effects such as anti-oxidation, anti-apoptosis and lipid-lowering. However, the effect of ginsenoside Rg1 on muscle degeneration after rotator cuff tear has not been reported. OBJECTIVE: To investigate the effect of ginsenoside Rg1 on muscle degeneration after massive rotator cuff tear in mice. METHODS: Sixty C57BL/6J mice were randomly divided into sham group, model group, ginsenoside Rg1 low dose group and ginsenoside Rg1 high dose group, with 15 mice in each group. The skin of the right shoulder of mice in the sham group was cut and sutured. Massive rotator cuff tear mouse models of the right shoulder were established in the other three groups. Supraspinatus tendon and suprascapular nerve compression were administrated. Mice in the sham and model groups were intraperitoneally injected with 0.5 mL of saline after operation, while those in the ginsenoside Rg1 low and high dose groups were intraperitoneally injected with ginsenoside Rg1 30 and 60 mg/kg respectively, once a day, for 6 weeks. Mice were assessed for limb function by gait analysis the day after the last injection. After euthanasia, the supraspinatus muscle on the operated side was taken to measure the muscle atrophy rate and muscle contractility. Muscle tissue was stained with oil red O and Masson. RT-PCR was used to detect the expression of atrophy, fibrosis, and fatty infiltration related genes. RESULTS AND CONCLUSION: Compared with the model group, low- and high-dose ginsenoside Rg1 significantly increased paw print area and step length (P < 0.05). Compared with the model group, low- and high-dose ginsenoside Rg1 significantly increased myofiber cross-sectional area and supraspinatus contractility (P < 0.05), and significantly decreased wet muscle mass reduction ratio, fatty infiltration area ratio, and collagen fiber area ratio (P < 0.05). Compared with the model group, low- and high-dose ginsenoside Rg1 significantly decreased the expression of atrophy, fibrosis, and fatty infiltration related genes (P < 0.05). There was no significant difference in paw print area, supraspinatus muscle contractility, and myofiber cross-sectional area between ginsenoside Rg1 low and high dose groups (P > 0.05), and all other indexes were better in the ginsenoside Rg1 high dose group than in the ginsenoside Rg1 low dose group (P < 0.05). To conclude, ginsenoside Rg1 could significantly reduce muscle atrophy, fibrosis and fatty infiltration following massive rotator cuff tear in mice, which is beneficial to improve muscle strength and limb function. Figures and Tables | References | Related Articles | Metrics

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Mechanisms by which high-intensity interval training influences bone health in a rat model of postmenopausal osteoporosis Yang Rui, Cao Kai, Zhao Wei, Wang Qingbo, Lu Chunmin, Zhang Yan 2024, 28 (32):  5141-5147.  doi: 10.12307/2024.498 Abstract ( 67 )   PDF (1134KB) ( 39 )   Save BACKGROUND: Resistance training and weight-bearing exercise are recommended modes for patients with osteoporosis to improve bone health. High-intensity interval training is a high-impact weight-bearing exercise with obvious time-efficient characteristics; however, little attention has been paid to its impact on bones. OBJECTIVE: To observe the effect of high-intensity interval training on the bone health of ovariectomized rat models. METHODS: Thirty-six female Sprague-Dawley rats were randomly divided into sham group, model group and model exercise group (n=12 per group). Bilateral ovariectomy was used to prepare an osteoporosis rat model in the latter two groups. Six weeks after modeling, the model exercise group was subjected to a high-intensity interval training on an electric treadmill at 90% peak running speed for 2 minutes and 50% peak running speed for 1 minute as one session, a total of nine sessions, 3 days per week, for 6 weeks. Rats in the sham and model groups were raised quietly in the mouse cage during the same period. The relevant indexes were tested 48-72 hours after the final training. RESULTS AND CONCLUSION: Compared with the sham group, bone mineral density, maximal load, stiffness, elasticity, trabecular volume fraction, and trabecular number decreased (P < 0.05), while trabecular separation increased (P < 0.05); the level of irisin in the serum, gastrocnemius and femur decreased (P < 0.05); the expression of peroxisome proliferator-activated receptor γ coactivator-1α protein and fibronectin type III domain-containing protein 5 mRNA and protein in the gastrocnemius muscle decreased (P < 0.05); the expression of type I collagen, Osterix, and Runx2 mRNA in the femur decreased (P < 0.05); and the expression of anti-tartrate acid phosphatase, receptor activator of nuclear factor κB ligand, and osteoclast-associated receptor mRNA increased in the model group (P < 0.05). Compared with the model group, bone mineral density, fracture load, maximal load, stiffness, elasticity, average trabecular thickness, and trabecular number increased (P < 0.05), and trabecular separation decreased (P < 0.05); the level of irisin in the serum, gastrocnemius and femur increased (P < 0.05); the expression of peroxisome proliferator-activated receptor γ coactivator-1α protein and fibronectin type III domain-containing protein 5 mRNA and protein in gastrocnemius increased (P < 0.05); the expression of type I collagen, Osterix, and Runx2 mRNA in the femur increased (P < 0.05); and the expression of anti-tartrate acid phosphatase, receptor activator of nuclear factor κB ligand, and osteoclast-associated receptor mRNA decreased in the model exercise group (P < 0.05). To conclude, short-term high-intensity interval training may improve bone health of ovariectomized rats through up-regulating the irisin level. Figures and Tables | References | Related Articles | Metrics

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Effects of electroacupuncture with “Zhi San Zhen” on Notch signaling pathway and synaptic plasticity in 5xFAD mice Wen Huaneng, Lin Run, Wang Yixiao, Wang Bingshui, Liu Lu, Liu Chuanyao, Cai Canxin, Cui Shaoyang, Xu Mingzhu 2024, 28 (32):  5148-5153.  doi: 10.12307/2024.507 Abstract ( 61 )   PDF (1218KB) ( 81 )   Save BACKGROUND: Alzheimer’s disease is a degenerative neurological disorder characterized primarily by cognitive impairment. Acupuncture is a kind of traditional Chinese medicine therapy for treating Alzheimer’s disease, but its mechanism is not yet clear. OBJECTIVE: To observe the effects of electroacupuncture with “Zhi San Zhen” on the Notch signaling pathway, β-amyloid protein (Aβ) and synaptic plasticity in 5xFAD mice. METHODS: Sixteen male, 6-month-old 5xFAD mice, SPF-grade, were randomly divided into the electroacupuncture with “Zhi San Zhen” group (electroacupuncture group) and the model group, with eight mice in each group. Eight SPF-grade, male, 6-month-old C57BL/6 mice were used as the wild control (wild) group. The electroacupuncture group received electroacupuncture with “Zhi San Zhen” intervention, 5 times a week for 4 consecutive weeks. The model group and the wild group did not receive electroacupuncture intervention. The Morris water maze was used to preliminarily assess their learning and memory abilities. Thioflavin S staining was performed to detect Aβ plaque deposition. Western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to measure the expression levels of transmembrane receptor protein Notch-1, Notch 1 intracellular domain (NICD), hairy and enhancer of split 1 (Hes 1), hairy and enhancer of split 5 (Hes 5), synaptophysin (SYN), postsynaptic density protein-95 (PSD-95), and Aβ.  RESULTS AND CONCLUSION: Compared with the model group, the wild group and the electroacupuncture group showed shortened escape latency, increased platform crossing times, and longer target quadrant dwell time (P < 0.05). Compared with the wild group, the model group had significantly increased deposition of Aβ plaques, while electroacupuncture with “Zhi San Zhen” inhibited the deposition of Aβ plaques in the hippocampus of 5xFAD mice  (P < 0.05). Compared with the wild group, the model group had decreased mRNA levels of SYN, PSD-95, Notch 1, NICD, Hes 1, and Hes 5 in the hippocampal tissue of mice, and increased mRNA levels of Aβ (P < 0.05). Electroacupuncture with “Zhi San Zhen” increased the mRNA levels of SYN, PSD-95, Notch 1, NICD, Hes 1, and Hes 5 in the hippocampal tissue, and decreased the mRNA level of Aβ (P < 0.05). Compared with the Wild group, the model group had decreased protein expression levels of SYN, PSD-95, Notch 1, NICD, Hes 1, and Hes 5 in the hippocampal tissue of mice, and increased protein expression levels of Aβ (P < 0.05). Electroacupuncture with “Zhi San Zhen” upregulated the protein expression levels of SYN, PSD-95, Notch 1, NICD, Hes 1, and Hes 5, and inhibited the protein expression of Aβ (P < 0.05). To conclude, electroacupuncture with “Zhi San Zhen” can improve the learning and memory abilities of 5xFAD mice, possibly by inhibiting the deposition of Aβ protein and activating the Notch signaling pathway in the hippocampus to enhance synaptic plasticity. Figures and Tables | References | Related Articles | Metrics

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Modulatory effect of resveratrol on oxidative stress and inflammatory factors in the joint fluid of rats with knee osteoarthritis Ren Weiliang, Jiao Yongwei, Zhang Jian, Yang Liying, Yang Qi 2024, 28 (32):  5154-5158.  doi: 10.12307/2024.497 Abstract ( 69 )   PDF (924KB) ( 108 )   Save BACKGROUND: Knee osteoarthritis is a common clinical degenerative joint disease characterized by chronic inflammation and oxidative stress. Resveratrol has anti-inflammatory and anti-oxidative stress biological effects, and therefore it can be used symptomatically and expected to provide a new strategy for the treatment of knee osteoarthritis. OBJECTIVE: To investigate the therapeutic effect and mechanism of resveratrol on knee osteoarthritis in rats through the silence information regulator 1 (SIRT1)/forkhead transcription factor O1 (FOXO1) pathway.   METHODS: Forty Sprague-Dawley rats were randomly divided into control group, model group, low-dose resveratrol group, and high-dose resveratrol group, with 10 rats in each group. Knee osteoarthritis models were established in the model group, low-dose resveratrol group, and high-dose resveratrol group. A mixture of 4% papain solution and 0.3 mol/L cysteine solution (1:1 for 0.5 hours; 20 μL) was injected at 1, 4, and 7 days after modeling. Rats in the low-dose and high-dose resveratrol groups were injected with 25 and 100 mg/kg resveratrol through the articular cavity at 1 day after successful modeling, while those in the control and model groups were injected with equivalent volume of physiological saline through the articular cavity. After 28 days of treatment, the maximum knee joint activity was measured; the levels of oxidative stress indicators and inflammatory factors in the synovial fluid of the knee joint were analyzed by radioimmunoassay and ELISA; the content of collagen fibers in the knee joint was analyzed by safranin O-fast green staining; the degree of arthritic lesions was analyzed using the Mankin histological score; and the levels of SIRT1 and FOXO1 in the knee joint were detected by western blot assay. RESULTS AND CONCLUSION: Compared with the model group, the maximum knee flexion and extension angles of rats significantly increased in the low-dose and high-dose resveratrol groups, and were significantly higher in the high-dose group than the low-dose group (P < 0.05). Compared with the model group, the levels of superoxide dismutase and glutathione peroxidase in the knee joint fluid of rats significantly increased in the low-dose and high-dose resveratrol groups. The level of malondialdehyde significantly decreased in both resveratrol groups, and the level in the high-dose resveratrol group was significantly better than that in the low-dose resveratrol group (P < 0.05). Compared with the model group, the low-dose and high-dose resveratrol groups showed a significant decrease in the levels of interleukin 1β, interleukin 6 and tumor necrosis factor α in the knee joint fluid of rats, and the levels of these inflammatory factors were significantly lower in the high-dose resveratrol group than the low-dose resveratrol group (P < 0.05). Compared with the model group, the content of collagen fibers in the knee joint was significantly increased in both resveratrol groups, and the high-dose resveratrol group showed a higher content of collagen fibers than the low-dose resveratrol group (P < 0.05). Compared with the model group, the expression level of SIRT1 in the knee joints of rats significantly increased in both resveratrol groups, while the level of acetylated FOXO1 significantly decreased (P < 0.05). The magnitude of changes was significantly better in the high-dose group than the low-dose group. To conclude, resveratrol significantly improves the levels of oxidative stress and inflammatory factors in the joint fluid of rats with knee osteoarthritis and alleviates arthritic symptoms in a dose-dependent manner, possibly through the SIRT1/FOXO1 pathway. Figures and Tables | References | Related Articles | Metrics

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Visualization of the biomechanical characteristics of long-distance running landing patterns Yang Juncong, Huang Rui, Wu Xie 2024, 28 (32):  5159-5166.  doi: 10.12307/2024.515 Abstract ( 90 )   PDF (2655KB) ( 50 )   Save BACKGROUND: In recent years, as the popularity of long-distance fitness running continues to rise, more research progress has been made on related scientific issues. Among them, the landing pattern of long-distance running is an important biomechanical research hotspot at the level of running technique. OBJECTIVE: Using CiteSpace to visualize and analyze the relevant literature, the article sorts through the last decade’s literature on the subject to identify the current state, hot spots, and trends in the footprint as well as to further discuss the main research hotspots of the foot strike pattern from a biomechanical perspective. METHODS: “Foot strike pattern,” “Rearfoot strike,” “non-Rearfoot strike,” “Forefoot strike” and “Midfoot strike” were used as keywords to search the Web of Science Core Collection database.  RESULTS AND CONCLUSION: A total of 896 relevant papers were finally included. The number of articles published in a year showed an overall upward trend. The top three countries in terms of the number of publications were the United States, China and the United Kingdom; the top three institutions were Harvard University, Shanghai University of Sports and the University of Massachusetts; and the top three authors were Davis Irene S, Hamill Joseph and Fu Weijie. The keywords “barefoot running, runner, injury, footing pattern, kinesiology” appear more frequently, and the keyword clusters include “energy cost, loading rate, footing pattern, risk factors, gait analysis”, and the relevant research still continues to be hot to this day. After analyzing the above data in detail, we found that the overall research intensity of foot strike pattern has remained stable in recent years, and the hotspot mainly focuses on the biomechanical research of foot strike pattern; the trend of this kind of research focuses on the influence and adaptability of different strike patterns (forefoot strike and rearfoot strike) on long-distance runners (barefoot, shoes, distance, speed, injury risk, running economy and energy consumption, etc.). Therefore, there is no “standardized optimal landing,” but there may be “individualized optimal landings.” It is suggested that researchers should select the optimal landing pattern and running technique strategy according to their own habitual way, movement pattern characteristics, exercise level and task attributes. Figures and Tables | References | Related Articles | Metrics

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Platelet-rich fibrin regulates apoptosis to promote cartilage repair in rats with knee osteoarthritis Hou Zengtao, Dong Zhiwei, Zhang Jinfeng, Yang Xiaohui, Fan Xiao 2024, 28 (32):  5167-5171.  doi: 10.12307/2024.511 Abstract ( 77 )   PDF (1051KB) ( 85 )   Save BACKGROUND: Platelet-rich fibrin (PRF) is a second generation platelet concentrate with the advantages of simple operation, no anticoagulant, and high bioactivity, which has been applied in the fields of trauma repair, bone defect repair, and tendon soft tissue repair, and has been proved to have a certain tissue repair-promoting effect. OBJECTIVE: To study the repair effect of PRF on articular cartilage tissue in rats with knee osteoarthritis.  METHODS: Thirty-six Sprague-Dawley rats were randomly divided into normal group, model group, and PRF group, with 12 rats in each group. Rats in the normal group did not undergo any treatment. In the model group, animal models of knee osteoarthritis were prepared and rat models were then given physiological saline into the joint cavity once a week after surgery. Rat models of knee osteoarthritis were also prepared in the PRF group, and autologous PRF was injected into the joint cavity once a week after surgery. After 5 weeks of continuous treatment, tissue samples were taken. Hematoxylin-eosin staining was used to observe the morphology of cartilage tissue. Tunel staining was used to detect chondrocyte apoptosis, ELISA was used to detect inflammatory factor levels. Western blot and RT-PCR were used to detect Bcl-2, Bax, and Caspase-3 expression in protein and mRNA levels, respectively.  RESULTS AND CONCLUSION: The model group had severe cartilage tissue damage, while the PRF group had significantly improved cartilage tissue morphology compared with the model group. The model group had more apoptotic chondrocytes. Compared with the model group, the mean absorbance of Tunel positive staining in the PRF group significantly decreased (P < 0.01). The levels of interleukin-1β, interleukin-6 and tumor necrosis factor-α were significantly increased in the model group and PRF group compared with the normal group (P < 0.01) and were significantly decreased in the PRF group compared with the model group (P < 0.01). The relative expressions of Bax and Caspase-3 at protein and mRNA levels were significantly increased in the model group and PRF group compared with the normal group (P < 0.01), while the relative expressions of Bcl-2 at protein and mRNA were significantly decreased (P < 0.01). Compared with the model group, the relative expression of Bax and Caspase-3 at protein and mRNA levels were significantly decreased in the PRF group (P < 0.01), while the relative expressions of Bcl-2 at protein and mRNA levels were significantly increased (P < 0.01). To conclude, PRF can inhibit chondrocyte apoptosis by inhibiting the expression of pro-inflammatory factors, thereby promoting cartilage tissue repair in knee osteoarthritis rats.  Figures and Tables | References | Related Articles | Metrics

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Effect and mechanism of short-chain fatty acids in aged rats with sarcopenia Xu Rui, Li Yanyan, Xu Hong 2024, 28 (32):  5172-5176.  doi: 10.12307/2024.512 Abstract ( 78 )   PDF (1130KB) ( 38 )   Save BACKGROUND: Studies have shown that short-chain fatty acids (SCFAs) are a potential regulator of skeletal muscle energy metabolism, but the exact mechanism is unclear.  OBJECTIVE: To observe the effect of SCFAs on aged rats with sarcopenia and to explore the underlying mechanism.  METHODS: Sprague-Dawley rats were randomly divided into control group, sarcopenia group, and sarcopenia+SCFAs group (SCFAs group). In the latter two groups, rat models of sarcopenia were established using ovariectomized rats injected with 5 mg/kg dexamethasone for 7 days. In the control group, the abdominal cavity was only exposed but not removed, and then sutured. Rats in the SCFAs group were administered drinking water containing 150 mmol/L short-chain fatty acids, 600 mg/kg sodium acetate, 200 mg/kg sodium propionate, and 200 mg/kg sodium butyrate for 4 weeks. Rats in the control and sarcopenia groups were given the same volume of normal saline. Successful modeling was assessed by measuring the bilateral gastrocnemius muscle mass and body mass to calculate the gastrocnemius index after modeling. Food intake, body mass and grip strength of rats were measured at 0, 1, 2 and 4 weeks after successful modeling; morphological changes of gastrocnemius muscle were observed by hematoxylin-eosin staining; and the expression of p-AMPK and p-ULK1 proteins in gastrocnemius muscle was detected by western blot.  RESULTS AND CONCLUSION: Compared with the control group, the sarcopenia group showed significantly decreased body mass, food intake, forelimb grip strength (P < 0.05), wet mass of gastrocnemius muscle (P < 0.05), and protein levels of p-AMPK and p-ULK1 (P < 0.05). Compared with the sarcopenia group, the SCFAs group showed a significant increase in food intake, body mass, grip strength, wet mass of gastrocnemius muscle, and protein levels of p-AMPK and p-ULK1 in gastrocnemius muscle (P < 0.05). All these findings indicate that SCFAs improve symptoms of sarcopenia in the elderly and may be associated with the upregulation of AMPK and ULK1 proteins in skeletal muscle. Figures and Tables | References | Related Articles | Metrics

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Effects of filament B knockdown on proliferation, migration and apoptosis of mouse MC3T3-E1 cells Wang Xi, Yu Li, Jia Qiyu, Huang Jinyong, Liu Zebiao, Zhang Jun, Jiayidaer•Dilimulati, Xie Zengru, Ma Hairong 2024, 28 (32):  5177-5181.  doi: 10.12307/2024.516 Abstract ( 71 )   PDF (1567KB) ( 49 )   Save BACKGROUND: Filamin B (FLNB) can crosslink the actin cytoskeleton into a dynamic structure that is essential for the directional movement of cells. It can regulate the proliferation, differentiation and apoptosis of chondrocytes. However, the effect of FLNB on osteoblast proliferation, migration and apoptosis has not been reported. OBJECTIVE: To investigate the effect of FLNB on the proliferation, migration and apoptosis of MC3T3-E1 cells. METHODS: The adenoviral vectors for knockdown of FLNB expression (sh-FLNB1, sh-FLNB2, sh-FLNB3) were constructed and infected with MC3T3-E1 cells. After screened by puromycin drug, the efficiency of FLNB knockdown was detected by western blot and RT-PCR. The MC3T3-E1 cell line with the best efficiency of FLNB knockdown was selected as the stable transient cell line of MC3T3-E1 for subsequent experiments. The cells were divided into blank group, mc3t3 group, sh-NC group (empty vector), and sh-FLNB group (sh-FLNB lentivirus). The blank group was cultured in cell-free α-MEM complete medium; the mc3t3 group was cultured in α-MEM complete medium alone; and the sh-NC and sh-FLNB groups were cultured with α-MEM medium containing 2.5 μg/mL puromycin. After 3 days of culture, cell counting kit-8 assay and cell scratch assay were used to detect the proliferation and migration ability of MC3T3-E1; flow cytometry was used to detect cell apoptosis; and RT-PCR was used to detect the expression of apoptosis-related genes.  RESULTS AND CONCLUSION: Western blot and RT-PCR results showed that the efficiency of FLNB knockdown was the best in the sh-FLNB3 (P < 0.000 1), which was used as a stable cell line for subsequent experiments. Cell counting kit-8 data showed that the proliferative ability of MC3T3 cells was significantly weakened after knockdown of FLNB (P < 0.05). Cell scratch assay results showed that the migration ability of MC3T3 cells was significantly decreased after knockdown of FLNB. Flow cytometry and RT-PCR results showed that the apoptotic rate of MC3T3-E1 cells increased after knockdown of FLNB, the expression of pro-apoptotic factor Bax increased significantly, and the expression of anti-apoptotic factor Bcl-2 decreased significantly (P < 0.05). To conclude, knockdown of FLNB can reduce the proliferation ability of MC3T3-E1 cells, decrease the migration ability of the cells, and increase cell apoptosis. Figures and Tables | References | Related Articles | Metrics

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Duhuo Jisheng Decoction treats gouty arthritis by inhibiting NLRP3 inflammasome activation Tao Guangyi, Wang Zhengzhen, Huang Jiajun, Wu Diyou, Wang Xinwei, Yang Shun, Yang Bin, Huang Junqing 2024, 28 (32):  5182-5189.  doi: 10.12307/2024.499 Abstract ( 82 )   PDF (1276KB) ( 24 )   Save BACKGROUND: The activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome has been found to be an important factor in the pathogenesis of gouty arthritis, and the activation of NLPR3 inflammasome can be effectively inhibited by regulating the PTEN-induced kinas 1 (PINK1)/Parkin signaling pathway. OBJECTIVE: To investigate the effect of Duhuo Jisheng Decoction on the PINK1/Parkin/NLRP3 signaling pathway. METHODS: (1) Animal experiment: Male Sprague-Dawley rats were randomly divided into control group, model group, positive control group (Qiushuixian tablets 0.3 mg/kg), and low-, medium-, and high-dose Duhuo Jisheng Decoction groups (6.9, 13.8, and 27.6 g/kg, respectively). A rat gouty arthritis model was constructed by injecting monosodium urate crystal suspension into the right hind ankle joint cavity of rats in all the groups except for the control group. (2) Cell experiment: Human monocytes (THP-1) were divided into blank control group, model group, Duhuo Jisheng Decoction-containing serum group, and PINK1 siRNA+Duhuo Jisheng Decoction-containing serum group. The cells in each group except the blank control group were stimulated with sodium urate to establish an in vitro gouty arthritis model. (3) The swelling degree, joint circumference, gait score, joint inflammation index and degree of pathological grading in the ankle joints of rats were observed. Enzyme-linked immunosorbent assay was used to detect the levels of uric acid, C-reactive protein, NLRP3, and interleukin 1β. Immunoblotting assay was used to detect the levels of proteins related to the PINK1/Parkin/NLRP3 pathway. Tetramethyl azolidine blue assay was used to detect cell activity. Immunofluorescent double staining was performed to detect the level of mitophagy. Immunofluorescence was used to detect the expression of NLRP3 and interleukin 1β.  RESULTS AND CONCLUSION: (1) Compared with the control group, rats in the model group showed elevated ankle swelling and ankle circumference at 6-48 hours (P < 0.05), elevated gait scores and joint inflammation indexes at 24 and 48 hours (P < 0.05), elevated serum uric acid and C-reactive protein levels, degree of pathological classification, expression of PINK1, Parkin, and NLRP3 proteins, and interleukin 1β level in synovial tissues (P < 0.05). Compared with the model group, the protein expression levels of PINK1 and Parkin in all the Duhuo Jisheng Decoction groups were elevated, while the levels of the other indexes were decreased (P < 0.05). (2) Compared with the model group, NLRP3 activity, interleukin 1β level and mitochondrial outer membrane translocator protein 20 protein level in the Duhuo Jisheng Decoction-containing serum group were decreased (P < 0.05), while the proliferation inhibition rate, PINK1, Parkin and LC3B protein level were increased (P < 0.05). Compared with the model group, the mitochondrial autophagy level of cells in the Duhuo Jisheng Decoction-containing serum group was elevated (P < 0.05), while NLRP3 and interleukin 1β protein levels were decreased (P < 0.05). (3) Compared with the Duhuo Jisheng Decoction-containing serum group, the mitochondrial autophagy level of cells in the PINK1 siRNA+Duhuo Jisheng Decoction-containing serum group was decreased (P < 0.05), and the expression levels of NLRP3 and interleukin 1β were elevated (P < 0.05). To conclude, Duhuo Jisheng Decoction inhibits the activation of NLRP3 inflammasome by regulating the PINK1/Parkin signaling pathway, thereby exerting a therapeutic effect on gouty arthritis.    Figures and Tables | References | Related Articles | Metrics

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Acupotomy prevents knee osteoarthritis in rats by modulating chondrocyte apoptosis in the mitochondrial pathway Lu Mengya, Wu Xian, She Zeyu, Xia Shuai, Lu Man, Yang Yonghui 2024, 28 (32):  5190-5195.  doi: 10.12307/2024.513 Abstract ( 56 )   PDF (1645KB) ( 14 )   Save BACKGROUND: Acupotomy is effective in the treatment of knee osteoarthritis, but its mechanism is not very clear.  OBJECTIVE: To observe the effect of acupotomy on the apoptosis of knee chondrocytes in knee osteoarthritis rats based on osteoclast associated receptor (OSCAR)-tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL)-osteoprotetin (OPG) pathway.  METHODS: Twenty-seven Sprague-Dawley rats were randomly divided into normal group (n=9), model group (n=9) and acupotomy group (n=9). Rats in the normal group were routinely housed without any treatment. Animal models of knee osteoarthritis were established by knee injection of papain. Acupotomy intervention was performed 1 week after modeling, once a week for a total of three times. Relevant tests were performed at the end of the intervention. RESULTS AND CONCLUSION: The Lequesne MG behavioral scores of rats in the model group were elevated  compared with the normal group (P < 0.01), while the Lequesne MG behavioral scores of rats in the acupotomy group were decreased comparedwith the model group (P < 0.01). Hematoxylin-eosin staining results showed that compared with the normal group, the cartilage surface of the rat’s knee joints in the model group was worn and uneven and the chondrocytes were swollen, ruptured, reduced in number, and arranged disorderly; while the cartilage surface of the rat’s knee joints in the acupotomy group was relatively smooth, and the chondrocytes were high in number and arranged in an orderly manner, with the structure basically clear. Immunohistochemical staining results showed that compared with the normal group, the positive expressions of OSCAR and TRAIL were increased in the model group (P < 0.01), while the positive expression of OPG was decreased (P < 0.01). Compared with the model group, the positive expressions of OSCAR and TRAIL in the acupotomy group were decreased (P < 0.01), while the positive expression of OPG was increased (P < 0.01). TUNEL staining results showed that compared with the normal group, the number of apoptotic cells in the model group were increased (P < 0.01); compared with the model group, the number of apoptotic cells in the acupotomy group decreased (P < 0.01). RT-qRCR and western blot results showed that compared with the normal group, the protein expressions of OSCAR, TRAIL and Bax in the model group were increased (P < 0.01), and the protein expressions of OPG and Bcl-2 were decreased (P < 0.01); compared with the model group, the protein expressions of OSCAR, TRAIL, and Bax in the acupotomy group were decreased (P < 0.01), and the protein expressions of OPG and Bcl-2 were increased (P < 0.01). To conclude, acupotomy can reduce cartilage injury of the knee joint in rats with knee osteoarthritis, which may be related to the blockage of mitochondrial pathway apoptotic signaling release by the OSCAR-TRAIL-OPG pathway. Figures and Tables | References | Related Articles | Metrics

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Trunk pressure biofeedback and its correlation with diaphragmatic functional parameters in young adults Kong Junfeng, Xiao Haibin, Ma Tian, Luo Yu 2024, 28 (32):  5196-5202.  doi: 10.12307/2024.514 Abstract ( 78 )   PDF (1246KB) ( 25 )   Save BACKGROUND: Trunk pressure biofeedback is considered a reliable indicator for assessing core muscle strength. It not only reflects the status of an individual’s trunk strength but also has a close relationship with the function of respiratory muscles.  OBJECTIVE: To explore the correlation between trunk pressure biofeedback and diaphragmatic function in young adults.  METHODS: A total of 80 young adults from Shangrao Normal University, China were enrolled, including 34 males and 46 females, with an average age of (19.83±1.45) years. Diaphragmatic thickness and mobility were measured using a bedside musculoskeletal ultrasound system. Maximum inspiratory pressure was determined using a portable pulmonary function tester. Lumbar and abdominal pressures in prone and supine positions were assessed using a pressure biofeedback device. The degree of correlation between trunk pressure biofeedback and diaphragmatic function was determined using Pearson or Spearman correlation coefficients. A multivariate linear regression analysis was used to determine predictive models for diaphragmatic function.  RESULTS AND CONCLUSION: Grouped by sex, age, height, body mass, trunk pressure biofeedback values, diaphragm thickness during quiet inspiration and expiration, diaphragmatic thickening ratio during quiet breathing, diaphragmatic thickness during deep inspiration and expiration, diaphragmatic thickening ratio during deep breathing, diaphragmatic mobility during deep inspiration, and maximum inspiratory pressure were higher in the male group than the female group (all P < 0.05). Grouped by physical activity level, trunk pressure biofeedback values and maximum inspiratory pressure were lower in the sedentary group than in the exercise group (both P < 0.05). Both anterior and posterior trunk pressure biofeedback were significantly correlated with diaphragmatic thickness during quiet inspiration and expiration, diaphragmatic thickening ratio during quiet breathing, diaphragmatic thickness during deep inspiration and expiration, diaphragmatic thickening ratio during deep breathing, diaphragmatic mobility during deep inspiration, and maximum inspiratory pressure (all P < 0.01). Anterior trunk pressure biofeedback entered the predictive model for diaphragmatic thickness during quiet inspiration (F=27.228, P < 0.001), during deep inspiration (F=38.615, P < 0.001), and along with age for diaphragmatic mobility during deep inspiration (F=15.408, P < 0.001). Anterior trunk pressure biofeedback, body mass, and age entered the predictive model for maximum inspiratory pressure (F=22.314, P < 0.001). To conclude, there is a strong correlation between trunk pressure biofeedback and diaphragmatic thickness, diaphragmatic mobility, and maximum inspiratory pressure. The rapid and simple measurement of trunk pressure biofeedback can serve as a method for screening the diaphragmatic function in healthy young adults. Figures and Tables | References | Related Articles | Metrics

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Sleep characteristics and risk of osteoarthritis: a two-sample and multivariate Mendelian randomization study Chen Jixin, Yu Weijie, Guo Tianci, Zhou Qinxin, Niu Puyu, Ye Yuntian, Liu Aifeng 2024, 28 (32):  5203-5209.  doi: 10.12307/2024.509 Abstract ( 99 )   PDF (1535KB) ( 198 )   Save BACKGROUND: In recent years, epidemiological studies have shown that sleep patterns are risk factors for osteoarthritis, but the causal relationship between sleep characteristics and osteoarthritis remains unknown. OBJECTIVE: To investigate the causal relationship between seven sleep phenotypes and osteoarthritis, thereby providing a theoretical foundation for clinical prevention and intervention of osteoarthritis.  METHODS: Seven sleep-related features, namely sleep duration, wake-up time, daytime napping, morning/evening preference, snoring, insomnia, and hypersomnia, were selected from published genome-wide association studies. Instrumental variables for these sleep-related features were extracted. Instrumental variables for knee osteoarthritis and hip osteoarthritis were obtained from publicly available genome-wide association studies. Causal relationships between sleep characteristics and outcome risks were evaluated using two-sample and multivariable Mendelian randomization analyses. The inverse variance weighted method was employed as the primary Mendelian randomization approach. Various methods, including weighted median, weighted mode, Mendelian randomization-Egger regression, Mendelian randomization pleiotropy-residual sum and outlier, were utilized to detect and correct for the presence of pleiotropy. RESULTS AND CONCLUSION: The results of the inverse variance-weighted method in the two-sample Mendelian randomization study revealed a detrimental causal association between the duration of sleep and the incidence risk of knee osteoarthritis [odds ratio (OR)=0.621, 95% confidence interval (CI): 0.470-0.822, P=0.001]. Concurrently, insomnia displayed a positive causal connection with hip osteoarthritis risk (OR=2.016, 95% CI: 1.249-3.254, P=0.005). Sensitivity analysis affirmed the robustness of these causal relationships, and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy (knee osteoarthritis: P=0.468, hip osteoarthritis: P=0.551). Moreover, the results from the multivariable Mendelian randomization analysis showed that the causal association between insomnia and hip osteoarthritis lacked statistical significance (P=0.715). In contrast, sleep duration exhibited a direct negative causal relationship with the incidence risk of knee osteoarthritis (OR=0.526, 95% CI: 0.336-0.824, P=0.005). Reverse Mendelian randomization analysis indicated that knee osteoarthritis did not influence sleep duration (P=0.757). These findings indicate a negative correlation between sleep duration and incidence risk of knee osteoarthritis, suggesting that correcting insufficient sleep might mitigate the incidence risk of knee osteoarthritis. Figures and Tables | References | Related Articles | Metrics

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Effectiveness of exercise interventions for fibromyalgia syndrome: a Meta-analysis Zhang Jinpu, Wang Junli, Zhang Siqi, Chen Jiahao, Yang Qiushi 2024, 28 (32):  5210-5216.  doi: 10.12307/2024.519 Abstract ( 60 )   PDF (1905KB) ( 171 )   Save OBJECTIVE: Exercise intervention is one of the main treatments for fibromyalgia, but there is no consistent conclusion on the choice of different exercise modalities. In this article, a network Meta-analysis was used to comprehensively and quantitatively evaluate the effects of different exercise modalities on fibromyalgia syndrome.  METHODS: PubMed, EMbase, Scoups, The Cochrane Library, Web of Science, CNKI, WanFang Database, and China Biomedical Literature Database were searched for relevant literature, with a search timeframe from the establishment of each database to June 2023. The outcome indicators included five continuous variables, including fibromyalgia impact questionnaire-revised (FIQ) scores, visual analogue scale (VAS) scores, quality of life, quality of sleep, and depression. The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of the included literature. RevMan 5.4 software was used to perform effect sizes, subgroup analyses, and sensitivity analyses of the data. Stata 17 software was used to perform reticulation and network Meta-analysis of the data.   RESULTS: A total of 13 articles with 14 randomized controlled trials were finally included. The overall methodological quality of the literature was high. The results of traditional Meta-analysis showed that, compared with the control group, exercise therapy significantly improved the FIQ score [standardized mean difference (SMD)=-0.67, 95% confidence interval (CI): -0.83 to -0.50, P < 0.01], VAS score (SMD=-0.72, 95% CI:-0.90 to -0.54, P < 0.01), quality of life (SMD=1.03, 95% CI: 0.45 to 1.61, P=0.000 5), sleep quality (SMD=-0.62, 95% CI: -0.98 to -0.25, P=0.001), and depression (SMD=-0.63, 95% CI: -1.09 to -0.18, P=0.007). Network Meta-analysis showed that the probability of optimal intervention effect of exercise modalities on FIQ scores was ranked as: mind-body exercise (86.5) > resistance exercise (70.5) > aerobic exercise (41.7); the probability of optimal intervention effect of exercise modalities on VAS scores was ranked as: resistance exercise (85.3) > mind-body exercise (74.3) > aerobic exercise (34.5).  CONCLUSION: Exercise therapy significantly improves FIQ scores, VAS scores, quality of life, sleep quality, and depression in patients with fibromyalgia syndrome. Mind-body exercise and resistance exercise are the most effective exercise modalities to reduce FIQ scores and VAS scores in patients with fibromyalgia syndrome. Figures and Tables | References | Related Articles | Metrics

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Effects of different exercise interventions on symptoms and dynamic balance ability of chronic ankle instability: a systematic review and Meta-analysis Su Yuying, Li Wei, Shi Yu, Pan Changbo 2024, 28 (32):  5217-5224.  doi: 10.12307/2024.518 Abstract ( 96 )   PDF (1386KB) ( 119 )   Save OBJECTIVE: Clinically, chronic ankle instability has symptoms such as muscle weakness, loss of control and repeated sprains. These symptoms can be effectively improved by means of exercise intervention. Here, we conducted a comprehensive quantitative evaluation of the effects of exercise intervention on chronic ankle instability at home and abroad through Meta-analysis, and examined the moderating effects of different exercise interventions on chronic ankle instability in terms of effect size and exercise dose.  METHODS: CNKI, WanFang, Web of Science, EBSCO-SPORTD and PubMed were searched and screened for relevant literature regarding randomized controlled trials of an exercise intervention program against chronic ankle instability. Included literature was analyzed by using Review Manager 5.3 and Stata-SE 15.  RESULTS: A total of 52 documents were included with 1 880 patients with chronic ankle instability. Meta-analysis showed that exercise intervention could improve the functional score of patients with chronic ankle instability to a large amount. Neuromuscular control training, a 12-week intervention cycle, and two weekly interventions of > 60 minutes are the best protocol for improving instability symptoms in patients with chronic ankle instability. Exercise intervention could improve the dynamic balance of patients with chronic ankle instability to reach the medium equivalent stress. The best exercise program to improve the dynamic balance ability is a combination of neuromuscular control training and hip strength training, with an exercise dose of 30-60 minutes, two or three times per week, for 8 weeks in total.  CONCLUSION: Different exercise forms have a good effect on improving the unstable symptoms and dynamic balance ability of patients with chronic ankle instability, among which neuromuscular control training has a more comprehensive effect on improving chronic ankle instability. It is recommended that a multifunctional combination of training forms be used as a means of rehabilitation rather than a single form of exercise.  Figures and Tables | References | Related Articles | Metrics

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Near-infrared fluorescence imaging for intraoperative neuroimaging: current applications and future development Gao Wenping, Zhang Zhihua, Han Fei, Hao Weiguo 2024, 28 (32):  5225-5230.  doi: 10.12307/2024.492 Abstract ( 121 )   PDF (937KB) ( 47 )   Save BACKGROUND: Existing neuroimaging techniques, including magnetic resonance imaging, computed tomography, and high-resolution ultrasound, lack the capability to provide real-time intraoperative positioning images to surgeons. However, the clinical implementation of near-infrared fluorescence imaging technology has made it possible to directly visualize surgical target areas, offering a novel solution for real-time nerve identification during surgery. OBJECTIVE: To provide a summary and overview of the research progress in near-infrared fluorescence imaging technology for intraoperative neuroimaging.  METHODS: The first author used the computer to search for the documents published from January 2010 to July 2023 in WanFang, CNKI, and PubMed with the key words of “near-infrared fluorescence imaging, optical imaging, nerve imaging” in Chinese and English. A few classic old documents were also included. Initial screening was performed by reading the titles and abstracts; duplicate, low-quality, and irrelevant content documents were excluded. A total of 69 articles were finally included for review. RESULTS AND CONCLUSION: Near-infrared fluorescence imaging guided by indocyanine green has been clinically used to identify and locate tubular organs such as blood vessels, ureters, and bile ducts, as well as various tumors during surgery. This technique is currently considered a well-established imaging method in precision surgery. In the field of intraoperative neurofluorescence imaging, indocyanine green is currently the only near-infrared fluorescent dye used in clinical research. The ideal neuroimaging agent should possess certain characteristics, including easy administration in the perioperative period, logD between 0.5 and 3 at pH=7.4, molecular mass below 500 Da, excitation and emission wavelengths within the near-infrared window, long-term retention in nerve tissue, high signal-to-background ratio, and high safety. In the future, the development of near-infrared neurofluorescence imaging agents should focus on synthesizing complexes of indocyanine green and neural-specific targets. This technology not only enables intraoperative neurofluorescence imaging, but also holds promising prospects for in-situ monitoring of nerve regeneration and diagnosis of neurological diseases. Figures and Tables | References | Related Articles | Metrics

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Research progress in the effect of estrogen on tendinopathy Sun Qingfeng, Bai Shuo, Zhang Zhen, Shen Liang, Gao Beiyao, Ge Ruidong 2024, 28 (32):  5231-5237.  doi: 10.12307/2024.501 Abstract ( 91 )   PDF (954KB) ( 66 )   Save BACKGROUND: Increasing studies have found that estrogen has a certain correlation with tendinopathy, but for a long time, there are few experiments and summaries of estrogen in tendinopathy, which makes it difficult for specialists and scholars in related fields to fully understand the research status. OBJECTIVE: To summarize the current clinical or preclinical original research, so as to summarize the role of estrogen in tendinosis, and make a certain prospect for the evaluation and management of estrogen in tendinosis in the future. METHODS: Relevant literature in PubMed, Web of Science, CNKI, WanFang, and VIP databases were searched by computer. Search time was from January 2008 to September 2023. The search terms were “oestrogen, estrogen, estrogen receptor, tendinopathy, tendonopathy, sinew, tendon, tendons, myotenositis” in English and “estrogen, estrogen receptor, tendinosis, tendon, tendinitis” in Chinese. According to the selection criteria, the search results were screened and excluded, and finally 60 documents were included for review and analysis. RESULTS AND CONCLUSION: In vivo studies have shown that estrogen can promote tendon anabolism. In vitro experiments have also proved that various estrogens can promote the proliferation of tendon cells and reduce inflammation and apoptosis, but most of the experiments are limited to animal models. Estrogen receptor β acts more in tendon injury and repair processes, but estrogen receptor α has not been found to have a major impact on tendon injury. The expression of estrogen receptor β can repair the tendon by affecting the formation of fat, the deposition of type I collagen and reducing the apoptosis of tendon cells, while its over-expression may promote inflammation and angiogenesis, thus promoting the inflammatory process and playing a role in tendon injury. Animal studies have shown that estrogen deficiency may reduce the synthesis efficiency of collagen in the tendon, decrease the elasticity of tendon, inhibit the synthesis and metabolism of the tendon, which is not conducive to the repair of tendon injury, while normal level of estrogen may stimulate the synthesis of type I collagen in tendon and promote the proliferation and metabolism of tendon cells. At present, the molecular mechanism of estrogen in tendon injury has not been fully explained. More experiments focus on tendon collagen synthesis, cell proliferation and apoptosis. Only a few documents have studied the molecular mechanisms of estrogen receptor β deficiency regulating interferon regulatory factor 5-chemokine ligand 3 axis, E2 regulating estrogen receptor α and PI-3K-Akt signaling pathways, and high levels of estradiol reducing the level of free-circulating insulin-like growth factor. Various estrogens, including endogenous estrogens and phytoestrogens, are beneficial to the repair of tendinopathy at normal levels, and estrogen receptor β mainly affects the formation of fat, the deposition of type I collagen and the reduction of apoptosis of tendon cells through, which lays a foundation for the future treatment of tendinopathy with different subtypes of estrogens in vivo and the influence of estrogen membrane receptors on tendinopathy. Figures and Tables | Related Articles | Metrics

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Characterization and mechanism by which nighttime exercise affects sleep Wang Longteng, Zhou Yuehui 2024, 28 (32):  5238-5242.  doi: 10.12307/2024.503 Abstract ( 94 )   PDF (1546KB) ( 65 )   Save BACKGROUND: With the extensive development of national fitness activities, nighttime exercise has gradually become a social trend. However, what effects nighttime exercise will have on sleep, the characterization of sleeping changes and the mechanisms of action are not clear. OBJECTIVE: To analyze the characterization and mechanisms of nighttime exercise on sleep. METHODS: We searched the China National Knowledge Infrastructure (CNKI), PubMed database, and Web of Science database with the search terms of “sport, exercise, physical activity, physical exercise, workout, sleep, asleep, daily routine” in Chinese, and “nocturnality, night, nighttime, exercise, sport, physical activity, sleep, slumber, dorm” in English for literature on how nighttime exercise affects sleep and its mechanism of action. Finally, 55 articles were included.  RESULTS AND CONCLUSION: Sleep consists of two phases: rapid eye movement and non-rapid eye movement. Sleep regulation relies on the close coordination of neural circuits and molecules in different brain regions, while the homeostatic components of the organism and circadian rhythms are also important factors in the regulation of sleep. The effects of exercise on sleep have evolved from an early focus on the central nervous system to the addition of somatic physiology, and now multiple dimensions have been investigated, revealing multifaceted effects of exercise on sleep, including subjective sleep quality, sleep continuity, and sleep quantity and sleep structure. Nighttime exercise-affected sleep is subjected to the constraints of exercise conditions and exercisers and shows certain complexity, but the heterogeneity, time-dependence, and instability characteristics of nighttime exercise-affected sleep can provide some guidance for nighttime exercisers in minimizing the impact on sleep. Mechanisms by which nighttime exercise affects sleep are related to the reduction of melatonin secretion, the increase of core body temperature, and energy expenditure. People with high sensitivity of their own sleep to nighttime exercise should avoid nighttime exercise as much as possible, and those with low sensitivity should also pay attention to the fact that the time of nighttime exercise should have a long interval with sleeping time, and the intensity should not be too high. Some measures can be adopted to safeguard sleep after exercise, such as energy replenishing after exercise, and reduced use of electronic devices. Figures and Tables | References | Related Articles | Metrics

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High tibial osteotomy promotes cartilage regeneration in the treatment of knee osteoarthritis Fu Qiangchang, Zheng Liming, Jiang Lifeng 2024, 28 (32):  5243-5248.  doi: 10.12307/2024.495 Abstract ( 83 )   PDF (850KB) ( 110 )   Save BACKGROUND: For early knee osteoarthritis in which total knee arthroplasty fails to achieve satisfactory results, high tibial osteotomy that has been found to promote regeneration of damaged cartilage and alleviate symptoms in patients is considered a classic knee-preserving procedure. OBJECTIVE: To review and discuss the effectiveness, mechanism, and application prospects of high tibial osteotomy in stimulating cartilage regeneration in knee osteoarthritis and to provide a theoretical basis for the use of high tibial osteotomy in the treatment of knee osteoarthritis. METHODS: A computerized search was conducted in PubMed, Web of Science, CNKI and WanFang databases for relevant literature published from 2013 to 2023. The search terms used were “knee osteoarthritis, high tibial osteotomy, limb alignment, chondrocytes, biomechanics, intra-articular” in both English and Chinese. Finally, 75 articles were included for review. RESULTS AND CONCLUSION: High tibial osteotomy correcting the lower limb alignment has been found to be effective in alleviating symptoms and potentially delaying or preventing the need for total knee arthroplasty. This is an important aspect of orthopedic step-down treatment in knee osteoarthritis. Maintaining a normal mechanical microenvironment is crucial for the proper functioning and maintenance of chondrocyte phenotype. Abnormal mechanical signals can be converted into intracellular chemical signals through mechanosensors like primary cilia, integrins, cytoskeleton and nucleoskeleton, resulting in disruptions to the balance of matrix metabolism and regulation of inflammatory responses. Chondrocytes after abnormal stress action still have the potential to revert to a normal phenotype under appropriate stress; correction of the mechanical microenvironment by high tibial osteotomy leads to spontaneous cartilage repair and remission of synovial inflammation. The combination of high tibial osteotomy and cartilage regeneration strategy holds promising prospects for patients with early knee osteoarthritis who are not candidates for total knee arthroplasty. Figures and Tables | References | Related Articles | Metrics