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    18 March 2023, Volume 27 Issue 8 Previous Issue    Next Issue
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    Comparison of bone metabolism markers between type 2 diabetes mellitus and non-type 2 diabetes mellitus patients with hip fracture
    Sun Jiajia, Zhu Haidi, Lu Yun, Zhang Kai
    2023, 27 (8):  1156-1160.  doi: 10.12307/2023.099
    Abstract ( 435 )   PDF (855KB) ( 31 )   Save
    BACKGROUND: Hip fracture and type 2 diabetes mellitus are common and frequently-occurring diseases in older adults and their internal relationship needs further studies.
    OBJECTIVE: To compare the levels of bone metabolism markers between type 2 diabetes mellitus and non-type 2 diabetes mellitus patients with hip fracture.
    METHODS: Total 743 patients with hip fracture from August 2014 to August 2020 were enrolled in this study. According to the presence or absence of diabetes history, they were further divided into type 2 diabetes mellitus group (T2DM group, n=118) and non-type 2 diabetes mellitus group (non-T2DM group, n=625). Biochemical parameters (fasting blood glucose, alkaline phosphatase, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, blood calcium, and blood phosphorus) and bone metabolism parameters (total serum procollagen type N-terminal propeptide, the age-related type I cross linked C-telopeptide and 25-hydroxyvitamin D) were collected and compared. The correlation between fast blood glucose and triglyceride and bone metabolism parameters was calculated by the Spearman correlation analysis.
    RESULTS AND CONCLUSION: The fast blood glucose and triglyceride levels in the T2DM group were significantly higher than those in the non-T2DM group. In addition, the total serum procollagen type N-terminal propeptide (P=0.017) and total serum procollagen type N-terminal propeptide (P=0.007) levels in the T2DM group were significantly lower than those in the non-T2DM group. The correlation coefficients between fasting blood glucose and age-related type I cross linked C-telopeptide, between fasting blood glucose and total serum procollagen type N-terminal propeptide, between triglyceride and total serum procollagen type N-terminal propeptide, and between blood calcium and 25-hydroxyvitamin D were -0.124 (P < 0.001), -0.174 (P < 0.001), 0.075 (P=0.04), and 0.108 (P=0.003), respectively. This cross-sectional study indicated that there is a low bone turnover state (both bone formation and bone resorption) in patients with type 2 diabetes mellitus after hip fractures and the fasting blood glucose levels is negatively correlated with total serum procollagen type N-terminal propeptide and age-related type I cross linked C-telopeptide levels. In addition, good glucose control may be beneficial to bone metabolism and prevent from delayed fracture healing after hip fracture.
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    Calcium phosphate cement/poly(lactic-co-glycolic acid) degradation products promote osteoclast differentiation of mouse monocytes
    Long Guiyue, Li Dongdong, Liao Hongbing
    2023, 27 (8):  1193-1198.  doi: 10.12307/2023.138
    Abstract ( 423 )   PDF (1176KB) ( 38 )   Save
    BACKGROUND: Preliminary studies found that calcium phosphate cement/poly(lactic-co-glycolic acid) composite can accelerate the process of bone remodeling, and the effect of its degradation products on the differentiation of mononuclear osteoclasts needs further study.
    OBJECTIVE: To observe the effect of calcium phosphate cement/poly(lactic-co-glycolic acid) degradation products on the differentiation of mouse RAW264.7 monocytes and osteoclasts. 
    METHODS: The experiment was divided into blank control group, glycolic acid group, and calcium phosphate cement/poly(lactic-co-glycolic acid) group. According to the experimental group assignment, the prepared solution and 50 μg/L ligand of nuclear factor κB receptor activator were added to complete medium to prepare media with different conditions. Mouse RAW264.7 cells were cultured for 5 days to induce their differentiation. Cell counting kit-8 assay was used to analyze the effect of different culture media on cell proliferation. RT-PCR and western blot assay were used to detect the changes of gene and protein expression levels of nuclear factor of activated T-cells cytoplasmic 1, matrix metalloproteinase-9, nuclear factor κB receptor activator and tartrate-resistant acid phosphatase activated by osteoclast differentiation-related factors in mouse RAW264.7 monocytes. The osteoclast-like cells were identified by tartrate-resistant acid phosphatase staining. 
    RESULTS AND CONCLUSION: Cell counting kit-8 assay results showed that the cells were in a rapid growth period within 72 hours, and then began to decline after 96 hours. The results of RT-PCR and western blot assay showed that the expression levels of nuclear factor of activated T-cells cytoplasmic 1, nuclear factor-κB receptor activator and tartrate-resistant acid phosphatase mRNA and protein expression levels of nuclear factor-1 and nuclear factor-κB receptor activator in activated T cells in calcium phosphate cement/poly(lactic-co-glycolic acid) group were significantly higher than those in glycolic acid group and control group (P < 0.05). There was no significant difference in gene and protein expression levels of matrix metalloproteinase-9 between glycolic acid group and calcium phosphate cement/poly(lactic-co-glycolic acid) group, but it was higher than that of the control group (P < 0.01). Tartrate-resistant acid phosphatase staining results showed that the number of osteoclast-like cells in the calcium phosphate cement/poly(lactic-co-glycolic acid) group was significantly higher than that in the control group and the glycolic acid group (P < 0.05). Overall, these results indicate that the microenvironment formed by the degradation products of calcium phosphate cement/poly(lactic-co-glycolic acid) can promote the osteoclast differentiation of mouse RAW264.7 monocytes. 
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    Naringin regulates the function of RAW264.7 macrophages to affect the osteogenic differentiation of MC-3T3-E1 cells
    Tang Liang, Li Xiheng, Niu Ruijuan, Li Xinyue, Zou Xinying, Mao Tianjiao, Li Jiang
    2023, 27 (8):  1205-1210.  doi: 10.12307/2022.946
    Abstract ( 606 )   PDF (1122KB) ( 65 )   Save
    BACKGROUND: Naringin, as a monomer of traditional Chinese medicine, has the anti-inflammatory and anti-cancer effects and can promote osteogenesis. RAW264.7 cells play an important role in bone destruction. Some studies have found that reducing inflammation can promote the osteogenic differentiation of MC-3T3-E1 cells. So, it may promote osteogenic differentiation by inhibiting inflammation-related pathways.
    OBJECTIVE: To observe whether naringin can regulate the function of RAW264.7 cells to affect the osteogenic differentiation of MC-3T3-E1 cells.
    METHODS: The cytotoxicity of different concentrations of naringin to RAW264.7 cells induced by lipopolysaccharide was tested by cell counting kit-8 method. RAW264.7 cells were divided into seven groups: control (DMEM culture), model group (1 mg/L lipopolysaccharide), and naringin groups (1 mg/L lipopolysaccharide+50, 100, 150, 200, 250 μmol/L naringin). In different concentration naringin groups, the mRNA levels of inflammatory factors were detected by RT-PCR. Data of three naringin groups with better anti-inflammatory concentrations (150, 200, 250 μmol/L) were selected for follow-up experiments. RAW264.7 cells were divided into four groups: inflammation model, 150, 200, 250 μmol/L naringin groups. The above four groups were used as inflammatory supernatant. The inflammatory supernatant prepared above was mixed with osteogenic induction medium in a ratio of 1:1 to co-culture MC-3T3-E1 cells. Culture cells were divided into five groups: control group, inflammation model group, 150, 200, 250 μmol/L naringin groups. Osteogenesis-related gene detection, alkaline phosphatase staining, and alkaline phosphatase activity experiment were carried out on 7 and 14 days of culture.
    RESULTS AND CONCLUSION: 1 mg/L lipopolysaccharide has no toxic effect on macrophages, but 200 μmol/L naringin showed a cytotoxic effect on macrophages induced by lipopolysaccharide (P < 0.05). In the process of screening the anti-inflammatory concentration of naringin, the concentration of naringin at 150, 200, and 250 μmol/L compared with the control group had good anti-inflammatory effects (P < 0.05). Therefore, 150, 200, and 250 μmol/L naringin were used for subsequent experiments. Alkaline phosphatase staining results showed that compared with the control group, 200 μmol/L naringin had the best dyeing result and the dyeing effect was better on 14 days than 7 days. The mRNA expression level of osteogenesis-related genes in the 200 μmol/L naringin was the closest to that in the control group and the inflammation model group had the worst osteogenic effect (P < 0.05). In the alkaline phosphatase activity experiment, compared with the control group and inflammation model group, 200 μmol/L naringin showed the strongest alkaline phosphatase activity on 7 days of culture (P < 0.05). Compared with the control group and inflammation model group, 200 μmol/L naringin showed no statistical significance in the alkaline phosphatase activity on 14 days of culture. Whilst compared with the inflammation group, the strongest alkaline phosphatase activity was found in the 200 μmol/L naringin group. The above results show that naringin can improve the osteogenic differentiation of MC-3T3-E1 cells in the inflammatory state by regulating the function of RAW264.7 macrophages.
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    Effects of estrogen combined with treadmill exercise on bone mass and articular cartilage in ovariectomized mice
    Huang Linke, Wei Linhua, Jiang Jie, Liu Qian, Chen Weiwei
    2023, 27 (8):  1166-1171.  doi: 10.12307/2022.1010
    Abstract ( 403 )   PDF (1441KB) ( 46 )   Save
    BACKGROUND: Postmenopausal women are prone to developing osteoporosis and osteoarthritis, and the effect of estrogen replacement therapy combined with treadmill exercise on bone mass and articular cartilage is unclear.
    OBJECTIVE: To investigate the effects of exogenous estrogen combined with low intensity treadmill exercise on bone mass and articular cartilage in an ovariectomized mouse model.
    METHODS: Thirty-five C57BL/6 mice were randomly divided into five groups: sham group, sham and low intensity treadmill exercise group (sham-sport group), ovariectomized group, ovariectomized and supplying exogenous estrogen group (estrogen group), ovariectomized and supplying exogenous estrogen combined with low intensity treadmill exercise group (estrogen-sport group). The mice were subjected to bilateral ovariectomy or sham operation. The mice in the estrogen and estrogen-sport groups were injected with estrogen every other day after the operation, and the mice in the sham-sport and estrogen-sport groups ran on a treadmill for 6 weeks. The changes in the number of osteoclasts and bone mass in the metaphysis of the distal femur of the mice were observed. Osteoarthritis Research Society International histopathology was used to evaluate the degeneration of knee joint cartilage in mice.
    RESULTS AND CONCLUSION: Bone volume per total volume in the estrogen-sport group was significantly higher than that in the ovariectomized group (P < 0.01). There was no statistical difference among the estrogen-sport, sham, sham-sport group, and estrogen groups (P > 0.05). Osteoclast number per bone surface and osteoclast surface per bone surface were significantly decreased in the estrogen-sport group compared with the ovariectomized group (P < 0.01). There was no statistical significance among the estrogen-sport, sham-sport, and estrogen groups (P > 0.05). The knee Osteoarthritis Research Society International histopathology of the estrogen-sport group was significantly higher than that of the other groups (P < 0.01). In conclusion, exogenous estrogen supplementation with low-intensity treadmill exercise can increase bone mass in ovariectomized mice but lead to articular cartilage degeneration.
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    Knee joint mechanics and activation characteristics of surrounding muscles during deep jumps at different heights and distances
    Bi Gengchao, Zhang Yanlong, Li Qiuyue, Hu Longwei, Zhang Yu
    2023, 27 (8):  1211-1218.  doi: 10.12307/2023.084
    Abstract ( 632 )   PDF (1794KB) ( 88 )   Save
    BACKGROUND: Previous research has indicated that the height of a drop jump has a significant impact on the knee joint and surrounding muscles; however, investigations on the distance of the drop jump are rare and relevant mechanical simulations combined with surface electromyography studies are particularly lacking.
    OBJECTIVE: To compare the mechanical features of the knee joint and the activation characteristics of the surrounding muscles during drop jumps at various heights and distances.
    METHODS: Based on varied heights and distances, the motions were separated into four groups (height×distance): group A (0.45 m×0.50 m), group B (0.45 m×0.90 m), group C (0.60 m×0.50 m), and group D (0.60 m×0.90 m). Sixteen male testers with no history of lower limb injury were recruited and selected. The Qualisys motion capture system, AMTI force plate, and Delsys surface electromyography system were used to collect data on kinematic, kinetic, and electromyographic signals during the subjects’ drop jumps. OpenSim 4.3 simulation software was used to calculate knee joint kinetics and muscle activation performance.
    RESULTS AND CONCLUSION: Under the 0.45 m×0.50 m condition, increases in both distance and height increased the knee flexion angle (P=0.033, P=0.024). Enhanced distance lowered the maximum muscle strength of the rectus femoris and middle femoris (P=0.010, P=0.007), but increased the maximum muscle strength of the anterior tibialis (P=0.018) at a height of 0.60 m. The activation of the hamstrings and antagonist muscles was impacted by drop jump height and distance during the pre-activation period. Increased distance raised the co-activation ratio of the knee (P=0.045) and lowered the co-activation indexes of the biceps femoris:lateralis femoris and medialis femoris:lateralis femoris (P=0.016, P=0.012). Increased height elevated the co-activation ratio of the knee joint, but no significant difference was found among groups. These findings indicate that increasing the distance within a given range reduces joint stresses on the knee joint during drop jumps while also increasing its stability and surrounding muscle activation, and reducing the peak strength of the rectus femoris and middle femoris muscles. A drop jump of 0.45 m×0.90 m in height and distance has better stability and muscle coordination and contraction than the other groups, but the height and distance should be modulated considering the sport-specific goals.
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    Effect of deep muscle stimulation on muscle tone and stiffness of erector spinaes in patients with chronic nonspecific low back pain: a digital muscle testing
    Zhang Qiming, Bao Sairong, Shan Sharui, Zhong Zhiliang, Liu Chunlong
    2023, 27 (8):  1250-1256.  doi: 10.12307/2022.1024
    Abstract ( 480 )   PDF (1192KB) ( 120 )   Save
    BACKGROUND: As a local vibration therapy, deep muscle stimulation therapy can relieve pain and loose fascia adhesion through a specific frequency of mechanical wave by hitting pain points, but less is reported on the changes of muscle tone and stiffness of erector spinaes after its effect on chronic non-specific low back pain.
    OBJECTIVE: To observe the effect of deep muscle stimulation on muscle tone and stiffness of erector spinaes as well as clinical efficacy in patients with chronic non-specific low back pain by a digital muscle detector.
    METHODS: A total of 60 patients with chronic non-specific low back pain admitted to the First Affiliated Hospital of Guangdong Pharmaceutical University from September 2019 to June 2021 were enrolled and randomly divided into two groups (n=30 per group): a control group and an experimental group. Patients in the control group received the routine physical therapies, including core muscle group practice, stereodynamic interference electrotherapy and health education, and patients in the experimental group received deep muscle stimulation therapy based on the routine physical therapies, five times per week, for 4 consecutive weeks. Pain degree, waist function, changes of muscle tone and stiffness of the erector spinae muscle, and clinical efficacy were statistically analyzed before treatment, after the first treatment, after the completion of all treatments, and 4 weeks after treatment. 
    RESULTS AND CONCLUSION: After the first treatment, the oscillation frequency (F value), visual analog scale scores and stiffness values of the two groups were significantly lowered (P < 0.05), except for the oscillation frequency of the control group (P > 0.05). After the completion of all treatments, the visual analog scale scores, oscillation frequency, dynamic stiffness, and Quebec Baclain Disability Scale scores of the two groups were significantly lower than before treatment (P < 0.05), while the experimental group was better than the control group (P < 0.05). Four weeks after treatment, the Quebec baclain disability scale scores of two groups were improved compared with those after the completion of all treatments (P < 0.05), and the Quebec baclain disability scale score in the control group was significantly improved compared with that in the experimental group (P < 0.05). The number of effective and total effective cases in the experimental group were both better than those in the control group (P < 0.05) after the completion of all treatments. The overall efficiency of the experimental group (97%) was higher than that of the control group (80%; P < 0.05). Four weeks after treatment, the number of effective and total effective cases in the experimental group were also better than those in the control group (P < 0.01). The overall efficiency of the control group (63%) was significantly decreased (P < 0.05). Although the overall efficiency of the experimental group (93%) decreased (P < 0.05), the clinical efficacy was mainly maintained. To conclude, deep muscle stimulation with routine physical therapies can effectively relieve pain, reduce muscle tone and stiffness of erector spinaes, and improve and keep the clinical efficacy in patients with chronic non-specific low back pain.
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    Expression of forkhead box protein 3 in refractory periapical periodontitis in rats with Enterococcus faecalis infection
    Li Mengfei, Zhang Hong, Zhao Shaojian, Yin Guanghao, Wang Qibao
    2023, 27 (8):  1187-1192.  doi: 10.12307/2022.943
    Abstract ( 414 )   PDF (1095KB) ( 23 )   Save
    BACKGROUND: Refractory periapical periodontitis, with Enterococcus faecalis as a dominant bacterium, is a disease that continues with persistent inflammation and bone resorption after repeated and multiple root canal treatments. Multiple experiments have shown that forkhead box protein 3 (Foxp3) is involved in various inflammatory diseases by influencing the body’s autoimmune response.
    OBJECTIVE: To observe the expression of Foxp3 in refractory periapical periodontitis in Enterococcus faecalis-infected rats.
    METHODS: Thirty-three Sprague-Dawley rats at the age of 6 weeks were selected as experimental objects, 32 of which were randomly selected and divided into control and experimental groups. These 32 rats were submitted to open pulp in the central fossa of bilateral mandibular first molars under painless conditions. PBS pellets and Enterococcus faecalis suspension pellets were placed into the pulp in the control and experimental groups, respectively, followed by light curing after placing flowing resin in the bilateral inner medullary cavities. At 1, 2, 3, 4 weeks after regular water and food feeding in room temperature, four rats from each group were randomly selected for euthanasia. Rats aged 0 week without dental pulp opening were used as blank controls. Hematoxylin-eosin staining was to observe the inflammatory histopathological changes in the experimental periapical sites of rats. RT-PCR and immunohistochemical detection were used to detect the expression of Foxp3 in the periapical tissue. 
    RESULTS AND CONCLUSION: Hematoxylin-eosin staining results showed that: the animal models of periapical periodontitis were successfully established in the control and experimental groups and obvious inflammatory cell infiltration was seen in the periapical tissue. The results of RT-PCR showed that the mRNA expression level of Foxp3 in the periapical tissue in the control group rose in a stepwise manner from 1 to 4 weeks, while the mRNA expression level of Foxp3 in the periapical tissue in the experimental group decreased after peaking at 3 weeks (P < 0.05). Immunohistochemical results showed that the Foxp3-positive cell expression in the control group increased with time, while that in the experimental group decreased at the 4th week after the expression peaked at the 3rd week, which was consistent with the results of RT-PCR (P < 0.05). To conclude, Foxp3 is involved in the progression of chronic and refractory periapical periodontitis. In the chronic phase of inflammation, the expression of Foxp3 is significantly decreased in refractory periapical periodontitis, suggesting that it may have some relationship with Enterococcus faecalis. 
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    Correlation between exercise intensity and lipid metabolism disorder and oxidative stress in a high-diet rat model
    Ruan Ling, Wang Guanghua, Wu Rongping, Jin Zhan, Lyu Zhenqing, Zhang Nan, Li Shoubang
    2023, 27 (8):  1149-1155.  doi: 10.12307/2022.1014
    Abstract ( 526 )   PDF (1229KB) ( 34 )   Save
    BACKGROUND: Obesity is a multifactorial chronic disease. Regular exercise can improve lipid metabolism disorders and oxidative stress in obese groups, but the specific exercise intensity is unclear.
    OBJECTIVE: To explore the effect of different-intensity exercises on lipid metabolism and oxidative stress in obese rats and to clarify the correlation of peroxisome proliferators-activated receptor α, liver X receptor α and related pathway proteins with lipid metabolism as well as the specific mechanism.
    METHODS: Rats were randomly divided into five groups: normal control group (n=10), obesity model group (n=10), low-intensity exercise group (n=10), moderate-intensity exercise group (n=9) and high-intensity exercise group (n=8). The normal control group was given ordinary feed, and the other four groups were fed with high-fat diet for 16 weeks to prepare the obese rat model. After modelling, rats in each group were arranged to run on the treadmill 1 hour per day and 5 days per week. After 6 weeks of training, body mass, liver mass, heart mass, and body fat percentage, lipids, lipases and oxidative stress were tested, and adipose tissue were cut into sections for cell morphological and structural observations. The protein expression of apolipoprotein A5, peroxisome proliferators-activated receptor α, sterol regulatory element-binding protein 1c and liver X receptor α in liver tissue were detected by western blot assay. 
    RESULTS AND CONCLUSION: Compared with the obesity model group, the levels of triacylglycerols, low-density lipoproteins, and free fatty acids were significantly reduced, while the activities of lipoprotein lipase and hepatic lipase increased significantly in the moderate-intensity exercise group (P < 0.01). Plasma malondialdehyde level showed a significant reduction in each exercise group (P < 0.01), but the activity of catalase increased significantly in all exercise groups (P < 0.01). Compared with the obesity model group, the protein expression of apolipoprotein A5 was significantly increased in each exercise group (P < 0.05, P < 0.01, P < 0.01) and the expression levels of sterol regulatory element-binding protein 1c (P < 0.01) and liver X receptor α (P < 0.01) were both decreased, whereas the expression of peroxisome proliferators-activated receptor α only increased significantly in the moderate-intensity exercise group (P < 0.05). Compared with the low- and high-intensity exercise groups, the expression of apolipoprotein A5 was significantly increased in the moderate-intensity exercise group (P < 0.01, P < 0.05). Compared with the low-intensity exercise group, the expression of sterol regulatory element-binding protein 1c was significantly lower in the moderate-intensity exercise group (P < 0.01). To conclude, lipid metabolism disorder and oxidative stress can be improved after different-intensity exercises. The moderate-intensity exercise has better effects, which may be related to the double regulation of exercise-dependent peroxisome proliferators-activated receptor α and liver X receptor α signaling pathways.
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    Effect of Gja1 gene recombinant lentivirus on Cx43 protein and mRNA expression in a diabetic guinea pig bladder model
    Zhang Yongqiang, Pan Feng, Sun Peng, Tan Minghui, Xuan Liuming, Wang Qinzhang
    2023, 27 (8):  1161-1165.  doi: 10.12307/2022.1017
    Abstract ( 375 )   PDF (1249KB) ( 35 )   Save
    BACKGROUND: Connexin 43 is also known as Gja1 protein. Gja1 recombinant lentivirus may improve bladder contractile dysfunction in diabetes.
    OBJECTIVE: To establish a guinea pig model of diabetic cystopathy, study the way of transurethral infusion of Gja1 recombinant lentiviral drugs, and observe the effect on the expression of connexin 43 protein and mRNA on the surface of detrusor muscle cells in the damaged bladder. 
    METHODS: Eighty healthy guinea pigs of similar age and body mass were selected, 15 of which were randomly selected and conventionally fed and the remaining 65 were given intraperitoneal injection of 1% streptozotocin (200 mg/kg) to establish a guinea pig model of diabetic cystopathy. Urodynamics screening was performed to identify guinea pigs with diabetic cystopathy, which were further randomized into three groups: blank group (n=12), control group (n=12) and experimental group (n=12). The blank group was perfused with 0.2 mL of phosphate buffered saline, the control group was perfused with 0.2 mL of empty recombinant lentivirus, and the experimental group was perfused with 0.2 mL of Gja1 recombinant lentivirus. Three guinea pigs from each group were killed at each observation time point (2, 7, 14, and 28 days) after transfection. Expression and distribution of connexin 43 protein in the bladder were observed by immunohistochemical staining, and the protein and mRNA levels of connexin 43 were detected by western blot and qRT-PCR assays, respectively, 
    RESULTS AND CONCLUSION: After transurethral infusion of Gja1 recombinant lentivirus, the expression levels of connexin 43 protein and mRNA were significantly higher in the experimental group than the blank and control groups (P < 0.01, P < 0.01), and the best expression levels of connexin 43 protein and mRNA were found at 14 days after transfection with Gja1 recombinant lentivirus. There were no significant differences in the expression levels of connexin 43 protein and mRNA between the blank and control groups (P > 0.01). To conclude, Gja1 gene via transurethral perfusion can stably express in bladder tissue and up-regulate the expression of connexin 43 at protein and mRNA levels, which may be beneficial to repair damaged signal transduction and exchange pathways between cells.
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    Expression of mitochondrial sirtuin 3 in mice with acute renal ischemia-reperfusion injury
    Jia Shengqi, Luo Wenlong, Tian Dingyuan, Zhang Xinhui, Cui Qian, Wang Chao, Pei Hanjun
    2023, 27 (8):  1172-1178.  doi: 10.12307/2022.1000
    Abstract ( 450 )   PDF (2311KB) ( 36 )   Save
    BACKGROUND: Contrast-induced nephropathy has become one of the main causes of hospital-acquired acute kidney injury and its essence is acute renal ischemia-reperfusion injury. However, the role of sirtuin 3 in it is still unclear.
    OBJECTIVE: To probe the dynamical changes of sirtuin 3 after different duration of renal ischemia and to establish the relationship of sirtuin3 expression with mitochondrial injury-related parameters. 
    METHODS: The mouse model of acute renal ischemia-reperfusion injury was established by ischemia for different time (15, 20, 25, 30 minutes) followed by 48 hours of reperfusion in C57BL/6 mice. According to the ischemic time, all animals were divided into six groups (n=8 per group): control group, sham group, 15-, 20-, 25- and 30-minute ischemia groups. Forty-eight hours after modeling, the serum levels of creatinine and blood urea nitrogen were measured. The apoptosis of renal tissue cells was monitored by TUNEL. Adenosine triphosphate content in the kidney was measured by luciferase luminescence method. Hematoxylin-eosin staining was used to observe pathological changes of the kidney. Mitochondrial changes were observed under a transmission electron microscope. The expression of mitochondrial dynamin related protein 1, mitofusion 1, and sirtuin 3 was determined by western blot. 
    RESULTS AND CONCLUSION: After ischemia, serum ccreatinine, blood urea nitrogen, histopathological score and apoptotic index increased gradually after ischemia; the injury of mitochondrial structure of the kidney gradually aggravated and the mitochondrial adenosine triphosphate content decreased in general. The sirtuin 3 expression showed no significant difference among control, sham and 15-minute ischemia groups. The expression of sirtuin 3 was higher at 20 minutes of ischemia than at 15 minutes of ischemia (P < 0.05), further increased significantly at 25 minutes of ischemia (P < 0.05), and reached a peak at 30 minutes of ischemia (P < 0.05). Mitofusion 1 expression significantly increased in the 15- and 20-minute ischemia groups compared with the sham group (P < 0.05) and further increased significantly in the 25- and 30-minute ischemia groups compared with the 15-minute ischemia group (P < 0.05). The expression of mitochondrial dynamin related protein 1 increased to the peak value at 15 minutes (P < 0.05) and then decreased at 20 and 25 minutes. Relationship study showed that the content of adenosine triphosphate was negatively correlated with the expression of sirtuin 3 (r=-0.77, P < 0.05). The expression of sirtuin 3 was negatively correlated with the expression of mitochondrial dynamin related protein 1 (r=-0.52, P < 0.05). The expression of sirtuin 3 was positively correlated with the expression of mitofusion 1 (r=0.72, P < 0.05). To conclude, during renal ischemia-reperfusion injury, the decreased adenosine triphosphate level time-dependently stimulates the expression of sirtuin 3. The over expression of sirtuin3 enhances mitochondrial fusion and inhibit its fission, then protect the mitochondria and maintain energy metabolism. All these findings indicate that sirtuin3 may be a potential target for reducing renal ischemia-reperfusion injury.
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    Expression of suppressor of Zeste 12 in kidney tissues of rats with diabetic nephropathy
    Zhao Lu, Zhao Yifei, Gao Da, Liu Yanfang, Fu Tingting, Xu Jiangyan
    2023, 27 (8):  1179-1186.  doi: 10.12307/2022.1001
    Abstract ( 398 )   PDF (1856KB) ( 33 )   Save
    BACKGROUND: Suppressor of zeste 12 (Suz12) can participate in the epithelial-mesenchymal transition of tubular epithelial cells.
    OBJECTIVE: To investigate the effect of Suz12 on the progression of diabetic nephropathy and its related mechanism. 
    METHODS: (1) Cell experiment: Rat renal tubular epithelial cells were set as normal control group (glucose 5.5 mmol/L), high glucose group (glucose 30 mmol/L), and hypertonic group (glucose 5.5 mmol/L+mannitol 24.5 mmol/L). After transfection of 100 nmol/L Suz12 small interfering RNA (siRNA) and its negative control (NC siRNA) into renal tubular epithelial cells cultured in high glucose, western blot, cell counting kit-8, and flow cytometry were used to detect the protein expression of type IV collagen, Suz12, α-smooth muscle actin, and E-cadherin, cell proliferation and apoptosis, respectively. Subsequently, chromatin immunoprecipitation was used to detect the binding of Suz12 and tissue inhibitor of metalloproteinases-3 (TIMP3). The inhibition of TIMP3 expression is associated with the increase of trimethylation of lysine 27 on histone 3 (H3K27me). Methylation-specific PCR method was used to detect the methylation level of TIMP3 histone H3K27me3. Renal tubular epithelial cells were treated with Wnt/β-catenin pathway activator TDZD-8 (10 μmol/L; 1 hour) to verify whether the activation of Wnt pathway influences the effects of Suz12 on cell injury. (2) Animal experiment: A diabetic rat model was established by intraperitoneal injection of 60 mg/kg streptozotocin, and then 0.1 mL of PBS solution containing 3×108 PFU empty adenovirus vector (NC siRNA) or Suz12 siRNA adenovirus (Suz12 siRNA) was injected through the tail vein. After the experiment, serum, urine, and kidney tissues were collected, and the contents of blood glucose, serum creatinine, urinary nitrogen and total urinary protein were detected by an automatic biochemical analyzer. Hematoxylin-eosin and Masson staining were used to observe the renal histomorphological changes. Western blot assay was used to detect the expressions of related proteins in kidney tissues.  
    RESULTS AND CONCLUSION: Compared with the normal control group, the expression levels of Suz12, type IV collagen, α-smooth muscle actin in the renal tubular epithelial cells were significantly increased, E-cadherin expression was decreased, cell proliferation was decreased, and the apoptotic rate was increased in the high glucose group, whilst transfection of Suz12 siRNA could reverse the damage of high glucose treatment to the renal tubular epithelial cells. Compared with the high glucose+Suz12 siRNA group, TDZD-8 treatment could reverse the effects of Suz12 knockdown on type IV collagen, α-smooth muscle actin, E-cadherin and Wnt pathway related protein expression levels, cell proliferation and apoptosis of renal tubular epithelial cells. Suz12 could specifically bind to TIMP3 protein, indicating that TIMP3 is modified by H3K27me3, and knockdown of Suz12 reduced the level of TIMP3 methylation in high glucose-stimulated renal tubular epithelial cells. Compared with the diabetic model group, serum glucose, serum creatinine, urinary nitrogen, and urinary total protein contents were significantly decreased, renal histopathological changes and fibrous hyperplasia were alleviated, and Suz12, collagen 4, α-smooth muscle actin, E-cadherin and Wnt pathway related protein expression levels were significantly decreased in the diabetic model+Suz12 siRNA group. The above results indicate that Suz12 may be involved in the development of diabetic nephropathy by promoting the methylation of TIMP3 in diabetic rats.
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    Effects of aerobic exercises with different load volumes on inflammatory response and insulin signaling pathway of skeletal muscle in obese rats
    Zhang Yan, He Ruibo, Wang Qingbo, Pi Yihua, Lu Chunmin, Xu Chuanyi, Ma Gang, Peng Peng
    2023, 27 (8):  1237-1244.  doi: 10.12307/2023.055
    Abstract ( 456 )   PDF (1119KB) ( 46 )   Save
    BACKGROUND: Obesity is an important risk factor for elevated blood pressure, impaired glucose tolerance and dyslipidemia, in which imbalance in skeletal muscle renin-angiotensin system homeostasis may play a key role. Aerobic exercise is an important non-drug treatment for obesity, but the effects of aerobic exercises with different volumes are not been clarified.
    OBJECTIVE: To compare the effects of different load volumes of aerobic exercises on inflammatory responses and insulin signaling pathways of the skeletal muscle in obese rats and to explore the possible mechanism of the renin-angiotensin system. 
    METHODS: Thirty Wistar-Kyoto rats were fed with high-fat diet. After 20 weeks, they were randomly divided into obese sedentary group, obese low-volume exercise group or obese high-volume exercise group. In the meantime, another 10 rats fed with standard chow were selected as the normal control group. Animals in the obese low- and high-volume exercise groups were subjected to aerobic exercise, 150 and 300 minutes per week, respectively; those in the normal control group and obese sedentary group were caged quietly. After 12 weeks, body mass, body composition, blood pressure, glucose and lipid metabolism, inflammatory factor levels, and the expression of insulin signaling, inflammatory pathway and renin-angiotensin system axis protein molecules in the skeletal muscle were detected. 
    RESULTS AND CONCLUSION:  Body mass and body composition: compared with the obese sedentary group, body mass decreased significantly in the obese low- and high-volume exercise groups (P < 0.05). Compared with the obese low-volume exercise group, retroperitoneal and epididymal fat mass decreased significantly in the obese high-volume exercise group (P < 0.05). Blood pressure: compared with the obese sedentary group, systolic and diastolic blood pressure decreased significantly in the obese low- and high-volume exercise groups (P < 0.05). Glucose and lipid metabolism and inflammatory factors: compared with the obese sedentary group, contents of the above biochemical indexes decreased significantly in the obese low- and high-volume exercise groups (P < 0.05). Skeletal muscle insulin signal pathway: compared with the obese sedentary group, the protein expressions of phosphorylated protein kinase B and glucose transporter 4 increased significantly in the obese low- and high-volume exercise groups (P < 0.05), while the protein expression of protein tyrosine phosphatase 1B decreased significantly in the obese high-volume exercise group (P < 0.05). Skeletal muscle inflammation pathway: compared with the obese sedentary group, the protein expression of phosphorylated inhibitor α of nuclear factor κB decreased significantly in the obese low- and high-volume exercise groups (P < 0.05), and the protein expression of interleukin-6 decreased significantly in the obese high-volume exercise group (P < 0.05); compared with the obese low-volume exercise group, the protein expression of phosphorylated inhibitor α of nuclear factor κB decreased significantly in the obese high-volume exercise group (P < 0.05). Renin-angiotensin system axis of the skeletal muscle: compared with the obese sedentary group, the expression of angiotensin II type 1 receptor and Mas receptor proteins, as well as the ratio of angiotensin-converting enzyme/angiotensin-converting enzyme 2 and angiotensin II type 1 receptor/Mas receptor decreased significantly in the obese high-volume exercise group (P < 0.05). To conclude, aerobic exercise with different load volumes can improve body composition, glucose and lipid metabolism and blood pressure, ameliorate skeletal muscle insulin signaling pathway, and relieve inflammatory response in obese rats. However, the effect of high load volume protocol (300 minutes per week) is better than that of low load volume (150 minutes per week) and the mechanism may be related to the transition of skeletal muscle renin-angiotensin system balance from angiotensin-converting enzyme/angiotensin II type 1 receptor axis to angiotensin-converting enzyme 2/Mas receptor axis induced by high-volume aerobic exercises.
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    Interventional effects of whole blood and platelet-rich plasma with different preparation methods on nucleus pulposus cells
    Lian Shilin, Zhang Yan, Jiang Qiang, Zhang Hanshuo, Li Tusheng, Ding Yu
    2023, 27 (8):  1199-1204.  doi: 10.12307/2023.061
    Abstract ( 559 )   PDF (1110KB) ( 116 )   Save
    BACKGROUND: Platelet-rich plasma therapy for disc degeneration has received increasing attention. Platelet-rich plasma preparation methods for intervertebral disc repair include manual preparation using one-spin centrifugation and kit preparation using two-spin centrifugation. There was insufficient evidence of which preparation method is better.
    OBJECTIVE: To compare the effects of intervention of porine nucleus pulposus cells with manually prepared platelet-rich plasma, kit-prepared platelet-rich plasma and whole blood and to explore the better preparation method of platelet-rich plasma for intervertebral disc repair.
    METHODS: The porcine venous blood was extracted to prepare platelet-rich plasma using the manual preparation method of one-spin centrifugation and OSP kit preparation method of two-spin centrifugation. Some whole blood was reserved as control. And PBS was used to be blank control. The concentration of platelets and leukocytes in platelet-rich plasma was detected to calculate fold enrichment. ELISA was used to detect the concentration of transforming growth factor-β1, platelet-derived growth factor-BB, tumor necrosis factor-α and interleukin-1β in platelet-rich plasma lysate. Porcine nucleus pulposus cells were cultivated to P3 and intervened with prepared platelet-rich plasma and whole blood lysate. Cell counting kit-8 was used to detect the proliferation of nucleus pulposus cells after intervention with platelet-rich plasma and whole blood lysate. Western blot was used to detect the anabolic effects of platelet-rich plasma on type II collagen and aggrecan in nucleus pulposus cells.
    RESULTS AND CONCLUSION: Compared with the manual group, the OSP group showed significantly longer preparation time and higher platelet and leukocyte concentrations in the preparation of platelet-rich plasma. The fold enrichment of platelet-rich plasma was 5.6 in the OSP group and 3.0 in the manual group, while the fold enrichment of leukocytes was 2.21 and 1.36 respectively. The concentrations of transforming growth factor-β1, platelet-derived growth factor-BB, tumor necrosis factor-α and interleukin-1β of the OSP group were significantly higher than those of the manual group (P < 0.05). In the cell counting kit-8 detection of cell proliferation, the absorbance value at 450 nm of the OSP group was significantly higher than that of the other groups (P < 0.000 1); there was no significant difference in the absorbance value at 450 nm of the manual group compared with the whole blood and control groups (P=0.192 7). The relative expression of type II collagen in the OSP group was significantly higher than that in the other groups (P < 0.000 1). As for the synthesis of aggrecan, the relative expression of aggrecan in the manual group was lower than that in the remaining groups (P=0.040 5). These findings indicate that compared with the manual preparation method, the kit preparation method represented by OSP consumes more time and can acquire significantly higher concentration of leukocytes and proinflammatory cytokines. However, the kit preparation method can obtain higher concentrations of platelets and growth factors and has better cell proliferation effect and synthesis effect of extracellular matrix. For a better therapeutic effect of platelet-rich plasma, it is suggested to enhance the isolation of leukocytes when using the kit preparation method.
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    Influence of blood components on blood flow characteristics of individualized communicating aneurysm
    Wu Chuang, Muhetaer · Kelimu, Maimaitili · Aisha, Yang Hang
    2023, 27 (8):  1219-1223.  doi: 10.12307/2022.944
    Abstract ( 457 )   PDF (1673KB) ( 82 )   Save
    BACKGROUND: Hemodynamics plays an indispensable role in the occurrence and development of aneurysms, but the mechanism of occurrence and rupture of aneurysms is still unclear.
    OBJECTIVE: To analyze the influence of blood components on the rupture of aneurysm and to explore the mechanism of blood components on the rupture of aneurysms. 
    METHODS: CT images of a 52-year-old female patient with posterior communicating artery aneurysm were acquired and imported into MIMICS 20.0 to establish a surface model of the aneurysm. The model was processed by Geomagic Studio software to export the three-dimensional vascular wall model. The blood was assumed to be single-phase flow and two-phase flow, and computational fluid dynamics was used to numerically simulate the blood flow in the aneurysm and the tumor-bearing artery and analyze the influence of blood components on hemodynamic characteristics, including blood streamline velocity, wall deformation and displacement, wall shear stress, and relative stagnation time. 
    RESULTS AND CONCLUSION: At the same time, the blood flow patterns in the two models remained consistent. Compared with the single-phase flow model, the two-phase flow model had a higher proportion of low-wall shear stress area and greater deformation displacement, and larger area of near-wall stagnation for a relatively long time. Compared with the single-phase flow model, the two-phase flow model was more likely to damage vascular wall endothelial cells, resulting in structural and functional abnormalities. Moreover, the two-phase flow model was more likely to form a thrombus, causing the obstruction of tumor-bearing aneurysms induced by thrombus shedding. To conclude, the two-phase flow model has greater displacement, that is, greater stress. Under this condition, the aneurysm is more likely to rupture.
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    Constructing the prediction model of maximal oxygen uptake by back-propagation neural network based on the cardiorespiratory optimal point
    Wu Dongzhe, Gao Xiaolin, Li Chuangtao, Wang Hao
    2023, 27 (8):  1224-1231.  doi: 10.12307/2023.054
    Abstract ( 371 )   PDF (1254KB) ( 57 )   Save
    BACKGROUND: Maximal oxygen uptake is considered as the “gold standard” for evaluating aerobic exercise capacity and cardiopulmonary health. However, the measurement of maximal oxygen uptake requires a strong exercise load, and there are some limitations such as low reproducibility of the index and subjective effect of the test participants.
    OBJECTIVE: To construct the prediction model of maximal oxygen uptake using the new sub-maximal exercise evaluation index - cardiorespiratory optimal point - through the back-propagation neural network.
    METHODS: The trial protocol was approved by the Ethics Committee of the China Institute of Sports Science. Eighty healthy college students (40 males and 40 females) were randomly recruited. They were fully informed of the trial process and purpose and voluntarily signed informed consent to cooperate with the whole trial process. The participants underwent an incremental load cardiopulmonary exercise test to identify the maximal oxygen uptake, cardiorespiratory optimal point, and other related indicators for correlation analysis to obtain statistically significant indicators. Then, the prediction model of maximal oxygen uptake was built.
    RESULTS AND CONCLUSION: There were significant correlations between maximal oxygen uptake and cardiorespiratory optimal point, body mass index, sex, oxygen uptake and power corresponding to the cardiorespiratory optimal point (P < 0.01). The prediction model of maximal oxygen uptake with classical three-layer topology was established using the back-propagation neural network, including 5 input layers, 10 hidden layers and 1 output layer. The mean absolute and relative errors between the predicted and measured values of the model were 0.227 L/min and 12%, respectively. This indicated that the back propagation neural network model built based on the cardiorespiratory optimal point could accurately and effectively predict the maximal oxygen uptake. There was no significant difference between the maximal oxygen uptake predicted value of the back propagation neural network model and that of the multiple linear regression model (P > 0.05). However, the prediction accuracy of the back propagation neural network model constructed according to the cardiorespiratory optimal point was better than that of the multiple linear regression model.
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    Intraoperative neurophysiological monitoring of functional changes following durotomy with decompression for acute spinal cord injury
    Yang Jiujie, Li Zhi, Wang Shujie, Tian Ye, Zhao Wei
    2023, 27 (8):  1232-1236.  doi: 10.12307/2023.070
    Abstract ( 363 )   PDF (1175KB) ( 61 )   Save
    BACKGROUND: Traditional spinal canal expansion and decompression for acute spinal cord injury can only relieve bony compression (i.e., epidural pressure), but cannot obviously reduce intradural pressure. Therefore, durotomy with decompression is proposed; however, the therapeutic effect of this surgery is mixed.
    OBJECTIVE: Using intraoperative neurophysiological monitoring (IONM) to estimate the efficacy of durotomy for acute spinal cord injury and to evaluate the significance of IONM of nerve function during surgery for acute spinal cord injury. 
    METHODS: The clinical data of 51 patients with acute spinal cord injury of American Spinal Injury Association (ASIA) grades A and B undergoing surgical treatment were retrospectively analyzed. According to the surgical procedures, they were divided into durotomy group (n=19, receiving durotomy with posterior spinal decompression) and bone decompression group (n=32, receiving posterior spinal decompression alone). The KEY PONIT multi-function monitor was used to monitor the spinal cord function in combination with somatosensory and motor evoked potentials. Intraoperative neurophysiological data and the spinal cord function scores before and 6 months after surgery were compared and analyzed between two groups.
    RESULTS AND CONCLUSION: The ASIA score was 236.47±31.29 in the durotomy group at 6 months postoperatively, which was significantly higher than that of the bone decompression group (205.48±26.28; P < 0.05). The motor evoked potential amplitude of the patients in the duratomy group increased by (82.30±30.01) µV compared with the baseline, which was significantly higher than that after bone decompression alone [(6.1±25.6) µV, P < 0.000 1]. Changes in motor evoked potential amplitudes after decompression were basically consistent with the outcomes of postoperative neurological function in all patients. These findings indicate that durotomy with bony decompression is recommended for patients with acute spinal cord injury of ASIA grades A and B, which can further improve spinal nerve function of such patients. The use of IONM during acute spinal cord injury surgery can promptly reflect the functional changes of the spinal cord, and the change of IONM parameters tend to be consistent with the postoperative neurological outcomes of the patients.
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    Effects of visual factors on balance function in young adults
    Zhong Jiamin, Huang Zhaoxin, Li Longxue, Qu Tongtong, Liu Zhuang, Fu Yifeng, Xiao Xiaofei
    2023, 27 (8):  1245-1249.  doi: 10.12307/2022.1025
    Abstract ( 530 )   PDF (810KB) ( 70 )   Save
    BACKGROUND: Vision is the primary sensory system to maintain balance. Approximately 50% of visually impaired youth have an increased risk of falling. Chinese reports focus more on the epidemiological survey of the number of people with visual impairment, but ignore balance performance and control strategies in such people, especially the study of influencing factors.
    OBJECTIVE: To explore the effects of visual factors (degree of visual impairment: blind, partially sighted and normal vision group; vision condition: eyes open and eyes closed conditions) on balance function of young adults. 
    METHODS: Forty-three young adults were recruited and divided into three groups: blind (n=12), partially sighted (n=9) and normal vision group (n=22), and then underwent the following tests: one-leg stance test (eyes open and eyes closed conditions) and functional reach test (normal vision group: eyes open and closed conditions; partially sighted or blind groups: daily state). Measurement parameters between groups were analyzed using one-way analysis of variance. Paired sample t-tests were used to compare differences between different vision conditions within groups.  
    RESULTS AND CONCLUSION: In the one-leg stance test, the center of pressure trajectory length in the normal vision group with eyes open was significantly shorter than that in the blind and partially sighted groups (P < 0.05), and there was no significant difference between the groups when the eyes were closed (P > 0.05). Degree of injury and visual status had no significant effect on the static balance of visually impaired youth (P > 0.05). In the functional reach test, the reaching distance with eyes open was significantly greater than that with eyes closed in the normal vision group (P < 0.05) and the distance with eyes closed was significantly less than that of the blind group (P < 0.05). To conclude, visual impairment dramatically reduces the static balance of young adults, and vision conditions remarkably affect postural stability of the sighted youth, while the degree of visual impairment has no significant effect on static and dynamic balance of visually impaired youth. The lack of visual feedback can be compensated by non-visual factors in visually impaired youth.
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    Methods and application of gait analysis of lower limbs after stroke
    Yu Wenqiang, Ren Fuchao, Shi Guohong, Xu Yuanjing, Liu Tongyou, Xie Youzhuan, Wang Jinwu,
    2023, 27 (8):  1257-1263.  doi: 10.12307/2023.088
    Abstract ( 567 )   PDF (931KB) ( 126 )   Save
    BACKGROUND: Stroke is one of the major diseases endangering the health of Chinese citizens, characterized by high morbidity, disability, mortality and recurrence. Gait dysfunction or impairment is considered to be one of the most common and devastating physiological consequences of stroke. Active lower extremity rehabilitation can promote the recovery of gait function, improve the ability to perform activities of daily living, and improve the quality of life of patients.
    OBJECTIVE: To review and summarize research findings applicable to post-stroke gait quantification and analysis, with a focus on the latest gait analysis system technologies, post-stroke gait data processing and analysis techniques, and their feasibility and potential value in the clinical setting.
    METHODS: Search terms included “stroke, gait analysis, assessment, lower limb, spatiotemporal, kinematics, kinetics, plantar pressure, electromyography (EMG), machine learning, statistics” in Chinese and English. CNKI and PubMed databases were searched for relevant articles published from January 2000 to December 2021. A few of classical distant documents were also included. The initial screening was performed by reading the titles and abstracts of the articles. Duplicate studies, low-quality journals and irrelevant documents were excluded and 62 articles were finally included for review.
    RESULTS AND CONCLUSION: Traditional qualitative gait analysis is primarily based on observational gait and is therefore subjective and largely influenced by the observer’s experience. Quantitative gait analysis, on the other hand, provides measured parameters with good accuracy and repeatability for diagnostic and comparative assessment throughout the rehabilitation process. The rapid development of smart wearable technologies and artificial intelligence is increasingly drawing more attention to gait research. Although their use in clinical settings is not yet well exploited, these tools are expected to change the status quo in stroke gait quantification by providing the means to acquire, store, and analyze multifactorial complex gait data while capturing its nonlinear dynamic variability and providing the valuable benefit of predictive analysis. Gait analysis is often characterized by a number of specific parameters that describe normal or abnormal gait, including temporal, kinematic, kinetic, and electromyographic parameters. Understanding the factors associated with walking function can help clinicians and researchers identify gait-related parameters that should focus on when assessing walking function. As conventional statistical methods are no longer adequate to handle the large data volumes with high heterogeneity and complexity generated by instrumented gait analysis, and gait analysis involves a large number of interdependent parameters that are difficult to interpret due to the large amount of data and their interrelationships. To simplify the evaluation, the application of machine learning to gait analysis is a promising solution.  
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    YAP/TAZ, a core factor of the Hippo signaling pathway, is involved in bone formation
    Yang Zhishan, Tang Zhenglong
    2023, 27 (8):  1264-1271.  doi: 10.12307/2023.089
    Abstract ( 534 )   PDF (1350KB) ( 55 )   Save
    BACKGROUND: As the role of mechanical signalling in the bone has been increasingly studied, YAP/TAZ as a mechanosensitive factor has gradually attracted public attention. Existing studies have found that YAP/TAZ may be involved as an important mediator in the process of bone formation, but the mechanism is not yet clear.
    OBJECTIVE: To summarize the latest research on the effects of YAP/TAZ in bone formation.
    METHODS: The first author used “Hippo pathway, YAP/TAZ, bone, osteogenesis” as English and Chinese search terms to search in the PubMed and CNKI databases for relevant articles published from 2016 to March 2022. After screening and summarizing, 56 relevant articles were finally included for review.
    RESULTS AND CONCLUSION: YAP/TAZ, as the core factor of the Hippo pathway, has special features in its functional regulation. In addition to regulating its activity at the molecular level, changes in the cellular microenvironment, such as cell density, cell shape and extracellular matrix stiffness, can also contribute to its altered activity and thus YAP/TAZ can play different functional roles. YAP/TAZ is involved in osteogenic signaling and its regulation is also influenced by the cellular microenvironment. Overexpression or silencing of YAP/TAZ in cells can contribute to or inhibit osteogenic signaling, thereby altering the outcome of cell differentiation. YAP/TAZ is involved in the osteogenesis process of bone tissue cells and has different functions for different types of bone tissue cells. However, different methods for overexpressing or silencing YAP/TAZ and different types of cell species selected for observation make it difficult to quantify the results uniformly. In animal experiments, it has been shown that YAP/TAZ is essential for the morphological development of normal bones and maxillofacial regions, and has different functions at different stages of osteogenic differentiation. However, there is no uniformity in the knockout of YAP/TAZ conditional genes in experimental animals and the timing of observations is inconsistent, which make it difficult to compare experimental results with each other. To conclude, YAP/TAZ has an important role in bone formation, but its mechanism still needs to be further investigated. We expect that more scholars will explore its mechanism in depth and use its properties to cure bone diseases.
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    A review of physical activity intervention in type 2 diabetes mellitus with sarcopenia
    Wang Ji, Zhang Min, Yang Zhongya, Zhang Long
    2023, 27 (8):  1272-1277.  doi: 10.12307/2023.057
    Abstract ( 614 )   PDF (972KB) ( 160 )   Save
    BACKGROUND: With the aging of population, sarcopenia in type 2 diabetes mellitus has gradually emerged in front of people. Increasing physical activity is an important approach to prevent and treat type 2 diabetes mellitus and its related sarcopenia. However, current intervention plan, effect evaluation and mechanism of different physical activities in type 2 diabetes-related sarcopenia are still not detailed.
    OBJECTIVE: To analyze the intervention program, effect evaluation and mechanism of physical activity in type 2 diabetes-related sarcopenia, thereby providing theoretical basis and practical suggestions for physical activity to improve the disease.
    METHODS: Search terms included “Diabetes Mellitus; T2DM; Sarcopenia; Muscular Atrophy; Exercise; Training; physical activity” in English and Chinese. PubMed and CNKI were searched for relevant literature published from January 1986 to February 2022, including review papers, research papers and meta-analysis. Finally, 53 literatures were included for the review.
    RESULTS AND CONCLUSION: Appropriate increase in non-leisure physical activity (daily steps above 5 401 per day) can reduce the probability of sarcopenia and maintain physical exercise function in elderly type 2 diabetes patients. Increasing leisure physical activity can prevent the incidence of sarcopenia in elderly type 2 diabetes patients, and any regular physical exercise can be effective. Resistance exercise is significantly superior to aerobic exercise in the prevention and treatment of type 2 diabetes-related sarcopenia. A resistance exercise of moderate intensity and above (3 times a week, 70%-85% 1RM) can effectively increase muscle mass and strength performance in type 2 diabetes patients with sarcopenia, while aerobic exercise mainly delays skeletal muscle loss. Combining resistance exercise with aerobic exercise, nutritional intervention and health education can increase patient compliance and improve treatment efficacy. Resistance exercise mainly improves protein synthesis by activating IRS-PI3K-Akt, mTORC1, p70S6K and 4EBP1 signaling pathways, and improve muscle mass and functions by stimulating muscle satellite cell proliferation and differentiation. Aerobic exercise mainly delays muscle loss by inhibiting ubiquitin protein ligases Atrogin-1 and MuRF1 and skeletal muscle autophagy.
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    Diabetic peripheral neuropathy: research and therapy
    Song Hehua, Wei Zairong
    2023, 27 (8):  1278-1285.  doi: 10.12307/2023.066
    Abstract ( 688 )   PDF (953KB) ( 85 )   Save
    BACKGROUND: Diabetic peripheral neuropathy has a high disability rate and is one of the most common chronic complications of diabetes. Because its pathogenesis is complex and diverse, there is no recognized treatment method currently. It is a challenge to treat and manage this chronic disease. However, there are few reviews in this area.
    OBJECTIVE: To explore the related pathogenesis of diabetic peripheral neuropathy and to review the application effect of different treatment methods in diabetic peripheral neuropathy.
    METHODS: The first author searched the relevant literature in CNKI, WanFang and PubMed databases. The Chinese search terms were “diabetic peripheral neuropathy, diabetic complications, pathogenesis, diagnosis, treatment, Chinese medicine, surgical treatment, surgery, electrical stimulation, nerve release, nerve decompression” and the English search terms were “DPN, diabetic peripheral neuropathy, pathogenesis, diagnosis, therapy, treatment, drug, surgery, nerve decompression, nerve electrical stimulation, gene, exosome.” The literature search time was limited from January 2000 to January 2022. The literature was initially screened by reading the abstracts of the articles and those unrelated to the theme of the article were excluded. Finally 88 articles were included for review.
    RESULTS AND CONCLUSION: Hyperglycemia is the root cause of diabetic peripheral neuropathy. Strengthening blood sugar control is the most basic and important step in the treatment of diabetic peripheral neuropathy. Analgesic drugs can significantly reduce pain symptoms of patients with diabetic peripheral neuropathy. α-Lipoic acid and epalrestat play an anti-oxidative stress role; mecobalamin and nerve growth factor can promote the recovery of nerve function. According to the pathogenesis of “double extrusion” of diabetic peripheral neuropathy, nerve decompression and nerve transferring can reduce the degree of neuropathy, relieve pain and increase nerve conduction velocity in patients with diabetic peripheral neuropathy. Gene and stem cell therapies are promising new therapies. They are targeted, but relevant clinical studies are currently lacking and there are also concerns on ethical and safety issues.
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    The regulatory role of circular RNAs in cerebral ischemia-reperfusion injury
    Nie Chenchen, Su Kaiqi, Gao Jing, Fan Yongfu, Ruan Xiaodi, Yuan Jie, Duan Zhaoyuan, Feng Xiaodong
    2023, 27 (8):  1286-1291.  doi: 10.12307/2023.090
    Abstract ( 361 )   PDF (944KB) ( 43 )   Save
    BACKGROUND: Ischemic stroke is a devastating cerebrovascular disease with high morbidity and mortality worldwide. Currently, clinical treatments for ischemic stroke have limited efficacies and its pathogenesis still needs to be further explored, which will help to find more novel therapeutic targets. Recent studies have shown that circular RNAs not only play an important role in the regulation of gene expression but also play an important role in the pathogenesis of cerebral ischemia.
    OBJECTIVE: To review the regulatory role of circular RNAs in the pathogenesis of cerebral ischemia from the aspects of apoptosis, autophagy, oxidative stress, inflammation, angiogenesis, and blood-brain barrier, which is expected to provide ideas for clinical research on the role of circular RNAs in ischemic stroke.
    METHODS: Relevant literatures published from March 2010 to March 2022 were retrieved in CNKI, WanFang Chinese database and PubMed using computer. Search terms included “ischemic stroke, acute ischemic stroke, RNA, ncRNA, RNA, Circular, circRNA, apoptosis, autophagy, oxidative stress, inflammation, angiogenesis, blood brain barrier” in Chinese and English. Finally 48 articles were included for further review.
    RESULTS AND CONCLUSION: Circular RNAs are a class of non-coding RNA molecules with a closed loop structure, characterized by back splicing and lack of 5’ end cap and 3’ end polyadenylation tail. It exists widely in eukaryotic cells and has many important regulatory functions. Existing evidence has revealed that circular RNAs play an important role in the development of ischemic stroke. For example, circSHOC2 functions as a sponge for miR-7670-3p that can reduce neuronal damage by regulating autophagy-promoting sirt1 expression. A microarray study showed that the level of circHECTD1 was dramatically increased in mice after middle cerebral artery occlusion. Knockdown of circHECTD1 remarkably reduced cerebral infarct volume in mice, which in turn reduced neuronal damage and improved astrocyte activation. Circular RNAs are highly stable and evolutionarily conserved, and their circular structures are insensitive to ribonucleases and are more stable than linear ones, thus making circular RNAs more potential for developing novel disease diagnosis and treatment methods. At present, there is only a small amount of research on the mechanism of circular RNAs in ischemic stroke and its specific mechanism is still unclear. Related treatment strategies need to be further improved. Therefore, it is extremely necessary to further study the mechanism by which circular RNAs regulate ischemic stroke and to explore new potential targets for precise treatment of ischemic stroke in the future.
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    Health benefit relationship between exercise and intestinal bacteria
    Liang Jiaqi, Liu Hengxu, Yang Jinxin, Yang Yi, Deng Xuhui, Tan Mingjian, Luo Jiong
    2023, 27 (8):  1292-1299.  doi: 10.12307/2023.087
    Abstract ( 609 )   PDF (986KB) ( 97 )   Save
    BACKGROUND: Exercise has become one of the indispensable ways to promote human health. In recent years, as an important target for disease prevention and improvement, intestinal flora has been gradually recognized as an important target for human health. Current studies have proven that exercise can effectively regulate the composition, structure, function, and diversity of intestinal flora, thereby influencing the health status of body tissues.
    OBJECTIVE: To systematically review the correlation among exercise, the intestinal flora, and the body health system and to further explore the possible mechanism by which exercise influences body health through the involvement in the intestinal flora and analyze the effect of bacterial flora changes under different exercise intensities on the body health condition, in order to provide new ideas and strategies for the improvement of relevant diseases.
    METHODS: Literature retrieval was conducted in the Web of Science, Elsevier, Springer, PubMed, ProQuest, CNKI database, WanFang Data, VIP Chinese Journal Service Platform and Airitilibrary. Chinese and English documents related to sports training, intestinal microflora, energy metabolism, anti-inflammatory response, and oxidative stress published before February 2022 were included. Corresponding inclusion criteria were established according to the research needs, and finally 97 documents were reviewed.
    RESULTS AND CONCLUSION: Exercise can promote the secretion of short-chain fatty acid to increase the level of interleukin-10 and reduce the production of lipopolysaccharide-induced inflammatory factors, thereby improving the anti-inflammatory ability of the body and promoting host health. Exercise for intervention of intestinal flora cannot only promote the production of short-chain fatty acid but also increase the secretion of bile acid to activate nuclear hormone farnitol X receptor and G protein-coupled receptor in human organs, thus regulating lipid, glucose and energy metabolisms of the host body and promoting the absorption and stability of energy metabolism in the body. Exercise can change the abundance of Lactobacillus and Bifidobacteria to regulate antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione, thereby regulating or eliminating oxidative stress, preventing pathogen invasion, and improving muscle tissue injury. In addition, it is found that different intensity exercises have obviously different effects on the intestinal flora, thereby producing different effects on the body health. Low-intensity exercise intervention can improve the gut bacteria abundance, promote the intestinal steady-state, and have a beneficial effect on the health of the body, whereas high-intensity exercise intervention for the intestinal flora has a controversy on the human health. At present, the relevant mechanism of exercise intervention for the intestinal flora to promote body health is still unclear and needs to be further studied. Moreover, there are few studies on the effect of exercise intervention for the intestinal flora on the body health under specific conditions such as different exercise intensity, exercise time, exercise mode and exercise object, all of which are worthy of further explorations.
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    Immunoinflammatory microenvironment after spinal cord ischemia-reperfusion injury
    Gao Yu, Han Jiahui, Ge Xin
    2023, 27 (8):  1300-1305.  doi: 10.12307/2023.051
    Abstract ( 595 )   PDF (1260KB) ( 124 )   Save
    BACKGROUND: The changes in the immunoinflammatory microenvironment after spinal cord ischemia-reperfusion injury affect injury repair and prognosis.
    OBJECTIVE: To review the research progress in the immunoinflammatory microenvironment after spinal cord ischemia-reperfusion injury
    METHODS: PubMed, CNKI, and WanFang databases were searched for relevant studies using the keywords of “spinal cord ischemia-reperfusion, inflammation, microglia, astrocytes, macrophages, crosstalk” in English and Chinese, respectively. Finally, 42 relevant articles were included for further review.
    RESULTS AND CONCLUSION: Changes in the immunoinflammatory microenvironment can regulate nerve cell injury and repair after spinal cord ischemia-reperfusion injury. For example, microglia can be differentiated into M1/M2 phenotypes to regulate inflammatory responses, resist infectious sources, remove apoptotic and damaged cells, and reshape inappropriate neural connections, thereby helping the nervous system restore homeostasis. Astrocytes can regulate immune process through differentiation into A1/A2 phenotype to maintain homeostasis in the central nervous system and neuronal function under the stimulation of inflammatory factors. Macrophages can regulate immune process and repair injured spinal cord tissue by differentiation into M1/M2 phenotype. Microglia, astrocytes and macrophages also affect each other. For example, after spinal cord injury, microglia are the first to activate and release inflammatory factors to induce the activation of astrocytes and then release corresponding cytokines, chemokines, and Ca2+ to regulate the phenotype and function of microglia. Maintaining the homeostasis of immunoinflammatory microenvironment is the key to the treatment of spinal cord ischemia-reperfusion injury.
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    History, current situation and prospect of tissue banks in China
    Bai Yulong, Li Zhonghai, Zhao Yantao, Xia Cencan, Shi Lei
    2023, 27 (8):  1306-1312.  doi: 10.12307/2023.064
    Abstract ( 932 )   PDF (1003KB) ( 52 )   Save
    BACKGROUND: Tissue bank receives donated human tissues and organs and performs various corresponding processing, including storage and transportation for the purposes to repair and to reconstruct various clinical tissue defects.
    OBJECTIVE: To predict the development of tissue banks in China by sorting out the development history of medical tissue banks and introducing the development status of tissue banks.
    METHODS: The first author searched the literature data published up to October 2021 through databases such as CNKI, WanFang, VIP, and PubMed. The search terms were “tissue bank, tissue transplantation, tissue donation, allograft, bone allograft, skin allograft, vascular allograft, organ donation, Red Cross Society of China, regulation, standard” in Chinese and English. The final manuscript was complete based on information inquiry on the official website of the National Medical Drugs Administration of China, as well as access to a professional book, Allogeneic Tissue Transplantation and Tissue Bank, exchange interviews with tissue bank practitioners, and on-the-spot investigations. 
    RESULTS AND CONCLUSION: Medical tissue banks in China started in the 1950s, and have gone through the development stages of small-scale hospital tissue bank, non-profit tissue bank, and large-scale enterprise tissue bank. In the 1990s, tissue banks with enterprise nature were established in succession, the development and application of allogeneic tissues as materials for tissue repair were gradually improved. Various materials including allogeneic bone, skin, tendon, nerve and other materials have obtained the third-class medical device registration certificate. After entering the 21st century, non-profit tissue banks have emerged. At this time, tissue banks are mainly composed of three types: hospital tissue banks, enterprise nature tissue banks and non-profit tissue banks. With the effective development of the work, the clinical use of tissue materials has also increased yearly, and allogeneic tissue repair materials have become indispensable biomaterials for tissue repair and reconstruction in clinical practice. In 2020, with the “Regulations on Human Organ Transplantation (Draft Amendment)” soliciting opinions from the public and the promulgation and implementation of the “Civil Code of the People’s Republic of China,” the development of tissue banks has ushered in opportunities and challenges. It is believed that under the continuous development of science and technology and humanities, medical tissue banks will have greater development.
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