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18 April 2022, Volume 26 Issue 11 Previous Issue    Next Issue

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Difference in osteogenesis- and angiogenesis-related protein expression in femoral head samples from patients with femoral head necrosis of different etiologies Luo Di, Liang Xuezhen, Liu Jinbao, Li Jiacheng, Yan Bozhao, Xu Bo, Li Gang 2022, 26 (11):  1641-1647.  doi: 10.12307/2022.345 Abstract ( 406 )   PDF (1378KB) ( 226 )   Save BACKGROUND: The etiology and pathogenesis of femoral head necrosis are still unclear, and in-depth research is urgently needed. OBJECTIVE: To detect the protein expression of Hedgehog signaling pathway-, osteogenesis- and angiogenesis-related indicators in the necrotic femoral head samples after total hip arthroplasty, and attempt to explore the pathogenic mechanisms of different factors such as alcohol, hormones, and trauma, providing theoretical support for the subsequent clinical prevention and treatment of femoral head necrosis. METHODS: The femoral head samples were collected from patients with femoral head necrosis who underwent total hip arthroplasty in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from December 2017 to December 2019. The femoral head samples meeting the inclusion criteria were selected and classified into control group, idiopathic group, alcohol group, hormone group and post-traumatic group according to the etiology. The expression of Hedgehog signaling pathway-, osteogenesis- and angiogenesis-related indicators in necrotic bone tissues of different etiologies were detected by western blot.  RESULTS AND CONCLUSION: By observing the general morphology and coronal plane of the femoral head samples in each group, it was found that the femoral head samples of patients with femoral head necrosis of different etiologies had similar pathological manifestations in general morphology and section, and had similar histological characteristics of necrosis and repair. Western blot results showed that the protein expression levels of osteogenesis-related indicators (alkaline phosphatase, type I collagen, osteopontin and RUNX2), angiogenesis-related indicators (CD31, vascular endothelial growth factor A, kinase insertion domain receptor, and von Willebrand factor), and Hedgehog signaling pathway indicators (hedgehog, zinc finger protein 1, and zinc finger protein 2) in the femoral head samples of patients with femoral head necrosis of different etiologies changed to different extents as compared with the control group. As the occurrence and development of femoral head necrosis may be closely related to osteogenesis, angiogenesis, and Hedgehog signaling pathway, further research is needed. Figures and Tables | References | Related Articles | Metrics

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Protective effect of astaxanthin on tert-butyl hydrogen peroxide-induced chondrocyte damage Zhu Chunhui, Zhang Yi, Song Huanghe, Liang Wenwei 2022, 26 (11):  1648-1655.  doi: 10.12307/2022.346 Abstract ( 514 )   PDF (1381KB) ( 45 )   Save BACKGROUND: Cartilage damage is a common orthopedic disease. Studies on the mechanism of cartilage repair are important for the improvement of therapeutic strategies in clinical practice. Astaxanthin has a protective effect on cartilage damage; however, the related mechanism is not yet elucidated.  OBJECTIVE: To study the protective effect of astaxanthin against tert-butyl hydrogen peroxide-induced damage to C28/I2 cells and to explore how circHP1BP3 is involved in this protect effect. METHODS: Tert-butyl hydrogen peroxide was used to induce damage to C28/I2 cells. The protective effect of astaxanthin was evaluated by cell viability, apoptosis, inflammation, oxidative stress, and degradation of extracellular matrix. RT-qPCR was used to explore the expression of circRNAs. The role of circHP1BP3 in the protective effect of astaxanthin was investigated by the use of circHP1BP3-overexpression plasmid or small-interference RNAs. RESULTS AND CONCLUSION: Tert-butyl hydrogen peroxide induced damage of C28/I2 cells by decreasing cell viability, and increasing cell apoptosis, inflammatory effect, oxidative stress, and degradation of the extracellular matrix. Astaxanthin protected C28/I2 cells from tBHP-induced cell damage. Tert-butyl hydrogen peroxide decreased the expression of circHP1BP3 in C28/I2 cells, while astaxanthin increased the expression of circHP1BP3 in tBHP-treated cells. circHP1BP3-overexpression recovered C28/I2 cells from tBHP-induced cell damage. circHP1BP3 silencing inhibited the protective effect of astaxanthin on tBHP-induced C28/I2 cell damage. To conclude, astaxanthin can protect C28/I2 chondrocytes from tBHP-induced cell damage via circHP1BP3. Figures and Tables | References | Related Articles | Metrics

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Effects of different types of abdominal support on lumbar-back muscle surface electromyography signals in people with abdominal obesity Shang Wandi, Wang Xingze, Wei Xiaoyan 2022, 26 (11):  1656-1661.  doi: 10.12307/2022.347 Abstract ( 501 )   PDF (772KB) ( 117 )   Save BACKGROUND: Scholars at home and abroad have developed various lumbar protective belts on prevention of low back pain. Following series of experiments in biomechanical studies and clinical applications, no suitable belts can provide definite benefit for people with abdominal obesity.  OBJECTIVE: To investigate the effects of several types of abdominal supports on trunk range of motion and surface electromyography of back muscles among subjects with abdominal obesity.  METHODS: Eighteen adult males with abdominal obesity were recruited. Different types of abdominal supports, no taping, elastic abdominal belt and non-elastic athletic white taping were randomly selected during flexion-extension phase of trunk at non-weight-bearing and heavy lifting (weight-bearing). Noranxon bipolar surface electromyography device was used to collected electromyography activities of back muscles, including the multifidus, lumbar erector spinae and thoracic erector spinae muscles. Kinematics of trunk was recorded with a Vicon T40 motion capture system. The protocol was approved by the Ethics Committee of Shanghai University of Sport (approval No. 102772020RT091).  RESULTS AND CONCLUSION: Multifidus: Compared with no taping and elastic abdominal belt, multifidus values of athletic white taping were significantly reduced during extension phase of non-weight-bearing (P < 0.05). Additionally, during extension phase of weight-bearing, multifidus values of elastic abdominal belt were significantly lower than no taping and athletic white taping (P < 0.05). Lumbar erector spinae: Compared with athletic white taping, lumbar erector spinae values of elastic abdominal belt were significantly decreased during flexion phase of non-weight-bearing (P < 0.05). Compared with no taping and athletic white taping, lumbar erector spinae values of elastic abdominal belt were significantly reduced during extension phase of non-weight-bearing and weight-bearing (P < 0.05). Thoracic erector spinae: Compared with no taping, thoracic erector spinae values of elastic abdominal belt were significantly reduced during flexion phase of non-weight-bearing (P < 0.05). Compared with no taping, thoracic erector spinae values of athletic white taping and elastic abdominal belt were significantly reduced during flexion phase of weight-bearing (P < 0.05). Compared with no taping, thoracic erector spinae values of athletic white taping and elastic abdominal belt were significantly reduced during extension phase of weight-bearing (P < 0.05), and compared to athletic white taping, thoracic erector spinae values of elastic abdominal belt were significantly reduced (P < 0.05). The maximum flexion angle in subjects supported by elastic abdominal belt was less than that in no taping and elastic abdominal belt (P < 0.05). The results suggest that both athletic white taping and elastic abdominal belt significantly reduce muscle activation of the back muscles in people with abdominal obesity, thereby potentially slowing spinal load and preventing occurrence of low back pain. Moreover, the elastic abdominal belt will not restrict the normal range of motion of the trunk, allowing for a wider application.   Figures and Tables | References | Related Articles | Metrics

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Baduanjin training for patellar tendinopathy in a randomized controlled trial: improving pain, muscle flexibility and lower limb balance stability Zhao Tianyu, Jin Song, Zhang Di, Liu Xiaoxiao, Ma Jiang, Wang Ju 2022, 26 (11):  1662-1668.  doi: 10.12307/2022.348 Abstract ( 749 )   PDF (772KB) ( 85 )   Save BACKGROUND: Existing treatments for patellar tendinopathy need to be further improved. It is of positive significance to explore universal exercise training for patellar tendinopathy in clinical practice. OBJECTIVE: To explore the clinical effect of Baduanjin training combined with shockwave therapy for patellar tendinopathy. METHODS: Patients with patellar tendinopathy were randomly divided into two groups, followed by 4 weeks clinical intervention: shockwave therapy was given in the control group, while Baduanjin training combined with shockwave therapy was given in the trial group. Pain, muscle flexibility, and motor function were assessed using several observational indicators, including Visual Analogue Scale score, time of standing on one foot with closed eyes, knee flexion angle in modified Thomas test, vertical jump state and three-dimensional gait. All the patients were followed up for 1 month in terms of pain assessment. Clinical efficacy of Baduanjin training for patellar tendinopathy was compared between two groups.  RESULTS AND CONCLUSION: Findings from the 1-month follow-up showed that Baduanjin training could significantly decrease the Visual Analogue Scale scores of patients patellar tendinopathy (t=-2.744, P < 0.05). After 4 weeks of intervention, Baduanjin training could significantly increase the knee flexion angle in the modified Thomas test (t=2.738, P < 0.05). The standing time of patients with closed eyes was significantly prolonged after Baduanjin training as compared with the shockwave therapy (z=-4.544, P < 0.05). Baduanjin training could increase the hip joint flexion angle (t=2.584, P < 0.05) and the knee joint flexion angle (t'=2.053, P < 0.05). Baduanjin training could decrease the knee extension angle during walking (t=-3.081, P < 0.05). To conclude, Baduanjin training could relieve the pain of patients with patellar tendinopathy, increase the balance stability and muscle flexibility of the lower limbs, improve the power and buffer ability of the lower limbs, reduce the abnormal knee extension during walking, and shorten the time of whole rehabilitation. Figures and Tables | References | Related Articles | Metrics

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Identification and expression analysis of mouse nucleus pulposus specific markers Zhang Lei, Xiu Chunmei, Ni Li, Chen Jianquan 2022, 26 (11):  1669-1674.  doi: 10.12307/2022.349 Abstract ( 440 )   PDF (1281KB) ( 49 )   Save BACKGROUND: Intervertebral disc degeneration is the main cause of low back pain, and nucleus pulposus cells play a vital role in intervertebral disc degeneration. A mouse model is an important animal model for studying the homeostasis and degeneration of the intervertebral disc. However, there is still a lack of systematic analysis of mouse nucleus pulposus specific markers. OBJECTIVE: To verify the expression and cell specificity of cytokeratin 19, glucose transporter 1, and glypican 3 in the intervertebral discs of mice at different stages and to explore the feasibility of the above proteins used as specific markers of the mouse nucleus pulposus. METHODS: Ten 6-week-old C57BL/6 male mice were randomly divided into a 2-month-old group and a 12-month-old group (n=5), and intervertebral disc samples were collected for subsequent analysis when the mice were raised to the corresponding months. Hematoxylin-eosin staining and Safranin O&Fast Green staining were used to evaluate the histological integrity of the intervertebral discs. Immunofluorescence or immunohistochemical staining was used to detect the protein expression of cytokeratin 19, glucose transporter 1, and glypican 3 on the coronal slices of the intervertebral discs, and protein expression changes in mice of different ages were statistically analyzed. RESULTS AND CONCLUSION: Cytokeratin 19, glucose transporter 1, and glypican 3 were specifically expressed in the nucleus pulposus tissues of 2-month-old mice. Only cytokeratin 19 was specially expressed in the nucleus pulposus tissues of 12-month-old mice, whereas glucose transporter 1 and glypican 3 appeared in the nucleus pulposus cells as well as in the endplate. Therefore, cytokeratin 19, glucose transporter 1, and glypican 3 can all be expressed in the nucleus pulposus tissues from 2- and 12-month-old mice, but only cytokeratin 19 can serve as the nucleus pulposus-specific marker for both young and aged mice. Figures and Tables | References | Related Articles | Metrics

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Pathological changes of the cervical intervertebral discs and rules of migration and apoptosis in endplate chondrocytes in a rabbit model of dynamic disequilibrium Yu Dong, Liu Kan, Shi Zongting, Yang Xiaoxia, Liu Hengping, Zhang Qingfeng 2022, 26 (11):  1675-1679.  doi: 10.12307/2022.350 Abstract ( 439 )   PDF (1970KB) ( 35 )   Save BACKGROUND: Cervical muscles play an important role in maintaining the mechanical balance of the vertebral body and the pathogenesis of cervical spondylosis at each stage and link. They are also the leading cause of various clinical cervical symptoms, and mechanical imbalance of the cervical spine and degeneration of the cervical discs can be regarded as the results of soft tissue lesions dominated by cervical muscles. OBJECTIVE: To observe the pathological changes of endplate chondrocytes in cervical intervertebral discs in a rabbit model of dynamic disequilibrium due to anterior cervical muscle spasm and to study the rules of apoptosis in intervertebral disc cells under abnormal stress. METHODS: Twenty-eight healthy adult New Zealand rabbits were divided randomly into model group and sham operation group (n=14 per group). The bilateral sternocleidomastoid muscles of the rabbits in the model group were shortened by a medical pipe approximately 1 cm below the outer and lower thyroid cartilage to establish an animal model of cervical dynamic disequilibrium. In the sham operation group, bilateral sternocleidomastoid muscles were only exposed followed by layer-by-layer suture. Endplate cartilage tissue of the cervical intervertebral discs was simultaneously taken from each group at 2 months after modeling, and morphological changes were observed using hematoxylin-eosin staining. The migration of endplate chondrocytes in the cervical intervertebral discs were observed under light microscope. TUNEL method was used to detect the apoptosis of cells in the endplate cartilage and annulus fibrosus. The study protocol was approved by the Animal Experimental Ethics Committee of the Third Affiliated Hospital of Beijing University of Chinese Medicine.  RESULTS AND CONCLUSION: Obvious pathological changes occurred in the cervical intervertebral disc in the model group, but not in the sham operation group. There was a clear boundary between the articular cartilage area and annulus fibrosus area of the endplate in the model group. No obvious migration was found in the model group, but the cells in the growth cartilage area of the endplate obviously migrated into the articular cartilage area. The model group showed excessive apoptosis in the articular cartilage area and growth cartilage area, and the apoptotic index was significantly higher than that of the sham operation group (P < 0.01). Apoptosis was also found in the annulus fibrosus area, and the apoptotic index was extremely significantly higher than that in the sham operation group (P < 0.05). To conclude, when a dynamic disequilibrium is caused by anterior cervical muscle spasm (abnormal stress caused by cervical muscular spasm), no obvious migration of cells between endplate cartilage and annulus fibrosus occurs in the short term. However, the cells in the growth cartilage area can migrate into the articular cartilage area at an early stage, and significant apoptosis occurs in the endplate cartilage and annulus fibrosus area of the intervertebral disc, which can provide experimental evidence for studying the etiological mechanism of early degeneration of the intervertebral disc. Figures and Tables | References | Related Articles | Metrics

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Quantitative analysis of transcriptome and proteome of knee joint synovial cells with osteopontin knockdown Xu Renjie, Zhong Qiao, Liu Yubo, Yu Xiao, Yan Yongqing, Saijilafu, Yang Huilin, Chen Guangxiang 2022, 26 (11):  1680-1685.  doi: 10.12307/2022.351 Abstract ( 426 )   PDF (1033KB) ( 60 )   Save BACKGROUND: The mRNA and protein levels of osteopontin in articular cartilage and synovial fluid of patients with osteoarthritis are significantly higher than those of normal controls. However, the role and specific mechanism of osteopontin in the development of knee osteoarthritis have not been clarified. OBJECTIVE: To investigate the level of osteopontin in synovial cells of knee joint osteoarthritis patients and its relationship with the severity of osteoarthritis, and to further elucidate the mechanism that affects the progression of osteoarthritis through transcriptome and proteome sequencing. METHODS: A total of 42 patients with primary knee osteoarthritis diagnosed and treated in 2019 were divided into unicompartment knee osteoarthritis group and bicompartment knee osteoarthritis group based on the involvement of the tibiofemoral joint. Synovial and joint fluid specimens were harvested. PCR method was used to measure the abundance of osteopontin gene expression in synovial specimens, and ELISA method was used to measure osteopontin protein level in synovial fluid specimens. Enzymatic digestion method was used to obtain and culture human knee osteoarthritis synovial fibroblast-like cells. After osteopontin-siRNA intervention for 24 hours, the samples were tested for transcriptome and proteome. RESULTS AND CONCLUSION: Compared with the unicompartment knee osteoarthritis group, the osteopontin levels in the synovium and synovial fluid of the bicompartment knee osteoarthritis group increased significantly (P < 0.05). In in vitro cultured human knee osteoarthritis synovial fibroblast-like cells, after osteopontin knockdown by siRNA, quantitative studies of the transcriptome and proteome identified 14 662 transcripts and 3 608 proteins, respectively. Among them, the transcriptome and proteome analysis results of five proteins showed a simultaneous decrease, and the transcriptome and proteome analysis results of two proteins showed a simultaneous increase. To conclude, osteopontin has an adverse effect on chondrocytes. The mechanism may be through the pro-inflammatory effect and the negative effect of insulin-like growth factor-binding protein 3 on cartilage. Figures and Tables | References | Related Articles | Metrics

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The mechanism by which bone morphogenetic protein 2 indirectly regulates sclerostin expression in osteocytes Tian Zhuang, Wang Diaodiao, Zhang Chu, Li Hanchen, Zhou Jian, Yao Qi 2022, 26 (11):  1686-1691.  doi: 10.12307/2022.352 Abstract ( 497 )   PDF (871KB) ( 66 )   Save BACKGROUND: Bone morphogenetic protein 2 (BMP-2) can promote osteogenesis, and osteocytes secrete sclerostin by expressing SOST gene to inhibit the osteogenic effect of osteoblasts. Some studies have found that BMPs family can promote the secretion of osteosclerotic protein when directly acting on osteocytes, but this contradicts the positive osteogenic effect of BMPs.  OBJECTIVE: To explore the mechanism of BMP-2 indirectly regulating the expression of sclerostin gene in osteocytes. METHODS: Mouse MC-3T3-E1 cells were treated with different concentrations of BMP-2 (4, 8, 16, 32, 64, 125, 250, 500 and 1 000 μg/L) in vitro. The best concentration of BMP-2 to promote the proliferation of MC-3T3-E1 cells was detected by cell counting kit-8. Then the effect of BMP-2 on the indirect regulation of sclerostin gene expression in osteocytes was studied by co-culture of MC-3T3-E1 cells and MLO-Y4 cells. The possible altered genes in MC-3T3-E1 cells were detected by RT-PCR, and the target genes of MC-3T3-E1 cells were screened to verify the effect of target genes on the expression of sclerostin in MLO-Y4 cells. RESULTS AND CONCLUSION: BMP-2 could significantly promote the proliferation of osteoblasts. Compared with other concentrations, 250 μg/L had the best effect. The results of RT-PCR experiment showed that BMP-2 could indirectly regulate the expression of sclerostin gene and promote the down-regulation of sclerostin expression in osteocytes (P < 0.01). The results of target gene screening showed that, compared with other genes, the expression of receptor activator of nuclear factor-κB ligand in osteoblasts was significantly downregulated and the expression of osteoprotegerin in osteoblasts was significantly upregulated (P < 0.01). The results of target gene verification showed that BMP-2 may indirectly affect the expression of osteoprotegerin and receptor activator of nuclear factor-κB ligand in osteocytes, and then affect the expression of sclerostin in MLO-Y4 cells, thus positively promoting osteogenesis. Figures and Tables | References | Related Articles | Metrics

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Morphological characteristics of subchondral bone in a mouse model of early osteoarthritis Li Jingyu, Su Yingying, Bai Ding 2022, 26 (11):  1692-1698.  doi: 10.12307/2022.353 Abstract ( 704 )   PDF (1108KB) ( 88 )   Save BACKGROUND: Osteoarthritis is a degenerative joint disease, and the main pathological features are cartilage degradation and subchondral bone sclerosis. The function and mechanism of osteocytes in subchondral bone sclerosis remains unclear. OBJECTIVE: To investigate the pathological characteristics, changes in bone mineralization, morphological changes of osteocytes and expression changes of sclerostin in mice with overloading induced knee osteoarthritis. METHODS: Twenty 10-week-old male C57BL/6 mice were randomly divided into osteoarthritis group and control group (n=10 per group). Anterior cruciate ligament transection was conducted to establish osteoarthritis models in the osteoarthritis group, and sham operation was carried out in the control group. Four weeks after operations, mice in each group were sacrificed. Knee samples collected were used for hematoxylin-eosin staining, toluidine blue staining and Osteoarthritis Research Society International (OARSI) scoring. Micro-CT was used to evaluate bone mineralization density and bone volume/trabecular volume of subchondral cancellous bone and subchondral lamina dura. Morphological changes of osteocytes and subchondral bone were observed using scanning electron microscope. Immunohistochemistry staining was used to detect SOST/sclerostin expression. RESULTS AND CONCLUSION: Hematoxylin-eosin staining and toluidine blue staining results showed that significant osteoarthritis phenotype was found in both articular cartilage and subchondral bone in the osteoarthritis group 4 weeks after anterior cruciate ligament transection, accompanied with increased OARSI scores (P < 0.05). Micro-CT scan results showed decreased bone mineralization density and increased bone volume/trabecular volume of subchondral cancellous bone and subchondral lamina dura 4 weeks after anterior cruciate ligament transection (P < 0.05), indicating that subchondral bone sclerosis consists of decreasing of bone mineralization density tissue and increasing of bone volume/trabecular volume. Under the scanning electron microscope, in the osteoarthritis group, normal morphology and arrangement of osteocytes were disturbed in the subchondral bone, while the morphology of mineralization of the subchondral bone was also distorted. Immunohistochemistry staining results showed that, compared with the control group, the number of sclerostin positive cells was significantly decreased in the osteoarthritis group, indicating the morphological changes of osteocytes may be related to changes in SOST/sclerostin expression. In conclusion, subchondral bone sclerosis in early osteoarthritis is mainly manifested as a decrease in bone mineralization density, an increase in bone volume/trabecular volume, and irregular changes in the microscopic morphology of the subchondral bone. After anterior cruciate ligament transection, significant changes in the morphological and arrangement of osteocytes are found in early osteoarthritis, and the secretion of sclerostin is also significantly changed.  Figures and Tables | References | Related Articles | Metrics

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Incidence of osteonecrosis in rats with jaw versus femoral defects following zoledronic acid injection Bao Hongyu Lü Dongmei, He Yun, Xia Delin, Chen Junliang 2022, 26 (11):  1699-1704.  doi: 10.12307/2022.354 Abstract ( 450 )   PDF (904KB) ( 43 )   Save BACKGROUND: Bisphosphonate drugs are a class of synthetic inorganic pyrophosphate analogs that can cause osteonecrosis of the jaw. However, the effects of bisphosphonate drugs on different parts of the same individual may be different, and the effect on the jaws or femurs with and without trauma is also unclear. OBJECTIVE: To compare the effect of zoledronic acid on the healing of rat jaw and femur defects, thereby providing theoretical support for the clinical use of zoledronic acid and other drugs as well as the prevention of medication-related osteonecrosis of the jaw. METHODS: Forty female Sprague-Dawley rats aged 8 weeks were included in this study. Among them, 20 rats were injected intraperitoneally with zoledronic acid and the remaining 20 rats were injected with normal saline. Ten weeks later, a 2 mm×2 mm×2 mm bone defect was made on the left mandible and femur of each rat, and no treatment was done on the right side. Therefore, there were eight groups: zoledronic acid+jaw defect group, zoledronic acid+femoral defect group, zoledronic acid+jaw untreated group, zoledronic acid+femur untreated group, normal saline+jaw bone defect group, normal saline+femoral defect group, normal saline+jaw bone untreated group, and normal saline+femur untreated group. The healing of the jaw and femur was observed after operation. At 8 weeks after operation, the samples were taken and the radiological and histological examinations were performed. RESULTS AND CONCLUSION: In the zoledronic acid+jaw defect group, 16 observation areas showed poor healing of mandibular defects, local gingival swelling and pus, soft tissues were still not fully healed at 8 weeks after surgery. The dead bone was still seen in the jaw defect area. The incidence rate of osteonecrosis was 80%. On the contrary, there was no osteonecrosis in the other groups. Radiological results: No bone healing was observed in the jaw defect area of the osteonecrosis specimens in the zoledronic acid+jaw defect group, while osteolytic destruction developed. The density of the defect area was similar to that of the surrounding bone in the zoledronic acid+femoral defect group. The density of the defect area was lower than that of the surrounding bone in the normal saline+jaw bone defect group and normal saline+femoral defect group. Histological results: The specimens with osteonecrosis in the zoledronic acid+jaw defect group demonstrated the disappearance of the nucleus, the disorder of the trabecular bone structure, and a small amount of fibrous tissue. The remaining specimens showed no obvious abnormalities. The above results suggest that the incidence of osteonecrosis in the mandible defect is very high after intraperitoneal injection of zoledronic acid, while there is no osteonecrosis in the femoral defect and non-defective jaw and femur. Figures and Tables | References | Related Articles | Metrics

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High-throughput sequencing-based osteoporotic circRNA-miRNA-mRNA network construction and Has_ circ_0076906 functional verification Wang Hailong, Li Long, Wang Jianyuan, Yan Bin, Xier Aili, Chen Hongtao, Yilihamu · Tuoheti 2022, 26 (11):  1705-1713.  doi: 10.12307/2022.355 Abstract ( 446 )   PDF (1458KB) ( 246 )   Save BACKGROUND: Studies have shown that circular RNA (circRNA) is an endogenous non-coding RNA widely present in a variety of tissues, which can act as a "sponge" of microRNA (miRNA) to regulate mammalian gene expression. However, the expression characteristics and molecular mechanism of circRNA in osteoporosis and its potential circRNA-miRNA-mRNA regulatory network have not been reported yet. OBJECTIVE: Based on the high-throughput and high-throughput sequencing data of osteoporosis-related non-coding RNAs, to construct an interaction network and functional enrichment analysis, screen the possible mechanisms of competitive endogenous RNA (ceRNA), and verify the function and mechanism of circRNAs involved in the development of osteoporosis.  METHODS: The circRNA-miRNA-mRNA network was constructed using the high-throughput sequencing data of liver cancer non-coding RNA in the GEO database. Subsequently, GO and KEGG analyses were performed on the co-expressed target genes predicted by miRNA. Through human mesenchymal stem cells-induced osteoblast differentiation, qRT-PCR and western blot were used to detect the expression of circ_0076906 and its targeted miR-29b and osteoglycoprotein (OGN) at mRNA and protein levels. Alkaline phosphatase activity and alizarin red staining were used to detect bone formation, and luciferase reporter assay used to detect gene interactions. RESULTS AND CONCLUSION: The experiment finally screened 5 co-expressed circRNAs (such as circ_0076906, circ_0004276 and circ_0003060, etc.), 10 co-expressed miRNAs (such as miR-183-5p, miR-29b and hsa-miR-15b-3p, etc.), and 241 co-expressed mRNAs (such as OGN, SMARCC1 and LRP6, etc.) from the GEO database, to successfully construct a circRNA-miRNA-mRNA network related to osteoporosis. GO analysis results revealed 78 biological processes, mainly including osteoblast proliferation, apoptosis and migration. KEGG analysis results indicated that FoxO signaling pathway and PI3K-AKT signaling pathway were closely related to the occurrence and development of osteoporosis. The verification results of circ_0076906, miR-29b and OGN, which have significant differences and target relationships, showed that circ_0076906, miR-29b and OGN were differentially expressed in the bone tissue and serum of patients with porosity and the control group. circ_0076906 could induce osteogenic differentiation, and its silencing could inhibit the expression of osteogenic genes (OCN and RUNX2) in human mesenchymal stem cells. circ_0076906 could act as miR-29b regulated OGN expression sponge. The above-mentioned data show that the osteoporosis circRNA-miRNA-mRNA network is successfully established in this study, and circ_0076906 and its targeted miR-29b and OGN screened out may play an important role in the progression of osteoporosis. The study further confirms that circ_0076906 in hMSCs promotes OGN expression by competitively inhibiting miR-29b, alleviating osteoporosis and promoting osteogenic differentiation.The study protocol was approved by the Ethics Committee of the Seventh Affiliated Hospital of Xinjiang Medical University (approval No.XY20190501-1). Figures and Tables | References | Related Articles | Metrics

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Acupuncture combined with moxibustion regulates the expression of circadian clock protein in the synovium of rats with osteoarthritis Tan Qian, Li Bocun, Li Jing, Li Jia, Xiang Hongchun, Cai Guowei 2022, 26 (11):  1714-1719.  doi: 10.12307/2022.356 Abstract ( 578 )   PDF (958KB) ( 47 )   Save BACKGROUND: Synovitis is one of the main pathological features of knee osteoarthritis. Previous studies have shown that acupuncture has a significant effect on knee osteoarthritis. Whether acupuncture can relieve the symptoms by regulating the related proteins in synovium is worthy of further study.  OBJECTIVE: To investigate the effects of acupuncture combined with moxibustion on circadian clock proteins (Clock, Bmal1), TRPV4, and interleukin-1β in the synovium of rats with osteoarthritis.  METHODS: Eighty 3-month-old male Sprague-Dawley rats were randomly divided into four groups: control group, model group, acupuncture group and acupuncture combined with moxibustion group (n=20 per group). Rat models of osteoarthritis were prepared by surgery in the latter three groups. Rats in the acupuncture group were treated with manual acupuncture at Zusanli (ST36), Dubi (ST35), and Neixiyan (EX-LE5) acupoints on the 7th day of modeling, at a depth of 5 mm, 15 minutes once a day, totally for 21 days. Rats in the acupuncture combined with moxibustion group were treated with acupuncture (same as that in the acupuncture group) combined with moxibustion. After corresponding treatments, the spontaneous activity ability of the rats was measured by an open field test. The pathological structure of the synovium was observed by hematoxylin-eosin staining. The expression of Clock, Bmal1 and transient receptor potential vanilloid 4 (TRPV4) in the synovium was detected by western blot. The expression of interleukin-1β in the synovium was detected by immunofluorescence labeling.  RESULTS AND CONCLUSION: Compared with the control group, the expression of Clock and Bmal1 in the synovium was significantly decreased (P < 0.01), the levels of interleukin-1β and TRPV4 in the synovium were significantly increased (P < 0.05), and moreover severer loss of synovial epithelium was observed in the model group. Compared with the model group, acupuncture and acupuncture combined with moxibustion could significantly improve the spontaneous activity ability of the rats, increase the expression of Clock and Bmal1 (P < 0.05), decrease the levels of interleukin-1β and TRPV4 in the rat synovium  (P < 0.05), and relieve the loss of synovial epithelium. Compared with the acupuncture group, these changes were more obvious in the acupuncture combined with moxibustion group (P < 0.05). To conclude, relative to acupuncture alone, acupuncture combined with moxibustion can effectively regulate arthritic injury in knee osteoarthritis rats, reduce the expression of TRPV4 in synovial cells, promote the expression of Clock and Bmal1 in the synovium, thereby regulating the circadian clock in synovial cells, reducing the expression of inflammatory factors and slowing the degeneration of knee osteoarthritis. Figures and Tables | References | Related Articles | Metrics

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Identification and analysis of potential key genes in osteonecrosis of the femoral head based on miRNA-mRNA regulatory network Liang Xuezhen, Xie Guoxin, Li Jiacheng, Wen Mingtao, Xu Bo, Li Gang 2022, 26 (11):  1720-1727.  doi: 10.12307/2022.357 Abstract ( 504 )   PDF (1674KB) ( 52 )   Save BACKGROUND: MicroRNAs (miRNAs) have been confirmed to be involved in the pathogenesis, prevention, and treatment of osteonecrosis of the femoral head. However, the mechanism is not yet elucidated.  OBJECTIVE: To screen miRNA-mRNA regulatory pairs related to osteonecrosis of the femoral head, to explain its potential mechanism, based on microarray data in the GEO database. METHODS: The miRNA microarray dataset (GSE89587) and mRNA microarray dataset (GSE74089) were retrieved from NCBI GEO database. Then, we identified the differentially expressed miRNAs and mRNAs for each dataset by the Limma package in R software. Potential downstream targets of these differentially expressed miRNAs were predicted using miRDB, miRTarbase, and TargetScan databases. Based on the relationship among miRNA and mRNA, the miRNA-mRNA regulatory network was visualized using Cytoscape. Next, gene ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of target genes in the regulatory network were carried out by clusterProfiler package in R software. Protein-protein interaction network was constructed by using the Search Tool for the Retrival of Interacting Genes/Protein (STRING) database.  RESULTS AND CONCLUSION: In total, 23 differentially expressed miRNAs, including 10 upregulated (e.g., hsa-miR-4325, hsa-miR-3654) and 13 downregulated miRNAs (e.g., hsa-miR-4680-5p, hsa-miR-4711-3p), were identified. Totally 3992 differentially expressed mRNAs, including 2503 upregulated (e.g., TGFBI, AMTN) and 1489 downregulated (e.g., MSMP, FLJ35424) mRNAs, were screened by the Limma package in R software. 255 miRNA downstream target genes predicted co-existed in  miRDB, miRTarbase, and TargetScan databases, and 10 miRNAs (e.g., hsa-miR-3920, hsa-miR-3675-5p) and 34 mRNAs (e.g., MAPK6, SP1 ) were sorted out to construct regulatory networks. These screened targets mainly were significantly enriched in the regulation of mRNA stability and transforming growth factor-β signaling pathway and autophagy. DDX3X, HNRNPC, and SP1 were analyzed as the hub genes in protein-protein interactions, which may be the target genes for osteonecrosis of the femoral head. In summary, the miRNA-mRNA regulatory network constructed in this study clarifies that miR-4725-3p may target ONFH by inhibiting SP1-mediated transforming growth factor-β signaling pathway, providing a strong data support and research direction for the prevention and treatment of ONFH. Figures and Tables | References | Related Articles | Metrics

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Electroacupuncture promotes facial nerve regeneration in a rat model of facial nerve crush Fei Jing, Tao Meihui, Li Leiji 2022, 26 (11):  1728-1733.  doi: 10.12307/2022.358 Abstract ( 508 )   PDF (1293KB) ( 104 )   Save BACKGROUND: The mechanism of electroacupuncture to promote facial nerve regeneration is unknown. Vascular endothelial growth factors (VEGF) are a type of cytokines that can promote revascularization and increase vascular permeability. OBJECTIVE: To observe the therapeutic effect of electroacupuncture on peripheral facial paralysis induced by crush injury of the buccal facial nerve in Sprague-Dawley rats, and to explore the role of VEGF/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway in the above process.  METHODS: Sprague-Dawley rats were randomly divided into a normal group (8 rats), a model group (24 rats) and an electroacupuncture group (24 rats). The facial nerve crush injury models were established in the model and the electroacupuncture groups. Rats in the electroacupuncture group then received electroacupuncture treatment at the right “Jiache” and “Dicang” acupoints every day after the operation. At 4, 14, and 28 days after the operation, the symptoms of facial paralysis in the rats of each group were recorded and scored. The morphology and Nissl body changes of facial motoneurons were observed. The expression site and intensity of VEGF as well as the expression levels of VEGF, ERK, and p-ERK proteins in facial motoneurons were measured. RESULTS AND CONCLUSION: The improvement of facial paralysis in the model group was not as obvious as that in the electroacupuncture group, and the behavioral scores were lower than those in the electroacupuncture group at all time points. The morphological recovery of facial motoneurons and Nissl bodies in the electroacupuncture group was earlier and more complete than that in the model group. The protein expressions of VEGF at all time points in the electroacupuncture group were higher than those in the normal and model groups. The expression of p-ERK in the electroacupuncture group was higher than that in the model group, and began to be higher than that in the normal group at 14 days after operation. To conclude, electroacupuncture can up-regulate the expression of VEGF in facial motoneurons and promote the recovery of peripheral facial paralysis caused by crush injury. The mechanism may be related to the activation of MAPK/ERK signaling pathway and the protective effect on facial motoneurons. Figures and Tables | References | Related Articles | Metrics

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Characteristics and influencing factors of carotid blood flow in younger adults in different body positions Yu Basuo, Sun Mingyun, Yang Hongmei, Bao Yaling, Qian Zhenyu, Meng Haijiang, Zhou Duoqi 2022, 26 (11):  1734-1740.  doi: 10.12307/2022.359 Abstract ( 470 )   PDF (961KB) ( 62 )   Save BACKGROUND: During rehabilitation training, handstand equipment is increasingly used for head-down tilt training. Concerns therefore have been paid to the characteristics of carotid blood flow changes in different positions during the head-down tilt training. OBJECTIVE: To explore the characteristics of carotid blood flow changes in different body positions.  METHODS: A total of 104 college volunteers (male, 60; female, 44) were recruited and their carotid hemodynamic changes in different positions were measured by using PHILIPS COLOR DOPPLER CV850 color ultrasound. RESULTS AND CONCLUSION: The blood flow of the left common carotid artery in female (P=0.031) and the blood flow of the left common carotid artery (P=0.033), right common carotid artery (P=0.003), and right internal carotid artery (P=0.030) in male were significantly reduced in the head-up position compared with the supine position. The blood flow of the left common carotid artery (P=0.018), right common carotid artery (P=0.001), and left vertebral artery (P=0.049) in female and the blood flow of the left common carotid artery (P=0.007) and right common carotid artery (P=0.005) in male were significantly reduced in -30o head-down tilt compared with the supine position. The blood flow of the left common carotid artery (P=0.000) and right common carotid artery (P=0.000) in male and female, the blood flow of the left internal carotid artery (P=0.002) and right internal carotid artery (P=0.002) in female, and the blood flow of the left internal carotid artery (P=0.001), right internal carotid artery (P=0.000), and left vertebral artery (P=0.003) in male were significantly reduced in -90o head-down tilt compared with the supine position. To conclude, compared with the supine position, the blood flow of the common carotid artery, internal carotid artery and vertebral artery changes a lot in the head-up position, -30o head-down tilt, and -90o head-down tilt, especially in -90o head-down tilt. Figures and Tables | References | Related Articles | Metrics

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Effects of minimally invasive surgery combined with metformin on inflammatory responses in rabbits with intracerebral hemorrhage Xu Lin, Qi Hongshun, Ge Rucun, Li Peipei, Zhen Lixiao, Feng Xiaoya 2022, 26 (11):  1741-1746.  doi: 10.12307/2022.360 Abstract ( 462 )   PDF (873KB) ( 56 )   Save BACKGROUND: Our preliminary results have shown that minimally invasive surgery combined with metformin can reduce secondary damage after cerebral hemorrhage and improve the prognosis. However the specific mechanism is still unclear. OBJECTIVE: To observe the effect of minimally invasive surgery combined with metformin on the inflammatory responses of brain tissue around hematoma in a rabbit model of intracerebral hemorrhage, and to explore its specific mechanism. METHODS: Forty-eight male New Zealand rabbits were randomly divided into sham operation group (sham group), intracerebral hemorrhage group (ICH group), minimally invasive surgery group (MIS group), and minimally invasive surgery combined with metformin treatment group (MIS+MET group). Animal models of intracerebral hemorrhage were established using Sawyer’s method in the latter three groups. Pseudohematoma removal surgery was performed in the ICH group, and minimal invasive surgery was performed in the MIS group and MIS+MET group 6 hours after successful modeling. Metformin (50 mg/kg) was administered by gavage to the rabbits in the MIS+MET group once a day for 3 continuous days, and the rabbits in the MIS and ICH groups were given the same amount of normal saline. Neurological deficit (Purdy) score was performed 3 days after treatment. The content of brain water and Evans blue were detected. The expression of tumor necrosis factor-α and interleukin-1β in serum was detected by ELISA. The expressions of Toll-like receptor 4, matrix metalloproteinase 9 and nuclear factor κB proteins in brain tissue were detected by immunohistochemistry and western blot. An ethical approval was obtained from the Experimental Animal Ethics Committee of Shandong Provincial Third Hospital (approval No. DWKYLL-2017001).  RESULTS AND CONCLUSION: Compared with the ICH group, Purdy score, brain water content and Evans blue content were significantly decreased in the MIS group and MIS+Met group (P < 0.05), the expression levels of tumor necrosis factor-α and interleukin-1β in serum were decreased (P < 0.05), and the expression of Toll-like receptor 4, matrix metalloproteinase 9 and nuclear factor κB proteins in brain tissue were significantly decreased (P < 0.05). The above indexes were decreased more obviously in the MIS+MET group. These findings indicate that minimally invasive surgery combined with metformin could reduce the inflammatory response and improve the neurological function of rabbits with intracerebral hemorrhage by inhibiting Toll-like receptor 4/nuclear factor κB signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which enalapril alleviates myocardial injury in a rat model of limb ischemia-reperfusion Xing Hongchang, Cao Jianping, Zhu Jing, Yao Kun 2022, 26 (11):  1747-1751.  doi: 10.12307/2022.361 Abstract ( 472 )   PDF (999KB) ( 37 )   Save BACKGROUND: Studies have confirmed that enalapril can alleviate myocardial injury caused by limb ischemia-reperfusion, but the mechanism of its action has not been reported. OBJECTIVE: To investigate the effect mechanism of enalapril reduction of myocardial injury by ischemia-reperfusion in the rat limb.  METHODS: Forty-eight healthy adult male Sprague-Dawley rats were randomly divided into control group, model group, enalapril group and inhibitor group. Except for the normal control group, rats were bundled around the ligation of the posterior limbs with a rubber band for 3 hours, followed by 3-hour reperfusion to establish the model of limb ischemia-reperfusion. Intravenous injection of 0.3 mg/kg LY294002 was given in the inhibitor group 30 minutes before reperfusion. Enalapril group and inhibitor group were given intravenous infusion of enalapril 13 μg/kg/h immediately after reperfusion until the end of reperfusion. An equal amount of normal saline solution was given in the other two groups immediately after reperfusion. After 3 hours of reperfusion, the rats were killed and the myocardial tissue was taken. Myocardial histopathological changes, apoptotic index, apoptosis gene expression and cell conduction pathway protein expression were detected. The study was approved by the Laboratory Animal Ethical Committee of Shenyang Medical College in October 2019 with an approval No. (2019)85. RESULTS AND CONCLUSION: Compared with the model group, myocardial histopathological injury was reduced in the enalapril group. Compared with the enalapril group, myocardial histopathological injury was aggravated in the inhibitor group. Compared with the model group, myocardial apoptosis index (AI) was decreased, Bax expression was downregulated, PI3K, p-Akt and Bcl-2 expression was up-regulated in the enalapril group (P < 0.05). Compared with the enalapril group, myocardial apoptosis index was increased, Bax expression was up-regulated, PI3K, p-Akt and Bcl-2 expression was downregulated in the inhibitor group    (P < 0.05). The mechanism by which enalapril reduces limb ischemia-reperfusion caused myocardial injury is related to activating PI3K/Akt signaling pathway and inhibiting cell apoptosis in rats. Figures and Tables | References | Related Articles | Metrics

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Osteosarcopenia: muscle-bone interactions Li Xiaowei, Deng Chengyuan, Zhou Guijuan, Chen Xiaocui, Liao Ying 2022, 26 (11):  1752-1757.  doi: 10.12307/2022.365 Abstract ( 756 )   PDF (708KB) ( 62 )   Save BACKGROUND: Studies have found that there is a reduction in the quality of life of patients with osteosarcopenia and an increase in the risk of hospitalization. Compared to patients with osteoporosis or sarcopenia alone, patients with osteosarcopenia have a higher risk of falls and fractures. However, there are few epidemiological reports on osteosarcopenia, with the relationship between bones and muscles being unknown, and few treatment measures have developed. OBJECTIVE: To elucidate the interaction between bone and muscle and the prevention and treatment of osteosarcopenia, thereby calling for an early intervention system. METHODS: PubMed and CNKI were searched for relevant articles published from 1996 to 2020 using the keywords of “osteosarcopenia, epidemiology, interaction between skeleton and muscle, intervention, treatment.” A total of 424 articles were initially examined, and 74 articles were finally included for analysis and summary after screening and sorting. RESULTS AND CONCLUSION: Bone and muscle have similar tissue origin and are differentiated from each other under in vivo or in vitro factors. The adjacent anatomical relationship provides the basic conditions for mechanical signals and chemical signals. The interaction between bone and muscle is mainly realized through mechanical stimulation and its secreted bioactive factors. Like most diseases, the prevention of osteosarcopenia is more important than its treatment. Bone and muscle mass peaks at a young age and then begins to decline with age. The complex and multifactorial characteristics of osteosarcopenia require multifaceted prevention and treatment strategies. The main prevention and treatment measures include: resistance training, nutrition diet therapy, drug therapy, etc. Currently, no enough attention has been paid to osteosarcopenia in China. Therefore, establishing the corresponding early intervention system in China is lagging behind or even a gap in relevant fields. Figures and Tables | References | Related Articles | Metrics

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Chinese herbal prescriptions for tonifying kidney and promoting blood circulation in the intervention of steroid-induced avascular necrosis of the femoral head: relevant signal pathways and targets Han Jie, Ren Guowu, Mo Jian, Zhang Xiaoyun, Wen Shuaibo, Wu Yukun 2022, 26 (11):  1758-1764.  doi: 10.12307/2022.362 Abstract ( 587 )   PDF (1358KB) ( 59 )   Save BACKGROUND: The pathological changes of steroid-induced osteonecrosis of the femoral head involve multiple signal pathways. To elucidate the signal pathway of steroid-induced femoral head necrosis and to find the target of traditional Chinese medicine (TCM) compound intervention are of great significance for the early prevention and treatment of the disease. OBJECTIVE: To summarize the research progress in the signal pathways related to TCM prescriptions for tonifying kidney and promoting blood circulation in the intervention of steroid-induced femoral head necrosis.  METHODS: PubMed, Medline, Embase, The Cochrane Library, CBM, CNKI, VIP and WanFang databases were retrieved with the keywords of “avascular necrosis of the femoral head, ANFH, glucocorticoids, pathogenesis, signal path, TCM compound, Wnt/β-catenin, HIF-1α, PPAR, TGF-β/Smad, AMPK, Notch” in English and Chinese, respectively. The articles concerning the signal pathways related to TCM prescriptions for tonifying kidney and promoting blood circulation in the intervention of steroid-induced femoral head necrosis were searched. Finally, 54 articles were included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION: At present, many clinical practices have shown that TCM prescriptions of tonifying kidney and promoting blood circulation have definite efficacy in the treatment of steroid-induced necrosis of the femoral head in the early and middle stages, but the mechanism of action is still unclear. TCM prescriptions of tonifying kidney and promoting blood circulation may intervene with steroid-induced femoral head necrosis through multiple signal pathways: increasing quantity and activity of osteoblasts via Wnt/β-catenin pathway, repairing partial necrotic vessels via hypoxia-inducible factor 1α pathway, promoting osteogenesis factor secretion via transforming growth factor-β/Smad pathway, regulating cell energy synthesis and metabolic rate via adenylate-activated protein kinase pathway, regulating cell autophagy via Notch pathway, restoring bone remodeling and absorption imbalances via receptor activator of nuclear factor kappa-B ligand/ nuclear factor kappa-B receptor activator/osteoprotegerin pathway, and regulating lipid metabolism and differentiation of bone marrow mesenchymal stem cells via peroxisome proliferator activated receptor γ pathway. To explore the influence of kidney-tonifying and blood-activating TCM compounds on the signal pathways related to femoral head necrosis, is expected to find a more effective TCM compounds for the prevention and treatment of steroid-induced femoral osteonecrosis in clinical practice. Figures and Tables | References | Related Articles | Metrics

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Regulatory role and mechanism of non-coding RNA on steroid-induced osteonecrosis of the femoral head Huang Yangjun, Zhou Honghai, Chen Longhao, Li Jilin, Lu Qingwang, Li Dongyang, He Xinyu 2022, 26 (11):  1765-1771.  doi: 10.12307/2022.363 Abstract ( 373 )   PDF (971KB) ( 89 )   Save BACKGROUND: Steroid-induced osteonecrosis of the femoral head is difficult to be detected in the early stage, and the pathogenesis is not clear. Therefore, steroid-induced osteonecrosis of the femoral head is liable to be ignored and misses the best treatment time, resulting in a high disability rate in the late stage. Studies have shown that non-coding RNA is associated with the development of steroid-induced osteonecrosis of the femoral head. OBJECTIVE: To summarize the relevant literature worldwide and to review the regulatory mechanism of non-coding RNA expression on the pathogenesis of steroid-induced osteonecrosis of the femoral head, so as to further understand its pathogenesis. METHODS: A search of PubMed, Web of Science, CNKI, WanFang, and VIP was performed for articles related to non-coding RNA and steroid-induced osteonecrosis of the femoral head. The keywords were “miRNA, lncRNA, circRNA, glucocorticoids, steroid, dexamethasone, osteonecrosis of the femoral head, bone marrow mesenchymal stem cells” in English and Chinese, respectively. Reproductive studies and non-reference literatures were excluded, and 48 eligible articles were finally included. RESULTS AND CONCLUSION: Non-coding RNA is involved in the pathogenesis of steroid-induced osteonecrosis of the femoral head by regulating the differentiation of bone marrow mesenchymal stem cells, osteocyte metabolism, vascular endothelial cell formation and lipid metabolism. Non-coding RNA is expected to be a biomarker for the clinical diagnosis and prognosis of steroid-induced osteonecrosis of the femoral head. Interference with abnormally expressed non-coding RNAs or miRNAs of exosomal origin may become a new strategy for the clinical treatment of steroid-induced osteonecrosis of the femoral head in the future. Figures and Tables | References | Related Articles | Metrics

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Active monomer composition of Epimedium influences the homeostasis of bone resorption and bone formation by regulating osteoporosis related signaling pathways Li Shibin, Xia Tian, Zhang Xiaoyun, Wang Weiwei, Zhou Yi, Lai Yu 2022, 26 (11):  1772-1779.  doi: 10.12307/2022.364 Abstract ( 445 )   PDF (979KB) ( 123 )   Save BACKGROUND: Osteoporosis is a metabolic bone disease that seriously affects the health of middle-aged and elderly people. At present, western medicine is the main clinical treatment for osteoporosis. With the rapid development of traditional medicine in China, a large number of studies in recent years have found that some monomer components in Epimedium, such as icaritin, icariin, icariside, total flavonoids of Epimedium, and Epimedium polysaccharides, can effectively inhibit bone resorption and bone destruction, promote the proliferation and differentiation of osteoblasts, and ultimately prevent and treat osteoporosis. OBJECTIVE: To explore the mechanism by which the main active monomer components of Epimedium mediate related signaling pathways to prevent and treat osteoporosis, thereby providing new ideas for the prevention and treatment of osteoporosis in the future. METHODS: WanFang, CNKI, VIP, PubMed, and MEDLINE databases were retrieved with the keywords of “Epimedium, Osteoporosis, Bone cell, Monomer component, Osteoblast differentiation, Cell proliferation, signaling pathway” in Chinese and English, respectively. Relevant literatures published from their inceptions to 2021, which detailed the prevention and treatment of osteoporosis by active monomer components of Epimedium mediate related signaling pathways, were retrieved.  RESULTS AND CONCLUSION: Epimedium has small adverse reactions, accelerates the proliferation and differentiation of osteoblasts, and directly inhibits the bone resorption of osteoclasts. Therefore, it has broad prospects in the prevention and treatment of osteoporosis. The total flavonoids of Epimedium and its active monomer components may play anti-osteoporosis effects through the regulation of bone metabolism via multi-channels and multiple levels such as endocrine hormones, protein, molecular biology, and genetics. Compared with other epimedium flavonoids, icariside II has better solubility and permeability. It may be another kind of Epimedium flavonoids with anti-osteoporosis effect. Currently, there are numerous studies about Epimedium regulating the main target genes of Wnt/β-catenin, mitogen-activated protein kinases, osteoprotegerin/receptor activator for nuclear factor-κB ligand/receptor activator of nuclear factor-κB, bone morphogenetic protein/Runt-related transcription factor 2/osterix, and Notch signaling pathways. However, further explorations are required on the secondary target genes and synergistic effects between signaling pathways. Figures and Tables | References | Related Articles | Metrics

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Activation of Nrf2/ARE signal pathway reduces radiotherapy-induced tissue injury Lin Peiqi, Long Yuanzhu, Zhang Nini, Huang Guilin 2022, 26 (11):  1780-1787.  doi: 10.12307/2022.366 Abstract ( 580 )   PDF (733KB) ( 37 )   Save BACKGROUND: Tissue damage induced by radioactive ionizing radiation is one of the serious complications of radiotherapy. Activation of endogenous antioxidative stress response through nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant responsive element (ARE) signaling pathway has shown preventive and therapeutic effects on radiation-induced tissue injuries. OBJECTIVE: To explain the preventive and therapeutic mechanisms of Nrf2/ARE signaling pathway on radiation-induced injuries, and provide new ideas for exploring the treatment and prevention strategies of radiotherapy complications. METHODS: PubMed, Web of Science, CNKI, WanFang and VIP databases were searched using the keywords of “radiation injury, radiation-induced tissue injury (intestine, liver, tongue, lung, bone marrow, skin, hematopoietic system, nervous system, circulatory system), radiation damage, radiation syndrome, Nrf2” in Chinese and English, respectively. A total of 67 literatures were finally included and reviewed.  RESULTS AND CONCLUSION: Radiation-induced injury is damage to tissues caused by the intramolecular bond homolysis of ionizing radiation biomolecules that lead to an increase in cytotoxic free radicals and reactive oxygen species. TheNrf2/ARE signaling pathway is an important endogenous antioxidant defense mechanism in the body. By enhancing the expression of antioxidant response elements, it can reduce DNA damage, promote damaged DNA repair, and inhibit radiation-induced cell apoptosis. Therefore, the Nrf2/ARE signaling pathway is of great significance for the prevention and correction of cellular redox imbalances including radioactive tissue damage. Current studies have found that the activation of Nrf2/ARE signaling pathway has two sides. On the one hand, the application of Nrf2/ARE signaling pathway activator cannot only prevent tissue loss caused by radiotherapy, but also induce the repair of damaged tissue after radiotherapy. On the other hand, the long-term and chronic activation of the Nrf2/ARE signaling pathway caused by various reasons may reduce the sensitivity of malignant tumors to radiotherapy and chemotherapy. Therefore, the Nrf2 /ARE signaling pathway has potential as a new strategy for the prevention and treatment of radiotherapy complications; however, whether it can be applied in clinical practice still needs further exploration and research. Figures and Tables | References | Related Articles | Metrics

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Cervical spondylotic amyotrophy: problems about classification, diagnosis, treatment, and prognosis Lü Shuaiyao, Guan Haishan, Hao Chen, Ding Zhuangzhi 2022, 26 (11):  1788-1792.  doi: 10.12307/2022.367 Abstract ( 689 )   PDF (647KB) ( 59 )   Save BACKGROUND: Treatments for cervical spondylotic amyotrophy are still controversial. For cervical spondylotic amyotrophy patients, conservative treatment can generally stabilize or improve symptoms, but there is no cure. Surgical treatment is recommended for cervical spondylotic amyotrophy with progressive or severe neurological deterioration; however, most clinicians choose surgical methods based on their own clinical experience, and there is no unified standard or industry consensus. The prognosis of different types of cervical spondylotic amyotrophy is significantly different, which may influence the selection of surgical options. OBJECTIVE: To summarize and analyze the pathogenesis, diagnosis, clinical manifestations, types, treatments, and prognosis of cervical spondylotic amyotrophy by reviewing the related researches of cervical spondylotic amyotrophy, in order to provide reference for the selection of clinical treatment and surgical options. METHODS: Articles related to cervical spondylotic amyotrophy published from 1952 to 2020 were retrieved by computer in PubMed, EMbase, Web of Science, CNKI, and WanFang databases. Finally 44 articles that met the inclusion criteria were selected.   RESULTS AND CONCLUSION: The clinical manifestations of cervical spondylotic amyotrophy are asymmetry, segmental and other characteristics of upper limb motor weakness accompanied by obvious muscle atrophy, while the lower limbs are not characterized by obvious sensory disturbance or spastic paralysis. Clinically, according to the position of muscle atrophy, it is classified into proximal type, distal type and mixed type. This disease needs to be distinguished from motor neuron disease and muscular dystrophy to avoid misdiagnosis and erroneous treatment. The pathogenesis of cervical spondylotic amyotrophy is yet unclear. There are two views on ventral nerve root and spinal anterior horn injury. The latter is recognized by most scholars. The diagnosis of cervical spondylotic amyotrophy is mainly based on clinical symptoms, imaging examinations, and neuroelectrophysiological examinations. Some diseases, such as motor neuron disease, should be excluded in differential diagnosis. Surgical treatment is mainly used for cervical spondylotic amyotrophy. Anterior cervical spine anterior surgery is the first choice, and posterior surgery is preferred for patients with multi-segment cervical posterior longitudinal ligament ossification, anterior decompression impossible or high risk of decompression. Different types of cervical spondylotic amyotrophy patients have different prognostic results after surgery. Prognosis of the proximal type is better than that of the distal type, and prognosis of the mixed type is the worst. Surgery via the anterior cervical approach has better results than that via the posterior cervical approach. Figures and Tables | References | Related Articles | Metrics

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Ankle joint fracture with deltoid ligament injury: repair and reconstruction Li Qichen, Han Shufeng, Jia Erlong, Jia Yanan 2022, 26 (11):  1793-1798.  doi: 10.12307/2022.368 Abstract ( 913 )   PDF (764KB) ( 66 )   Save BACKGROUND: The deltoid ligament is the most important structure to maintain the biomechanical stability of the medial malleolus. Improper handling for deltoid ligament injuries can cause traumatic arthritis and chronic ankle instability. However, there are still controversies regarding the diagnosis and treatment of ankle fractures with deltoid ligament injury.  OBJECTIVE: To review the progress in the diagnosis and treatment of ankle fractures with deltoid ligament injury. METHODS: PubMed, CNKI and VIP were searched for relevant articles using the keywords of “ankle, deltoid ligament, diagnosis, management” in English and Chinese, respectively. After initial retrieval, 290 articles were enrolled and finally 69 eligible articles were included for further review.  RESULTS AND CONCLUSION: The deltoid ligament limits the valgus and external rotation of the talus and stabilizes the medial malleolus. After deltoid ligament injury, the stability of the medial malleolus is reduced, and the force line of the hind foot gradually changes. Subsequently, related deformities occur, such as flat feet, which will lead to osteochondral degeneration of the ankle joint in the long term. Medial malleolus injuries can be confirmed based on an overall consideration of patient symptoms, imaging data, and ankle arthroscopy. Different types of ankle injuries have different coping strategies. The repair of the deltoid ligament is crucially important for ankle fractures combined with distal tibiofibular syndesmosis injury. In view of the various problems that may occur in distal tibiofibular joint fixation using screws, an exploration on the use of deltoid ligament instead of distal tibiofibular joint fixation is going on, avoiding secondary operations and poor reduction of the distal tibiofibular joint. Deltoid ligament repair has the disadvantages of long operation time, and suture-button fixation method can also avoid a series of problems caused by distal tibiofibular joint fixation using screws. Therefore, large-sample clinical trials are necessary to compare the postoperative effects of deltoid ligament repair and suture-button fixation for distal tibiofibular syndesmosis injury. Anchoring technique with wire is currently the most common method for the clinical repair of the medial collateral ligament. Figures and Tables | References | Related Articles | Metrics

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Role and mechanism of tetramethylpyrazine in spinal cord injury repair Jiang Shengyuan, Deng Bowen, Xu Lin, Liu Gang, He Feng, Zhao Yi, Ren Jingpei, Mu Xiaohong 2022, 26 (11):  1799-1804.  doi: 10.12307/2022.369 Abstract ( 574 )   PDF (686KB) ( 94 )   Save BACKGROUND: Tetramethylpyrazine has a wide range of pharmacological effects, such as improving microcirculation, anti-inflammatory, inhibiting apoptosis and other functions, which has a significant effect in repairing spinal cord injury.  OBJECTIVE: To review the mechanism of tetramethylpyrazine in the repair of spinal cord injury in order to provide references for the research and treatment of spinal cord injury. METHODS: A computer-based online search of China National Knowledge Infrastructure database and PubMed was performed for relevant articles published from 2003 to 2020, using the keywords of “tetramethylpyrazine, spinal cord injury, ischemia-reperfusion injury” in Chinese and English, respectively. Finally, 85 articles were included for further review. RESULTS AND CONCLUSION: The mechanism of tetramethylpyrazine in spinal cord injury repair has not yet been fully elucidated in animal experiments. The main mechanisms of tetramethylpyrazine in the treatment of spinal cord injury include inhibition of endothelin generation, inhibition of vascular endothelial cell apoptosis, antagonism of calcium ion influx, regulation of interleukin, inhibition of nuclear factor-кB signaling pathway, inhibition of neutrophil infiltration and inhibition of nerve cell apoptosis. There are few reports on the clinical use of tetramethylpyrazine monomer injection to treat spinal cord injury, and its clinical efficacy remains to be further explored. Figures and Tables | References | Related Articles | Metrics