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    18 January 2023, Volume 27 Issue 2 Previous Issue    Next Issue
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    Diagnostic value of peripheral blood interferon-gamma and monocyte chemoattractant protein-1 in postmenopausal osteoporosis
    Lin Shi, Yuan Jiayao, Lin Xiancan, Yang Binbin, Wu Jianjun, Dongzhi Zhuoma, Tang Zijia, Yang Zhijie, Wan Lei, Huang Hongxing
    2023, 27 (2):  165-170.  doi: 10.12307/2022.1013
    Abstract ( 475 )   PDF (1173KB) ( 35 )   Save
    BACKGROUND: Interferon-γ (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1) play an important role in bone immunity and are closely related to the occurrence of osteoporosis. However, few studies have reported the diagnostic value of IFN-γ and MCP-1 in osteoporosis.
    OBJECTIVE: To explore the predictive value of peripheral blood IFN-γ and McP-1 in postmenopausal osteoporosis. 
    METHODS: A total of 71 subjects were collected from the Outpatient department of the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from December 2019 to January 2021 according to the prospective case-control principle, who were divided into osteoporosis group (n=35) and control group (n=36). Baseline data and levels of IFN-γ and MCP-1 were compared between the two groups. Risk factors were analyzed by binary logistics regression analysis. The correlation between the levels of IFN-γ and MCP-1 and bone mineral density and bone mineral content were analyzed. Receiver operating characteristic curve (ROC) was used to evaluate the predictive efficacy of IFN-γ and MCP-1 in postmenopausal osteoporosis. 
    RESULTS AND CONCLUSION: There were no significant differences in age, height, body mass, body mass index and menopause time between the two groups (P > 0.05), but significant differences existed in T value, lumbar bone mineral density, lumbar bone mineral content, overall bone mineral density and overall bone mineral content between the two groups (P < 0.05). The level of IFN-γ in the osteoporosis group was significantly lower than that in the control group (P < 0.05), while the level of MCP-1 was significantly higher than that in the control group (P < 0.05). Univariate and multivariate logistic regression analyses showed that IFN-γ and MCP-1 were independent risk factors for postmenopausal osteoporosis. Receiver operating characteristic curve further confirmed that IFN-γ and MCP-1 had good predictive value for postmenopausal osteoporosis (IFN-γ AUC=0.7992, MCP-1 AUC=0.8001). The critical predictive values (IFN-γ < 1 456 ng/L, sensitivity 100%, specificity 50%; MCP-1 > 365.9 ng/L, sensitivity 85.29%, specificity 67.57%) were determined. Indeed, IFN-γ value < 1456 ng/L and MCP-1 value > 365.9 ng/L suggest that there may be bone loss in postmenopausal women.
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    Mechanism of Bushen Huoxue Capsule in repair of bone defects due to steroid-induced osteonecrosis of the femoral head in rats
    Luo Di, Liang Xuezhen, Yan Bozhao, Li Jiacheng, Xu Bo, Li Gang
    2023, 27 (2):  184-191.  doi: 10.12307/2022.923
    Abstract ( 489 )   PDF (2105KB) ( 33 )   Save
    BACKGROUND: Glucocorticoids can inhibit the expression of key genes in the Hedgehog signaling pathway, thereby disrupting the differentiation of bone marrow mesenchymal stem cells into osteogenesis, adipogenesis, and angiogenesis, thereby destroying the blood supply and bone tissue structure in the bone. We found that Bushen Huoxue Capsule has a certain therapeutic effect on these changes.
    OBJECTIVE: To observe the effect of Bushen Huoxue Capsule on the repair and reconstruction of bone defect due to steroid-induced osteonecrosis of the femoral head in Sprague-Dawley rats, and to further study the mechanism of Bushen Huoxue Capsule on osteogenesis and hedgehog signaling pathway related factors.
    METHODS: Animal model of steroid-induced osteonecrosis of the femoral head was established by injecting methylprednisolone sodium succinate into the gluteal muscle of Sprague-Dawley rats, and low-, middle- and high-dose Bushen Huoxue Capsule was given by gavage. Another rats given normal saline to the gluteal muscles were used as controls. After 8 weeks of injection, the effect of Bushen Huoxue Capsule on bone tissue repair in rats with steroid-induced osteonecrosis of the femoral head and its mechanism were comprehensively evaluated at different aspects through gross observation, histopathological examination, qPCR and western blot analysis. 
    RESULTS AND CONCLUSION: Gross observation indicated no significant difference in the femoral head samples from different groups after 8 weeks of intervention. Hematoxylin-eosin staining revealed that Bushen Huoxue Capsule at different doses could significantly increase the trabecular area and decrease the empty bone lacuna ratio in rats. Immunohistochemical staining indicated that Bushen Huoxue Capsule at different doses could significantly upregulate the expression of alkaline phosphatase, core binding factor α1, type I collagen and osteopontin in rats. qPCR findings showed that compared with the control group, Bushen Huoxue Capsule at different doses could upregulate the mRNA expression of alkaline phosphatase, type I collagen, core binding factor α1 and Hedgehog signaling pathway-related indicators (sonic hedgehog, nuclear transcription factor 1, and nuclear transcription factor 2). Findings from western blot assay indicated that compared with the control group, Bushen Huoxue Capsule at different doses could upregulate the protein expression of alkaline phosphatase, type I collagen, core binding factor α1, osteopontin and Hedgehog signaling pathway-related indicators (sonic hedgehog and nuclear transcription factor 2). This study has preliminarily confirmed that Bushen Huoxue Capsule has a certain therapeutic effect on steroid-induced osteonecrosis of the femoral head, and its mechanism of action is related to the Hedgehog signaling pathway.
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    Effects of asiatic acid on biomechanical properties, trabecular area and Runx2 protein in osteoporotic rats
    Chen Xiaosi, Tan Xiaoyan, Liu Tianfeng, Han Dengpeng, Wei Bo, Hu Zibing, Wu Shaoke
    2023, 27 (2):  246-251.  doi: 10.12307/2022.895
    Abstract ( 522 )   PDF (1123KB) ( 44 )   Save
    BACKGROUND: Studies have confirmed that asiatic acid promotes osteoblast differentiation and inhibits osteoblast apoptosis in a concentration-dependent manner. However, the specific mechanism of asiatic acid on bone biomechanics and Runx2 protein is still unclear.
    OBJECTIVE: To investigate the effects of asiatic acid on biomechanical characteristics, trabecular area and Runx2 protein expression in osteoporotic rats. 
    METHODS: Forty-eight Sprague-Dawley rats were selected and randomly divided into four groups (n=12 per group): sham operation group, model group, low-dose asiatic acid group, and high-dose asiatic acid group. Except for the sham operation group, rats in the other groups were bilaterally ovariectomized to establish osteoporosis models. The rats in the sham operation and model groups were given 3 mL/(kg·d) normal saline after surgery, while those in the low- and high-dose asiatic acid groups were given 60 and 120 mg/(kg·d) asiatic acid by gavage, respectively. Intervention in each group lasted for 60 days. RT-PCR and western blot were used to detect osteoprotegerin and Runx2 at mRNA and protein levels, respectively. Biomechanical characteristics, trabecular bone area and inflammatory factor levels of rats were compared among groups. 
    RESULTS AND CONCLUSION: (1) The maximum load, stiffness, total energy and elastic modulus of rats in the sham operation group were higher than those in the model group (P < 0.05). Compared with the model group, both high- and low-dose asiatic acid could increase the above-mentioned indexes (P < 0.05). Moreover, the maximum load, stiffness, total energy and elastic modulus were higher in the high-dose asiatic acid group than the low-dose asiatic acid group (P < 0.05). (2) The trabecular bone area was higher in the sham operation group than the model group (P < 0.05). The trabecular bone area was lower in the model group than the low- and high-dose asiatic acid group (P < 0.05). The trabecular bone area was higher in the high-dose asiatic acid group than the low-dose asiatic acid group (P < 0.05). (3) The serum level of transforming growth factor-β1 was significantly lower in the model group than the other three groups (P < 0.05) and significantly higher in the high-dose asiatic acid group than the low-dose asiatic acid group (P < 0.05). The levels of osteocalcin, alkaline phosphatase and tumor necrosis factor-αwere significantly higher in the model group than the other three groups (P < 0.05) and significantly lower in the high-dose asiatic acid group than the low-dose group (P < 0.05). (4) The mRNA expression levels of osteoprotegerin and Rnux2 were higher in the sham operation group than the model and low-dose asiatic acid groups (P < 0.05), and the mRNA expression levels of osteoprotegerin and Rnux2 in the high-dose asiatic acid group were higher than those in the sham operation group (P < 0.05). (5) The protein expression levels of osteoprotegerin and Rnux2 were lower in the model group than the other three groups and higher in the high-dose asiatic acid group than the low-dose asiatic acid group. To conclude, asiatic acid can improve the biological characteristics of bone tissue, increase the area of trabecular bone, and reduce the level of inflammation in osteoporotic rats. Its mechanism of action may be related to the promotion of Runx2 expression.
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    Differential expression of Piezo1 in osseous tissue of steroid- and alcohol-induced osteonecrosis of the femoral head
    Wei Tengfei, He Xiaoming, Wei Yurou, Zhan Zhiwei, He Mincong, He Wei, Wei Qiushi
    2023, 27 (2):  270-275.  doi: 10.12307/2022.1022
    Abstract ( 1136 )   PDF (1482KB) ( 32 )   Save
    BACKGROUND: Both hormones and alcohol can inhibit bone marrow mesenchymal stem cells and thus affect bone formation and repair. The occurrence of femoral head collapse is related to mechanical stress stimulation and the ability to repair necrotic tissue. Piezo1 may be a mechanosensitive protein that senses femoral head collapse due to osteonecrosis of the femoral head (ONFH).
    OBJECTIVE: To observe the differential expression of Piezo1 in osseous tissue of patients with steroid- and alcohol-induced ONFH. 
    METHODS: Thirty patients who underwent total hip arthroplasty due to ONFH from August 2020 to April 2021 were enrolled, and their femoral head samples (a total of 30, all were ARCO III stage; 20 males, 10 females; 15 cases in the steroid-induced ONFH group and 15 cases in the alcohol-induced ONFH group), clinical and imaging data were collected. The morphological and structural changes of bone specimens in necrotic area were observed by hematoxylin-eosin staining. The semi-quantitative expression of Piezo1 protein in osseous tissue was detected by western blot. The localization expression of Piezo1 protein in osseous tissue was detected by immunohistochemistry.
    RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that bone structure disorder, bone marrow necrosis and a large number of empty bone lacunae were found in the necrotic area of the steroid- and alcohol-induced ONFH groups. The results of western blot assay showed that the expression of Piezo1 in the necrotic, sclerotic and normal area of the femoral head in steroid-induced ONFH group was higher than that in the alcohol-induced ONFH group (P < 0.05). The immunohistochemical results showed that the positive expression of Piezo1 in the necrotic, sclerotic and normal area in the steroid-induced ONFH group was more obvious than that in the alcohol-induced ONFH group. All these findings indicate that Piezo1 may be a mechanosensitive protein that senses ONFH collapse and may be involved in the process of osteogenic repair. The differential expression of Piezo1 in osseous tissue of patients with steroid- and alcohol-induced ONFH may be related to their different repair characteristics of bone formation.
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    Etiological analysis of discoid meniscus based on whole exome sequencing
    Zhang Jian, Lin Jianping, Zhou Gang, Wang Benchao, Wu Yongchang
    2023, 27 (2):  192-199.  doi: 10.12307/2022.931
    Abstract ( 397 )   PDF (1096KB) ( 26 )   Save
    BACKGROUND: Discoid meniscus is a morphological change of the meniscus and its pathogenesis is unknown. There is yet no genomics research on discoid meniscus.
    OBJECTIVE: To screen the suspected pathogenic genes of discoid meniscus using whole exome sequencing combined with bioinformatics analysis methods.
    METHODS: The peripheral blood DNA of seven patients with discoid meniscus was extracted, and the whole exome sequencing was performed after the DNA database was established. The sequencing data were compared with the public genome database to screen the mutation sites, and the suspicious pathogenic mutations were annotated and interpreted.
    RESULTS AND CONCLUSION: A total of 6 943 mutation sites were identified in 7 patients, including 3 620 missense mutations, 732 synonymous mutations, 488 mutations near the splice site, 45 splice site mutations, 20 exon duplications, 84 exon deletions, 136 non-frameshift mutations, 54 truncation mutations, 5 extension mutations, and 8 start site mutations. Based on shared mutation genes and public genomic databases, 6 suspected pathogenic genes, PADI4, FLNB, SYNE1, COL11A2, COL2A1, and MYO9A, were identified, including 15 mutation sites. Combined with mutation frequency database, protein hazard analysis results and related studies have determined that the suspected genes of this disease are PADI4, FLNB, SYNE1, COL11A2, and COL2A1.
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    Effect of nucleus pulposus cells-derived exosomes under cyclic mechanical tension on endplate chondrocytes
    Zhang Weiye, Zhan Jiawen, Zhu Liguo, Wang Shangquan, Chen Ming, Wei Xu, Feng Minshan, Yu Jie, Han Tao, Cai Chuhao, Zhou Shuaiqi, Shao Chenchen
    2023, 27 (2):  223-229.  doi: 10.12307/2022.914
    Abstract ( 519 )   PDF (1290KB) ( 38 )   Save
    BACKGROUND: Endplate chondrocytes are regulated by many factors in the microenvironment of the intervertebral disc and the influence of microenvironmental changes inside the intervertebral disc caused by abnormal stress on endplate chondrocytes still needs to be explored.
    OBJECTIVE: To observe the exosome secretion of nucleus pulposus cells under cyclic mechanical tension conditions and the effect of exosomes on endplate chondrocytes under this condition.
    METHODS: Nucleus pulposus cells were isolated and cultured from the nucleus pulposus of patients undergoing lumbar surgery in vitro. The cells were loaded with cyclic mechanical tension by FX-5000T system. Exosomes secreted from nucleus pulposus cells under stress and non-stress conditions were extracted by magnetic bead method. Purity and concentration of nucleus pulposus cells-derived exosomes were identified by flow cytometry. The exosomes were labeled with PKH67 fluorescent dye and incubated with endplate chondrocytes for 24 hours. Endplate chondrocytes cultured alone were used as control. The uptake of exosomes by endplate chondrocytes was observed under inverted fluorescence microscope. Then the apoptosis and activity of endplate chondrocytes were observed. Type II collagen, depolymerized protein like metalloproteinase 5, matrix metalloproteinase 3, bone morphogenetic protein 2, and β-catenin mRNA expression were detected. 
    RESULTS AND CONCLUSION: Under certain cyclic mechanical tension conditions, nucleus pulposus cells could be promoted to secrete exosomes, and the particle concentration of nucleus pulposus cells-derived exosomes was higher than that under non-stress conditions. Under the inverted fluorescence microscope, both stress and non-stress nucleus pulposus cells-derived exosomes could be ingested by endplate chondrocytes. Compared with the control group, the viability of endplate chondrocytes decreased significantly (P < 0.05) and the apoptosis rate increased in the stress group (P < 0.05). Compared with the control group, the mRNA expression of matrix metalloproteinase 3 and bone morphogenetic protein 2 in endplate chondrocytes decreased significantly in the non-stress group (P < 0.05). Compared with the control group, the mRNA expression of type I collagen decreased significantly in the stress group (P < 0.05), while the mRNA expression of depolymerized protein like metalloproteinase 5, matrix metalloproteinase 3 and β-catenin increased significantly in the stress group (P < 0.05). Compared with the non-stress group, the mRNA expression of type II collagen decreased significantly in the stress group, while the mRNA expression of depolymerized protein like metalloproteinase 5, matrix metalloproteinase 3 and bone morphogenetic protein 2 increased significantly in the stress group (P < 0.05). Therefore, abnormal stress could promote the exosome secretion of nucleus pulposus cells, and the exosomes under this condition could inhibit the viability of endplate chondrocytes and cause the disorder of cell matrix synthesis and catabolism.
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    Effect of ligustrazine and overexpression of miR-20b-5p on synovial, cartilage and subchondral bone angiogenesis in rats with early-stage knee osteoarthritis: a histological observation
    Xie Pingjin, Luo Zhen, Lu Qigui, Guo Yanxing, Chen Qunqun, Li Feilong
    2023, 27 (2):  237-245.  doi: 10.12307/2022.1023
    Abstract ( 439 )   PDF (2393KB) ( 37 )   Save
    BACKGROUND: Angiogenesis is involved in the progression of early-stage knee osteoarthritis. Synovium, cartilage and subchondral bone all have pathological manifestations of angiogenesis. To explore the inhibitory ability and related pathways of ligustrazine and overexpression of miR-20b-5p on pathological angiogenesis in these tissues will help to develop new drugs for the treatment of early-stage knee osteoarthritis.
    OBJECTIVE: To investigate the effects of ligustrazine and overexpression of miR-20b-5p on synovial, cartilage and subchondral bone angiogenesis in rats with early-stage knee osteoarthritis.
    METHODS: Twenty-five Sprague-Dawley rats were randomly divided into five groups (n=5 per group): model group, agomir NC group, agomir group, ligustrazine+agomir NC group, and ligustrazine+agomir group. The rats in the agomir group and ligustrazine+agomir group were intraarticularly injected with miR-20b-5p agomir solution, while the rats in the agomir NC group and ligustrazine+agomir NC group were intraarticularly injected with the same dose of miR-20b-5p agomir NC solution. The model group was injected with the same amount of normal saline intraarticularly and intragastrically. The rats in the ligustrazine+agomir group and ligustrazine+agomir NC group were also given intragastric administration of ligustrazine. Intraarticular administration was done only once and intragastric administration was performed once a day for 4 weeks. Four weeks later, the rats in each group were killed and the left knee joint was fixed and made into paraffin sections for hematoxylin-eosin staining, Safranin O-fast green staining, and immunohistochemical staining.
    RESULTS AND CONCLUSION: In synovial tissue, the vascular density, inflammatory cell infiltration, vascular endothelial growth factor protein and Notch1 protein in the agomir group, ligustrazine+agomir NC group and ligustrazine+agomir group were significantly lower than those in the model group and agomir NC group (P < 0.05). The vascular density, inflammatory cell infiltration, vascular endothelial growth factor protein and Notch1 protein in the ligustrazine+agomir group were significantly lower than those in the agomir group and ligustrazine+agomir NC group (P < 0.05). In cartilage and subchondral bone tissues, the loss of cartilage matrix and vascular invasion in the agomir group, ligustrazine+agomir NC group and ligustrazine+agomir group were slighter than those in the model group and agomir NC group. In cartilage and subchondral bone tissues, Osteoarthritis Research Society International score, vascular endothelial growth factor protein and Notch1 protein in the agomir group, ligustrazine+agomir NC group and ligustrazine+agomir group were significantly lower than those in the model group and agomir NC group (P < 0.05). Osteoarthritis Research Society International score, vascular endothelial growth factor protein and Notch1 protein expression in the ligustrazine+agomir group were significantly lower than those in the agomir group and ligustrazine+agomir NC group (P < 0.05). To conclude, ligustrazine and overexpression of miR-20b-5p in synovium, cartilage and subchondral bone may inhibit vascular endothelial growth factor/Notch1 mediated angiogenesis, improve various histological manifestations to some extent, and alleviate disease progression in rats with early-stage knee osteoarthritis.
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    Effects of extracorporeal shock wave on the proliferation and autophagy of chondrocytes from osteoarthritis rats
    Wang Huanhuan, Wang Qing, Tang Peng, Zhang Rui, Min Hongwei
    2023, 27 (2):  252-257.  doi: 10.12307/2022.932
    Abstract ( 453 )   PDF (1715KB) ( 28 )   Save
    BACKGROUND: Extracorporeal shock wave is a new treatment method that has been widely used in various medical fields and plays an important role in the occurrence and development of osteoarthritis.
    OBJECTIVE: To investigate the effects of extracorporeal shock wave on the proliferation and autophagy of chondrocytes from osteoarthritis rats in vitro and to explore the mechanism of extracorporeal shock wave in the treatment of osteoarthritis.
    METHODS: Primary chondrocytes were isolated and cultured from the articular cartilage of extremities of 1-week-old clean-grade Sprague-Dawley rats. Chondrocytes at passage 3 were randomly divided into control group (without any treatment), interleukin-1β group (10 μg/L interleukin-1β for 24 hours), extracorporeal shock wave group (1.5×105 Pa extracorporeal shock wave for 500 times), interleukin-1β+extracorporeal shock wave group (10 μg/L interleukin-1β for 24 hours+1.5×105 Pa extracorporeal shock wave for 500 times). The viability and proliferation of chondrocytes were detected by cell counting kit-8 method. The mRNA expressions of Beclin 1, P62, Atg5 and LC3 were detected by real-time fluorescence quantitative PCR. 
    RESULTS AND CONCLUSION: Stimulation with interleukin-1β for 24 hours decreased the viability and proliferation of chondrocytes compared with the control group (P < 0.05). Compared with the interleukin-1β group, chondrocyte viability and proliferation were increased in the interleukin-1β+extracorporeal shock wave group (P < 0.05). The expression of Beclin 1, Atg5 and LC3 was down-regulated and P62 expression was increased in the interleukin-1β group compared with the control group (P < 0.05), whilst the expression of Beclin 1, Atg5 and LC3 was significantly increased and the expression of P62 was decreased in the interleukin-1β+extracorporeal shock wave group compared with the interleukin-1β group (P < 0.05). These results suggest that extracorporeal shock wave can promote the proliferation and autophagy of osteoarthritic chondrocytes, thus regulating the progression of osteoarthritis.
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    Hip and knee coordination patterns in relation to lower limb muscle activity during drop jumps at different heights
    Wang Jiawei, Liu Ye
    2023, 27 (2):  276-281.  doi: 10.12307/2022.1019
    Abstract ( 554 )   PDF (1225KB) ( 46 )   Save
    BACKGROUND: Abnormal joint movements are associated with injury. Joint coordination is commonly used to analyze joint movements and muscle activity can potentially affect inter-joint coordination. However, there are yet no sufficient studies in this field. 
    OBJECTIVE: To identify the inter-segment coordination patterns and muscle activity levels of the hip and knee joints during drop jump at different heights and the correlation between them. 
    METHODS: Nineteen young men were tested with 40, 60, and 80 cm drop jumps, and the electromyographic activity of the gluteus maximus, semitendinosus, rectus femoris, vastus lateralis was measured, hip and knee joint angles were calculated and coordination patterns were calculated using a vector coding technique. Changes in lower limb muscle activity and hip and knee coordination patterns were compared using one-way repeated measures of variance. Pearson and Spearman analyses were used to relate the percentage of inter-segment coordination patterns to EMG activity levels. 
    RESULTS AND CONCLUSION: There were significant differences in the percentage of in-phase and knee-phase in the sagittal plane between 40 and 60 cm, 40 and 80 cm, and 60 and 80cm during the contact - take-off of drop jumps at different heights (P < 0.001). There were significant differences in the percentage of in-phase and knee-phase in the horizontal plane between 40 and 80 cm as well as between 60 and 80 cm (P < 0.001). Muscle activity of the semitendinosus was significantly different between 40 and 60 cm (P < 0.05). Muscle activity of the rectus femoris was significantly different between 40 and 80 cm (P < 0.05). Muscle activity of the semitendinosus at 40 cm was positively correlated with the percentage of in-phase in the sagittal plane (r=0.46, P=0.046). Muscle activity of the gluteus maximus at 40 cm and that of the rectus femoris at 80 cm both had a positive correlation with the percentage of in-phase in the horizontal plane (r=0.43, P=0.064; r=0.45, P=0.069). To conclude, as height increases, hip and knee in-phase coordination decreases and distal knee dominant coordination increases, with better coordination of the lower limb joints at the height of 40 cm and 60 cm, predicting a lower risk of injury when training at this gradient. Muscle activity levels can increase with height and muscle activities of the semitendinosus, gluteus maximus and rectus femoris are associated with coordinated hip and knee movements.
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    Effects of different exercises on renal interstitial fibrosis in type 2 diabetic mice
    Zhang Luyao, Yang Kang
    2023, 27 (2):  200-207.  doi: 10.12307/2022.933
    Abstract ( 629 )   PDF (1484KB) ( 98 )   Save
    BACKGROUND: The incidence of renal interstitial fibrosis as a complication of type 2 diabetes is increasing. However, the mechanism by which exercises intervene with renal interstitial fibrosis as a complication of type 2 diabetes remains to be revealed.
    OBJECTIVE: To explore the effects of different exercises on renal interstitial fibrosis in type 2 diabetic mice and the regulatory mechanism of Klotho-mediated transforming growth factor-β1/Smad3 pathway in this process. 
    METHODS: Forty-four 4-week-old C57BL/6 male mice were randomly divided into a normal control group and a type 2 diabetic model group after 1 week of adaptive feeding. The mouse model of type 2 diabetes mellitus was prepared by high-fat diet and one injection of streptozotocin, and the mouse models were randomly divided into a model control group, a high-intensity intermittent training group, and a downhill running group, followed by 8 weeks of exercise intervention. After the end, ELISA was used to detect the biochemical indicators of renal function; hematoxylin-eosin staining was used to detect renal tissue structure; Masson staining was used to detect the degree of renal interstitial fibrosis; RT-PCR was used to detect the mRNA expression of relevant factors; western blot assay was used to detect the protein expression of relevant factors; and immunohistochemical staining was used to detect the expression of type I collagen protein in the kidney. 
    RESULTS AND CONCLUSION: Compared with the normal control group, the levels of serum creatinine, urea nitrogen and 24-hour urine protein were significantly increased in the model control group; the renal pelvis was expanded, the renal parenchyma narrowed, and the number of renal tubules decreased; the percentage of collagen area increased; the expression of Klotho mRNA and protein in the kidney was down-regulated and the expressions of transformed growth factor β1, type I collagen, type III collagen at mRNA and protein levels were up-regulated, and the expressions of Smad3 mRNA and p-Smad3 protein were significantly up-regulated; the positive area of type I collagen protein expression in the kidney was significantly increased. Compared with the model control group, the mRNA expression of Klotho, type I collagen, and type III collagen in the high-intensity interval training group showed remarkable changes, and the expression of transforming growth factor β1 and type III collagen was up-regulated. Compared with the high-intensity intermittent training group, the levels of serum creatinine, urea nitrogen and 24-hour urine protein were significantly down-regulated in the downhill running group; renal structural lesions involving the renal pelvis, renal tubules, and glomeruli were remarkably improved; the percentage of collagen area was significantly reduced; Klotho mRNA and protein expression was up-regulated, the expressions of transforming growth factor β1, type I collagen and type III collagen at mRNA and protein levels were down-regulated, the expressions of Smad3 mRNA and p-Smad3 protein were significantly down-regulated; the positive area of type I collagen protein expression was significantly decreased. To conclude, type 2 diabetic mice develop fibrosis in the renal interstitium; downhill running improves renal interstitial fibrosis in type 2 diabetic mice by up-regulating Klotho and inhibiting the transforming growth factor-β1/Smad3 pathway; however, high-intensity intermittent exercises have no remarkable effects.
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    Treadmill exercise improves cognitive dysfunction in diabetic rats
    Wu Shuangshuang, Zhang Ying, Kou Xianjuan
    2023, 27 (2):  208-215.  doi: 10.12307/2022.1015
    Abstract ( 397 )   PDF (1573KB) ( 61 )   Save
    BACKGROUND: Some studies have shown that down-regulation of Wnt/β-catenin signaling is closely related to the pathogenesis of cognitive impairments and exercise can delay the pathological process of diabetes, but its molecular mechanism needs further investigation.
    OBJECTIVE: To investigate the effect and molecular mechanism of 8-week treadmill training on cognitive impairment in diabetic rats. 
    METHODS: A total of 30 male Sprague-Dawley rats were randomly divided into a control group (n=10) and a diabetes model group (n=20) according to the random number table. After the model was successfully established, 10 model rats were randomly selected as the diabetes exercise group. After 8 weeks of exercise intervention, the expressions of neurotrophic factors, cell cycle, apoptosis, aging and Wnt signaling pathway-related proteins in the rat hippocampus of each group were detected by Morris water maze, Nissl and NeuN staining, and western blot assay.
    RESULTS AND CONCLUSION: The results of Morris water maze showed that compared with the control group, the escape latency of rats was longer, the number of platform crossing was significantly reduced, and the swimming trajectory was more complex in the diabetes model group (P < 0.05). After 8 weeks of treadmill intervention, the escape latency was significantly shortened and the behavioral trajectory was simpler. The Nissl staining results showed that compared with the control group, the Nissl bodies in the hippocampus of diabetic rats were smaller and the number was decreased, with the cell body shrinking, nucleus shrinking and loose arrangement. However, compared with the diabetes model group, the hippocampal Nissl bodies in the diabetes exercise group were increased in size and number, and the morphological structure tended to be normal. Western blot results showed that the expression levels of cAMP response element binding protein and brain-derived neurotrophic factor protein in the diabetes model group were significantly decreased compared with those in the control group (P < 0.001, P < 0.05), while the 8-week treadmill exercise increased their expressions. Meanwhile, compared with the control group, the expression levels of CDK5, cyclin D1 and Caspase-3 were significantly increased in the diabetes model group (P < 0.001, P < 0.05), while the 8-week treadmill exercise reduced the expression of cell cycle and apoptosis-related proteins. In addition, compared with the control group, the expression of Sirt1 protein was significantly down-regulated in the diabetes model group (P < 0.001), and the expressions of p53 and p16 were increased (P < 0.001, P < 0.05). However, the 8-week treadmill exercise reduced the expressions of p53 and p16 proteins (P < 0.05) and increased the level of longevity protein Sirt1 (P < 0.001). In terms of mechanism, the expression level of DKK-1, a negative regulator of Wnt signaling, was increased in the rat hippocampus of the diabetes model group (P < 0.001), while the 8-week treadmill exercise inhibited the expression of DKK-1 (P < 0.001) and reduced the expression levels of Axin1 and β-catenin, downstream key proteins of the Wnt signaling pathway (P < 0.05, P < 0.001). To conclude, treadmill exercise may regulate cell cycle, inhibit apoptosis and promote the secretion of neurotrophic factors by up-regulating the Wnt/β-catenin signaling pathway, thereby improving aging and cognitive impairment in diabetic rats.
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    miR-132-3p targets and modulates Ptch1 to reduce neuropathic pain in mice with chronic constriction injury
    Zhao Feng, Fan Shaoqing, Cheng Xiaoyan, Li Xiaona, Li Changsheng, Ma Haojie
    2023, 27 (2):  230-236.  doi: 10.12307/2022.934
    Abstract ( 506 )   PDF (1146KB) ( 37 )   Save
    BACKGROUND: The pathogenesis of neuropathic pain involving many pathological processes is complex. miR-132, which is abnormally expressed in neuropathic pain conduction pathway, affects the occurrence and development of pain.
    OBJECTIVE: To investigate the role and mechanism of miR-132-3p in neuropathic pain in mice with chronic constriction injury. 
    METHODS: Mouse microglia BV2 cells were stimulated with 100 ng/mL lipopolysaccharide to establish an activation model. The expression of ionized calcium binding adapter molecule 1 (IBA1), a marker for microglia activation, was detected by western blot. The expression of miR-132-3p was detected by RT-qPCR. After transfecting miR-132-3p mimic or inhibitor into activated BV2 cells, the expression of IBA1 and P2X4 receptor (P2X4R) was detected by western blot. miR-132-3p targeted and regulated Ptch1, which was predicted and verified. pcDNA-Ptch1 or si-Ptch1 was transfected into BV2 cells for 24 hours and then stimulated with lipopolysaccharide for 24 hours. The expression of IBA1, P2X4R and Sonic Hedgehog (Shh) signaling pathway marker proteins was detected by Western blot. BV2 cells were co-transfected with miR-132-3p-mimic and pcDNA-Ptch1 for 24 hours and then stimulated by lipopolysaccharide for 24 hours. The expression of the above proteins was further detected by western blot. Thirty C57BL/6 mice were randomly divided into control group (n=6), sham group (n=6), model group (n=6), NC-mimic group (n=6) and miR-132-3p-mimic group (n=6). The latter two groups were injected intrathecally with NC-mimic and miR-132-3p-mimic, respectively. The mechanical withdrawal threshold and thermal withdrawal latency were monitored. The expression of miR-132-3p, Ptch1, P2X4R and Shh pathway marker proteins in dorsal root ganglion was detected by RT-qPCR and western blot to clarify the role and mechanism of miR-132-3p in chronic constriction injury-induced neuropathic pain. 
    RESULTS AND CONCLUSION: Compared with the control group, lipopolysaccharide stimulation promoted the activation of BV2 cells (P < 0.05) and down-regulated the expression of miR-132-3p (P < 0.05). miR-132-3p inhibited the activation of Shh signaling pathway through targeted regulation of Ptch1, and further inhibited the activation of BV2 cells and the expression of P2X4R. Overexpression of Ptch1 could reverse the effect of miR-132-3p-mimic (P < 0.05). The chronic constriction injury model was successfully established. Compared with the NC-mimic injection group, intrathecal injection of miR-132-3p-mimic could down-regulate the expression of Ptch1 (P < 0.05), inhibit the activation of the Shh signaling pathway (P < 0.05), reduce the expression of P2X4R (P < 0.05), and significantly increase the mechanical withdrawal threshold and thermal withdrawal latency of mice with chronic constriction injury (P < 0.01). Overall, miR-132-3p can reduce neuropathic pain in mice with chronic constriction injury by targeting Ptch1 and inhibiting the activation of Shh signaling pathway.
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    Total flavonoids of Hippophae rhamnoides L. interfere with the regression of hypertrophic scar tissue blocks in a rabbit ear model
    Niu Zihan, Yu Yang, Ai Jiang, Bu Panpan, Li Wenbo, Suriye·Reheman, Ma Shaolin
    2023, 27 (2):  258-263.  doi: 10.12307/2022.940
    Abstract ( 431 )   PDF (1382KB) ( 30 )   Save
    BACKGROUND: Total flavonoids of Hippophae rhamnoides L. can inhibit fibrosis in the kidney, liver and myocardium. However, related studies on hypertrophic scar fibrosis are rarely reported.
    OBJECTIVE: To observe the effect of total flavonoids of Hippophae rhamnoides L. on the regression of hypertrophic scar in a rabbit ear model and to explore its mechanism. 
    METHODS: Eight New Zealand white rabbits were selected for the study. Three round wounds with a diameter of 8 mm were made on both sides of each ear along the ventral midline, a total of 96 wounds. After 21 days of wound epithelization, all rabbits were randomly divided into five groups: 0.5, 1.0, 2.0 g/L total flavonoids of Hippophae rhamnoides L. groups, two rabbits in each group, and dimethyl sulfoxide group (drug solvent control) and blank control group, one rabbit in each group. Corresponding drugs were injected into the base of tissue once every 3 days for 4 continuous weeks. The pathological changes of hypertrophic scar tissue blocks were observed and compared by hematoxylin-eosin staining and Masson staining. The expressions of type I and III collagen mRNAs in rabbit ear scar tissue were detected by real-time PCR. Western blot was used to detect the expression of type I and III collagen, transforming growth factor β1, α-smooth muscle actin, and vascular endothelial growth factor proteins in rabbit ear scar tissue blocks.
    RESULTS AND CONCLUSION: General observation: The scar tissue was softened and flattened significantly after the injection of different concentrations of total flavonoids of Hippophae rhamnoides L. In the blank control group, there were a large number of infiltrated inflammatory cells, angiogenesis and irregular arrangement of collagen fibers. Compared with the blank control group, the neat distribution and loose arrangement of fascicular collagen fibers could be observed in different concentration treatment groups, especially in the 2 g/L group. Scar elevation index and collagen fiber area density in different concentration treatment groups were significantly lower than those in the blank control group and dimethyl sulfoxide group (P < 0.05). The expression levels of type I and III collagen mRNAs in scar tissue were significantly lower in different concentration treatment groups than the blank control group (P < 0.05). The collagen transcription was most significantly downregulated in the 2 g/L treatment group. Compared with the blank control group, dimethyl sulfoxide could partly inhibit the expression of type III collagen, transforming growth factor β1, α-smooth muscle actin, and vascular endothelial growth factor. However, different concentrations of total flavonoids of Hippophae rhamnoides L. could sufficiently inhibit the expression of type I and III collagen, transforming growth factor β1, α-smooth muscle actin, and vascular endothelial growth factor in rabbit ear scar tissue in a concentration-dependent manner. To conclude, total flavonoids of Hippophae rhamnoides L. can inhibit scar hyperplasia, soften and flatten the scar tissue and lighten the color of scar tissue, which treat hypertrophic scar by reducing the expressions of transforming growth factor β1, type I and III collagen in rabbit ear scar tissue blocks, inhibiting the transformation of fibroblasts into myofibroblasts and reducing angiogenesis in scar tissue.
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    Effects of aerobic and resistance exercise on antioxidant stress index and brain-derived neurotrophic factor expression in the hippocampus of type 2 diabetic rats
    Shui Xiaoping, Li Chunying, Li Mingjuan, Li Shunchang, Sun Junzhi, Su Quansheng
    2023, 27 (2):  264-269.  doi: 10.12307/2022.1002
    Abstract ( 486 )   PDF (1323KB) ( 44 )   Save
    BACKGROUND: Diabetes mellitus will cause damage to the hippocampus and induce cognitive dysfunction. Oxidative stress and reduced neurotrophic factor expression are the main mechanism of diabetes-induced hippocampal damage. Long-term regular exercise is a positive intervention for diabetes-induced hippocampal damage; however, the related mechanism still needs further research.
    OBJECTIVE: To observe the effects of aerobic and resistance exercise on the expression of heat shock protein 70, nuclear factor erythroid 2 p45-related factor 2, heme oxygenase 1, and brain-derived neurotrophic factor in the hippocampus of type 2 diabetic rats.
    METHODS: The rats that had been fed with high-fat and high-sugar diet for 8 weeks were given a single intraperitoneal injection of streptozotocin to prepare a model of type 2 diabetes. Type 2 diabetic rats were randomly divided into diabetic control group, diabetic aerobic exercise group and diabetic resistance exercise group, with seven rats in each group. Another control rats were randomly divided into quiet control group, aerobic exercise group, and resistance exercise group, with seven rats in each group. The control rats continued to be fed with ordinary feed, while the diabetic rats continued to be fed with high-fat and high-sugar diet. The aerobic and resistance exercise lasted for 8 weeks in each exercise group. After 8-week exercises, fasting blood glucose and insulin resistance index were measured. Hematoxylin-eosin staining was used to observe the changes of hippocampal structure. The level of malondialdehyde and the activity of superoxide dismutase in brain were measured. The expression of heat shock protein 70, nuclear factor erythroid 2 p45-related factor 2, heme oxygenase 1, and brain-derived neurotrophic factor in the hippocampus were detected by western blot assay.
    RESULTS AND CONCLUSION: After 8 weeks of exercise, compared with the quiet control group, fasting blood glucose and insulin resistance index of all diabetic rats were significantly increased (P < 0.01). The hippocampus of all diabetic rats showed pathological changes such as decreased number of vertebral cell layers, cell cavitation, cell necrosis, and disappearance of nucleoli. Compared with the diabetic control group, fasting blood glucose and insulin resistance index were significantly decreased (P < 0.01, P < 0.05) and the pathological changes of the hippocampus, such as cell cavitation, cell necrosis, and disappearance of nucleoli, were alleviated in the two diabetic exercise groups. Compared with the quiet control group, the malondialdehyde level was significantly increased in all diabetic rats (P < 0.01) and the superoxide dismutase activity was significantly decreased in the quiet diabetic group (P < 0.01). Compared with the diabetic control group, the malondialdehyde level was significantly decreased and the superoxide dismutase activity was significantly increased in the two diabetic exercise groups (P < 0.01, P < 0.05). Compared with the quiet control group, the expression levels of heat shock protein 70, nuclear factor erythroid 2 p45-related factor 2, heme oxygenase 1, and brain-derived neurotrophic factor were significantly decreased in all diabetic rats (P < 0.01). Compared with the diabetic control group, the expression levels of heat shock protein 70, nuclear factor erythroid 2 p45-related factor 2, and brain-derived neurotrophic factor were significantly increased in the two diabetic exercise groups (P < 0.05), and the expression of heme oxygenase 1 was significantly increased in the diabetic aerobic exercise group (P < 0.05). To conclude, aerobic and resistance exercises can both increase the expression of heat shock protein 70, nuclear factor erythroid 2 p45-related factor 2, heme oxygenase 1, and brain-derived neurotrophic factor proteins in the hippocampus of diabetic rats, thereby reducing hippocampal oxidative stress and promoting hippocampal nerve repair. 
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    Tetramethylpyrazine improves hemorheological indexes in rats with complete spinal cord transection: a dynamic observation
    Liu Gang, Deng Bowen, Jiang Shengyuan, Xu Lin, Fan Xiao, Tao Jingwei, Zhang Houjun, He Feng, Zhao Yi, Mu Xiaohong
    2023, 27 (2):  282-286.  doi: 10.12307/2022.1003
    Abstract ( 474 )   PDF (1033KB) ( 20 )   Save
    BACKGROUND: Hemorheological changes following spinal cord injury can cause microcirculation disorder, induce tissue ischemia and hypoxia, and aggravate the secondary injury to spinal cord tissue.
    OBJECTIVE: To observe the changes in hemorheological indexes at different time points after tetramethylpyrazine intervention in rats with complete spinal cord transection.
    METHODS: Fifty-four 8-week-old female Sprague-Dawley rats were randomly divided into three groups (n=18 per group): sham operation group, model group, and tetramethylpyrazine group. Only laminectomy was performed in the sham operation group, while the T10 segment was completely transected with a 2 mm defect gap in the model and tetramethylpyrazine groups by a self-made double-edge microshear. After model preparation, tetramethylpyrazine group was given intraperitoneal injection of tetramethylpyrazine hydrochloride, 200 mg/kg per day, for 5 consecutive days. Abdominal aorta blood samples were taken 7, 14, and 28 days after operation for measuring whole blood viscosity (low, high and medium shear rates), plasma viscosity, hematocrit, erythrocyte aggregation index, erythrocyte deformability index, erythrocyte rigidity index, and erythrocyte electrophoresis index.
    RESULTS AND CONCLUSION: The whole blood viscosity (low, high, and medium shear rates) and plasma viscosity in the model group were significantly higher than those in the sham group at 7, 14, and 28 days after spinal cord injury (P < 0.05). Hematocrit was significantly higher but erythrocyte rigidity index and erythrocyte electrophoresis index were significantly lower in the model group than the sham group at 14 days after spinal cord injury (P < 0.05). Tetramethylpyrazine significantly reduced whole blood viscosity (low, high, and medium shear rates) and plasma viscosity at 7 days after spinal cord injury (P < 0.05). Tetramethylpyrazine significantly increased erythrocyte deformability index (P < 0.05) and certainly but not significantly improved blood viscosity at 14 days after spinal cord injury (P > 0.05). Tetramethylpyrazine significantly improved whole blood viscosity (hyposhear) and plasma viscosity at 28 days after spinal cord injury (P < 0.05). To conclude, after spinal cord injury, the whole blood viscosity and plasma viscosity can increase and erythrocyte indexes can also change to varying degrees. The use of tetramethylpyrazine can improve the deterioration of early hemorheological indexes and improve microcirculation disorders.
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    Ginsenoside Rg3 protects PC12 cells against oxygen-glucose deprivation/reoxygenation-induced damage
    Zhong Jinglin, Cao Huimin, Pan Yaru, Jian Wenxuan, Wang Qi
    2023, 27 (2):  177-183.  doi: 10.12307/2022.1007
    Abstract ( 421 )   PDF (1964KB) ( 43 )   Save
    BACKGROUND: Ginsenoside Rg3 can protect the brain from ischemia injury. However, it is unclear whether ginsenoside Rg3 can protect PC12 cell against oxygen-glucose deprivation/reoxygenation (OGD/R) injury. 
    OBJECTIVE: To investigate the protective role and underlying mechanism of ginsenoside Rg3 in OGD/R-injured PC12 cells. 
    METHODS: A model of OGD/R-injured PC12 cells was constructed. Protective effects of ginsenoside Rg3 at different concentrations on OGD/R-injured PC12 cells were detected using MTT, lactic dehydrogenase, Calcein-AM/PI cell apoptosis double staining assay, western blot assay, and flow cytometry. PI3K/AKT pathway inhibitor LY294002 and AKT activator SC79 were involved to reveal the potential mechanisms of ginsenoside Rg3.
    RESULTS AND CONCLUSION: (1) In this study, OGD/R exposure successfully induced cell injury, which reduced cell survival and promoted cell apoptosis in a time-dependent manner, up-regulated p-AKT/AKT and p-PI3K/PI3K ratio, increased the levels of NLRP3 inflammasomes, tumor necrosis factor-α, interleukin-1β and BAX, and promoted the release of lactic dehydrogenase. (2) Ginsenoside Rg3 at a certain range enhanced the viability and reduced apoptosis and lactic dehydrogenase release of OGD/R-injured PC12 cells. Ginsenoside Rg3 down-regulated the ratio of p-AKT/AKT and p-PI3K/PI3K, reduced NLRP3, interleukin-1β, tumor necrosis factor-α and BAX levels. Ginsenoside Rg3 also suppressed the expression of activated caspase-9 and up-regulated the expression of activated caspase-3. (3) LY294002 shared the same protective effect as ginsenoside Rg3 whereas SC79 reversed this outcome. Therefore, ginsenoside Rg3 protects PC12 cells from OGD/R injury mainly through inhibiting the PI3K/AKT pathway and phosphorylation of PI3K and AKT, which may exert an anti-inflammatory and anti-apoptotic effect.
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    Construction of a lentiviral vector overexpressing fibronectin type III domain containing 5 to inhibit apoptosis of endothelial cells
    Ou Hangjun, Zhao Guangjian, Pan Yujia, Gong Caiwei, Zhao Quanwei, Liu Danan
    2023, 27 (2):  216-222.  doi: 10.12307/2022.928
    Abstract ( 316 )   PDF (1763KB) ( 28 )   Save
    BACKGROUND: Fibronectin type III domain containing 5 (FNDC5) is a protein molecule that regulates glycolipid metabolism, regulates cell apoptosis and participates in the inhibition of atherosclerosis.
    OBJECTIVE: By constructing a lentiviral vector overexpressing FNDC5 for transfecting human umbilical vein endothelial cells, to verify the effect of FNDC5 in regulating endothelial cell apoptosis.
    METHODS: The lentiviral vector overexpressing FNDC5 was constructed. Human umbilical vein endothelial cells in logarithmic growth phase were cultured and divided into three groups: blank group was not transfected with lentivirus, control group was transfected with an empty vector lentivirus without FNDC5, and experimental group was transfected with the lentiviral vector overexpressing FNDC5. At 7 days after transfection, RT-PCR and western blot were used to detect the mRNA and protein expression of FNDC5. After 7 days of transfection, oxidized low-density lipoprotein solution was added to the three groups of cells, and the cell viability was determined by cell counting kit-8 method, and cell apoptosis was detected by Hoechst 33342/PI double staining and flow cytometry.
    RESULTS AND CONCLUSION: The mRNA and protein expressions of FNDC5 in the experimental group were higher than those in the blank and control groups (P < 0.05). Cell counting kit-8 test results showed that the cell viability in the experimental group was higher than that in the blank and control group at 1 and 2 hours after addition of oxidized low-density lipoprotein (P < 0.05). However, there was no significant difference in the cell viability between the three groups at 4 hours after addition of oxidized low-density lipoprotein (P > 0.05). Flow cytometric results showed that the apoptotic rate was lower in the experimental group than the blank and control group at 24 hours after addition of oxidized low-density lipoprotein (P < 0.05). Hoechst 33342/PI double staining results showed that the number of apoptotic cells in experimental group was less than that in the blank and control groups. To conclude, overexpression of FNDC5 could inhibit the apoptosis of human umbilical vein endothelial cells.
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    Application of improved geodesic active contour model in kidney CT image segmentation
    Quan Meilin, Liu Qi, Chen Xi, Deng Xiaobo, He Kechen, Liu Yanli
    2023, 27 (2):  171-176.  doi: 10.12307/2022.945
    Abstract ( 511 )   PDF (1267KB) ( 54 )   Save

    BACKGROUND: Kidney CT image with poor quality shows similar gray scale to that of surrounding tissues on abdominal CT images. Therefore, it is difficult to segment the kidney accurately by traditional image segmentation method. 

    OBJECTIVE: To assist the diagnosis of renal diseases and improve the accuracy of renal segmentation in CT images based on an improved geodesic active contour model. 

    METHODS: Based on the comparative analysis of various traditional medical image segmentation algorithms, a kidney segmentation algorithm based on the improved geodesic active contour model was designed. The region of interest was delineated according to prior knowledge, and the initial contour of the kidney was obtained during the pretreatment stage. Based on the geodesic active contour model of the level set method, the boundary response of the kidney region was enhanced and the improved edge indicator function was used to make the contour curve evolution result closer to the real target boundary. 

    RESULTS AND CONCLUSION: The mean Dice coefficient and mean overlap degree of 328 two-dimensional CT images of the kidney were 0.974 9 and 0.907 1, respectively, which were improved compared with other level set methods. Experimental results show that this model can improve the segmentation accuracy and efficiency of the kidney region in abdominal CT images.

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    Predicting vascular mild cognitive impairment based on vascular risk factors: construction and application of a support vector machine model
    Zhang Qian, Bian Minjie, He Qin, Huang Dongfeng
    2023, 27 (2):  287-292.  doi: 10.12307/2022.1016
    Abstract ( 653 )   PDF (801KB) ( 68 )   Save
    BACKGROUND: With the aging of the population, the number of patients with mild cognitive impairment is gradually increased. Increasing evidence has shown that vascular cognitive impairment has a significant correlation with vascular risk factors. Therefore, vascular risk factors can be used to identify and predict vascular cognitive impairment. 
    OBJECTIVE: To explore the clinical value of support vector machine model in the recognition of vascular mild cognitive impairment (VaMCI) based on vascular risk factors, which is expected to be used as a screening tool in grassroots institutions, communities and home rehabilitation.
    METHODS: Participants enrolled in the study were assessed for cognitive function and then divided into three groups: normal group, VaMCI group, and dementia group. Vascular risk factors with statistically significant differences were selected by analysis of variance among the three groups. The factors mentioned above were used to build the support vector machine model for screening VaMCI. Sensitivity, specificity, positive predictive value, negative predictive value, and area under curve were used to evaluate the predictive performance of the model.
    RESULTS AND CONCLUSION: In the study, 80 participants enrolled were assessed for cognitive function and then divided into three groups: normal group (39 cases), VaMCI group (24 cases), and dementia group (17 cases). Systolic blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein and blood uric acid were observed to be significantly different among the three groups (P < 0.05) and they were therefore used to construct the prediction model. The sensitivity, specificity, positive predictive value, and negative predictive value of screening for VaMCI were 0.845 3, 0.919 4, 0.818 0, and 0.932 7, respectively and the area under the receiver operating curve was 0.892 3. To conclude, the support vector machine model has high diagnostic value in VaMCI screening based on vascular risk factors, and it is simple and easy to operate and can be applied to grassroots institutions, communities and home rehabilitation.
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    Receptor activator of nuclear factor-kappa B ligand signal transduction mechanism and osteoclast activation
    Chen Feng, Ren Guowu, Zhang Xiaoyun, Chen Yueping, Shi Rusheng
    2023, 27 (2):  293-299.  doi: 10.12307/2022.920
    Abstract ( 784 )   PDF (2082KB) ( 48 )   Save
    BACKGROUND: Osteoclasts are the only known type of bone resorption cells, and its life activities are essential to the normal development of bones and the repair of bone damage. Osteoclasts show abnormal proliferation and differentiation and increased bone resorption activity in most bone diseases, while receptor activator of nuclear factor-kappa B (RANK) is a key signal pathway that regulates osteoclastogenesis.
    OBJECTIVE: To summarize the latest research progress on the downstream targets of osteoclast RANK signal and DNA transcription factors at home and abroad, and provide a basis for the research and treatment of related diseases.
    METHODS: A computer-based retrieval was conducted in CNKI, WanFang, VIP, PubMed, Embase and Web of Science databases. The search terms were “osteoclasts, osteoclast precursor cells, osteoporosis, bone metabolism, pathogenesis, epigenetics, signaling pathway, signal transduction, transcription factors, tissue engineering” in Chinese and English. The retrieval time was set to 2017-2021. Finally 52 articles were included according to the inclusion and exclusion criteria.
    RESULTS AND CONCLUSION: The special structure of RANK determines that its signal transduction needs to be combined with tumor necrosis factor receptor-associated factor 6 to recruit a variety of proteins, active enzymes and cytokines to form a RANK complex with intrinsic enzyme activity. This complex then activates nuclear factor-κB, mitogen-activated protein kinase and other signal pathways, ultimately regulating osteoclast differentiation, proliferation, and bone resorption.
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    An osteoarthritis model in vitro: characteristics and new design idea
    Li Mingxiu, Wang Xuan, Yang Jie, Li Yi
    2023, 27 (2):  300-306.  doi: 10.12307/2022.1004
    Abstract ( 694 )   PDF (1145KB) ( 79 )   Save
    BACKGROUND: In domestic and foreign literature, an in vitro model is an important tool to study the pathogenesis and effective treatment of osteoarthritis. All kinds of in vitro models have their advantages and disadvantages and related applications; however, so far, there is no ideal experimental model that can study all the characteristics of osteoarthritis.  
    OBJECTIVE: To review relevant literature in recent years and summarize the advantages and disadvantages of various osteoarthritis models in vitro and their related applications, providing further understanding of osteoarthritis and its therapeutic methods.  
    METHODS: The articles related to PubMed, CNKI, VIP, and WanFang databases from 2010 to 2021 were searched by computer with the English search words: “osteoarthritis, in vitro, model” in English and Chinese. Sixty-three qualified literature with strong correlation and relatively new publication years were selected for review.  
    RESULTS AND CONCLUSION: Two-dimensional cell culture models of osteoarthritis are easy to be constructed and produced on a large scale, but they are only suitable for studies at the cellular level due to the lack of typical three-dimensional microstructure and interactions with surrounding cells and extracellular matrix. Explant model and three-dimensional cell culture provide an internal environment close to the physical condition of the human body, which can be used to study not only cytokines stimulation but also physical injuries and biomechanical changes. Therefore, we can better study the molecular mechanism of osteoarthritis and propose available interventions. However, from the view of tissue volume and cell vitality, mass production of these models is difficult.  In addition, the article also discusses advanced tissue engineering models such as three-dimensional biofabrication models, organoids, and organ-on-a-chip models. Three-dimensional bio-printing technologies and bioreactors have obvious advantages in precise control of tissue structure, transport of bioactive molecules, dynamic cell culture and other aspects, but it still needs further improvement and innovation at present. In general, compared with the two-dimensional cell culture model, the in vitro three-dimensional tissue model is more suitable for current research and individualized treatment of osteoarthritis. In the future, it is expected to integrate emerging technologies such as organ chip technology, three-dimensional bio-printing technology and bioreactor, and eventually develop a more suitable platform for osteoarthritis treatment and drug testing.
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    Mechanism and implication of angiogenesis in osteoarthritis
    Liu Yinghong, Yi Yating
    2023, 27 (2):  307-313.  doi: 10.12307/2023.052
    Abstract ( 964 )   PDF (910KB) ( 63 )   Save
    BACKGROUND: Osteoarthritis is one of the most common degenerative diseases worldwide. Angiogenesis plays an important role in the occurrence and development of osteoarthritis, which is involved in the process of synovitis, cartilage destruction and degeneration, and osteophyte formation. However, the specific mechanism of angiogenesis-mediated osteoarthritis and the regulatory factors affecting angiogenesis have not been determined.
    OBJECTIVE: To review the pathogenesis of angiogenesis-mediated osteoarthritis, thereby providing reference for future basic research and clinical practice.
    METHODS: “Osteoarthritis, angiogenesis, angiogenesis inhibitors” were used as the key words in Chinese and English, respectively, for literature retrieval in PubMed and CNKI databases. Retrieval time was from 1980 to 2021. Documents regarding the role and influential factors of angiogenesis in osteoarthritis as well as angiogenesis inhibitors in the treatment of osteoarthritis were collected, including original articles, reviews, dissertations, academic papers, etc. According to the inclusion and exclusion criteria, a total of 74 articles were selected after primary screening and re-screening through reading title, abstract and full-text.
    RESULTS AND CONCLUSION: Angiogenesis promotes synovitis, cartilage destruction and degeneration, osteophyte formation, and joint pain, which is one of the important factors in the formation and exacerbation of osteoarthritis. The influential factors are angiogenic factors, inflammatory cytokines, interaction between nerves and vessels, exosomes, and non-coding RNAs. Therefore, inhibiting angiogenesis is a potent target for osteoarthritis therapy. Up to date, angiogenesis inhibitors are only confined to vitro experiments and animal models and their clinical application in osteoarthritis should be further discussed.
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    Advances in the signaling pathway of M2 macrophages involved in bone regeneration
    Zhang Jie, Tian Ai
    2023, 27 (2):  314-321.  doi: 10.12307/2022.1006
    Abstract ( 658 )   PDF (1530KB) ( 174 )   Save
    BACKGROUND: Studying the molecular mechanisms of M2 macrophage-induced bone regeneration and collating and analyzing the comprehensive gene regulatory network of multiple signaling pathways are important for targeting and regulating the immune response mediated by bone replacement materials to promote alveolar bone defect repair.
    OBJECTIVE: To review relevant literature and summarize the research progress in relevant signaling pathways of M2 macrophages in bone regeneration, in order to find accurate and proactive immunomodulatory strategies for the regenerative treatment of alveolar bone defects in clinical settings.
    METHODS: Relevant literature in CNKI, Web of Science and PubMed were searched. Search terms were “macrophages, polarization, bone regeneration, osteogenesis, signaling pathway” in Chinese and English. According to the inclusion criteria, 55 articles were included for review.
    RESULTS AND CONCLUSION: The role of macrophages in bone healing is complex, and switching M0/M1 macrophages to the M2 phenotype through a fine-tuned and precise strategy leads to the formation of an appropriate M2 dominance, which is more conducive to bone regeneration. Once the M2 macrophage phenotype is altered, their cell surface markers, secreted cytokines and chemokines, as well as transcriptional and epigenetic pathways (signaling pathways) are changed accordingly. The article summarizes the molecular mechanisms involved in the polarization of M2 macrophages and thus inducing bone defect repair or osteogenic differentiation by various signaling pathways over the past 7 years. Each signaling pathway plays an important role in participating in or regulating the inflammatory response, osteogenesis and chondrogenic differentiation during bone metabolism. Numerous in vivo and ex vivo studies have shown that targeting and modulating signaling pathways may be an effective way to promote bone regeneration by targeting macrophage polarization. Further clinical studies are needed to elucidate whether modulating signaling pathways in favor of reducing the M1/M2 macrophage ratio may be an effective way to promote alveolar bone defect repair. Once this mechanism is clearly elucidated, pharmacology and novel biomaterials targeting the macrophage polarization state may be used as a strategy to promote bone regeneration.
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    Exercise regulates lactic acid metabolism
    Zhu Miaomiao, Kong Fanming, Zhao Qian
    2023, 27 (2):  322-328.  doi: 10.12307/2022.1028
    Abstract ( 674 )   PDF (1010KB) ( 143 )   Save
    BACKGROUND: Blood lactic acid is one of the longest used and most widely used indicators in the field of sports science. It plays an important role in formulating training programs, controlling load intensity, and evaluating training effects. 
    OBJECTIVE: To re-examine the function and role of lactic acid, systematically review the latest developments in lactic acid metabolism in the field of sports science, summarize the biological mechanism of exercise regulating lipid oxidation, and look forward to the future research directions in this field. 
    METHODS: We searched for relevant literature in Bailian Cloud Library, PubMed and EBSCO Sports Science Full Text and Researcher and ResearchGate academic social platforms. The search terms included “exercise; lactic acid; lactic acid threshold; lactic acid metabolism; gluconeogenesis” in Chinese and English. Included documents were classified, summarized, and refined.
    RESULTS AND CONCLUSION: Exercise-regulated lactic acid metabolism is a complex nonlinear process with the characteristics of stages. Exercise style, exercise intensity, exercise time, exercise level, age, sex, muscle fiber type, nutritional status, and environmental temperature are interrelated and mutually restricted. In essence, lactic acid is actually a biomarker of metabolic stress response, rather than an indicator of hypoxia in the body. It can be used as an important signaling molecule. Meanwhile, lactic acid is also an indispensable energy source and plays an important role in the process of gluconeogenesis. Lactic acid indicators have good effects on guiding and monitoring endurance training, but its validity is weak in monitoring strength qualities such as explosive power. Therefore, the use of lactic acid indicator should be individualized in sports practice combined with several indicators such as anaerobic threshold, heart rate, maximal oxygen uptake, creatine kinase, urine protein and creatinine whenever possible, so as to improve its scientificity and validity. There are many reasons for the production of lactic acid. Oxygen is not a necessary condition for the production of lactic acid, but changes in lactic acid are affected by oxygen supply in the body. The important reasons for the production of lactic acid include the increased rate of glycolysis, imbalance of lactic acid production and clearance, and large recruitment of fast-twitch fibers during exercise, which may be related to the ability of the respiratory system to take up oxygen, the ability of the heart to pump blood, the ability of the blood circulatory system to transport oxygen, and the ability of skeletal muscle to utilize oxygen. Regulation of lactic acid metabolism by exercise is a physiological and biochemical process involving multiple organs and nervous, exercise, circulatory, respiratory, digestive and endocrine systems.
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