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18 August 2024, Volume 28 Issue 23 Previous Issue   

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Fucoxanthin alleviates glucocorticoid-induced osteoblast apoptosis by activating nuclear factor erythroid-2-related factor 2 Xie Ting, Liu Tingting, Zeng Xuehui, Li Yamin, Zhou Panghu, Yi Nianhua 2024, 28 (23):  3609-3614.  doi: 10.12307/2024.416 Abstract ( 221 )   PDF (2025KB) ( 74 )   Save BACKGROUND: Osteoporosis has a high incidence, leading to fracture and other complications. However, existing drugs have great side effects and are difficult to meet the clinical application.  OBJECTIVE: To explore the effect and potential mechanism of fucoxanthin on osteoporosis induced by glucocorticoid. METHODS: Primary rat osteoblasts were inoculated in 6-well plates. When the cell fusion reached 80%, the cells were divided into four groups: the control group was cultured alone for 24 hours, the glucocorticoid group was intervened with dexamethasone for 24 hours, the fucoxanthin group was intervened with fucoxanthin for 24 hours, and the glucocorticoid + fucoxanthin group was intervened with dexamethasone and fucoxanthin at the same time for 24 hours. After intervention, cell proliferation, apoptosis, intracellular reactive oxygen species level, and protein expression of apoptosis-related proteins, bone formation-related proteins, and nuclear factor erythroid-2-related factor 2 were detected. RESULTS AND CONCLUSION: Cell counting kit-8 results showed that the cell viability was decreased in the glucocorticoid group compared with the control group (P < 0.05) but increased in the glucocorticoid+fucoxanthin group compared with the glucocorticoid group (P < 0.05). JC-1 mitochondrial membrane potential staining and flow cytometry assay showed that the percentage of apoptosis increased in the glucocorticoid group compared with the control group (P < 0.05) but decreased in the glucocorticoid+fucoxanthin group compared with the glucocorticoid group (P < 0.05). Western blot assay showed that compared with the control group, the protein expression of BAX and cleaved poly (ADP-ribose) polymerase was elevated in the glucocorticoid group (P < 0.05), and the protein expression of BCL2, type I collagen α1 peptide chain, alkaline phosphatase, osteocalcin, and RUNX2 was decreased in the glucocorticoid group (P < 0.05). Compared with the glucocorticoid group, the protein expression of BAX and cleaved poly (ADP-ribose) polymerase was decreased (P < 0.05), and the protein expression of BCL2, type I collagen α1 peptide chain, alkaline phosphatase, osteocalcin, and RUNX2 was elevated (P < 0.05) in the glucocorticoid+fucoxanthin group. Fluorescent probe assay showed an increase in reactive oxygen species level in the glucocorticoid group compared with the control group (P < 0.05) and a decrease in reactive oxygen species level in the glucocorticoid+fucoxanthin group compared with the glucocorticoid group (P < 0.05). Immunofluorescence staining and western blot assay showed that the protein expression of nuclear factor erythroid-2-related factor 2 in the glucocorticoid group was decreased compared with that in the control group (P < 0.05); and the protein expression of nuclear factor erythroid-2-related factor 2 in the glucocorticoid+fucoxanthin group was elevated compared with that in the glucocorticoid group (P < 0.05). To conclude, fucoxanthin can improve glucocorticoid-induced osteoblast apoptosis and the expression of bone formation-related molecules by activating nuclear factor erythroid-2-related factor 2. Figures and Tables | References | Related Articles | Metrics

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NLRP3 inflammasome and inflammatory factor levels predict early infection after flap repair of diabetic foot ulcers Sheng Yu, Yang Qiuna, Wang Qiang, Yi Jianyun 2024, 28 (23):  3615-3620.  doi: 10.12307/2024.425 Abstract ( 196 )   PDF (1015KB) ( 95 )   Save BACKGROUND: Studies have shown that nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, interleukin-18, and interleukin-1β levels can induce an inflammatory cascade response to release inflammatory factors, affect metabolic stress, and damage endothelial cells involved in the development and progression of diabetic foot ulcers, which can provide a reference for early infections. OBJECTIVE: To investigate the predictive effect of peripheral blood mononuclear cell NLRP3 inflammasome, interleukin-18 and interleukin-1β levels on early infection after flap repair of diabetic foot ulcers.  METHODS: A total of 147 patients with diabetic foot ulcers were selected and divided into infection group and non-infection group according to whether they were infected within 1 week after operation. Logistic regression was used to analyze the relationship between NLRP3 inflammasome, interleukin-18 and interleukin-1β levels in peripheral blood mononuclear cells and early postoperative infections, and to evaluate their predictive values.  RESULTS AND CONCLUSION: In 147 patients with diabetic foot ulcers, 35 cases (23.81%) were infected within 1 week after operation, and 47 strains of pathogenic bacteria were isolated, including 25 strains of Gram-positive bacteria (53.19%) and 22 strains of Gram-negative bacteria (46.81%). Univariate analysis showed that Wagner grade, presence of comorbid diabetic nephropathy, operation time, peripheral blood NLRP3 mRNA, Caspase-1 mRNA, ASC mRNA, interleukin-18 and interleukin-1β levels were risk factors for early postoperative infections (all P < 0.05). Multivariate analysis suggested that Wagner grade, NLRP3 mRNA, Caspase-1 mRNA, ASC mRNA, high interleukin-18, interleukin-1β were independent risk factors (all P < 0.05). Receiver operator characteristic curve results showed that the area under the receiver operator characteristic curve of NLRP3 mRNA, Caspase-1 mRNA, ASC mRNA, interleukin-18 and interleukin-1β for early postoperative infections in patients with diabetic foot ulcers was 0.823, 0.705, 0.676, 0.811 and 0.853, respectively, and the area under the curve of combined predictive efficacy was 0.915. To conclude, patients with diabetic foot ulcers are mainly affected by Gram-positive bacteria, and the levels of NLRP3 inflammasome, interleukin-18 and interleukin-1β in peripheral blood mononuclear cells are independent risk factors for early postoperative infections. The combined prediction efficacy of these indicators is better and deserves further in-depth study.   Figures and Tables | References | Related Articles | Metrics

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Effect of warm-needling moxibustion on anterior cruciate ligament injury repair and related growth factors in rabbits with knee osteoarthritis Li Chun, Zhang Yanlin, Liu Di, Wang Minglei, Wang Duo, Liu Junwei, Wu Yongli 2024, 28 (23):  3621-3626.  doi: 10.12307/2024.415 Abstract ( 228 )   PDF (1796KB) ( 24 )   Save BACKGROUND: Warm-needling moxibustion can effectively treat knee osteoarthritis. Degeneration, injury and fracture of the anterior cruciate ligament can affect the local stability of the knee joint, and then induce the formation of knee osteoarthritis. Whether warm-needling moxibustion can repair the injured cruciate ligament and the mechanism of action are still unclear. OBJECTIVE: To observe the effects of warm-needling moxibustion on the morphology of the anterior cruciate ligament and the expression of insulin growth factor-1 and transforming growth factor-β in rabbits with knee osteoarthritis and to clarify the mechanism of anterior cruciate ligament repair by warm-needling moxibustion. METHODS: Thirty New Zealand rabbits were randomly divided into blank group, model group and warm-needling moxibustion group, with 10 rabbits in each group. Knee osteoarthritis model was established by plaster cast immobilization. The blank group was not intervened. Rabbits in the model group rabbits were fixed in a rabbit holder for 15 minutes every day. The warm-needling moxibustion group was treated with warm acupuncture, once a day, 7 days as a course of treatment, a total of two courses. After treatment, the imaging changes of the anterior cruciate ligament were observed by MRI and MRI grading statistics were performed. Morphological changes of the anterior cruciate ligament were observed by transmission electron microscope and hematoxylin-eosin staining. mRNA and protein expressions of insulin growth factor-1 and transforming growth factor-β were detected by RT-PCR and western blot, respectively.  RESULTS AND CONCLUSION: MRI examination: Compared with the blank control group, the anterior cruciate ligament in the model group was thickened, edematous, and partially torn, and the difference in grading statistics was statistically significant (P < 0.05). Compared with the model group, the anterior cruciate ligament in the warm-needling moxibustion group was slightly thickened, with mild edema and no tearing, and the difference in grading statistics was statistically significant (P < 0.05). General observation: In the model group, the surface of the anterior cruciate ligament was glossy and faded, with the edge being covered with flocculent periosteum and obvious tissue necrosis; in the warm-needling moxibustion group, the surface of the ligament was glossy, and the ligament was in a normal helical shape. Hematoxylin-eosin staining: In the model group, there was obvious tissue necrosis in the anterior cruciate ligament, a large number of new capillaries, loosely arranged fibroblasts and collagen fibers. In the warm-needling moxibustion group, there was a small amount of tissue necrosis and few new vessels in the anterior cruciate ligament, and the cells and collagen fibers were loosely and irregularly arranged. Transmission electron microscopy: In the model group, the fibers in the anterior cruciate ligament were arranged in a disordered way with uneven thickness and distribution, and there are more fibroblasts that were irregular in morphology; in the warm acupuncture group, the fibers were basically arranged longitudinally, with uneven thickness and distribution, and a small number of oval-shaped fibroblasts were observed. RT-PCR and western blot assay: mRNA and protein expressions of insulin growth factor-1 and transforming growth factor-β were significantly decreased in the model group compared with the blank control group (P < 0.05), but significant increased after treatment with warm-needling moxibustion (P < 0.05). To conclude, warm-needling moxibustion can alleviate anterior cruciate ligament injury and regulate the expression of insulin growth factor-1 and transforming growth factor-β to treat knee osteoarthritis. Figures and Tables | References | Related Articles | Metrics

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Yi medicine Sambucus adnata Wall methanol extract in a rat osteoarthritis model: therapeutic effect and target prediction Zheng Jianbin, Lu Yuchun, Jiang Zixian, Li Xiufang, Wang Tao, Wang Wenjing 2024, 28 (23):  3627-3635.  doi: 10.12307/2023.968 Abstract ( 228 )   PDF (2734KB) ( 23 )   Save BACKGROUND: The Yi people have used Sambucus adnata Wall to treat fractures, bruises, arthritis, etc. The author’s group found that the active site aqueous extract (SAW-A) and dichloromethane extract (SAW-B) can promote fracture healing by promoting the expression of genes related to osteoblast proliferation, differentiation and maturation, differentiation and maturation. However, the therapeutic effect of methanol extract (SAW-C) at its active site on osteoarthritis is unclear. OBJECTIVE: To investigate the therapeutic effect of Sambucus adnata Wall extract on osteoarthritis, and to identify the effective targets of Sambucus adnata Wall extract in the treatment of osteoarthritis by network pharmacology technology. METHODS: A rat osteoarthritis model was replicated by anterior cruciate ligamentectomy and model rats were then treated with methanol extract of Sambucus adnata Wall by gavage for 21 days. On the 21st day after modeling, the knee joint of rats was detected by X-ray, the width of the knee joint was measured, oxidative stress indexes and inflammatory factors levels in serum and joint lavage fluid were detected, the morphology of the knee joint was observed by hematoxylin-eosin staining, full-thickness cartilage and hyaline cartilage thickness were measured, and the content of articular cartilage proteoglycan was observed by safranin O-fast green staining. The "drug-component-disease-target" network was constructed. Gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes enrichment analysis of effective targets were performed, and protein-protein interaction network maps were constructed using cytoscape software. RESULTS AND CONCLUSION: Sambucus adnata Wall extract could reduce tumor necrosis factor-α level in joint lavage fluid and serum levels of prostaglandin E2 and malondialdehyde, while increase the level of superoxide dismutase; relieve joint swelling caused by osteoarthritis; improve the histopathological state of articular cartilage, maintain the thickness of full-thickness articular cartilage, hyaline cartilage and the area of bone trabeculae in subchondral bone; and effectively prevent the loss of proteoglycans in articular cartilage and have a chondroprotective effect. Network pharmacological results showed that the methanol extract of Sambucus adnata Wall may have some targets related to inhibition of tumor necrosis factor, AKT1, interleukin-6, MAPK3, and SRC as well as inhibition of over-activation of EGFR signaling pathway and AGE-RAGE signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Biomechanical analysis of the bones in a rat model of osteoporosis based on the combination of disease and syndrome Lin Chubin, He Xingpeng, Qiu Yuhui, Wu Wenjin, Chang Yu, Ye Tao, Li Pengfei, Yang Jian 2024, 28 (23):  3636-3641.  doi: 10.12307/2024.420 Abstract ( 183 )   PDF (2123KB) ( 23 )   Save BACKGROUND: Kidney deficiency is the main pathogenesis of osteoporosis. To study the relationship between the two major syndrome types of kidney deficiency, Kidney-Yang deficiency and Kidney-Yin deficiency, is beneficial for the development of clinical diagnosis and treatments based on the combination of disease and syndrome. OBJECTIVE: To evaluate the biomechanical differences of the rat femurs with Kidney-Yang deficiency and Kidney-Yin deficiency caused by Yougui pills, and to demonstrate the scientific efficacy of medication based on the combination of disease and syndrome in osteoporosis from a biomechanical perspective. METHODS: The bilateral ovaries of 60 female Sprague-Dawley rats were surgically removed to establish an ovariectomized osteoporosis model. At 10 weeks after modeling, all the rats were randomly divided into a Kidney-Yang deficiency group (n=30) and a Kidney-Yin deficiency group (n=30). Rats with Kidney-Yang deficiency were given gluteal intramuscular injection of hydrocortisone, while rats with Kidney-Yin deficiency were orally administered with thyroid tablet suspension, once a day, for 14 consecutive days. After successful modeling, 20 rats in each group were given a suspension of Yougui pills by gavage once a day for 12 consecutive weeks and the remaining 10 rats were used as the control group without intervention. After gavage, the microstructural parameters of the bone were measured using Micro-CT scanning. Three-point bending, finite element simulation, femoral head compression, and surface indentation distribution experiments of the femurs were performed on a mechanical testing machine. RESULTS AND CONCLUSION: Micro-CT revealed that the femoral bone density, bone volume fraction, bone surface density, trabecular number, and trabecular separation were improved in the Kidney-Yin deficiency+Yougui pills group compared with the Kidney-Yin deficiency group (P < 0.05); the femoral bone volume fraction, bone surface density, trabecular number, and trabecular thickness were improved in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group (P < 0.05). The three-point bending experiment showed that the femur elastic modulus, maximum bending strength and bending fracture strength were decreased (P < 0.05) and toughness was increased (P < 0.05) in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group. Finite element simulation showed that Yougui pills could significantly improve the bending resistance of the femurs in the Kidney-Yang deficiency group, but had no significant effect on the Kidney-Yin deficiency group. The femoral head compression experiments showed that Yougui pills could enhance the ability of the femoral head to resist deformation in the Kidney-Yang deficiency group, but there was no significant difference in the effect of Yougui pills on the surface properties of the femoral head in the Kidney-Yin deficiency group and the Kidney-Yang deficiency group. To conclude, Yougui pills can significantly enhance the biomechanical properties of the osteoporotic bones with Kidney-Yang deficiency, but have no significant effect on the osteoporotic bone with Kidney-Yin deficiency.  Figures and Tables | References | Related Articles | Metrics

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Mechanism by which alendronate promotes rapid mandibular distraction osteogenesis in rabbits Ye Zhikui, Zhang Zhimin, Cui Linna, Jiang Xiaowen 2024, 28 (23):  3642-3648.  doi: 10.12307/2024.414 Abstract ( 171 )   PDF (1614KB) ( 45 )   Save BACKGROUND: Some studies have found that local application of alendronate can promote osteogenesis, but less is reported on the process of distraction osteogenesis. OBJECTIVE: To observe the promoting effect of alendronate on rapid mandibular distraction in a rabbit model and explore its possible mechanism.  METHODS: Thirty-six male New Zealand white rabbits were randomly divided into groups A, B and C (n=12 per group) after operation and rapid distraction (3-day delay period followed by 3-day distraction at 1.5 mm/12 hours). At the 1st, 3rd and 7th days of the consolidation period, animal were injected with 200 μg/kg alendronate in group A and 100 μg/kg alendronate in group B, while those in group C were treated as controls. CT scanning and dual energy X-ray bone mineral density measurement were performed at 4 and 8 weeks of the consolidation period. After the radionuclide scanning was completed at the 4th week, several animals were sacrificed and the samples were collected for western blot assay and tartrate resistant acid phosphatase staining. A three-point bending test was performed after the animals were sacrificed at the 8th week.  RESULTS AND CONCLUSION: CT results showed that bone formation in the distraction space of group B was significantly better than that in groups A and C. At the 4th week, the bone mineral density in group B was (0.092±0.010) g/cm2, which was 1.26 times higher than that in group A (P < 0.001) and 1.28 times higher than that in group C (P < 0.001). At the 8th week, the bone mineral density in group B was (0.175±0.029) g/cm2, which was 1.38 times higher than that in group A (P < 0.001) and 1.45 times higher than that in group C (P < 0.001). Tartrate resistant acid phosphatase staining showed that the number of osteoclast-like cells in group C were 2.83 times more than that in group A (P < 0.001) and 2.21 times more than that in group B (P < 0.001). The radionuclide intensity was higher in group C than in groups A and B. Western blot assay results showed that the expression of Runx2 was significantly stronger in group B than in groups A and C. The maximum biomechanical load in group B was (158.48 ± 23.21) N, which was 1.26 times higher than that in group A (P=0.007) and 1.31 times higher than that in group C (P=0.003). To conclude, the low concentration of alendronate may promote rapid distraction osteogenesis of the rabbit mandible by inhibiting osteoclast signals. Figures and Tables | References | Related Articles | Metrics

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Overexpression of SMAD4 interferes with the expression of iron metabolism related proteins in osteoporotic rats Yao Ting, Guan Rongwei, Gao Yuan 2024, 28 (23):  3648-3653.  doi: 10.12307/2024.413 Abstract ( 186 )   PDF (2208KB) ( 78 )   Save BACKGROUND: SMAD family member 4 (SMAD4) can promote bone remodeling in osteoporotic rats, but it is unclear whether SMAD4 interferes with the expression of iron metabolism related proteins in osteoporotic rats. OBJECTIVE: To explore the effect of SMAD4 overexpression on the expression of iron metabolism related proteins in osteoporotic rats.  METHODS: Rats were randomized into sham group, ovariectomy group, transfection control group and SMAD4 overexpression group. Animal models of osteoporosis were established in the latter three groups by ovariectomy, and only adipose tissue was removed in the sham group. One week later, adenovirus was injected into the femoral bone marrow cavity. SMAD4 overexpression group and transfection control group were injected with adenovirus overexpressing SMAD4 gene and control empty virus, respectively. Index detection was performed at 1 month after injection. Micro-CT, hematoxylin-eosin staining and tartrate resistant acid phosphatase staining were used to detect bone formation and bone resorption in osteoporotic rats. ELISA was used to detect serum ferritin and hepcidin levels. Immunohistochemical staining was used to detect alkaline phosphatase, osteocalcin, receptor activator for nuclear factor-κB ligand and tartrate resistant acid phosphatase levels in femoral tissue. RT-qPCR was used to detect SMAD4, hepcidin, divalent metal transporter 1, transferrin receptor1 and ferroportin1 mRNA levels in femoral tissue. Western blot was used to detect SMAD4, alkaline phosphatase, osteocalcin, osteoprotegerin, receptor activator for nuclear factor-κB ligand, tartrate resistant acid phosphatase, β-Crosslaps, hepcidin, divalent metal transporter 1, transferrin receptor 1, and ferroportin 1 protein levels. RESULTS AND CONCLUSION: In the sham group, bone trabeculae in femur tissue were intact, and almost no osteoclasts were found. In the ovariectomy and transfection control groups, the bone trabeculae were sparse and a large number of osteoclasts were present. In the SMAD4 overexpression group, the number of bone trabeculae was increased and the number of osteoclasts was decreased. Compared with the sham group, the ovariectomy group showed a significant reduction in the protein expression of SMAD4, alkaline phosphatase, osteocalcin, and osteoprotegerin in femoral tissue and hepcidin levels in serum and femoral tissue, while receptor activator for nuclear factor-κB ligand, tartrate resistant acid phosphatase, β-Crosslaps protein levels, divalent metal transporter 1, transferrin receptor1, ferroportin1 mRNA and protein levels were significantly increased (P < 0.05). Compared with the transfection control group, the SMAD4 overexpression showed a significant increase in SMAD4, alkaline phosphatase, osteocalcin, and osteoprotegerin protein levels in femoral tissue and hepcidin levels in serum and femoral tissue, while the expressions of receptor activator for nuclear factor-κB ligand, tartrate resistant acid phosphatase, β-Crosslaps protein levels, divalent metal transporter 1, transferrin receptor1, and ferroportin 1 at mRNA and protein levels were significantly decreased (P < 0.05). To conclude, overexpression of SMAD4 promotes bone remodeling in osteoporotic rats by interfering with the expression of iron metabolism related proteins. Figures and Tables | References | Related Articles | Metrics

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Protective effect and mechanism of icariin against carbon tetrachloride-induced acute liver injury in mice Xiao Dongyan, He Wei, Xiao Zhiying, Liao Yue, Mao Jiahao, He Yihuai, Jiang Zhigang 2024, 28 (23):  3654-3660.  doi: 10.12307/2024.347 Abstract ( 204 )   PDF (1303KB) ( 24 )   Save BACKGROUND: Icariin, with antiinflammatory, antioxygenatory and immunoregulatory effects, can be a potential drug for preventing and treating acute liver injury. OBJECTIVE: To investigate the protective effect and possible mechanism of icariin in mice with acute liver injury induced by carbon tetrachloride. METHODS: Thirty-two Kunming mice were equally and randomly divided into the following groups: normal, model, low-dose icariin and high-dose icariin groups. The low- and high-dose icariin groups were continuously gavaged with icariin (100 and 200 mg/kg, respectively) once a day for 7 continuous days. The normal group and model group were injected with physiological saline (10 mL/kg) at the same time point. After the last administration, all the groups except for the normal group were injected with carbon tetrachloride to induce acute liver injury. The mice were killed 24 hours later, and the liver index was detected. Serum levels of alanine aminotransferase and aspartate aminotransferase were detected by automated biochemical analysis. Tumor necrosis factor α and interleukin 6 levels in serum were detected using ELISA. The levels of superoxide dismutase, glutathione peroxidase and malondialdehyde in liver tissue were detected through a reagent kit. The histopathology changes of the liver were observed by hematoxylin-eosin staining. TUNEL method was used to detect the apoptosis in hepatocytes. Western blot was performed to detect the expression levels of glucose-regulated protein 78 kDa, endoplasmic reticulum stress-related protein (C/-EBP homologous protein), mixed lineage kinase domain-like protein and Caspase-3 in liver tissue. RESULTS AND CONCLUSION: Compared with the normal group, the liver index and serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor α and interleukin 6 were increased in the model group (P < 0.05). Compared with the model group, the above indexes were decreased in the low-dose and high-dose icariin groups (P < 0.05). Compared with the normal group, the activities of superoxide dismutase and glutathione peroxidase in the liver tissue of mice were decreased in the model group (P < 0.05) and the level of malondialdehyde was increased (P < 0.05). Compared with the model group, the activities of superoxide dismutase and glutathione peroxidase were increased in the low- and high-dose icariin groups (P < 0.05) and the level of malondialdehyde was decreased (P < 0.05). Hematoxylin-eosin and TUNEL staining showed that mice in the model group had severe structural destruction of liver tissue, extensive necrosis of hepatocytes and high apoptotic rate of hepatocytes, while the structural destruction of liver tissue and the area of necrosis of hepatocytes in the low- and high-dose icariin groups were significantly milder than those in the model group, and the apoptotic rate of hepatocytes was lower than that in the model group (P < 0.05). Western blot assay showed that the protein expression of glucose-regulated protein 78 kDa, C/-EBP homologous protein, mixed lineage kinase domain-like protein and Caspase-3 in liver tissue of mice in the model group was increased compared with that in the normal group (P < 0.05), while the expression levels of these proteins in liver tissue of mice were significantly reduced after low- and high-dose icariin intervention (P < 0.05). To conclude, icariin can produce a protective effect against carbon tetrachloride-induced acute liver injury, and its mechanism may be related to the regulation of endoplasmic reticulum stress and reduction of programmed necrosis. Figures and Tables | References | Related Articles | Metrics

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Mechanisms by which baicalein protects against steriod-induced osteonecrosis of the femoral head in rats Ma Wanli, Yang Hongsheng, Qu Bo, Zhang Zhengdong, Gong Kai, Lin Yanshui 2024, 28 (23):  3661-3668.  doi: 10.12307/2024.391 Abstract ( 203 )   PDF (2649KB) ( 52 )   Save BACKGROUND: The development of steroid-induced osteonecrosis of the femoral head is a complex process involving multiple mechanisms. There is still no standard therapeutic drug for early intervention of this disease. Current studies have shown that baicalein has various pharmacological activities such as regulating lipid metabolism, bone metabolism, apoptosis and anti-oxidative stress, which provides an idea for the prevention and treatment of steroid-induced osteonecrosis of the femoral head. OBJECTIVE: To observe the preventive effect of baicalein against steroid-induced osteonecrosis of the femoral head and to investigate its possible mechanism. METHODS: Thirty-six 10-week-old male Sprague-Dawley rats were randomly divided into three groups (n=12 per group): blank control group, model group, and baicalein intervention group. In the model group and baicalein intervention group, intraperitoneal lipopolysaccharide and intramuscular injection of methylprednisolone sodium succinate were performed for modeling, while normal saline was used as a substitute for the modeling drug in the blank control group. Baicalein 300 mg/kg was administered by gavage (once a day for 6 weeks) at the time of initial intramuscular glucocorticoid injection in the baicalein intervention group, and baicalein was replaced by normal saline in the other two groups. The serum level of malondialdehyde in rats was detected at 2 weeks of the experiment. Blood lipid indicators and bone formation metabolic markers were detected at 6 weeks of the experiment, the histomorphometric changes of the femoral head were analyzed by hematoxylin-eosin staining, anti-tartaric acid phosphatase staining and TUNEL staining, and the femoral head was subjected to Micro-CT scanning and three-dimensional reconstruction of the bone in order to analyze the alterations of bone tissue structure and parameters. RESULTS AND CONCLUSION: The serum levels of malondialdehyde, triglyceride, β-collagen type I carboxy-terminal peptide were increased and the serum levels of bone specific alkaline phosphatase and pre-collagen type I amino-terminal peptide were decreased in the model group compared with the blank control group (P < 0.05). The serum level of malondialdehyde decreased in the baicalein intervention group compared with the model group (P < 0.05), but there was no significant difference between the baicalein intervention group and blank control group (P > 0.05). The serum level of triglyceride was higher in the baicalein intervention group than the blank control group (P < 0.05), but had no significant difference between the baicalein intervention group and model group (P > 0.05). There were also no significant differences in the levels of bone specific alkaline phosphatase and β-collagen type I carboxy-terminal peptide between the baicalein intervention group and the other two groups (P > 0.05). The serum level of the baicalein intervention group was lower in the baicalein intervention group than the blank control group (P < 0.05) but had no significant difference between the baicalein intervention group and model group (P > 0.05). Histomorphological analysis of the femoral head showed that the rate of bone empty lacuna, osteoclast counting and cell apoptosis rate in the femoral head of model group rats were significantly higher than those of the other two groups (P < 0.05). There was a significant increase in the number of adipocytes in the bone marrow cavity of the femoral head, bone trabeculae were thinned and sparsely arranged with more disruptions in the continuity. The incidence of osteonecrosis was higher in the model group (75%) than in the baicalein intervention group (25%; bilateral and unilateral exact significance results were both 0.05). There was also an increase in the number of adipocytes in the bone marrow cavity of the femoral head in the baicalein intervention group, and the trabecular changes were roughly similar to those in the model group. Micro-CT results showed that bone volume fraction, trabecular thickness, trabecular number, and bone mineral density decreased and trabecular separation increased in the model group compared with the blank control group (P < 0.05). Overall significant bone mass loss was observed in the model group. Bone tissue parameters in the baicalein intervention group were significantly improved than those in the model group, which were reflected in bone volume fraction, trabecular thickness and trabecular separation (P < 0.05), and trabecular number and bone mineral density had no significant difference between the baicalein intervention group and blank control group (P > 0.05). Although baicalein failed to significantly ameliorate dyslipidemia and promote bone formation in rats with steroid-induced osteonecrosis of the femoral head, it could reduce the incidence of steroid-induced osteonecrosis of the femoral head by reducing oxidative stress damage, decreasing cell apoptosis, inhibiting osteoclasts, suggesting its effectiveness in the early prevention of steroid-induced osteonecrosis of the femoral head. Figures and Tables | References | Related Articles | Metrics

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Effect of povidone-iodine on the immersion and flushing of wound tissue in rabbits Zhang Qiang, Xu Yan, Ma Zhuangzhuang, Zhang Hao, Li Zihao, Liu Senhan, Chen Wei 2024, 28 (23):  3669-3673.  doi: 10.12307/2024.427 Abstract ( 182 )   PDF (1059KB) ( 58 )   Save BACKGROUND: Clinically, the most dangerous and serious complication of artificial joint replacement is periprosthetic infections. It is urgent to find a way to prevent periprosthetic infections after artificial joint replacement. OBJECTIVE: To study the effect of povidone-iodine on muscle, blood vessel, fat and bone of rabbits after immersion and flushing. METHODS: Forty male New Zealand rabbits aged 10 weeks were selected. The left hind leg of each rabbit served as the experimental group and the right hind leg served as the control group. After anesthesia, the hind limbs of each rabbit were cut open to expose the muscle, blood vessels, fat and bone. The control group was soaked and flushed with normal saline inside the surgical incision, while the experimental group was soaked and flushed with povidone-iodine inside the surgical incision. After being soaked in povidone-iodine for 0, 1, 3, 5 minutes, 10 rabbits were randomly selected and executed to collect wound tissue samples. The samples were made into pathological slices for hematoxylin-eosin staining observation as well as statistical analysis and comparison of cell counts. RESULTS AND CONCLUSION: Compared with the control group, the muscle, blood vessels, fat and bone after immersion and flushing with povidone-iodine showed no obvious difference in cell structure, morphology and number under microscope. The paired t-test was used to explore the difference between the control and experimental groups, and the paired data did not show any difference (P > 0.05). It is suggested that povidone-iodine shows no significant difference from normal saline after immersion and flushing of rabbit tissues such as muscle, blood vessels, fat and bone, indicating that povidone-iodine solution as an intra-incisional antiseptic is safe and effective. Figures and Tables | References | Related Articles | Metrics

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Shujin Jiannao Prescription alleviates inflammation in the cerebral cortex of rats with hypoxic-ischemic cerebral palsy Liu Gang, Zeng Jie, Zhao Yalin, Deng Bowen, Jiang Shengyuan, Zhang Yaqi, Zhao Yi, Ren Jingpei, Hu Chuanyu, Xu Lin, Mu Xiaohong 2024, 28 (23):  3674-3679.  doi: 10.12307/2024.396 Abstract ( 184 )   PDF (1559KB) ( 14 )   Save BACKGROUND: Shujin Jiannao Prescription is an empirical formula for the treatment of cerebral palsy in Dongzhimen Hospital, Beijing University of Chinese Medicine, with clear clinical efficacy, but the specific mechanism needs to be elucidated. OBJECTIVE: To explore the possible mechanism of Shujin Jiannao Prescription in treating cerebral palsy.  METHODS: Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into a normal group (n=12) and a model group (n=52). An animal model was established by the Rice-Vannucci method. After successful modeling, 52 model rats were randomly divided into control model group (n=12), minocycline group, and the low-, medium-, and high-dose groups of the Shujin Jiannao Prescription (n=10 per group). Rats in the minocycline group were given 40 mg/kg•d  minocycline by gavage; rats in the low-, medium, and high-dose groups were given 4, 8, and 16 g/kg•d Shujin Jiannao Prescription granules by gavage, respectively; and rats in the normal group and control model group were given an equal dose of normal saline by gavage. Medication in each group was given once a day for 1 week. The rats in each group were evaluated behaviorally using suspension test, abnormal involuntary movement score, and Bederson score. The pathological changes of the cerebral cortex were observed by hematoxylin-eosin staining. The levels of tumor necrosis factor α, interleukin 1β, and interleukin 10 in the cerebral cortex were determined using ELISA. The positive expressions of Janus kinase 2 (JAK2), phosphorylated Janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the cerebral cortex were detected using immunohistochemistry. The protein expression levels of JAK2, p-JAK2, and p-STAT3 were detected using western blot.  RESULTS AND CONCLUSION: Compared with the normal group, the suspension test score and involuntary movement score were decreased in the control model group (P < 0.01 or P < 0.05). The pathological results showed structural disruption of nerve cells, formation of large numbers of vacuoles, cell swelling, and increased intercellular space in the control model group. In addition, the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were significantly increased (P < 0.01), the expression of interleukin 10 was decreased (P < 0.05), and the protein expressions of JAK2, p-JAK2, and p-STAT3 in the cerebral cortex were significantly increased (P < 0.01) in the control model group compared with the normal group. Compared with the model group, minocycline and Shujin Jiannao Prescription at each dose could improve the behavioral indexes of rats (P < 0.01 or P < 0.05) and ischemic-hypoxic pathological changes were attenuated, with only a small amount of necrotic nerve cells and a few vacuoles, and reduced intercellular space. Moreover, the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were decreased in each drug group compared with the control model group (P < 0.05), while the protein expressions of JAK2, p-JAK2, and p-STAT3 in the cerebral cortex were significantly decreased (P < 0.01). The most obvious improvement was observed in the high-dose Shujin Jiannao Prescription group. To conclude, Shujin Jiannao Prescription can inhibit inflammation in the cerebral cortex of rats with hypoxic-ischemic brain injury. The mechanism may be related to the regulation of the JAK2/STAT3 signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which interleukin-1beta regulates the expression of Semaphorin 3A to induce intervertebral disc degeneration Huang Jie, Jiang Qiang, Han Jiaheng, Liu Jiang, Zhang Yan, Lu Zhencao, Ding Yu 2024, 28 (23):  3680-3685.  doi: 10.12307/2024.397 Abstract ( 180 )   PDF (1821KB) ( 33 )   Save BACKGROUND: Semaphone 3A (Sema3A) is an important neurovascular growth inhibitor. It is not clear how Sema3A is involved in the pathogenesis of discogenic low back pain. Exploring the potential mechanism of Sema3A in intervertebral disc degeneration can provide a new target and theoretical basis for the prevention and treatment of discogenic low back pain. OBJECTIVE: To explore the mechanism of interleukin-1β inhibiting the expression of Sema3A by activating the nuclear factor-κB signaling pathway to induce intervertebral disc degeneration in rats.  METHODS: RT-qPCR was used to detect the expression of Sema3A mRNA in normal and degenerative human nucleus pulposus tissues. Nucleus pulposus cells of Sprague-Dawley rats were isolated, cultured, and passaged to the 3rd generation. Then, passage 3 cells were divided into three groups: the blank control group was routinely cultured for 48 hours, the degeneration group was intervened with 10 ng/mL interleukin 1β for 48 hours, and the degeneration+inhibitor group was treated by 5 µmol/L nuclear factor-κB signaling pathway-specific inhibitor BAY11-7082 for 1 hour, followed by interleukin-1β for 48 hours. At the end of the intervention, cell viability was detected by cell counting kit-8, cell apoptosis was detected by Annexin V/FITC staining, mRNA expression of cellular matrix, vascular and neural markers and Sema3A was detected by RT-qPCR, and protein expression of marker proteins, p65 and p-p65 was detected by western blot. RESULTS AND CONCLUSION: RT-qPCR assay showed that the expression of Sema3A mRNA was lower in degenerative human nucleus pulposus tissue than in normal human nucleus pulposus tissue (P < 0.05). Compared with the blank control group, the nucleus pulposus cell viability decreased and the apoptotic rate increased in the degeneration group (P < 0.05); compared with the degeneration group, the nucleus pulposus cell viability increased and the apoptotic rate decreased in the degeneration + inhibitor group (P < 0.05). Compared with the blank control group, mRNA expression of type II collagen, polyproteoglycan, and Sema3A was decreased in the degeneration group (P < 0.05), while mRNA expression of CD31 and neurofilament 200 was increased (P < 0.05). Compared with the degeneration group, mRNA expression of type II collagen, polyproteoglycan, and Sema3A was elevated in the degeneration+inhibitor group (P < 0.05) and mRNA expression of CD31 and neurofilament 200 decreased (P < 0.05). Compared with the blank control group, the protein expression of type II collagen, polyproteoglycan, and Sema3A was decreased in the degeneration group (P < 0.05), and the protein expression of CD31, neurofilament protein 200, p65, and p-p65 was elevated (P < 0.05); compared with the degeneration group, the protein expression of type II collagen, polyproteoglycan, and Sema3A was elevated in the degeneration+inhibitor group (P < 0.05), and protein expression of CD31, neurofilament 200, p65, and p-p65 was decreased (P < 0.05). To conclude, interleukin-1β does inhibit the expression of Sema3A by activating the nuclear factor-κB signaling pathway, which can also increase the degradation of extracellular matrix, promote the innervation and angiogenesis in degenerative intervertebral disc, and may be one of potential factors that contribute to intervertebral disc degeneration and discogenic low back pain. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which lycium barbarum polysaccharides inhibit keratinocyte apoptosis in burn wounds via autophagy Zhu Yongzhao, Fang Chao, Zhao Fang, Zhang Qing, Zhao Dan 2024, 28 (23):  3686-3691.  doi: 10.12307/2024.390 Abstract ( 205 )   PDF (1733KB) ( 22 )   Save BACKGROUND: Lycium barbarum polysaccharide has many biological activities and has been found to have potential effects on promoting wound healing.  OBJECTIVE: To investigate the mechanism of lycium barbarum polysaccharide in tumor necrosis factor-α-mediated keratinocyte apoptosis and its effect on the healing of burn wounds.  METHODS: (1) In vitro experiment: Keratinocytes were divided into four groups: cells were cultured in the α-MEM medium (complete medium) containing 15% fetal bovine serum and 1% glutamine in normal group, cultured in the complete medium containing lycium barbarum polysaccharide in positive control group, cultured in the complete medium containing tumor necrosis factor-α in model group, and cultured in the complete medium containing lycium barbarum polysaccharide and tumor necrosis factor-α in experimental group. After 24 hours of culture, cell proliferation was detected using cell counting kit-8 assay; Cleaved caspase-8, TNF R1, FADD, and LC3 were detected using western blot. Then an autophagy inhibitor group (the complete medium containing 3-methyladenine) and an autophagy inhibitor+lycium barbarum polysaccharide group (the complete medium containing lycium barbarum polysaccharide, tumor necrosis factor-α, and 3-methyladenine) were set up. After 24 hours of culture, keratinocyte apoptosis was detected by flow cytometry. (2) In vivo experiment: Six Sprague-Dawley rats were randomly divided into a control group and an experimental group, with three rats in each group. Four deep II degree burn wounds with a diameter of 2 cm were made on the back of each rat. At 24 hours after modeling, mice in the control and experimental groups were coated with normal saline and lycium barbarum polysaccharide solution, respectively, once a day. Wound healing was observed regularly after treatment. Samples were taken 28 days after treatment and the pathologic pattern of the wound was observed.  RESULTS AND CONCLUSION: (1) In vitro experiment: Addition of lycium barbarum polysaccharide alone did not affect cell proliferation and apoptosis and the expression of apoptotic and autophagic proteins in keratinocytes. After the addition of tumor necrosis factor α, the proliferation of keratinocytes was inhibited, the apoptotic rate increased, and the expression of apoptotic and autophagic proteins was elevated, while lycium barbarum polysaccharide could antagonize the above effects of tumor necrosis factor-α. Lycium barbarum polysaccharide combined with autophagy inhibitors further reduced the apoptotic rate of keratinocytes. (2) In vivo experiment: The wound healing rate of rats in the experimental group was higher than that of the control group at 12, 16, 20, 24, and 28 days after treatment (P < 0.05, P < 0.01). Hematoxylin-eosin staining results at 28 days after treatment showed an intact and well-defined epidermis of the wound in the experimental group compared with the control group. To conclude, lycium barbarum polysaccharide protects the integrity of skin epidermal tissue and promotes wound healing by inhibiting autophagy and apoptosis of keratinocytes. Figures and Tables | References | Related Articles | Metrics

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Frontier hot trends in ischemic stroke and vascular regeneration based on bibliometric analysis Xia Tianqing, Rong Mengwei, Dan Cunyan, Yang Ting, Ding Zhibin, Song Lijuan, Ma Cungen 2024, 28 (23):  3692-3698.  doi: 10.12307/2024.418 Abstract ( 233 )   PDF (1972KB) ( 64 )   Save BACKGROUND: Vascular regeneration, as one of the crucial repair processes after its onset, necessitates visual analysis between the two. OBJECTIVE: To analyze the literature on ischemic stroke and vascular regeneration in the past decade using bibliometrics and sort out the current status, hotspots, and future research trends in this field.  METHODS: We used a bibliometric approach to search the Web of Science database for literature on ischemic stroke and vascular regeneration published between January 2011 and May 2023. The obtained data were systematically analyzed using the VOSviewer visualization software to identify the number of articles, countries, keywords, institutions, authors, citations, and trends. RESULTS AND CONCLUSION: We searched and selected 1 484 articles and found that the relationship between ischemic stroke and vascular regeneration has emerged as a research hotspot in the cerebrovascular field, with the number of published articles continuing to rise. Most of these articles were authored by institutions from China and the United States. Shanghai Jiao Tong University was the most cited institution. The most influential author was Hermann DM, whose article had been cited 1 003 times. The current hot research topics in the field include extracellular vesicles, microRNAs and mesenchymal stem cells, which are being studied for their correlations with relevant diseases. To conclude, the bibliometric analysis provides a visual analysis of ischemic stroke and vascular regeneration, which is found to be an emerging focus as well as a valuable reference for future trends and highlights in ischemic stroke and vascular regeneration. Figures and Tables | References | Related Articles | Metrics

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The causal relationship between blood lipids and muscle atrophy based on Mendelian randomization analysis of two samples Peng Zhihua, Pan Junxi, Feng Qinghui, Tian Tianzhao, Zhang Sheng, Li An, Cai Yingfeng 2024, 28 (23):  3699-3703.  doi: 10.12307/2024.417 Abstract ( 366 )   PDF (1129KB) ( 54 )   Save BACKGROUND: Osteoporosis is often accompanied by sarcopenia and an increased risk of fractures from falls. Recent studies have indicated a close relationship between lipid metabolism and sarcopenia. Abnormal lipid metabolism may directly impact muscle physiological function and metabolism.  OBJECTIVE: To investigate the relationship between lipid metabolism and sarcopenia and evaluate their causal relationship using Mendelian randomization. METHODS: Mendelian randomization was used to explore the causal relationship between low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and muscle mass. Research data from genome-wide association studies were used and a sensitivity analysis was conducted to verify the reliability of the results. Approximate indicators of muscle mass, including trunk lean mass and appendicular lean mass, were used as outcome measures. RESULTS AND CONCLUSION: The study found a negative correlation of low-density lipoprotein cholesterol and triglycerides with muscle mass, while no correlation was observed between high-density lipoprotein cholesterol and muscle mass. The results of the sensitivity analysis indicated a robust causal relationship. Using Mendelian randomization, this study provides evidence of a causal relationship between low-density lipoprotein cholesterol and triglycerides and muscle mass. This finding deepens our understanding of the effects of lipids on sarcopenia and has important clinical implications for the prevention and treatment of sarcopenia and osteoporosis. Figures and Tables | References | Related Articles | Metrics

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Construction of an animal model for treating early postoperative infected bacterial biofilms by irrigating after internal fixation Huang Jiacheng, Shao Xinxin, Li Haomiao, Du Shaohua, Dai Shuangwu 2024, 28 (23):  3704-3708.  doi: 10.12307/2024.400 Abstract ( 105 )   PDF (1605KB) ( 26 )   Save BACKGROUND: The treatment for bacterial biofilms after internal fixation surgery is a very difficult problem in clinic. It is a great significance to establish an animal model of irrigation for treating bacterial biofilms in the early stage after internal fixation surgery. OBJECTIVE: To establish an animal model for treating bacterial biofilms with different drugs through irrigation in early stage after internal fixation surgery. METHODS: Six New Zealand white rabbits were selected. Bilateral femoral surfaces were exposed and drilled holes were made, and bone plates colonized with Pseudomonas aeruginosa (experimental group) and blank bone plates (blank control group) were implanted around the drilled holes on one side, and two drainage tubes were retained and fixed to serve as the “inlet” and “outlet,” respectively. The model was immersed for a certain period of time after simulated perfusion before rinsing. After the simulated irrigation, the plates were soaked for a certain time before washing. At 5 days postoperatively, the rabbits were observed for body temperature, wound condition, bacterial culture of drainage fluid, and crystalline violet staining and scanning electron microscopy of the bone plate. RESULTS AND CONCLUSION: Six rabbits had difficulty in moving the affected limbs after surgery and showed elevated body temperature at 2-4 days after surgery. Local swelling could be touched at some wounds in the experimental group, and the wounds in the blank control group healed well. The results of bacterial culture of drainage fluid showed that Pseudomonas aeruginosa diffused or spread in the experimental group. At 5 days after surgery, the plate in the experimental group became purple shown by crystalline violet staining, and the absorbance value at 570 nm detected by the microplate reader was 2.621±0.088, indicating the presence of bacteria. Scanning electron microscopy at 5 days after surgery showed that a large number of bacterial microcolonies appeared on the surface of the plate in the experimental group, forming a highly inhomogeneous three-dimensional structure similar to the “mushroom-like” and “tower-like” structures, with filamentous water channels connecting the “mushroom-like” structures, which were typical biofilm structures with high densities, while no obvious colonies were seen in the blank control group. Overall, this animal model simulates the state of infected biofilm formation due to early infection after internal fixation and provides an available method of irrigation with different drugs. Figures and Tables | References | Related Articles | Metrics

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Effects of icariin on proliferation and differentiation of MC3T3-E1 cells in an inflammatory environment Han Yue, Wang Yufei, Liu Wanqing, Dong Ming, Niu Weidong 2024, 28 (23):  3709-3714.  doi: 10.12307/2024.455 Abstract ( 169 )   PDF (1178KB) ( 19 )   Save BACKGROUND: Studies have shown that chronic apical periodontitis is one of the common inflammatory bone destruction diseases. Icariin can promote osteogenic differentiation, inhibit bone resorption, and may play a protective role in bone destruction caused by chronic apical periodontitis. OBJECTIVE: To investigate the effect of icariin on the proliferation and differentiation of MC3T3-E1 cells in the inflammatory environment stimulated by lipopolysaccharides. METHODS: Lipopolysaccharides were used to stimulate MC3T3-E1 cells to establish an inflammatory environment in vitro, and cell counting kit-8 was used to detect the best concentration and optimal action time of lipopolysaccharides. Cell counting kit-8 was used to detect the optimal concentration of icariin under the stimulation of lipopolysaccharides at a concentration of 1 μg/mL. Alkaline phosphatase detection, Real-time PCR and western blot assay were used to detect the effect of icariin on osteogenic differentiation of MC3T3-E1 cells in the inflammatory environment. Real-time PCR and western blot were used to detect the effects of icariin on the expression of interleukin-1β and interleukin-6 in MC3T3-E1 cells in the lipopolysaccharide-stimulated inflammatory environment. RESULTS AND CONCLUSION: Cell counting kit-8 results showed that the optimal concentration of icariin was 0.1 μg/mL. In the inflammatory environment, icariin enhanced the expression of alkaline phosphatase and promoted osteoblast differentiation. Compared with the lipopolysaccharide group, the expression of osteogenesis-related factors alkaline phosphatase and Runx2 was increased in the lipopolysaccharide+icariin group. Compared with the lipopolysaccharide group, the expression levels of inflammation-related factors interleukin-1β and interleukin-6 decreased in the lipopolysaccharide+icariin group. To conclude, lipopolysaccharides weaken the osteogenic ability of MC3T3-E1 cells and aggravate the inflammatory response, but icariin has a protective effect on them. Figures and Tables | References | Related Articles | Metrics

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Mendelian randomization study on the association between rheumatoid arthritis and osteoporosis and bone mineral density Wu Ruiqi, Zhou Yi, Xia Tian, Zhang Chi, Yang Qipei, Zhang Xuan, Zhang Yazhong, Cui Wei 2024, 28 (23):  3715-3721.  doi: 10.12307/2024.412 Abstract ( 321 )   PDF (1891KB) ( 121 )   Save BACKGROUND: Many clinical research observations have indicated a close association between rheumatoid arthritis and osteoporosis as well as bone mineral density (BMD). However, it remains unclear whether there is a causal genetic relationship between rheumatoid arthritis and the development of osteoporosis and alterations of BMD. OBJECTIVE: To assess the potential causal relationship between rheumatoid arthritis and osteoporosis as well as BMD using a two-sample Mendelian randomization approach, provide meaningful insights from a genetic perspective into the underlying mechanisms and offer a reference for early prevention of osteoporosis and improvement in the progression of the disease. METHODS: We conducted a study using data from publicly available genome-wide association studies databases to identify single nucleotide polymorphisms associated with rheumatoid arthritis as instrumental variables (P < 5×10-8). The main outcomes of the study included osteoporosis and BMD at five different sites, including total body BMD, lumbar spine BMD, femoral neck BMD, heel BMD, and forearm BMD. The inverse variance-weighted method was used as the primary analysis method to evaluate causal effects. Weighted median, simple median, weighted mode and MR-Egger regression were used as supplementary analyses. Causal relationships between rheumatoid arthritis and the risk of osteoporosis and BMD were assessed using odds ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using Cochran’s Q test and horizontal pleiotropy was evaluated using MR-Egger intercept tests. RESULTS AND CONCLUSION: The inverse variance-weighted analysis demonstrated a positive association between genetically predicted rheumatoid arthritis and osteoporosis (OR=1.123, 95% CI: 1.077-1.171; P=4.02×10-8). Heterogeneity test (P=0.388) indicated no significant heterogeneity among the single nucleotide polymorphisms. MR-Egger intercept (P=0.571) tests did not detect horizontal pleiotropy, and sensitivity analysis showed no evidence of bias in the study results. There was no causal relationship between rheumatoid arthritis and BMD at the five different sites. The total body BMD (OR=1.000, 95% CI: 0.988-1.012; P=0.925), lumbar spine BMD (OR=0.999, 95% CI: 0.982-1.016; P=0.937), femoral neck BMD (OR=1.001, 95% CI: 0.986-1.016; P=0.866), heel BMD (OR=0.996, 95% CI: 0.989-1.004; P=0.419), and forearm BMD (OR=1.063, 95% CI: 0.970-1.031; P=0.996) indicated no significant association. MR-Egger intercept analysis did not detect potential horizontal pleiotropy (total body BMD: P=0.253; lumbar spine BMD: P=0.638; femoral neck BMD: P=0.553; heel BMD: P=0.444; forearm BMD: P=0.079). Rheumatoid arthritis may contribute to the development of osteoporosis through the interaction between chronic inflammation and bone formation, resorption, and absorption. Additionally, the use of glucocorticoids and the presence of autoantibodies (such as anti-citrullinated protein antibody) in patients with rheumatoid arthritis showed associations with osteoporosis. Future research should focus on monitoring systemic inflammatory markers, standardized use of glucocorticoids, and regular screening for osteoporosis risk in patients with rheumatoid arthritis. Figures and Tables | References | Related Articles | Metrics

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Comparison of the effects of mental fatigue induction tasks Yang Wei, Li Jundong, Zhao Shaocong 2024, 28 (23):  3722-3728.  doi: 10.12307/2024.428 Abstract ( 207 )   PDF (1291KB) ( 122 )   Save BACKGROUND: Conducting mental fatigue research in sports depends on appropriate mental fatigue induction tasks. However, the different types and time settings for the tasks in this field have interfered with the selection and determination of the appropriate task for mental fatigue research. OBJECTIVE: To compare the effects of three mental fatigue tasks and their commonly used time settings for mental fatigue induction.  METHODS: In this randomized crossover study, 16 male amateur soccer players performed four tasks of 60-minute duration with an interval ≥ 48 hours in a randomized counter-balanced order: STROOP task (psychological cognition group), social media use in smartphone (electron exposure group), whole-body coordination task (exercise group) and emotionally neutral video watching as controls (control group). Before each task, the visual analogue scale (VAS)-motivation, VAS-mental fatigue, VAS-physical fatigue, and average heart rate were measured. Also, the VAS-mental fatigue, VAS-mental exertion, VAS-physical fatigue, and average heart rate were recorded every 15 minutes during the task. Repeated measures analysis of variance was mainly used for statistical analysis.  RESULTS AND CONCLUSION: The baseline level of VAS-mental fatigue in the four groups were similar (P=0.806).  (2) The VAS-mental fatigue of the psychological cognition group at 30, 45 and 60 minutes was significantly higher than that of the other three groups (all P < 0.05). The VAS-mental fatigue of psychological cognition, electron exposure, and exercise groups at 45 minutes were similar with that at 60 minutes (all P > 0.05), but significantly higher than that of pretest, 15 minutes and 30 minutes (all P < 0.05). To conclude, the psychological cognition task is superior to the electron exposure and exercise tasks for mental fatigue induction and 45 minutes is the appropriate length of time to effectively induce mental fatigue. Figures and Tables | References | Related Articles | Metrics

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Conical beam CT measurement of alveolar bone structure remodeling in patients with skeletal class III malocclusion after orthodontic-orthognathic treatment Zhao Qihang, Lu Xin, Tong Lei, Shang Yonghui, Li Shuai, Liu Wen, Zhou Jianhua, Yuan Rongtao, Guo Qingyuan 2024, 28 (23):  3729-3735.  doi: 10.12307/2024.383 Abstract ( 187 )   PDF (1475KB) ( 53 )   Save BACKGROUND: Most of the studies on combined orthodontic-orthognathic treatment of skeletal class III malocclusions have focused on the improvement of the patient’s lateral appearance and recovery in the later stages of the treatment, while there are fewer studies observing the microcosmic nature of the alveolar bone remodeling of the lower anterior teeth. OBJECTIVE: To evaluate the therapeutic effect of lower anterior tooth decompensation and alveolar bone remodeling in patients with skeletal class III malocclusion before and after orthodontic-orthognathic treatment based on oral X-ray lateral films and oral cone-beam CT. METHODS: From January 2015 to May 2023, 15 patients with skeletal class III malocclusion who underwent orthodontic-orthognathic surgery at Qingdao Hospital of Rehabilitation University were enrolled. All patients underwent lateral cephalography and cone beam computed tomography before and after treatment. Cephalometric measurement items related to the angle and line distance, lip/lingual bone cracking length (d-La/d-Li) and bone cracking/bone fenestration of the lower anterior teeth before and after treatment were measured. RESULTS AND CONCLUSION: Lateral X-ray films showed that the amount of alveolar bone remodeling after decompensation of the lower anterior teeth showed significant changes compared to before treatment. The root of the tooth moved significantly towards the center of the alveolar bone, and the specific data was closer to normal data, but there were still some differences compared with normal individuals. Based on the cone-beam CT measurement, the bone cracking/bone fenestration length and width of the alveolar bone were improved in almost all the teeth after orthodontic-orthognathic combined treatment, alveolar bone remodeling in some teeth even reached the level of healthy individuals. Before treatment, most patients often experienced bone fenestration/cracking on the lip/lingual side of the lower incisor due to compensatory tooth growth. However, during the preoperative orthodontic stage, decompensation triggered alveolar bone remodeling and significant changes in tooth angle. Preoperative orthodontic treatment caused the upper anterior teeth to retract and the lower anterior teeth to tilt and control the root, but the amount of decompensation before surgery was often insufficient. In the orthognathic surgery stage, the jaw was removed through the positioning guide plate, the maxilla moved forward, and the mandible retreated. During the postoperative orthodontic process, the effect of fine adjustment was better. Although there is a certain degree of recurrence trend in the position of teeth and jawbones, the postoperative orthodontic treatment is closer to the normal value. Figures and Tables | References | Related Articles | Metrics

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Osteoprotegerin/receptor activator of nuclear factor kappa-B/receptor activator of nuclear factor kappa-B ligand and the application of relevant target therapy in oral medicine Zhou Jing, Zhang Zhao 2024, 28 (23):  3736-3742.  doi: 10.12307/2024.341 Abstract ( 160 )   PDF (990KB) ( 32 )   Save BACKGROUND: Osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/receptor activator of nuclear factor-κB ligand (RANKL) are important cytokines for coupling osteoclast and osteoblast differentiation and activation, and are key factors for regulating bone metabolism, which affect the immune system, bone regeneration and remodeling, and are closely related to the physiological and pathological remodeling of the alveolar bone. OBJECTIVE: To analyze the effects of the OPG/RANK/RANKL signaling pathway on alveolar bone remodeling and the progress in its targeted therapy application in the dental field. METHODS: We searched relevant articles included in CNKI and PubMed databases with the keywords of “OPG, anti-RANKL antibody, RANKL, periodontitis, orthodontic tooth movement, implant, tooth eruption, periapical lesion, alveolar bone resorption” in Chinese and English, respectively. A total of 63 articles were finally included for review. RESULTS AND CONCLUSION: Anti-RANKL therapy can treat oral diseases by targeting the inhibition of osteoclast formation and alveolar bone absorption. Local and systemic anti-RANKL therapy can inhibit the progression of periodontitis, peri-implantitis and periapical lesions, and it also plays an important role in preventing orthodontic relapse, strengthening orthodontic anchorage and implant osseointegration. RANKL therapy can treat oral diseases by promoting osteoclast differentiation and alveolar bone absorption. RANKL treatment can accelerate orthodontic tooth movement, shorten the treatment cycle and reduce the incidence of orthodontic complications. Although there are limitations in anti-RANKL therapy, they can be avoided by rational applications, such as excluding local and systemic risk factors before treatment, regular oral maintenance and avoiding traumatic alveolar surgery as much as possible during treatment. Figures and Tables | References | Related Articles | Metrics

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Blood flow restriction training interventions for sarcopenia in older adults: biological mechanisms and proposed application protocols Kong Jianda, Xie Yingao, Chen Shijuan, Zhu Lei 2024, 28 (23):  3743-3750.  doi: 10.12307/2024.351 Abstract ( 234 )   PDF (1116KB) ( 69 )   Save BACKGROUND: Sarcopenia is a chronic condition that leads to strength loss and functional decline, increasing the risk of frailty, disability, falls, and death in older adults. Blood flow restriction training can be effective in the treatment of sarcopenia, but a comprehensive review of its advantages, disadvantages, biological mechanisms, and application options is lacking. OBJECTIVE: To review the advantages, limitations, and biological mechanisms of blood flow restriction training interventions for sarcopenia and to give recommendations for application protocols based on current published evidence. METHODS: A search of major databases was conducted for literature published in the time frame up to February 2023. The search terms were “blood flow restriction training, KAATSU, elderly, sarcopenia, muscle” in English and Chinese. Finally, 82 included papers were compiled and analyzed. RESULTS AND CONCLUSION: Blood flow restriction training as an intervention for sarcopenia has been effective in peripheral muscle groups, but there are limitations in its application. Blood flow restriction training is highly operational and safe. This training can improve muscle strength and physical performance, but there are potential risks, including adverse events on skeletal muscle, cardiovascular and endothelial cells. Therefore, blood flow restriction training needs to be performed under scientific guidance and further studies are needed to verify its efficacy in patients with sarcopenia. The biological mechanisms of blood flow restriction training intervention in sarcopenia may include: increasing muscle hypertrophy due to reactive muscle congestion, improving muscle protein synthesis capacity, inducing metabolic stress adaptation, promoting skeletal muscle growth and repair, activating vascular endothelial growth factor signaling pathway to promote angiogenesis, and promoting satellite cell proliferation. However, these specific roles and combined effects of these mechanisms need to be determined by more in-depth studies. Blood flow restriction training interventions for sarcopenia are mainly influenced by training and cuffs. To avoid adverse events, it is recommended that 20% to 50% 1RM, 20 to 75 repetitions, 2 to 3 times per week, 30-60 seconds interval between sessions, smaller size cuffs with a pressurization value ≤ 140 mmHg for upper limb training, and larger size cuffs with a pressurization value ≤180 mmHg for lower limb training, usually 50% to 80% of the pressure value in the completely occluded artery. However, more research is needed on the training frequency and interval between sessions in older adults, and further research is needed on the optimal choice of cuff pressurization values. Figures and Tables | References | Related Articles | Metrics

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Active ingredients of Panax notoginseng regulate signaling pathways related to steroid-induced necrosis of the femoral head Han Jie, Peng Qinglin, Xu Zhiwei, Wu Yukun, Ren Guowu, Xie Xiaozhong, Jin Wanqing, Yang Ling 2024, 28 (23):  3751-3758.  doi: 10.12307/2024.381 Abstract ( 185 )   PDF (1748KB) ( 28 )   Save BACKGROUND: Steroid-induced osteonecrosis of the femoral head is a refractory disease in the field of orthopedics. There is no definitive idea to fully explain its pathogenesis. With the increased research on the active ingredients of Panax notoginseng interfering with the signaling pathways related to various diseases, the active ingredients of Panax notoginseng that treat steroid-induced necrosis of the femoral head via the regulation of relevant signaling pathways have gradually become a hot research topic.  OBJECTIVE: To systematically summarize the literature on the pathological mechanism of steroid-induced osteonecrosis of the femoral head and the regulation of signaling pathways by the active ingredients of Panax notoginseng in recent years, thereby providing a reference for the follow-up study on the active ingredients of Panax notoginseng in the treatment of this disease. METHODS: CNKI, WanFang, and PubMed were searched for relevant literature with the key words of “glucocorticoid, steroid-induced osteonecrosis of the femoral head, pathological mechanism, signaling pathway, Panax notoginseng, active ingredient” in Chinese and English. Documents related to the pathological mechanism of steroid-induced osteonecrosis of the femoral head as well as related to the intervention of active ingredients of Panax notoginseng on the signaling pathway of steroid-induced osteonecrosis of the femoral head were retrieved. A total of 63 documents were finally included according to the inclusion and exclusion criteria.  RESULTS AND CONCLUSION: The main ingredients of Panax notoginseng include Panax notoginseng saponins, ginsenoside, Panax notoginseng saponins, quercetin, kaempferol, etc. Panax notoginseng saponins, ginsenoside Rb1 and quercetin can promote bone repair and angiogenesis by acting on the transforming growth factor-β/bone morphogenetic protein pathway. Panax notoginseng saponins, ginsenoside CK and kaempferol can promote osteogenic differentiation and lipid metabolism by acting on the Wnt/β-catenin pathway. Panax notoginseng saponins and Panax notoginseng saponins R1/R2 act on the MAPK pathway to inhibit osteoclastogenesis and promote bone repair. Panax notoginseng saponins, ginsenoside Rb2 and quercetin can inhibit osteoclast proliferation and promote osteoblastic differentiation by acting on the RANKL/RANK/OPG pathway. Panax notoginseng saponins, quercetin and kaempferol can repair vascular injury and promote osteogenesis by acting on the hypoxia-inducible factor-1α pathway. Panax notoginseng saponins R1, quercetin combined with hydroxyapatite nanoparticles, Panax notoginseng saponins combined with polyethylene-L-lactic acid and other biomaterials have good research prospects in the treatment of steroid-induced osteonecrosis of the femoral head. The active ingredients of Panax notoginseng can regulate the signaling pathways related to steroid-induced osteonecrosis of the femoral head through various mechanisms, and play an active intervention role in the disease. However, the depth and breadth of relevant research are insufficient at present, and the future research should be based on the existing mechanism to explore the specific mechanism of Panax notoginseng regulating different pathways and the interaction between pathways, which will be beneficial to the multi-development of the active ingredients of Panax notoginseng in the treatment of steroid-induced osteonecrosis of the femoral head. Figures and Tables | References | Related Articles | Metrics

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Mechanisms of exercise-regulated telomere length and health promotion Qi Yuqing, Liu Xiaoran 2024, 28 (23):  3759-3765.  doi: 10.12307/2024.384 Abstract ( 239 )   PDF (921KB) ( 40 )   Save BACKGROUND: As we age, the function of various systems in the human body gradually decreases and the telomeres, located at the ends of chromosomes, consequently shorten, leading to the development and progression of various chronic age-related diseases. As a cost-effective intervention, scientific exercise has been shown to reduce the rate of telomere wear, maintain telomere length, delay the aging process and reduce the probability of disease. At the same time, better health level is important for healthy aging. OBJECTIVE: To sort out the role of telomeres in health promotion by analyzing telomere and physical fitness, the common adverse factors of telomere length shortening and chronic disease occurrence, and the influence of telomere length on the regulation of the occurrence and development of common chronic diseases such as cardiovascular disease, cancer, diabetes, obesity and mental disease, as well as to summarize the possible regulatory mechanism of exercise regulating telomere length, and to explore the role of telomere in the regulation of exercise on the above-mentioned chronic diseases for the purpose of health promotion. METHODS: The search terms of “exercise, telomere, aerobic capacity, muscle strength, aging” in Chinese and English were used to search the relevant literatures in CNKI and PubMed, respectively. A total of 108 articles were included for final review. RESULTS AND CONCLUSION: In terms of physical fitness and health promotion, there is a strong correlation between the maximum aerobic exercise capacity and muscle strength of the human body and telomere length. Long-term physical exercise can enhance the level of physical fitness to maintain telomere length and promote the heath of the human body. In terms of chronic diseases and health promotion, abnormal telomere length can promote the occurrence of some chronic diseases such as cardiovascular diseases, cancer, diabetes, obesity, and mental diseases, and the factors that accelerate the shortening of telomere length, such as oxidative stress, inflammation, and telomerase activity, also have adverse effects on the development of these diseases. The regulation of telomere length by exercise can reduce the levels of oxidative stress and inflammation, improve the activity of telomerase and enhance the stability of telomere protein complex. Through these regulatory mechanisms, exercise slows the rate of telomere wear and maintains consistent telomere length, thereby reducing the risk of chronic diseases associated with abnormal telomere length, such as cardiovascular disease, cancer, diabetes, obesity, and mental diseases. Therefore, telomeres play a positive role when exercise is used to regulate related diseases and promote human health. Figures and Tables | References | Related Articles | Metrics

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Effects of endurance training with blood flow restriction on aerobic capacity, lower limb muscle strength, and sports performance: a Meta-analysis Dong Kuan, Xu Chengli, Tian Jing, Xu Changchun 2024, 28 (23):  3766-3772.  doi: 10.12307/2024.398 Abstract ( 223 )   PDF (1481KB) ( 113 )   Save OBJECTIVE: To systematically assess the effect of blood flow restriction combined with endurance training on aerobic capacity, lower limb muscle strength, and sports performance of athletes using Meta-analysis.  METHODS: 3210 studies were searched in CNKI, VIP, WanFang, PubMed, Embase, Web of Science, ScienceDirect, and Cochrane databases before March 2023. After screening, 12 studies and 14 research reports were included. The traditional Meta-analysis and network Meta-analysis were performed by Review Manager 5.4 and Stata 14.  RESULTS: Endurance training with blood flow restriction had a medium effect size on maximal oxygen uptake (standardized mean difference (SMD)=0.59, 95% confidence interval (CI): 0.28-0.90, P < 0.05) and no heterogeneity. The effect of continuous pressure was better than the other pressure types (P < 0.05). Compared with sports events by anaerobic energy supply, sports events by aerobic energy supply showed better effects (P < 0.05), which was set as follows: 4-8 weeks of aerobic training, 20-30 minutes once,  3 or more sessions per week, for a total of 12 or more  sessions. Secondly, endurance training with blood flow restriction showed a large effect on the lower limb muscle strength (SMD=0.99, 95% CI: 0.61-1.37, P < 0.05) and no heterogeneity. A subgroup analysis showed muscle endurance was the best improved (SMD=1.11; 95% CI: 0.37-1.85), followed by knee extension strength (SMD=1.02, 95% CI: 0.37-1.67) and knee flexion strength (SMD=0.87, 95% CI: 0.24-1.51). Finally, endurance training with blood flow restriction showed a medium effect on sports performance (SMD=0.59, 95% CI: 0.13-1.06, P < 0.05), and the subgroup analysis showed a medium effect on running performance (SMD=0.55, 95% CI: 0.05-1.06, P < 0.05) and no heterogeneity. There was only one item of soccer specific performance that was not analyzed.  CONCLUSION: Endurance training combined with blood flow restriction can improve the aerobic capacity, lower limb muscle strength, and sports performance of the athletes. And there is a large effect on lower limb muscle strength and a medium effect on aerobic capacity and sports performance. A training schedule of progressive mixed-intensity aerobic endurance training under continuous pressure for no less than 4 weeks, 3 sessions per week, 20-30 minutes per session, for 12 or more sessions in total is easy to obtain better training results. Figures and Tables | References | Related Articles | Metrics