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    18 January 2024, Volume 28 Issue 2 Previous Issue   
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    Correlation between the expression of miRNA-142-3p, mixed lineage kinase 3 and interleukin-1beta in nucleus pulposus and the degree of lumbar intervertebral disc degeneration
    Zhou Shuliang, Xu Liang, Qian Xuefeng, Zeng Jincai, Zhu Lifan
    2024, 28 (2):  165-171.  doi: 10.12307/2023.966
    Abstract ( 256 )   PDF (1163KB) ( 40 )   Save
    BACKGROUND: MicroRNA (miRNA) levels are closely related to cell apoptosis and proliferation, extracellular matrix metabolism and inflammatory response in intervertebral disc cells. However, the specific role of miR-142-3p in lumbar intervertebral disc degeneration remains unclear.
    OBJECTIVE: To investigate the correlation between the expression of miRNA-142-3p, mixed lineage kinase 3 and interleukin-1β in nucleus pulposus tissue and degree of human lumbar intervertebral disc degeneration. 
    METHODS: A total of 82 patients with lumbar intervertebral disc degenerative diseases in Suzhou Ninth People’s Hospital from January 2020 to March 2022 were collected as the study subjects, all of whom underwent MRI examination before operation. According to the Videman classification, the patients were divided into mild degeneration group (n=36), moderate degeneration group (n=26) and severe degeneration group (n=20). Eighty-two specimens of the nucleus pulposus were obtained. The mRNA expression of miRNA-142-3p as well as the mRNA and protein expression of mixed lineage kinase 3, interleukin-1β, type I collagen, type II collagen in nucleus pulposus tissue were detected by qPCR and western blot assay. The correlation between the degree of human lumbar intervertebral disc degeneration and the expression levels of miRNA-142-3p, mixed lineage kinase 3, and interleukin-1β was also assessed using the Spearman correlation coefficient method. Thirty adult Sprague-Dawley rats were divided into sham-operated group (executed after puncturing skin and muscle only), mild degeneration group (executed 1 week after puncturing Co7/8 segments) and severe degeneration group (executed 2 weeks after puncturing Co7/8 segments), with 10 rats in each group. After that, we detected the protein expression of mixed lineage kinase 3 and interleukin-1β as well as the gene expression of miRNA-142-3p, mixed lineage kinase 3 and interleukin-1β in the nucleus pulposus tissue.
    RESULTS AND CONCLUSION: In human nucleus pulposus tissue, the miRNA-142-3p expression ranked from high to low as follows: mild degeneration group > moderate degeneration group > severe degeneration group (P < 0.05); the gene and protein expression of mixed lineage kinase 3 and interleukin-1β from low to high was as follows: mild degeneration group < moderate degeneration group < severe degeneration group (P < 0.05); the gene and protein expression of type I collagen from low to high was as follows: mild degeneration group < moderate degeneration group < severe degeneration group (P < 0.05), and the gene and protein expression of type I collagen from high to low was as follows: mild degeneration group > moderate degeneration group > severe degeneration group (P < 0.05). Spearman correlation analysis showed that the degree of disc degeneration was negatively correlated with miRNA-142-3p expression (P < 0.05) and positively correlated with mixed lineage kinase 3 and interleukin-1β expression (P < 0.05). In rat nucleus pulposus tissue, compared with the sham-operated group, the expression of mixed lineage kinase 3 and interleukin-1β gene and protein was elevated in the mild degeneration group (P < 0.05) while miRNA-142-3p expression was decreased (P < 0.05); compared with the mild degeneration group, the expression of mixed lineage kinase 3 and interleukin-1β gene and protein was increased in the severe degeneration group (P < 0.05) while miRNA-142-3p expression was decreased (P < 0.05). To conclude, the degree of human lumbar intervertebral disc degeneration is negatively correlated with miRNA-142-3p expression and positively correlated with mixed lineage kinase 3 and interleukin-1β expression in nucleus pulposus tissue. 
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    Reliability and validity of My Jump 2 application to measure lower limb vertical stiffness of college students
    Song Weijun, Mao Xinyu, Chen Chao, Wang Zhihai, Qu Kaiyuan, Yang Mingming, Wang Dan
    2024, 28 (2):  172-176.  doi: 10.12307/2023.850
    Abstract ( 262 )   PDF (935KB) ( 38 )   Save
    BACKGROUND: Confirming the reliability and validity of the My jump 2 application for measuring lower limb vertical stiffness may offer the possibility of it as an alternative to the Kistler three-dimensional force platform for measuring lower limb stiffness.
    OBJECTIVE: To verify the reliability and validity of the My Jump 2 application in measuring lower limb vertical stiffness of college students.
    METHODS: The drop jump data of the participants were collected through the Kistler three-dimensional force platform and the My Jump 2 application, and the vertical stiffness of the participants’ lower limb vertical stiffness was calculated. The intraclass correlation coefficient was used to analyze the data measured by the My Jump 2 application and the Kistler three-dimensional force platform, attempting to verify the reliability of the My Jump 2 application. The bias and average between the two devices were drawn into a Bland-Altman diagram to verify the consistency between the two test methods. Finally, the test-retest reliability of the My Jump 2 applications at 30 cm and 40 cm was analyzed using the Cronbach’s alpha (α) and coefficient of variation. Pearson product-moment correlation was used to analyze the correlation of My Jump 2 applications.
    RESULTS AND CONCLUSION: My Jump 2 application has high reliability and validity when measuring the vertical stiffness of the lower limb. At the same time, due to its advantages of low cost, convenient portability and field testing for large samples, it can be used as an alternative to the Kistler three-dimensional force platform to test the vertical stiffness of the lower limb in college students and similar populations.
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    Effects of early and late aerobic exercise on right heart failure induced by monocrotaline in rats with pulmonary hypertension
    Sun Yuan, Wang Qingbo, Pi Yihua, Lu Chunmin, Xu Chuanyi, Zhang Yan
    2024, 28 (2):  177-185.  doi: 10.12307/2023.851
    Abstract ( 259 )   PDF (2078KB) ( 30 )   Save
    BACKGROUND: Clinical studies have shown that aerobic exercise is an important supplement to the clinical treatment of patients with pulmonary hypertension, which can alleviate the disease condition, increase exercise tolerance and improve the quality of life. However, it is not clear whether patients at different stages of pulmonary hypertension can benefit equally from exercise training. 
    OBJECTIVE: To compare the intervention effects of early or late aerobic training on right heart failure in rats with pulmonary hypertension and explore its possible mechanism.
    METHODS: Sixty male Wistar rats were randomly divided into control group, model sedentary group, model early exercise group and model late exercise group, with 15 rats in each group. The model of pulmonary hypertension was established by intraperitoneal injection of monocrotaline (60 mg/kg) in the latter three groups. The model early exercise group was given 8 weeks of treadmill aerobic exercise (60% maximum running speed, 60 minutes per day, 5 days a week) after modeling, while the model late exercise group was trained for 6 weeks after 2 weeks of modeling. The control and model sedentary groups were fed quietly in the rat cage for 8 weeks. After training, the exercise performance, right ventricular hemodynamics, cardiopulmonary function, cardiopulmonary histopathology, reactive oxygen species level in mitochondria, activity of mitochondrial respiratory chain complex and expressions of myocardial tissue proteins were detected. 
    RESULTS AND CONCLUSION: Compared with the model sedentary group, exercise performance and right ventricular function improved (P < 0.05), myocardial collagen content, endothelin-1, tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio decreased (P < 0.05), vascular endothelial growth factor and sarcoplasmic reticulum calcium-adenosine triphosphate enzyme expression increased (P < 0.05), immunofluorescence intensity of mitochondrial reactive oxygen species and the protein expression of 3-nitrotyrosine decreased (P < 0.05), the activities of complex I, II, IV and V increased in the model early exercise and model late exercise groups (P < 0.05), but there were no significant changes in right ventricular maximum pressure, pulmonary acceleration time and pulmonary artery wall area/total vascular area ratio (P > 0.05). Compared with the model late exercise group, the model early exercise group further improved exercise performance and right ventricular function, and downregulated collagen content, brain natriuretic peptide protein expression, tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio (P < 0.05). To conclude, although pulmonary vascular remodeling and right ventricular overload persist in rats with pulmonary hypertension, exercise training at different stages of the disease has a cardioprotective effect. The mechanism is related to the improvement of cardiac remodeling, neurohormone system imbalance, inflammatory response and mitochondrial oxidative stress. Greater benefit is gained from initiating exercise in the early stage of the disease. 
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    CXCL5 participates in carotid plaque formation by inducing vascular calcification
    Qi Ming, Wang Lei, Zhang Zhen
    2024, 28 (2):  186-192.  doi: 10.12307/2024.204
    Abstract ( 317 )   PDF (1792KB) ( 27 )   Save
    BACKGROUND: CXC motif chemokine 5 (CXCL5) is a neutrophil activating peptide derived from epithelial cells, which may be involved in arterial diseases. However, there is yet no report on the effect of CXCL5 in vascular calcification.
    OBJECTIVE: To explore the role of CXCL5 in the vascular calcification of carotid atherosclerosis (CAS).
    METHODS: (1) Cytological experiment: Mouse vascular smooth muscle cells (VSMCs) were divided into five groups: osteogenic medium group, Vector group (vector, blank plasmid transfected into VSMCs), CXCL5 group (CXCL5 plasmid transfected into VSMCs), si-NC group (CXCL5 negative control siRNA transfected into VSMCs), si-CXCL5 group (CXCL5 siRNA transfected into VSMCs), Vector+LY2157299 group and CXCL5+LY2157299 group (LY2157299 transferred into the cells 24 hours after cell transfection). Alizarin red staining, alkaline phosphatase staining, and calcium content determination were performed to evaluate the osteogenic differentiation level of VSMCs. (2) Animal experiment: Forty-eight ApoE-/- mice were randomly divided into four groups (n=12 per group): Con+si-NC group, Con+si-CXCL5 group, CAS+si-NC group and CAS+si-CXCL5 group. Animal models were not prepared in the first two groups, in which si-NC or si-CXCL5 lentivirus was injected into the tail vein; carotid atherosclerosis models were made in the latter two groups, in which si-NC or si-CXCL5 lentivirus was injected into the tail vein. Von Kossa staining and immunohistochemical staining were used to evaluate carotid vascular calcification and the expression of CXCL5 and transforming growth factor-β receptor 1 (TGFBR1) in mice. 
    RESULTS AND CONCLUSION: In the CXCL5 group, the protein level of runt-related transcription factor 2 (RUNX2) was up-regulated and the level of α-smooth muscle actin was down-regulated, in contrary to the findings in the si-CXCL5 group. In addition, CXCL5 overexpression upregulated the level of TGFBR1, while CXCL5 knockdown inhibited the level of TGFBR1. Compared with the Vector group, the intensity of alizarin red staining, alkaline phosphatase activity and calcium content in the CXCL5 group increased significantly (P < 0.05). Compared with the si-NC group, the intensity of alizarin red staining, alkaline phosphatase activity and calcium content in the si-CXCL5 group decreased significantly (P < 0.05). When LY2157299 inhibited TGFBR1 expression, the osteogenic differentiation of VSMCs induced by CXCL5 was reduced. Compared with the Con+si-NC group, the expression of CXCL5 protein in the carotid artery and calcification area in the CAS+si-NC group increased significantly (P < 0.05). Compared with the CAS+si-NC group, the expression of CXCL5 protein in the carotid artery and vascular calcification area in the CAS+si-CXCL5 group decreased significantly (P < 0.05). In addition, compared with the Con+si-NC group, the expression of RUNX2 protein in the carotid artery in the CAS+si-NC group increased significantly (P < 0.05), while the expression of α-smooth muscle actin protein decreased significantly (P < 0.05). Compared with the CAS+si-NC group, the expression of RUNX2 protein in the carotid artery in CAS+si-CXCL5 group decreased significantly (P < 0.05), while the expression of α-smooth muscle actin protein increased significantly (P < 0.05). In conclusion, CXCL5 can induce osteogenic transformation of VSMCs by activating the TGFBR1 pathway, and inhibition of CXCL5 expression is effective in improving carotid arterial calcification in CAS mice.
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    Pueraria decoction in the treatment of osteoarthritis: network pharmacology analysis and animal model validation
    Liu Baofang, Xu Bin, Chen Lei
    2024, 28 (2):  193-199.  doi: 10.12307/2023.996
    Abstract ( 298 )   PDF (2050KB) ( 165 )   Save
    BACKGROUND: Pueraria decoction is a famous prescription of traditional Chinese medicine, which has good anti-inflammatory and analgesic effects. The mechanism of Pueraria decoction in osteoarthritis was analyzed using network pharmacology to obtain the main therapeutic components of Pueraria decoction.
    OBJECTIVE: To analyze the mechanism of Pueraria decoction in the treatment of osteoarthritis through network pharmacology and animal experiments.
    METHODS: First, the active ingredients of Pueraria decoction were screened through the Chinese Herbal Medicine Analysis platform (TCMSP) and the genes related to osteoarthritis were collected in the GeneCards database. Second, Cytoscape software was used to construct the “active ingredient-target-disease” network diagram, explore hub genes and analyze gene expression differences. Subsequently, the therapeutic effect of luteolin, one of the main components of Pueraria decoction, was verified in a mouse model of osteoarthritis. Finally, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the gene ontology (GO) enrichment analyses of the target genes were conducted to further explore the relevant mechanisms.
    RESULTS AND CONCLUSION: 115 active ingredients and 147 target genes related to osteoarthritis were identified. GO and KEGG analyses found that Pueraria decoction could affect osteoarthritis through a variety of reaction mechanisms and metabolic pathways. Six hub genes and compounds acting on these genes were determined. Luteolin, the main component of Pueraria decoction, could better promote cartilage repair, accelerate the decrease of typy II collagen and inhibit the expression of matrix metalloproteinase 1 and cyclooxygenase 2 in animal experiments. To conclude, Pueraria decoction contains various active ingredients to prevent the progression of osteoarthritis through oxidative stress and metabolic pathways.
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    Mechanism of compound Shengmai Chenggu capsule in the repair of steroid-induced osteonecrosis of the femoral head
    Lin Tianye, Wu Zhiming, Zhang Wensheng, He Xiaoming, He Mincong, Zhang Qingwen, He Wei, Wei Qiushi, Li Ziqi
    2024, 28 (2):  200-207.  doi: 10.12307/2023.830
    Abstract ( 346 )   PDF (2166KB) ( 48 )   Save
    BACKGROUND: Compound Shengmai Chenggu capsule has good therapeutic effects on early steroid-induced osteonecrosis of the femoral head, but the exact mechanism of treatment is not fully understood.
    OBJECTIVE: To observe the effect of compound Shengmai Chenggu capsule on fucosyltransferase 8, osteogenic gene and Wnt/β-catenin in bone tissue of rats with steroid-induced osteonecrosis of the femoral head.
    METHODS: Sixty Sprague-Dawley rats were randomized into blank group, model group, low-, middle-, and high-dose drug groups (n=12 per group). In the latter four groups, animal models of steroid-induced osteonecrosis of the femoral head were established by subcutaneous injection of imiquimod (once every 2 weeks, 2 times in total) and gluteal muscle injection of methylprednisolone (once a week, 4 times in total). The low-, middle- and high-dose drug groups were given 1.89, 3.78 and 7.56 g/kg per day compound Shengmai Chenggu capsule solution by gavage respectively on the second day after the last modeling. The same amount of saline was given by gavage to the model group. Administration lasted 8 weeks. After the administration, micro-CT scan, histological staining, compression test, RT-qPCR and western blot were performed on the femoral head.
    RESULTS AND CONCLUSION: Micro-CT scan results showed that compared with the blank group, trabecular volume fraction, trabecular number and trabecular thickness were significantly decreased (P < 0.05), while trabecular separation was increased in the model group (P < 0.05). Compared with the model group, the compound Shengmai Chenggu capsule could increase trabecular volume fraction, trabecular number and trabecular thickness (P < 0.05), and decrease trabecular separation (P < 0.05) in a dose-dependent manner. Hematoxylin-eosin staining results showed that compared with the model group, the rate of empty bone lacunae was reduced in a dose-dependent group in the low-, middle-, and high-dose compound Shengmai Chenggu capsule groups 
    (P < 0.05). Immunohistochemical staining results showed that compared with the blank group, the protein expression of fucosyltransferase 8, Runx2 and bone morphogenetic protein 2 was reduced in the model group (P < 0.05); compared with the model group, the compound Shengmai Chenggu capsule increased the protein expression of fucosyltransferase 8, Runx2 and bone morphogenetic protein 2 in a dose-dependent manner (P < 0.05). Results from the compression test showed that there was a dose-dependent increase in the maximum load and elastic modulus of the femoral head in the low-, middle-, and high-dose compound Shengmai Chenggu capsule groups compared with the model group (P < 0.05). RT-qPCR and western blot results showed that the mRNA and protein expressions of fucosyltransferase 8, Runx2, alkaline phosphatase, osteocalcin, osteoblast-specific transcription factor and bone morphogenetic protein 2 were decreased in the model group compared with the blank group (P < 0.05); compared with the model group, there was a dose-dependent increase in the mRNA and protein expressions of the above indicators in the low-, middle-, and high-dose compound Shengmai Chenggu capsule groups compared with the model group (P < 0.05). Compared with the blank group, the mRNA and protein expression of Wnt2, low-density lipoprotein receptor-related protein 5 and β-catenin were decreased (P < 0.05) and the mRNA and protein expressions of glycogen synthase kinase 3β were increased (P < 0.05) in the model group; compared with the model group, there was a dose-dependent increase in the mRNA and protein expressions of Wnt2, low-density lipoprotein receptor-related protein 5 and β-catenin (P < 0.05) but a dose-dependent decrease in the mRNA and protein expressions of lycogen synthase kinase 3β (P < 0.05) in the low-, middle-, and high-dose compound Shengmai Chenggu capsule groups. To conclude, the mechanism by which the compound Shengmai Chenggu capsule treats steroid-induced osteonecrosis of the femoral head may activate the Wnt/β-catenin signaling pathway through the up-regulation of fucosyltransferase 8, thereby promoting bone formation.
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    Molecular docking analysis of the anti-inflammatory mechanism of Cibotium barometz and Epimedium for rheumatoid arthritis: animal experiment validation
    Ran Lei, Han Haihui, Xu Bo, Wang Jianye, Shen Jun, Xiao Lianbo, Shi Qi
    2024, 28 (2):  208-215.  doi: 10.12307/2023.874
    Abstract ( 246 )   PDF (4568KB) ( 165 )   Save
    BACKGROUND: In clinical practice, Cibotium barometz and Epimedium have shown significant efficacy in the treatment of rheumatoid arthritis, but the complex active ingredients contained in the two have an unclear mechanism of action at the molecular level for the treatment of rheumatoid arthritis.
    OBJECTIVE: Based on network pharmacology and molecular docking technology, to establish a collagen-induced arthritis model and to verify the potential targets and pathways of Cibotium barometz and Epimedium in the treatment of rheumatoid arthritis, providing reliable experimental evidence for the use of clinical formulas with Cibotium barometz and Epimedium as the main components.
    METHODS: Utilizing traditional Chinese medicine research platforms, traditional Chinese medicine encyclopedias, and databases of traditional Chinese medicine and chemical components from the Shanghai Institute of Organic, effective ingredients were retrieved and identified. 3D molecular formulas were obtained from the PubChem platform and target predictions were made using PharmMapper and SwissTargetPrediction. Disease targets for rheumatoid arthritis were obtained from gene databases such as DrugBank, GeneCards, and OMIM. The intersections of targets and Cibotium barometz and Epimedium were plotted using VENNY 2.1 after calibration with the Uniport database. A protein-protein interaction network graph was constructed using the STRING platform. Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the Metascape platform for data visualization. A four-layered network model of traditional Chinese medicine, ingredients, targets, diseases, and pathways was constructed using Cytoscape 3.9.0. The main effective ingredients were docked with core targets using AutoDock-Vina software to explore the best binding targets. A type II collagen+adjuvant-induced arthritis rat model was established, and the effects of Cibotium barometz and Epimedium on relevant pathway targets and inflammatory cell factors were observed after 21 days of intervention.
    RESULTS AND CONCLUSION: A total of 28 active ingredients from Cibotium barometz and Epimedium were selected, yielding 288 intersection targets for rheumatoid arthritis. The main ingredients included isobavachalcone, cibotium, and epimedium. The main targets included protein kinase 1 for serine/threonine (AKT1), tumor necrosis factor, and vascular endothelial growth factor A. Gene ontology analysis yielded 2 232 biological processes, mainly related to serine protein phosphorylation, positive regulation of serine/threonine protein kinase, and reactive oxygen metabolism. Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 202 pathways, mainly involving the PI3K/AKT signaling pathway and epidermal growth factor receptor signaling pathway, which may exert therapeutic effects by regulating synovial cell apoptosis and proliferation and suppressing inflammatory factors. Molecular docking results showed the strongest binding activity and stable structure of Cibotium barometz and Epimedium with AKT1 and estrogen receptor transcription factor 1, which was closely related to apoptosis and proliferation and inflammatory signaling pathways such as PI3K/AKT. Cibotium barometz and Epimedium reduced the expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the serum of collagen-induced arthritis rat models. Cibotium barometz and Epimedium reduced the expression of p-PI3K, p-AKT, and p-FOXO1 in the synovium of collagen-induced arthritis rat models. The results indicate that the combination of Cibotium barometz and Epimedium may exert therapeutic effects by inhibiting the proliferation of synovial cells and suppressing the expression of inflammatory factors via the PI3K/AKT/FOXO1 signaling pathway. This may be closely related to the occurrence of inflammation and bone destruction in rheumatoid arthritis, and provides a reference for the rational use and development of new drugs in clinical practice.
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    Mechanism of beta-sitosterol on hypertrophic scar fibroblasts: an analysis based on network pharmacology
    Zuo Jun, Ma Shaolin
    2024, 28 (2):  216-223.  doi: 10.12307/2023.991
    Abstract ( 259 )   PDF (2489KB) ( 51 )   Save
    BACKGROUND: At present, effective preventive and therapeutic measures for hypertrophic scar are still limited. In contrast, most of botanical herbs have few side effects and abundant sources, offering new ideas and approaches for the prevention and treatment for hypertrophic scar.
    OBJECTIVE: To explore the potential molecular mechanism of plant-derived β-sitosterol on hypertrophic scar fibroblasts by network pharmacology and molecular docking techniques and to initially verify it by cytological experiments.
    METHODS: Through the network pharmacology, the relevant database and software were used to screen the drug targets of β-sitosterol and obtain the hypertrophic scar-related disease targets. The potential (intersection) targets of β-sitosterol on hypertrophic scar were obtained. Cytoscape software and STRING database were used to construct the “drug-target-disease” network and protein-protein interaction network, and screen out the core targets in the protein-protein interaction network. Gene ontology (GO) biological function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of intersection targets were conducted through the DAVID database, and the signaling pathways and core target genes closely related to the intersection targets were further identified through literature analysis. AutoDock software was used to perform the molecular docking of β-sitosterol and core target proteins. In vitro cellular assays were used to verify the effects of β-sitosterol on proliferation, apoptosis, cell cycle distribution and mRNA expression of core target genes in human hypertrophic scar fibroblasts.

    RESULTS AND CONCLUSION: There were 56 intersection targets of β-sitosterol and hypertrophic scar and 10 core targets were identified in the protein-protein interaction network, including tyrosine kinase, mitogen-activated protein kinase 3 (MAPK3), cysteine protease 3 (CASP3), apolipoprotein E, estrogen receptor 1, sterol regulatory element-binding transcription factor 1, peroxisome proliferator-activated receptor alpha, C-reactive protein, intercellular adhesion molecule 1, and catalase. Combined with the literatures and the functional analysis of the KEGG and GO, the MAPK signaling pathway was further identified to be closely related to the intersection targets, and MAPK3 (ERK1-MAPK), CASP3, P53 and tumor necrosis factor were identified as the core targets. The molecular docking results indicated that β-sitosterol was well bound to the core target proteins. Cellular assays showed that 100 μmol/L β-sitosterol inhibited hypertrophic scar fibroblast proliferation, decreased mitochondrial membrane potential and induced apoptosis (P < 0.01), increased the proportion of G1-phase cells and decreased the proportion of S-phase cells (P < 0.05), upregulated the mRNA expression of CASP3, P53 and tumor necrosis factor (P < 0.05), and downregulated the mRNA expression of MAPK3 (P < 0.001). To conclude, β-sitosterol may induce cell apoptosis in hypertrophic scar fibroblasts by activating the tumor necrosis factor pathway and upregulating the expression of CASP3 and P53, while inhibiting the ERK-MAPK pathway to arrest cell cycle and thus reduce the proliferation of hypertrophic scar fibroblasts.

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    Sinomenine effectively inhibits interleukin-1beta-induced apoptosis in nucleus pulposus cells
    Wang Qian, Lu Ziang, Li Lihe, Lyu Chaoliang, Wang Meng, Zhang Cunxin
    2024, 28 (2):  224-230.  doi: 10.12307/2023.873
    Abstract ( 216 )   PDF (1676KB) ( 56 )   Save
    BACKGROUND: Intervertebral disc degeneration is the basis of spinal degenerative diseases; however, there is no effective treatment.
    OBJECTIVE: To investigate whether sinomenine can inhibit interleukin-1β-induced apoptosis in nucleus pulposus cells and its molecular mechanism.
    METHODS: Rat nucleus pulposus cells were cultured in vitro by trypsin combined with type II collagenase digestion, and the cell growth curve was plotted. An appropriate sinomenine concentration was determined using the cell counting kit-8 kit. Nucleus pulposus cells were divided into control group, sinomenine group, interleukin-1β group, sinomenine+interleukin-1β group, zinc protoporphyrin group, zinc protoporphyrin+sinomenine group, zinc protoporphyrin+interleukin-1β group, and sinomenine+zinc protoporphyrin+interleukin-1β group. Proliferative activity, reactive oxygen species content, apoptosis rate, and heme oxygenase-1 expression in nucleus pulposus cells were detected.
    RESULTS AND CONCLUSION: The rat nucleus pulposus cells cultured in vitro were polygonal, triangular, and short wedge-shaped, and the cell growth showed an “S” curve. The cells grew slowly in the first 3 days of culture, rapidly in 4-6 days, and slowly again in 7-8 days. The cells then entered the “platform stage” where the number of cells no longer increased. The proliferative activity of myeloid cells showed no significant changes when the concentration of sinomenine was ≤ 80 μmol/L (P > 0.05). Interleukin-1β significantly reduced the proliferative activity of nucleus pulposus cells, increased the content of reactive oxygen species and led to apoptosis (P < 0.01). Sinomenine intervention not only promoted heme oxygenase-1 expression (P < 0.05) but also inhibited interleukin-1β-induced decrease in proliferative activity and increase in reactive oxygen species content and apoptosis rate in nucleus pulposus cells (P < 0.05). These effects could be reversed by zinc protoporphyrin (P < 0.01).
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    Effects of treadmill exercise on osteoporosis and wnt/beta-catenin signal pathway in aged rats
    Yin Linwei, Huang Xiarong, Qu Mengjian, Yang Lu, Wang Jinling, Jia Feiyang, Liao Yang, Zhou Jun
    2024, 28 (2):  231-236.  doi: 10.12307/2023.859
    Abstract ( 157 )   PDF (1062KB) ( 46 )   Save
    BACKGROUND: Exercise training can improve osteoporosis, but its effects and mechanisms on senile osteoporosis are not fully understood.
    OBJECTIVE: To observe the effect of treadmill exercise on osteoporosis and wnt/β-catenin signal pathway in aged rats. 
    METHODS: Sixteen 24-month-old male Sprague-Dawley rats were randomly divided into osteoporosis group (n=8) and treadmill group (n=8) and eight 6-month-old male Sprague-Dawley rats were used as young control group. The model of senile osteoporosis was replicated by natural aging and the rats in the treadmill group were treated with treadmill exercise once a day, 5 days a week, for 8 weeks. Levels of bone metabolic markers such as type I collagen cross-linked C-terminal peptide, tartrate resistant acid phosphatase, osteocalcin and bone specific alkaline phosphatase were detected by ELISA; bone mineral density of the left femur and L5 was measured by dual energy X-ray; bone scanning and bone microstructure quantitative analysis were performed by bone micro-CT; and the mRNA and protein expression levels of wnt3a, β-catenin, LRP5, DKK1 and GSK3β were detected by RT-PCR and western blot, respectively. 
    RESULTS AND CONCLUSION: Compared with the young control group, the osteoporosis group showed a reduction in serum bone specific alkaline phosphatase and osteocalcin levels (P < 0.05), bone mineral density of the femur and L5, the number of tibia and L4 bone trabeculae, bone volume, bone volume fraction (P < 0.05), and mRNA and protein expression of wnt3a, β-catenin, and LRP5 in bone marrow tissue (P < 0.05) as well as an increase in serum levels of tartrate resistant acid phosphatase and type I collagen cross-linked C-terminal peptide (P < 0.05), the intertrabecular space between the tibia and L4, structural model index (P < 0.05), and mRNA and protein expression of DKK1 and GSK3 β in bone marrow tissue (P < 0.05). In addition to the reduced number of trabeculae in the tibia and L4 vertebrae, the trabeculae were structurally disturbed and sparsely aligned and fractured. Compared with the osteoporosis group, the treadmill group showed an increase in serum bone specific alkaline phosphatase and osteocalcin levels (P < 0.05), bone mineral density of the femur and L5 (P < 0.05), the number of tibial trabeculae, bone volume, bone volume fraction (P < 0.05), mRNA and protein expression of wnt3a, β-catenin, and LRP5 in bone marrow tissue (P < 0.05) but a reduction in the serum levels of tartrate resistant acid phosphatase and type I collagen cross-linked C-terminal peptide, L4 trabecular space, tibial trabecular space, structural model index, and mRNA and protein expression of DKK1 and GSK3 β in bone marrow tissue (P < 0.05). In addition to the increased number of tibial and L4 trabeculae, the trabeculae were arranged in a regular and dense pattern and were connected to a network. To conclude, treadmill exercise may improve osteoporosis in aged rats by activating the wnt/β-catenin signal pathway.
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    Establishment and evaluation of a streptozotocin-induced diabetic encephalopathy rat model
    Chen Simin, Hu Yingjun, Yan Wenrui, Ji Le, Shao Mengli, Sun Ze, Zheng Hongxing, Qi Shanshan
    2024, 28 (2):  237-241.  doi: 10.12307/2023.898
    Abstract ( 162 )   PDF (1507KB) ( 28 )   Save
    BACKGROUND: Animal models of diabetic encephalopathy that have been studied mainly include streptozotocin-induced model, high-sugar and high-fat diet-induced model and spontaneous animal model. Establishing a simple, easy, short-cycle, safe and effective model of diabetic encephalopathy can help to explore the subsequent pathogenesis and screen therapeutic drugs. 
    OBJECTIVE: To further explore and evaluate the method of building diabetic encephalopathy rat models.
    METHODS: Twenty Sprague-Dawley rats were randomly divided into control (n=10) and model (n=10) groups. Rats in the model group were given a single injection of 45 mg/kg streptozotocin in the left lower abdominal cavity, and those in the control group were given the same amount of citrate buffer. During the experiment, the body mass, feed intake, water intake and blood glucose were measured. After 8 weeks, the glucose tolerance and oxidative stress levels were measured, and the pathological changes of brain tissue and the expression of apoptotic proteins were compared between groups.
    RESULTS AND CONCLUSION: Compared with the control group, the food intake, water intake, encephalization quotient, blood glucose and area under the blood glucose curve were significantly increased in the model group, while the body mass decreased significantly (P < 0.01). Histopathological examination of the brain showed that compared with the control group, the number of surviving nerve cells was significantly reduced in the model group (P < 0.01), with more significant pathological damage of nerve cells. Compared with the control group, the activities of serum superoxide dismutase, catalase and glutathione in the model group were significantly decreased (P < 0.01), and the content of oxidative malondialdehyde was significantly increased (P < 0.05). The expression levels of apoptosis-related proteins Bax and Caspase-3 in brain tissue increased in the model group compared with the control group, while the expression of Bcl-2 decreased (P < 0.01). In conclusion, an 8-week injection of 45 mg/kg streptozotocin can cause obvious pathological damage to the brain tissue of diabetic rats, to successfully establish the rat model of diabetic encephalopathy.
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    Effects of fascia gun versus stretching on exercise-induced muscle fatigue
    Dai Jiansong, Xin Dongling, Chen Gangrui
    2024, 28 (2):  242-246.  doi: 10.12307/2023.899
    Abstract ( 419 )   PDF (807KB) ( 142 )   Save
    BACKGROUND: There are increasing scientific and technological ways to promote the recovery of muscle fatigue after sports, such as vibrating foam shaft, fascia gun relaxation, and ultra-low temperature cold therapy. Fascia gun relaxation has been widely used in practice, but there is still relatively little research on fascial guns.
    OBJECTIVE: To compare the effects of three relaxation methods (fascia gun, stretching, fascia gun+stretching) on muscle status and muscle strength during the recovery of exercise-induced muscle fatigue, and to provide scientific basis for the application of the three methods in practice.
    METHODS: Forty college students were randomly divided into control group (n=10), stretching group (n=10), fascia gun group (n=10), and fascia gun+stretching group (n=10). All subjects completed leg flexion and extension training at 60%1 RM, 15 times per set, for 10 sets in total, to make exercise fatigue models. After modeling, the subjects were intervened with supine rest, static stretching, fascia gun relaxation, fascia gun+stretching relaxation respectively. Muscle status and muscle strength indexes were tested before exercise, immediately after exercise, immediately after relaxation, 24 and 48 hours after exercise.
    RESULTS AND CONCLUSION: The muscle tension and dynamic hardness of the control group and the stretching group immediately after relaxation were significantly higher than those before training (P < 0.01). However, there was no significant difference in the fascia gun group and fascia gun+stretching group before and after training (P > 0.05). At 24 hours after training, the peak torque of the control group and fascia gun group was significantly lower than that before training (P < 0.01), and there was no significant difference in the stretching group and fascia gun+stretching group before and 24 hours after training (P > 0.05). To conclude, the fascia gun can immediately and effectively improve the muscle state of sports fatigue and stretching can promote the effective recovery of muscle strength within 24 hours after sports fatigue. Relaxation using fascia gun plus stretching can achieve the superposition of the two effects.
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    Effect of different stretching lengths of lingual movable wing on the adduction of mandibular anterior teeth: a biomechanical study
    Zhang Guorui, Zhang Kunwu, Chen Wenyuanfeng, Liu Yining, Li Duhong, Zhang Xinzhu, Cao Baocheng
    2024, 28 (2):  247-251.  doi: 10.12307/2023.988
    Abstract ( 202 )   PDF (1211KB) ( 99 )   Save
    BACKGROUND: Lingual movable wing is a new type of lingual orthodontic technique and the different stretching lengths of the wring affect the torque control effect of anterior teeth. However, there is yet no related biomechanical research. 
    OBJECTIVE: To investigate the displacement trend of dentition during adduction of mandibular anterior teeth and the effect of different wing stretching lengths on the biomechanical effect of mandibular anterior teeth. 
    METHODS: The data of the mandible and lower dentition were collected by cone-beam CT and reconstructed using Mimics software to establish a three-dimensional finite element model of mandibular anterior teeth adducted by the lingual movable wing. The ANSYS software was used to analyze the initial displacement of the mandibular anterior teeth under the following conditions: A, 2 mm stretching length; B, 2.5 mm stretching length; C, 3 mm stretching length; and D, 3.5 mm stretching length.
    RESULTS AND CONCLUSION: The trend of initial displacement of lower dentition: The central incisors moved lingually with depression, the lateral incisors and canines moved mildly lingually with mesial lingual torsion, the second premolar was tilted distally with a marked lingual inclination and the first molar showed an overall mesial inclination with mesial crown eversion. Therefore, in the adduction cases of mandibular tooth extraction, attention should be paid to the lingual movement of the second premolar, which could be offset by corresponding techniques in clinic. The trend of anterior tooth displacement in all directions: from condition A to condition D, in the sagittal direction, the difference value in crown-root displacement of central incisors changed from -11.891 μm to -5.757 4 μm, indicating that the central incisor changes from oblique movement to overall movement. The difference value in crown-root displacement of lateral incisors changed from -11.828 1 μm to -6.711 45 μm, and that of canines changed from -7.572 3 μm to  -4.695 5 μm, indicating that the oblique movement of the lateral incisors and canines is also changing to an overall movement. In the vertical direction, from condition A to condition D, the reduction of incisors was gradually increased, while that of canines was gradually decreased. These findings indicate that the stretching length of the wing can affect the oblique movement trend of the anterior teeth. As the wing continues to stretch, the torque control of the lower anterior teeth will become better.
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    Computer aided design of 3D dental segmentation and its application scenarios
    Cui Jiali, Huang Minhui, Liu Donglin, Jia Ruiming, Li Han
    2024, 28 (2):  252-257.  doi: 10.12307/2023.951
    Abstract ( 231 )   PDF (1492KB) ( 50 )   Save
    BACKGROUND: Traditional 3D dental segmentation methods usually utilize predefined spatial geometric features, such as curvature and normal vectors, as the reference information for tooth segmentation.
    OBJECTIVE: To propose an algorithm for complex 3D dental segmentation and deeply explore the correlation between segmentation results and application scenarios. 
    METHODS: A 3D dental segmentation algorithm based on dual stream extraction of structural features and spatial features was established, and the modular design of split flow was used to avoid feature confusion. Among them, the attention mechanism on the structural feature flow was used to capture the fine-grained semantic information required for tooth segmentation, and the Tran Net based on the spatial feature flow was used to ensure the robustness of the model to complex tooth and jaw segmentation. This algorithm verified its effectiveness and reliability based on clinical datasets including healthy dental jaws and complex dental jaws such as missing teeth, malocclusion and dentition crowding. The segmentation performance of the model was measured in terms of overall accuracy, mean intersection over union, and directional cut discrepancy. 
    RESULTS AND CONCLUSION: The overall segmentation accuracy of this algorithm in the clinical data set is 97.08%, and the segmentation effect is superior to that of other competitive methods from the qualitative and quantitative perspectives. It is verified that the structural feature flow designed in this paper can extract more precise local details of tooth shape from coordinate and normal information by constructing an attention aggregation mechanism, and the spatial feature flow designed in this paper can ensure the robustness of the model to complex teeth such as missing teeth, dislocated teeth, and crowded dentition by constructing a transformation network (Tran Net). Therefore, this tooth segmentation algorithm is highly reliable for clinicians' practical reference.
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    Application trends of blood flow restriction training in clinical rehabilitation
    Xie Enli, Tao Huimin
    2024, 28 (2):  258-262.  doi: 10.12307/2023.872
    Abstract ( 372 )   PDF (819KB) ( 109 )   Save
    BACKGROUND: The use of blood flow restriction training in clinical rehabilitation is becoming more common, in part due to technological advances and increased interest in research and medicine.
    OBJECTIVE: To explore the global trend and development prospects of clinical rehabilitation-related blood flow restriction training application, identify research gaps, and propose future research directions. 
    METHODS: Web of Science, PubMed, and Elsevier were searched for literature related to clinical rehabilitation using blood flow restriction training published from 2001 to 2022. A total of 515 articles were included for further review. Bibliometrics, exploratory factor analysis and cluster analysis were used to reveal the emerging research fields and topics. 
    RESULTS AND CONCLUSION: First of all, the overall research trend of the number of published articles shows a steady rise. The United States is the main research area in this field, and universities contribute the most to journals. Secondly, a core group of authors, led by Loenneke JP, Abe T and Dankel SJ, has been formed, with less collaboration among highly productive authors. Finally, research on blood flow restriction training focuses on skeletal muscle rehabilitation, cognitive functional activity, and chronic disease rehabilitation in clinical rehabilitation, with particular attention to the application of blood flow restriction in the recovery of symptoms such as muscle atrophy, knee pain, and joint effusion after anterior cruciate reconstruction surgery. Theoretical research on low-pressure blood flow restriction that is effective in relieving musculoskeletal symptoms has been hot in recent years, which can systematically guide the musculoskeletal rehabilitation in clinical practice. In the future, clinicians will extend follow-up periods, register larger and more diverse sample sizes, and use randomization techniques to determine appropriate prescribing indications for rehabilitating patients, ensure clinical safety, and quantitatively analyze and develop rehabilitation protocols with the maximum effect at the minimum effective dose for different clinical populations.
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    A systematic review of mouse model construction for sarcopenia
    Xie Peng, Zhang Jiang, Deng Xiaolei, Wei Bo, Hou Decai
    2024, 28 (2):  263-266.  doi: 10.12307/2023.895
    Abstract ( 414 )   PDF (785KB) ( 51 )   Save
    BACKGROUND: Sarcopenia is a progressive, generalized skeletal muscle disease that is closely related to the occurrence of osteoarthritis, fractures, limb disability and death in the elderly. Establishing animal models of sarcopenia is essential to understand the pathophysiology of sarcopenia and to identify effective treatment strategies.
    OBJECTIVE: To review the evaluation criteria of mouse models of sarcopenia and the modeling methods of mouse models of sarcopenia, and to analyze and compare the advantages and disadvantages of various modeling methods, in order to provide reference for the research and diagnosis and treatment of sarcopenia.
    METHODS: “Sarcopenia, skeletal muscle aging, mouse model, animal model” in Chinese and English were used as Chinese and English search terms, respectively. The search formula was “(sarcopenia OR skeletal muscle aging) AND (mouse model OR animal model).” CNKI, WanFang and PubMed were searched for related articles published from January 2010 and October 2022. A total of 59 articles were finally included for analysis.

    RESULTS AND CONCLUSION: There is a faster modeling time in SAMP8 mice and the type of muscle atrophy is consistent with that of patients with sarcopenia. Therefore, it is an ideal model. Although the surgical method can successfully induce muscle atrophy, it requires precise surgical operation, which is difficult and time-consuming. Hindlimb suspension modeling in mice is similar to that of the elderly and can be regarded as an effective model of senile sarcopenia. Although reagent injection molding is simple to perform, both the dose and number of days of administration of reagents are not clear and need to be further investigated. Transgenic mouse models are less commonly used and their model stability needs further study. The search for a mouse model with low cost, short time consumption and high simulation of human sarcopenia is still a future research direction.

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    Resistance exercise improves body composition in overweight and obese people: an umbrella review
    Dai Xinyu, Yan Jihong, Hua Lingjun, Zheng Xiaohong
    2024, 28 (2):  267-271.  doi: 10.12307/2023.848
    Abstract ( 319 )   PDF (914KB) ( 52 )   Save
    BACKGROUND: Resistance exercise increases muscle mass and improves muscle strength, but there is a lack of conclusive evidence on its effects on body composition. Controversial results from randomized controlled trials and multiple Meta-analyses pose a problem for clinical decisions on exercise interventions.
    OBJECTIVE: Based on the methodological paradigm of umbrella review, to explore the efficacy and safety of resistance exercise in improving the body composition of overweight and obese people.
    METHODS: We searched PubMed, Cochrane Library, Web of Science, and CNKI for systematic reviews on the effect of resistance exercise in overweight and obese people published from database inception to August 31, 2022. Chinese search terms included “anti-resistance, resistance, self-weight, Meta, Meta-analysis, body composition, body fat percentage, fat mass, lean body mass, body mass.” English search terms included “resistance training, strength training, weight-lifting strengthening program, body composition, body fat distribution, Meta-analysis, data pooling, overviews, clinical trial, clinical trial overviews.” PRISMA was used to evaluate the methodological quality of the included studies, and a GRADE evaluation system was used to grade the quality of evidence.
    RESULTS AND CONCLUSION: A total of 14 Meta-analyses were included, and GRADE evidence quality evaluation showed that 2 outcome indicators were intermediate, 12 were low, and 14 were extremely low. Compared with the control group, 23 of the 32 outcome measures showed significant improvement. The intervention effect of resistance exercise on body fat percentage has reached a consensus, but the intervention effects on lean body mass, body mass index and visceral fat still need further confirmation. Resistance exercise is an effective and safe method to improve the body composition of overweight and obese people. The overall quality of the research and the evidence quality of the outcome indicators included in the systematic evaluation are generally low. In the future, the initial state, exercise goal and willingness of the subjects should be fully combined on the basis of clarifying the sample characteristics and refining the scheme design. Through multiple, scientific and personalized exercise prescription designs of water, air and elastic resistance, the safety and compliance of resistance exercise can be improved, providing clear evidence-based support and decision-making basis for resistance exercise intervention.
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    MiRNA-122 contributes to the effect of exercise on non-alcoholic fatty liver
    Guo Xiangying, Peng Zifu, He Yimin, Fang Hongbo, Jiang Ning
    2024, 28 (2):  272-279.  doi: 10.12307/2023.475
    Abstract ( 286 )   PDF (1120KB) ( 29 )   Save
    BACKGROUND: In recent years, with the improvement of living standards, non-alcoholic fatty liver disease has a gradually increasing trend. miRNA-122 is one of the most abundant microRNAs in the liver, which plays an important role in maintaining the environmental stability and differentiation of the liver. Exercise training is a non-drug treatment for non-alcoholic fatty liver disease, which may improve liver lipid metabolism by regulating the expression of miRNA-122.
    OBJECTIVE: To review the effects of miRNA-122 on the pathological factors related to non-alcoholic fatty liver disease as well as the effects of exercise on the expression of miRNA-122 and the occurrence and development of nonalcoholic fatty liver disease.
    METHODS: The first author searched the databases of CNKI, WanFang, VIP, PubMed, Geenmedical, EBSCO, Medline, Web of Science, and Elsevier using “non-alcoholic fatty liver disease, microRNA, microRNA-122, lipid metabolism, inflammatory response, insulin resistance, exercise, physical exercise, exercise training” as the English and Chinese search terms for all relevant literature published before June 5, 2022. All included documents were screened, summarized, and analyzed. Finally, 68 documents were included for review.
    RESULTS AND CONCLUSION: Compared with the healthy control group, the expression of circulating miRNA-122 is increased in patients with non-alcoholic fatty liver disease. The level of miRNA-122 may show different expression levels at different stages of non-alcoholic fatty liver disease. miRNA-122 can regulate the expression of downstream-related proteins, influence lipid metabolism, inflammatory response, insulin resistance and other pathogenic factors in non-alcoholic fatty liver disease by targeting base complementary pairing sites on mRNA or directly acting as physiological ligands of some RNA receptors. Different exercise modes can improve non-alcoholic fatty liver disease. Therefore, patients with non-alcoholic fatty liver disease need to complete at least 120 minutes of moderate-intensity exercise every week to have a positive effect. For patients who can tolerate various exercises, priority should be given to the combination of aerobic and resistance exercises 4-5 times a week. The exercise intensity should be 50%-70% of the maximum heart rate and the exercise should last for > 3 months. For patients with poor tolerance, resistance exercise may be more feasible than aerobic exercise. In addition, patients with non-alcoholic fatty liver disease can also choose proper exercise modes according to their own disease conditions (such as liver enzymes and lipid levels). Exercise can be used as a feasible strategy to prevent non-alcoholic fatty liver disease, reduce liver steatosis, and alleviate liver inflammatory response and insulin resistance. Exercise training can regulate the expression of miRNA-122, but in patients with non-alcoholic fatty liver disease, the effect of exercise on miRNA-122 and its related signal pathways remains to be studied.
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    Effects of immune cells and related cytokines in the pathogenesis and treatment of osteoarthritis
    Meng Zhicheng, Qiao Weiping, Zhao Yang, Liu Hongfei, Li Kaijie, Ma Bo
    2024, 28 (2):  280-287.  doi: 10.12307/2023.679
    Abstract ( 258 )   PDF (1018KB) ( 39 )   Save
    BACKGROUND: The occurrence and development of osteoarthritis is strongly associated with immune abnormalities, and the importance of various immune cells and immune mediators in the pathogenesis of osteoarthritis has been continuously elucidated.  
    OBJECTIVE: To review the role of immune cells and related cytokines in osteoarthritis disease, and provide new ideas for future research and prevention of osteoarthritis.
    METHODS: Taking “osteoarthritis, knee, macrophages, T cells, B cells, natural killer cells, dendritic cells, cytokines, inflammatory factors, immune cells” as search terms, relevant published literature was searched on CNKI, WanFang, VIP, PubMed and Web of Science databases. After reading the title and abstract for preliminary screening, 98 articles were selected for review after reading the full text again.  
    RESULTS AND CONCLUSION: In the past, it was believed that the pathogenesis of osteoarthritis was associated with cartilage wear. In recent years, studies have suggested that osteoarthritis is a chronic inflammatory state in which immune cells are widely involved. With the in-depth study of the pathogenesis of osteoarthritis, scholars believe that the pathogenesis of osteoarthritis is driven by early innate immune response, which will gradually catalyze degenerative changes and eventually lead to changes in the joint microenvironment. Various immune cells and cytokines are the key factors affecting the repair of osteoarthritis. Macrophages and natural killer cells participate in synovial inflammatory reaction, and T cell immune reaction participates in the degradation of osteoarthritis cartilage and aggravates the condition of osteoarthritis. Interleukin-1β secreted by immune cells, interleukin-6, tumor necrosis factor α, interleukin-17 and interleukin-37 play an important role in the pathophysiology of osteoarthritis, among which interleukin-1β is the most important inflammatory factor causing articular cartilage damage. Assessing immunological risk factors at the early stage of osteoarthritis can effectively treat the disease at an early stage, which can significantly reduce disability, morbidity and costs associated with osteoarthritis. At present, the immunomodulatory effect of stem cells and their derived secretions and biomaterials on the treatment of osteoarthritis has been confirmed in different experimental models, but there is still a lot of research to be done before they are used in clinical practice. With the discovery of new therapeutic targets, targeted treatment will bring new hope for the repair of clinical osteoarthritis.
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    Mechanism of Chinese medicine for promoting blood circulation and removing blood stasis combined with platelet-rich plasma to improve steroid-induced necrosis of the femoral head
    Li Chengming, Xue Dongling, Yang Xinyu, Xiao Chi, Cui Daping
    2024, 28 (2):  288-294.  doi: 10.12307/2023.690
    Abstract ( 243 )   PDF (1115KB) ( 35 )   Save
    BACKGROUND: At present, it is found that both Chinese medicine for activating blood circulation and removing blood stasis and platelet-rich plasma technology can repair damaged blood vessels, promote vascular regeneration, rebuild blood supply in the femoral head, restore normal blood supply, and further promote osteogenesis. Both of them have certain advantages in early intervention of steroid-induced necrosis of femoral head. It can also further understand the mechanism of blood activating and stasis removing herbs and platelet-rich plasma technology in improving steroid-induced necrosis of the femoral head, and provide new ideas for future treatment.  
    OBJECTIVE: To review the research progress of the mechanism of the combination of blood activating and blood stasis removing herbs and platelet-rich plasma technology on steroid-induced necrosis of the femoral head according to the related literature at home and abroad.
    METHODS: PubMed, Web of Science, Metstr, CNKI and WanFang databases were searched for relevant articles. “Traditional Chinese medicine, signal pathways, steroid induced necrosis of femoral head, vascular endothelial growth factor, platelet rich plasma” were used as the Chinese and English search terms separately. The time limit for searching the literature was from January 2000 to July 2022, and 75 related articles were finally included.  
    RESULTS AND CONCLUSION: Both Chinese medicine for activating blood circulation and removing blood stasis and platelet-rich plasma technology have certain advantages in intervening the early stage of steroid-induced necrosis of femoral head. For traditional Chinese medicine, both single and compound drugs can effectively alleviate the further development of steroid-induced necrosis of the femoral head. The specific mechanism is as follows: (1) The traditional Chinese medicine for activating blood circulation and removing blood stasis has a significant anticoagulation effect, which can antagonize the abnormal (hypercoagulable) state of blood caused by hormone drugs, and further restore the normal blood supply in the femoral head. (2) Traditional Chinese medicine for activating blood circulation and removing blood stasis can repair damaged vascular endothelium, regenerate blood vessels and remodel blood supply in the femoral head by activating vascular endothelial growth factor. (3) The traditional Chinese medicine of promoting blood circulation and removing blood stasis has the obvious effect of removing blood stasis, which can reduce the accumulation of fat cells in the bone marrow cavity and relieve the pressure in the femoral head. (4) Traditional Chinese medicine for promoting blood circulation and removing blood stasis can regulate relevant signal pathways, maintain bone metabolism, promote the differentiation and balance of osteoblasts and osteoclasts, and effectively reduce steroid-induced necrosis of the femoral head. In addition, platelet-rich plasma contains a large amount of high concentration of cell growth factor, which plays a positive role in osteogenesis and vascular regeneration, and can also improve the abnormal state of the blood. Traditional Chinese medicine for activating blood circulation and removing blood stasis combined with platelet-rich plasma technology can play their biological roles, and the intervention effect is more significant.
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    Atg-mediated autophagy, exercise and skeletal muscle aging
    Wang Jingfeng, Wen Dengtai, Wang Shijie, Gao Yinghui
    2024, 28 (2):  295-301.  doi: 10.12307/2023.863
    Abstract ( 594 )   PDF (1005KB) ( 80 )   Save
    BACKGROUND: Exercise as a viable non-pharmacological treatment has the potential to reverse skeletal muscle aging that deteriorates with age. The role of autophagy in the skeletal muscle aging process is indispensable. During skeletal muscle aging, Atg genes involved in regulating autophagy regulate the autophagic process in either a facilitative or inhibitory manner to improve the physiological morphology of skeletal muscle. However the specific molecular mechanisms of autophagy in the exercise regulation of skeletal muscle aging remain puzzling. 
    OBJECTIVE: To search for general patterns of the effects of autophagic mechanisms on skeletal muscle aging during exercise through a review of articles in this field. 
    METHODS: (1) CNKI and Web of Science were searched, reviewed, and screened for relevant literature using the keywords of”Atg genes (proteins), autophagy, exercise, and skeletal muscle aging” to lay the theoretical foundation for the full-text analysis. (2) The comparative analysis method was used to compare the similarities and differences among the included documents to provide reasonable theoretical support for the arguments. By the further comparative analysis of the literature, the relationship between relevant indicators was clarified, to provide the ideas for the full-text analysis. 
    RESULTS AND CONCLUSION: Atg family-mediated autophagy is indispensable for delaying skeletal muscle aging. Atg genes involved in regulating autophagy regulate the autophagic process in either a facilitative or inhibitory manner to improve the physiological morphology and function of skeletal muscle. Different exercise patterns, such as age, time, or intensity at initiation, may have heterogeneous effects on the expression of autophagy-related proteins, but long-term aerobic exercise regulates Atg-related proteins, induces skeletal muscle autophagy, and delays the loss of muscle mass.
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    New trends and developments of functional training research in the field of health care
    Lyu Moran, Xu Wenxin, Wang Di, Li Ming
    2024, 28 (2):  302-307.  doi: 10.12307/2023.894
    Abstract ( 284 )   PDF (1410KB) ( 57 )   Save
    BACKGROUND: Functional training has been popular in recent years, but it is mainly applied in sports training field. There are still insufficient studies and applications in medical and health fields.
    OBJECTIVE: To provide a theoretical basis for relevant research in sports, medical and health fields, through a more comprehensive and in-depth exploration and analysis of the research hot spots, ideological trends, frontiers and development trends of international functional training in the field of medical and health care.  
    METHODS: The 2 206 high-quality articles addressing health-related functional training during 2012-2022 were exported from the Web of Science Core Set Database as the object of analysis. Combined with research methods such as literature analysis, Citespace V analysis software was used for visual analysis of keywords, subject categories and highly cited literatures. 
    RESULTS AND CONCLUSION: The number of articles published on functional training in the field of health is on the rise. There are more articles from the United States, with a larger impact. China also has a high volume of publications, but the impact and depth of research is lacking. Improving physical and mental health and cognitive ability of middle-aged and older people is the main focus, followed by preventing sports injuries and promoting recovery in athletes. In the future, more research will be conducted on teenagers, the disabled and other groups, and there will be a continued increase in injury prevention and recovery promotion for athletes. Chinese scholars have less research on the effects of functional training on the physical health of the general public, and more attention should be paid to improving the physical and mental health of the general public.
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    Role and mechanism of intestinal flora metabolites in obesity regulation
    Yang Qihang, Pu Rui, Chen Ziyang, Leng Siyi, Song Yongjing, Liu Hui, Du Guangyou
    2024, 28 (2):  308-314.  doi: 10.12307/2023.875
    Abstract ( 370 )   PDF (878KB) ( 60 )   Save
    BACKGROUND: Gut microbiota is closely related to host energy balance and metabolism. The metabolites of intestinal flora can regulate the occurrence and development of obesity and can be a new target for the prevention and treatment of obesity.
    OBJECTIVE: To summarize the interaction between the intestinal flora and obesity, as well as the specific mechanism underlying regulation of obesity by metabolites of intestinal flora, thereby providing a new reference and basis for the prevention and treatment of obesity.
    METHODS: “Intestinal microbiota, intestinal bacteria, intestinal microbiota metabolites, short-chain fatty acids, bile acids, ipopolysaccharide, trimethylamine N-oxide, medium-chain fatty acids, tryptophan derivatives, obesity” were used as search terms in Chinese and English. Literature related to obesity from 1990 to 2022 was retrieved in PubMed and CNKI databases. According to inclusion and exclusion criteria, 88 articles were finally selected.
    RESULTS AND CONCLUSION: Intestinal flora is closely related to the occurrence and development of obesity. For example, changes in the  Firmicutes to Bacteroidetes ratio can be used as a biomarker for the diagnosis of obesity, and the occurrence of obesity can be delayed by the colonization of probiotics such as Bifidobacterium breve, Lactobacillus and Akkermansia. Intestinal flora is mainly mediated by the metabolites of intestinal flora to participate in the regulation of obesity. For example, short-chain fatty acid can regulate adipogenesis by regulating signaling pathways such as G protein-coupled receptors 41, 43 and peroxisome proliferator-activated receptor γ, thus delaying the occurrence and development of obesity. Bile acids can increase insulin sensitivity and body energy expenditure by promoting the activation of G protein-coupled receptor 5 and farnesol X receptor. In addition, lipopolysaccharide, trimethylamine oxide, medium-chain fatty acids and tryptophan derivatives are also widely involved in the occurrence and development of obesity through various signaling pathways. Further studies have found that metabolites of the same bacterial community exert heterogeneous effects in the specific process of regulating obesity via different signaling pathways. For example, under the influence of high-fat diet, acetic acids can activate the parasympathetic nervous system, leading to hyperphagia and liver insulin resistance and thus accelerating the physiological course of obesity. 
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    Extracellular vesicles in sarcopenic obesity: roles and mechanisms
    Long Yi, Yang Jiaming, Ye Hua, Zhong Yanbiao, Wang Maoyuan
    2024, 28 (2):  315-320.  doi: 10.12307/2023.867
    Abstract ( 205 )   PDF (1278KB) ( 63 )   Save
    BACKGROUND: Extracellular vesicles can regulate insulin resistance and control inflammatory response by participating in intercellular communication, while repairing skeletal muscles and promoting skeletal muscle regeneration, which is expected to be a novel treatment modality for sarcopenic obesity.
    OBJECTIVE: To review the biogenesis of extracellular vesicles, their biological functions, their relationship with sarcopenic obesity, and recent advances in the pathogenesis, diagnosis, and treatment of sarcopenic obesity.
    METHODS: The first author performed a computer search of PubMed, Embase, CNKI and other databases for relevant studies involving extracellular vesicle in sarcopenic obesity. The search keywords were “extracellular vesicle, exosome, sarcopenic obesity, obese sarcopenia, skeletal muscle regeneration, skeletal muscle mass regulation” in English and Chinese, respectively. The search period was from June 2022 to November 2022. After screening, 87 articles were included for further review.
    RESULTS AND CONCLUSION: Extracellular vesicles are important vectors of bidirectional cell communication and participate in the regulation of normal physiological and pathological processes through autocrine, paracrine and endocrine ways. Sarcopenic obesity is a complex multi-factor disease. Extracellular vesicles are involved in the occurrence and development of sarcopenic obesity mainly by regulating the inflammatory response of skeletal muscle and the homeostasis of muscle cells. Cytokines secreted by adipose tissue and skeletal muscle are released into the extracellular circulation through extracellular vesicle encapsulation and interact with each other to promote skeletal muscle insulin resistance and lipogenesis, which is the main pathophysiology of skeletal muscle atrophy in sarcopenic obesity. Extracellular vesicles not only promote the development of sarcopenic obesity by providing specific pathogenic markers, but also are a valuable diagnostic indicator of sarcopenic obesity. Release of extracellular vesicles from skeletal muscle during exercise enhances metabolic response and promotes skeletal muscle regeneration. Extracellular vesicles can not only be used as therapeutic targets for sarcopenic obesity but also be used to treat sarcopenic obesity by loading drugs to effectively improve drug bioavailability.
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    Efficacy of rehabilitation exoskeleton robots on post-stroke lower limb motor dysfunction: a Meta-analysis
    Chang Wanpeng, Zhang Zhongwen, Yang Yulin, Zi Yang, Yang Mengqi, Du Bingyu, Wang Nan, Yu Shaohong
    2024, 28 (2):  321-328.  doi: 10.12307/2023.868
    Abstract ( 288 )   PDF (1712KB) ( 93 )   Save
    OBJECTIVE: To systematically evaluate the efficacy of rehabilitation exoskeleton robots on the lower limb motor function of stroke patients using Meta-analysis and to compare the efficacy of different lower limb exoskeleton robots, so as to provide a theoretical basis for the scientific selection of suitable exoskeleton robots for patients with post-stroke lower limb motor dysfunction.
    METHODS: Computer searches of the Cochrane Library, PubMed, Web of Science, Embase, CNKI, VIP, and WanFang Data were conducted to collect randomized controlled clinical studies on exploring lower extremity rehabilitation exoskeleton robots to improve lower limb motor function in stroke patients published from database inception to November 2022. Two researchers conducted the literature search and screening. The quality of the included literature was evaluated using the Cochrane 5.1.0 risk of bias assessment tool and the Jadad scale. Meta-analysis was performed using RevMan 5.4 and Stata 17.0 software.
    RESULTS: (1) Finally 22 publications were included, involving 865 patients (n=436 in the test group and n=429 in the control group), and the Jadad score showed that all the included articles were  of high quality. (2) Meta-analysis results showed that the exoskeleton robot significantly improved the Fugl-Meyer Assessment of Lower Extremity score (mean difference [MD]=2.63, 95% confidence interval [CI]: 1.87-3.38, P < 0.05), Berg Balance Scale score (MD=3.62, 95% CI: 1.21-6.03, P < 0.05), Timed Up and Go score (MD=-2.77, 95% CI: -4.48 to -1.05, P < 0.05) and step frequency score (MD=3.15, 95% CI: 1.57-4.72, P < 0.05) in stroke patients compared with the control group. However, there was no significant improvement in the Functional Ambulation Category Scale score (MD=0.30, 95% CI: -0.01 to 0.61, P > 0.05) and 6-minute walk test score (MD=3.77, 95% CI: -6.60 to 14.14, P > 0.05). (3) Network Meta-analysis results showed that  compared with the conventional rehabilitation therapy, both the level-walking exoskeleton (MD=10.23, 95% CI: 3.81-27.49, P < 0.05) and the body-weight support exoskeleton (MD=33.66, 95% CI: 11.49-98.54, P < 0.05) improved the Fugl-Meyer Assessment of Lower Extremity score. Compared with the conventional rehabilitation therapy, body-weight support exoskeleton significantly improved the Berg Balance Scale scores (MD=79.86, 95% CI: 2.34-2 725.99, P < 0.05). In terms of Fugl-Meyer Assessment of Lower Extremity and Berg Balance Scale scores, the ranking results were body-weight support exoskeleton > level-walking exoskeleton > conventional rehabilitation therapy. Compared with the conventional rehabilitation therapy, level-walking exoskeleton significantly improved the Functional Ambulation Category Scale score (MD=1.38, 95% CI: 1.00-1.90, P < 0.05) and body-weight support exoskeleton significantly improved the Timed Up and Go score (MD=0.07, 95% CI: 0.01-0.51, P < 0.05). In terms of Functional Ambulation Category Scale and Timed Up and Go scores, the ranking results were level-walking exoskeleton > body-weight support exoskeleton > conventional rehabilitation therapy.
    CONCLUSION: Rehabilitation exoskeleton robots can improve balance, walking and activities of daily living in stroke patients, with body-weight support exoskeleton being more effective in improving lower limb motor function and balance and level walking exoskeleton being more effective in improving functional walking and transfer.
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