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18 October 2022, Volume 26 Issue 29 Previous Issue   

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Effects of total flavonoids of Rhizoma drynariae on bone remodeling and expression of bone morphogenetic protein-2, vascular endothelial growth factor and CD31 Zhao Dun, Fang Bin, Yi Chunzhi, He Mincong, Zheng Jiaqian, Li Yue 2022, 26 (29):  4638-4642.  doi: 10.12307/2022.840 Abstract ( 405 )   PDF (1261KB) ( 69 )   Save BACKGROUND: Numerous studies have shown that the total flavonoids of Rhizoma drynariae can promote bone healing, but the specific molecular mechanism is still unclear. OBJECTIVE: To investigate the effect of total flavones of Rhizoma drynariae on bone remodeling after bone defects. METHODS: Thirty-six male Sprague-Dawley rats were randomly divided into three groups (n=12 per group): blank group, induced membrane group, induced membrane+traditional Chinese medicine group). After a 4-mm bone tissue sample was taken from the middle part of the right femur of each rat, the femur was fixed with a steel plate and inserted with polymethylmethacrylatebone cement. Four weeks after fixation, the second operation was performed to remove the previously detached bone cement. The blank group did not receive bone graft, and the induced membrane group and the induced membrane+Chinese medicine group received autologous coccyx bone graft. Afterwards, the induction membrane+traditional Chinese medicine group was given the total flavonoids of Rhizoma drynariae 0.22 g/(kg•d) by gavage, and the other two groups were given the same amount of normal saline by gavage. Six weeks after bone grafting, X-ray and histomorphological examinations were performed to observe the formation of new bone tissue in the defect area. Immunohistochemistry staining was used to detect the protein expressions of bone morphogenetic protein 2, vascular endothelial growth factor, and CD31 (platelet-endothelial cell adhesion molecule) in bone tissue.        RESULTS AND CONCLUSION: X-ray films indicated that there was continuous bone tissue in the bone defect area, the medullary cavity was formed, and the bone cortex was reconstructed well in the induced membrane+traditional Chinese medicine group; the induced membrane group did not form a complete cortical bone, in which the medullary cavity was not completely formed and no continuous bone tissue formed; the bone defect area in the blank group was still visible. Histomorphological observations indicated that there was no continuous bone formation in the defect area of the blank group, while new bone tissue was formed to different extent in the defect area of the other two groups. The induced membrane+traditional Chinese medicine group was in the stage of bone shaping. In the induced membrane group, new bone tissue formed unevenly and there was still inflammatory cell infiltration and connective tissue hyperplasia in the defect area. Immunohistochemical findings revealed that the protein expression of bone morphogenetic protein-2 and vascular endothelial growth factor was significantly higher in the induced membrane+traditional Chinese medicine group than the other two groups (P < 0.05), while the protein expression of CD31 was significantly higher in the induced membrane+traditional Chinese medicine group than the blank group (P < 0.05). To conclude, total flavones of Rhizoma drynariae can regulate the expression of bone morphogenetic protein-2 and vascular endothelial growth factor proteins and promote bone mineralization and remodleing in the bone defect area.  Figures and Tables | References | Related Articles | Metrics

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Bushen Jianpi Huoxue Recipe is closely related to the target of histone demethylase JMJD2B in promoting osteogenic differentiation in osteoporosis: an in vitro cell experimental verification Luo Zhen, Huang Yuxi, Chai Shengting, Li Feilong, Chen Qunqun 2022, 26 (29):  4643-4650.  doi: 10.12307/2022.904 Abstract ( 426 )   PDF (1791KB) ( 57 )   Save BACKGROUND: Bushen Jianpi Huoxue Recipe is an empirical prescription commonly used in the treatment of osteoporosis. However, its potential molecular mechanism needs to be further explored. OBJECTIVE: To explore the potential molecular mechanism of Bushen Jianpi Huoxue Recipe in the treatment of osteoporosis based on network pharmacology, and to verify the possibility of its effect through histone methylation modification. METHODS: Based on the network pharmacology, the active drug components and action targets of Bushen Jianpi Huoxue Recipe were screened from relevant database using relevant software, and the targets of osteoporosis-related diseases were obtained. The intersected targets were obtained and identified as the potential targets of Bushen Jianpi Huoxue Recipe in the treatment of osteoporosis. The drug component-target network was constructed by String and Cytoscape software, and the core targets were screened out. The functions and genes related to histone modification were extracted based on the results of GO biological analysis, and the target genes related to histone modification were screened from the core targets. Literature analysis was performed to indicate the possible biological role of target genes in osteoporosis and histone modification. In vitro cell experiments were conducted to verify the effect of Bushen Jianpi Huoxue Recipe on osteogenic differentiation in the treatment of osteoporosis via the regulation of histone demethylase JMJD2B that is closely related to the target. RESULTS AND CONCLUSION: A total of 118 active drug components related to osteoporosis were identified, with 165 corresponding targets. The core targets were IL6, TP53, FOS, JUN, STAT3, RELA, CCND1, MYC, MAPK1, MAPK8, MAPK14, VEGFA, AKT1, ESR1, TNF, NR3C1 and so on. GO biological function analysis showed that the biological functions such as drug response, nutrition level response, oxidative stress response, steroid hormone response, transcriptional regulation, transcription factor binding, phosphatase binding, protease binding, and steroid hormone receptor activity were closely related to the common targets. The core targets such as MAPK8, VEGFA and TP53 were related to histone modification; luteolin, quercetin, and kaempferol might be the main drug components affecting histone modification in the treatment of osteoporosis. Results from the in vitro cell experiment revealed that the expression of osteogenesis-related alkaline phosphatase, JMJD2B and RUNX2 protein increased significantly in rat bone marrow mesenchymal stem cells treated with Bushen Jianpi Huoxue Recipe. Histone demethylase JMJD2B, which is closely related to the pharmacological target of Bushen Jianpi Huoxue Recipe, might promote osteogenic differentiation in the treatment of osteoporosis. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which SC79, an Akt activator, inhibits dexamethasone-induced apoptosis and programmed necrosis of osteoblasts Song Jianzhi, Xu Lisen, Zhang Chen, Tu Feng, Niu Fei 2022, 26 (29):  4699-4703.  doi: 10.12307/2022.908 Abstract ( 687 )   PDF (904KB) ( 43 )   Save BACKGROUND: SC79 is an Akt activator that has a certain cytoprotective effect. It cannot only inhibit excitotoxicity, but also reduce neuronal cell death caused by stroke. OBJECTIVE: To investigate the mechanism of SC79 inhibiting dexamethasone-induced apoptosis and programmed necrosis of osteoblasts. METHODS: Human osteoblasts, OB-6 cells, in logarithmic growth phase were divided into four groups: normal culture group, dexamethasone group treated with 2 μmol/L dexamethasone for 24 hours, SC79 group treated with 20 μmol/L SC79 for 24 hours, and SC79+dexamethasone group treated with 20 μmol/L  SC79 for 2 hours and then 2 μmol/L dexamethasone for 24 hours. Cell activity, lactate dehydrogenase release, and apoptosis rate were detected. Activities of apoptosis-related factors Caspase-3, Bax, and Bcl-2, and the protein expression of oxidative stress-related factors cyclophilin D and cytochrome C were measured. RESULTS AND CONCLUSION: Compared with the normal control group, the dexamethasone group significantly decreased cell activity (P < 0.05), increased lactate dehydrogenase release and mitochondrial membrane potential intensity (P < 0.05), elevated Caspase-3 and Bax activities and apoptosis rate (P < 0.05), decreased the expression of Bcl-2 protein (P < 0.05), and upregulated the expression levels of cyclophilin D and cytochrome C proteins (P < 0.05). Compared with the dexamethasone group, the SC79+dexamethasone group significantly increased cell activity (P < 0.05), reduced lactate dehydrogenase release and mitochondrial membrane potential intensity (P < 0.05), decreased Caspase-3 and Bax activities and apoptosis rate (P < 0.05), elevated the expression of Bcl-2 protein (P < 0.05), and downregulated the expression levels of cyclophilin D and cytochrome C proteins (P < 0.05). To conclude, SC79 can inhibit dexamethasone-induced apoptosis and programmed necrosis of osteoblasts by enhancing cell activity and inhibiting apoptosis, mitochondrial membrane potential and oxidative stress. Figures and Tables | References | Related Articles | Metrics

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Correlation between TCM syndrome types and ERK in lipid metabolism of senile osteoporosis Liao Rongzhen, Chen Dejun, He Mincong, Huang Xingru, Fang Jian, Zhu Genfu 2022, 26 (29):  4704-4708.  doi: 10.12307/2022.907 Abstract ( 409 )   PDF (855KB) ( 90 )   Save BACKGROUND: It has been found that the increase of adipocytes is accompanied by the decrease of bone mineral density and bone mass, while the differentiation of adipocytes is affected by extracellular regulated protein kinases (ERK)1/2 signaling pathway. Up to now, there are few studies on the expression characteristics and correlation of ERK1/2 in lipid metabolism of different syndrome types in patients with osteoporosis. Therefore, this study was designed to explore their internal relationship. OBJECTIVE: To explore the correlation and characteristics between traditional Chinese medicine (TCM) syndrome types and ERK in senile osteoporosis.  METHODS: A total of 94 eligible patients with senile osteoporosis were divided into three groups according to TCM syndrome types, including 39 cases of liver-kidney deficiency type, 30 cases of spleen-kidney yang deficiency type, and 25 cases of qi stagnation and blood stasis type. Peripheral venous blood samples were collected on an empty stomach in the next morning after admission to detect total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, apolipoprotein A1, and apolipoprotein B. Generally, patients underwent artificial hip replacement on the 3rd day after admission and the cancellous bone specimens excavated from the femoral neck were kept in a cryopreservation tube at -80℃. The protein expression of ERK1/2 and p-ERK1/2 in the cancellous bone was then detected and analyzed.  RESULTS AND CONCLUSION: There were significant differences in serum triglyceride, high-density lipoprotein, and low-density lipoprotein levels among the patients with three types of TCM syndromes (P < 0.05). The serum triglyceride level of the patients with spleen-kidney yang deficiency was higher than that of the patients with liver-kidney deficiency and qi stagnation and blood stasis (P=0.009, P=0.035). The serum high-density lipoprotein level of the patients with liver-kidney deficiency was higher than that of the patients with spleen-kidney yang deficiency and qi stagnation and blood stasis (P=0.004, P=0.017). The serum low-density lipoprotein level of the patients with qi stagnation and blood stasis was lower than that of the patients with spleen-kidney yang deficiency and liver-kidney deficiency (P=0.009, P=0.003). The levels of p-ERK1 and p-ERK2 in the cancellous bone were higher than those in the patients with qi stagnation and blood stasis than those with spleen-kidney yang deficiency and liver-kidney deficiency (p-ERK1: P=0.000, P=0.000; p-ERK2: P=0.024, P=0.000). The level of p-ERK2 in the patients with liver-kidney deficiency was higher than that in the patients with spleen-kidney yang deficiency (P=0.006). In the spleen-kidney yang deficiency group, there was a positive correlation with triglyceride (r=0.124, P=0.006) and a negative correlation with p-ERK1/2 (r=-0.512, P=0.013); in the qi stagnation and blood stasis group, there was a positive correlation with p-ERK1/2 (r=0.331, P=0.000). In conclusion, among the three syndrome types of osteoporosis, the lipid metabolism of spleen-kidney yang deficiency group is significantly different from the other two groups, and is negatively correlated with p-ERK1/2. Figures and Tables | References | Related Articles | Metrics

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MicroRNA-20b-5p effects on cartilage and subchondral bone angiogenesis in early-stage osteoarthritis rats Lu Qigui, Xie Pingjin, Luo Zhen, Li Feilong, Chen Qunqun, Chai Shengting 2022, 26 (29):  4658-4665.  doi: 10.12307/2022.852 Abstract ( 373 )   PDF (1435KB) ( 81 )   Save BACKGROUND: Angiogenesis is an important pathological feature of early-stage knee osteoarthritis. Intra-articular injection of microRNA for the inhibition of angiogenesis may provide a new target for the treatment of early-stage knee osteoarthritis. OBJECTIVE: To observe the effect of microRNA-20b-5p (miR-20b-5p) agomir on the angiogenesis of articular cartilage and subchondral bone in rats with early-stage knee osteoarthritis, and to explore the possible protective mechanism of miR-20b-5p. METHODS: Twelve male Sprague-Dawley rats were enrolled, three of which were randomly selected as blank group, and the remaining nine rats were randomly divided into model group, miR-20b agomir group and miR-20b agomir NC group, with three rats in each group. One week after modeling, the blank group was not treated, while in the model, miR-20b agomir and miR-20b agomir NC groups, 0.2 mL of normal saline, miR-20b-5p agomir saline solution and miR-20b-5p agomir NC saline solution was injected into the rat bilateral knee joints, respectively. Four weeks later, the rats in each group were killed and the knee joints were taken for saffron O-fast green staining, immunohistochemical staining, and Osteoarthritis Research Society International scoring. Real-time fluorescence quantitative PCR and western blot assay were used to detect the expression of hypoxia inducible factor 1α and vascular endothelial growth factor at mRNA and protein levels in the cartilage and subchondral bone.  RESULTS AND CONCLUSION: The score of Osteoarthritis Research Society International in the miR-20b agomir group was significantly lower than that in the model group and miR-20b agomir NC group (P < 0.05), but there was no significant difference between model group and miR-20b agomir NC group (P > 0.05). The pathological sections of the knee joint showed that there was an increase in the loss of cartilage matrix and the expression of hypoxia inducible factor-1α and vascular endothelial growth factor proteins in the cartilage and subchondral bone in all intervention groups compared with the blank group. The degree of cartilage matrix loss and the expression of hypoxia inducible factor 1α and vascular endothelial growth factor proteins in the cartilage and subchondral bone in the miR-20b agomir group were lower than those in the model group and miR-20b agomir NC group. The mRNA and protein expression levels of hypoxia inducible factor 1α and vascular endothelial growth factor in the cartilage and subchondral bone in the miR-20b agomir group were significantly lower than those in the model group and miR-20b agomir NC group (P < 0.05). To conclude, overexpression of miR-20b-5p can protect early-stage osteoarthritis cartilage and subchondral bone by inhibiting angiogenesis mediated by the hypoxia-inducible factor 1α/vascular endothelial growth factor pathway. Figures and Tables | References | Related Articles | Metrics

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Correlation between articular fossa space and bone destruction location of the condyle in adolescents with temporomandibular joint osteoarthrosis Zhang Ning, Gao Siwen, Guo Jun, Li Zekui, Zhang Juan 2022, 26 (29):  4593-4597.  doi: 10.12307/2022.848 Abstract ( 466 )   PDF (980KB) ( 71 )   Save BACKGROUND: Research on adolescent patients with temporomandibular joint osteoarthritis is less reported. In the past, traditional X-ray examination was used. In recent years, cone-beam CT analysis shows marked advantages in image data analysis, which can not only be used to understand the changing characteristics of the condyle but also provide reference for the clinical diagnosis and treatment of temporomandibular joint osteoarthrosis in adolescents. OBJECTIVE: To evaluate the abnormal morphology and influential factors based on cone-beam CT images of adolescent patients with temporomandibular joint osteoarthrosis.  METHODS: Eighty adolescents with temporomandibular joint osteoarthrosis (experimental group) and 80 healthy adolescents (control group) were subjected to the cone-beam CT scan in the intercuspal position. The three-dimensional reconstruction images of the temporomandibular joint were measured by Invivo 5.2 software in both groups. (1) Sagittal measurements: upper, anterior and posterior joint spaces; (2) axis measurements: anterior and posterior diameters, internal and external diameters of the condyle; (3) three-dimensional imaging: the height of the mandibular ramus; and (4) the percentage of different pathological change types due to temporomandibular joint osteoarthrosis in the experimental group.  RESULTS AND CONCLUSION: According to statistics, there were 27 males and 53 females in the experimental group, and the ratio of male to female was about 1:2. Intra-group comparison: there were significant differences between the supra-articular and posterior spaces of the bilateral temporomandibular joints in the experimental group (P < 0.05). There was no significant difference between the measurements of the bilateral temporomandibular joints (P > 0.05). Inter-group comparison: Compared with the control group, the supra-articular space, posterior space, anterior and posterior diameters of the condyle, internal and external diameters were significantly reduced in the experimental group (P < 0.05), while the other measurements showed no significant difference (P > 0.05). The experimental group had the highest incidence of local osteolysis, defect or extensive erosion or destruction of the condyle (about 27%), followed by flattened and shortened condyle (about 24%), blurred and disappeared condylar cortical bone (about 21%), displaced condyle in the articular fossa (about 16%), hyperosteogeny and formation of osteophytes (about 8%), and micro-cystoid degeneration of the condyle (about 4%) in order. To conclude, the condyle in the articular fossa is displaced in adolescent patients with temporomandibular joint osteoarthrosis. The condylar process tends to become small, the height of the mandibular ramus tends to become short, and condylar bone destruction appears. The changes of the condylar process in the intraarticular fossa space are correlated with the location of bone destruction.  Figures and Tables | References | Related Articles | Metrics

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Pancreatic autophagy and protein expression of insulin-related genes in type 2 diabetic rats with periodontitis Du Shasha, Cai Zhiguo, Yang Kun, Liu Qi 2022, 26 (29):  4605-4610.  doi: 10.12307/2022.926 Abstract ( 451 )   PDF (1743KB) ( 146 )   Save BACKGROUND: Diabetes is prone to cause multiple organ diseases in the body. Periodontitis is one of the complications. The more severe the inflammation of periodontitis is, the less favorable it is for glycemic control.   OBJECTIVE: To investigate the effect of periodontitis on autophagy of pancreatic tissue in a rat model of type 2 diabetes mellitus. METHODS:  Forty 6-week-old male Sprague-Dawley rats were randomly divided into a control group and an experimental group, and rats in the experimental group were subdivided into three groups (n=10 per group): a diabetes group, a periodontitis group, and a diabetes+periodontitis group. High fat and high sugar feeding+intraperitoneal injection of streptozotocin was used to establish a diabetic model, and silk thread ligation was used to establish a periodontitis model. Enzyme-linked immune sorbent assay was used to detect the expression of inflammatory factors in rat serum. Real-time fluorescent quantitative PCR was used to detect the expression of autophagy and insulin secretion-related genes in rat pancreatic tissue. Western blot was used to detect the protein expression of autophagy-related in rat pancreatic tissue.   RESULTS AND CONCLUSION: The results of enzyme-linked immunosorbent assay showed that the expression of tumor necrosis factor α, interleukin 1β, and interleukin 6 was increased sequentially in the diabetes group, the periodontitis group, and the diabetes+periodontitis group compared with that in the control group (P < 0.05). The results of real-time fluorescent quantitative PCR showed that, compared with the control group, the mRNA expression of glucokinase and recombinant glucose transporter 2 was decreased in the diabetes group and the diabetes+periodontitis group, especially in the diabetes+periodontitis group (P < 0.05). At the same time, the mRNA expression of uncoupling protein 2, Beclin1, and LC3II was increased in the diabetes group and the diabetes+periodontitis group, and increased most in the diabetes+periodontitis group (P < 0.05). However, there was no significant difference between the periodontitis group and the control group (P > 0.05). The results of western blot showed that, compared with the control group, the expression of Beclin1, LC3II/LC3I was increased in the diabetes group and the diabetes+periodontitis group, and increased most in the diabetes+periodontitis group (P < 0.05). And there was no significant difference between the periodontitis group and the control group (P > 0.05). Therefore, it is speculated that type 2 diabetes mellitus with periodontitis may induce excessive autophagy of pancreatic islet cells, then impact the secretion function of insulin in islet cells, and finally aggravate the development of diabetes mellitus in the rat models. Figures and Tables | References | Related Articles | Metrics

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Displacement and rate changes of orthodontic tooth movement in Sprague-Dawley rats with chronic fluorosis Ding Xue, Jia Ying, Liu Chun, Yang Shirong, Lai Lingyan, Yang Hua, Ding Qi 2022, 26 (29):  4687-4692.  doi: 10.12307/2022.898 Abstract ( 333 )   PDF (1072KB) ( 67 )   Save BACKGROUND: The orthodontic course is clinically reported to be longer in patients with dental fluorosis than in non-fluorosis patients. However, it is unclear in which parts of the tooth movement cycle the slowing down of the tooth movement rate is mainly reflected. OBJECTIVE: To study the displacement and rate changes of orthodontic tooth movement in Sprague-Dawley rats with chronic fluorosis during a tooth movement cycle, thereby providing an experimental basis for future related mechanistic studies and orthodontic treatment of patients with dental fluorosis. METHODS: Twelve 3-week-old Sprague-Dawley rats of both sexes were randomly divided into fluoride group and control group, with six rats per group. Rats in the fluoride group were fed with 150 mg/L sodium fluoride solution daily to replicate the fluorosis model. Two groups of rats were then fitted with a nickel-titanium tension spring orthodontic loading device. The bilateral maxillary first molars were moved mesially under a force of 70 g. The the distance from the midpoint of the proximal surface of maxillary first molars to the distal-lingual-gingival angle of the Ipsilateral maxillary central incisors was measured with a digital vernier caliper and the proximal displacement and movement rate of first molars was observed on days 0, 3, 7, 14, 21, and 28. RESULTS AND CONCLUSION: In the fluoride group, Grade II-III dental fluorosis appeared, and the urine fluoride level was higher than normal (P < 0.05), indicating the successful replication of chronic fluorosis model. There was no significant sex difference in the total displacement and total rate of tooth movement between the two groups. There was a tendency for the total displacement and total rate of tooth movement to be lower in the fluoride group than in the control group, but no statistical difference was observed during the observation period. The segmental displacement and segmental rate of tooth movement of rats in both groups showed a trend of increasing, then decreasing and increasing again with time, and the second increase was more obvious in the fluoride group. All these findings indicate that tooth movement in rats with chronic fluorosis is inhibited to some extent in a full tooth movement cycle. The total displacement and total rate of rats with chronic fluorosis are reduced, and there is no significant sex difference. Orthodontic tooth movement in rats with chronic fluorosis conforms to the typical tooth movement cycle involving three phases of “rapid–retarded–rebound.” The shortened retarded phase in rats with chronic fluorosis suggests possible destructive alterations. Figures and Tables | References | Related Articles | Metrics

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MiR-204-5p alleviates neuropathic pain in rats with chronic constriction injury Mao Ke, Gao Yuhua, Zhou Songlin, Zhao Yanfen, Zhang Yuanyuan, Du Silong, Li Xilong 2022, 26 (29):  4680-4686.  doi: 10.12307/2022.839 Abstract ( 377 )   PDF (1321KB) ( 135 )   Save BACKGROUND: MiR-204-5p is a potential biomarker of neuropathic pain, but its role and mechanism in neuropathic pain have not been clarified. OBJECTIVE: To investigate the effect and molecular mechanism of miR-204-5p on neuropathic pain caused by chronic constriction injury in rats.  METHODS: (1) A total of 90 male Sprague-Dawley rats were randomized into sham group, model group, empty vector group, miR-204-5p overexpression group, scramble group, and aurora kinase B (AURKB) interference group, with 15 rats in each group. The rat neuropathic pain model was established based on chronic constriction injury of the sciatic nerve. After modeling, rats in each group were injected with the following recombinant lentiviruses (empty vector, miR-204-5p  overexpression vector, scrambled shRNA, AURKB shRNA), and the injection volume was 1 μg. The expression levels of miR-204-5p and AURKB mRNAs in the dorsal root ganglia of rats were measured by RT-qPCR before surgery and on the 7th and 14th days after surgery. Mechanical allodynia and thermal hyperalgesia were assessed by paw withdrawal threshold and paw withdrawal latency before surgery and on the 3rd, 7th, 14th, and 21st days after surgery. The levels of inflammatory cytokines in dorsal root ganglion tissues of rats were determined by ELISA on the 7th day after surgery. (2) 100 nmol/L lipopolysaccharide was used to induce inflammation in rat microglia cell line (HAPI). The cells were divided into control group, lipopolysaccharide group, lipopolysaccharide+NC mimic group, lipopolysaccharide+miR-204-5p mimic group, lipopolysaccharide+miR-204-5p mimic+empty vector group, lipopolysaccharide+miR-204-5p mimic+AURKB overexpression group. The levels of inflammatory cytokines in HAPI cells were detected using enzyme-linked immunosorbent assay. The expression levels of AURKB and Wnt/β-catenin pathway proteins in HAPI cells were detected by western blot assay. The targeting relationship between miR-204-5p and AURKB was verified by dual luciferase reporter gene assay.  RESULTS AND CONCLUSION: Compared with the sham operation group, the expression of miR-204-5p in the dorsal root ganglion of rats with chronic constriction injury was significantly reduced. Compared with the model group, overexpression of miR-204-5p significantly increased the paw withdrawal threshold value and paw withdrawal latency. In rats with chronic constriction injury of the sciatic nerve and HAPI cells activated by lipopolysaccharide, overexpression of miR-204-5p could inhibit the secretion of inflammatory cytokines. The dual luciferase reporter gene confirmed AURKB as the downstream target gene of miR-204-5p. The expression level of AURKB mRNA was significantly increased in the dorsal root ganglion of rats with chronic constriction injury. Whereas silencing of AURKB could inhibit neuropathic pain and neuroinflammation. In lipopolysaccharide-induced HAPI cells, the overexpression of miR-204-5p reduced the expression of Wnt/β-catenin signaling pathway proteins by inhibiting the expression of AURKB, thereby reducing neuroinflammation. All the findings indicate that miR-204-5p relieves neuropathic pain in rats with chronic constriction injury of the sciatic nerve through the AURKB/Wnt/β-catenin pathway. Figures and Tables | References | Related Articles | Metrics

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Establishment of the equation for calculating peak oxygen pulse rate of young people Feng Zhanpeng, Jiang Yan, Feng Xuesong 2022, 26 (29):  4693-4698.  doi: 10.12307/2022.880 Abstract ( 667 )   PDF (854KB) ( 31 )   Save BACKGROUND: Peak oxygen pulse can reflect the state of cardiovascular function. However, it needs to be measured in the subjects who are at a state of exhaustion using precision instruments under the guidance of professionals. OBJECTIVE: To establish a simple and easy method for evaluating cardiovascular function.  METHODS: Totally 140 young people were randomly recruited and their height, body mass, body fat rate, resting heart rate, resting blood pressure, vital capacity, waist circumference, and hip circumference were measured. Each subject wore a gas metabolism analyzer to perform a cardiopulmonary exercise test on an ergometry. Peak oxygen pulse, maximum oxygen uptake, respiratory quotient, and peak heart rate when the subject reached the maximum performance capacity were collected, and the multiple linear regression method was used to establish the regression equation between peak oxygen pulse and body shape and cardiovascular function indicators.  RESULTS AND CONCLUSION: The peak oxygen pulse equation was established: peak oxygen pulse (mL/beat)=37.287-3.062×sex+0.114×body mass-0.202×resting heart rate-0.063×systolic blood pressure. The peak oxygen pulse equation was verified to have good reliability by analysis of variance, goodness-of-fit test, Durbin-Watson test, and Shapiro-Wilk test. The back-substitution test indicated that the equation established in this study had good validity. There was no significant difference between the measured and predicted value of peak oxygen pulse, and the correlation reached 0.89. To conclude, the peak oxygen pulse equation using sex, body mass, resting heart rate, and systolic blood pressure was established in this study. Figures and Tables | References | Related Articles | Metrics

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Recombinant human interferon alpha-2b inhibits the proliferation and migration of scar fibroblasts Wang Rui, Yu Fei, Liu Taibin, Hou Xiuli, Liu Zhendong, Huo Jing, Song Jianbo 2022, 26 (29):  4611-4615.  doi: 10.12307/2022.846 Abstract ( 443 )   PDF (2595KB) ( 70 )   Save BACKGROUND: Recombinant human interferon α-2b is a cytokine with antiviral, antiproliferative, antitumor, and immunomodulatory activities, which has certain preventive and curative effects on scar tissue.   OBJECTIVE: To explore the effects of recombinant human interferon α-2b on scar fibroblasts and to observe its effects on the proliferation and migration abilities of scar fibroblasts.   METHODS: In vitro scar fibroblasts were cultured to logarithmic growth phase and treated with 0, 5 000, 10 000, 20 000 IU/mL recombinant human interferon α-2b for 48 hours. Cell proliferation was observed by EdU staining and cell migration was detected through cell scratch test and Transwell test. Expression levels of proliferating cell nuclear antigen and matrix metalloproteinase 2, proliferation- and migration-associated proteins of scar fibroblasts were detected by western blot assay.   RESULTS AND CONCLUSION: The results of in vitro cell experiments showed that, compared with the control group, recombinant human interferon α-2b could significantly decrease the number of EdU-positive cells, the wound healing rate, the number of migrated cells, and the protein levels of proliferating cell nuclear antigen and matrix metalloproteinase 2 (P < 0.05). All these findings indicate that recombinant human interferon α-2b can inhibit the proliferation and migration of scar fibroblasts. Figures and Tables | References | Related Articles | Metrics

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Effects of hypoxic exercise on skeletal muscle energy metabolism of rats with alimentary obesity Wu Juhua, Yang Yanan, Weng Xiquan, Zhao Fangfang, Xu Guoqin, Lin Wenta 2022, 26 (29):  4598-4604.  doi: 10.12307/2022.881 Abstract ( 371 )   PDF (1518KB) ( 115 )   Save BACKGROUND: The incidence of obesity is gradually increasing, which is prone to cause a variety of secondary diseases. Therefore, numerous weight-loss intervention strategies have been proposed, among which exercise intervention or/and hypoxic exposure have better effects on the prevention and treatment of obesity.  OBJECTIVE: To explore the effect of hypoxic exercise on the protein expression levels of peroxisome proliferators-activated receptor α (PPARα)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1)/Lipin1 in the skeletal muscle of rats with alimentary obesity.  METHODS: Animal models of alimentary obesity were established in rats, and the rat models were then randomized into normoxic quiet group and exercise group, 16.3% hypoxic quiet group and exercise group, and 13.3% hypoxic quiet group and exercise group. The rats were fed with high fat, and all exercise groups received an endurance exercise, 20 m/min, 40 min/d, 5 days per week for 8 weeks. The rats were killed under anesthesia and sampled at 24 hours after the last exercise. The protein expression levels of PGC-1α, PPARα, and Lipin1 in the skeletal muscle of rats were then determined by western blot and immunohistochemistry.  RESULTS AND CONCLUSION: The rat model of alimentary obesity was induced by a 7-week high-fat diet. Compared with the normoxic quiet group, the expression of PGC-1α protein in the skeletal muscle of rats was significantly increased in the normoxic exercise group, 16.3% hypoxic exercise group, and 13.3% hypoxic exercise group (P < 0.05-0.01). Compared with the 16.3% hypoxic quiet group, the expression of PGC-1α protein in the skeletal muscle of rats was significantly increased in the 16.3% hypoxic exercise group (P < 0.05). Compared with the 13.3% hypoxic exercise group, the expression of PGC-1α protein in the skeletal muscle of rats was significantly reduced in the normoxic exercise group, 16.3% hypoxic quiet group, and 13.3% hypoxic quiet group (P < 0.05-0.01). Compared with the normoxic quiet group, the expression of PPARα protein in the skeletal muscle of rats was significantly increased in the normoxic exercise group, 13.3% hypoxic quiet and exercise groups (P < 0.05-0.01). Compared with the 13.3% hypoxic exercise group, the expression of PPARα protein in the skeletal muscle of rats was significantly reduced in the 16.3% hypoxic quiet and exercise groups (P < 0.05). Compared with the normoxic quiet group, the expression of Lipin1 protein in the skeletal muscle of rats was reduced in the other five groups, and reduced significantly in the 13.3% hypoxic exercise group (P < 0.05). To conclude, hypoxic exercise can increase the expression of PGC-1α and PPARα and reduce the expression of Lipin1 protein in the skeletal muscle of obese rats, and promote the oxidative metabolism of fatty acids in the skeletal muscle, which is beneficial to improving skeletal muscle energy metabolism of obese rats. Figures and Tables | References | Related Articles | Metrics

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Protective effects of tertiary butylhydroquinone on various organs in type 2 diabetic rats Tian Min, Liu Yuting, Xie Like, Cao Yang, Lyu Hongbin 2022, 26 (29):  4616-4623.  doi: 10.12307/2022.845 Abstract ( 420 )   PDF (2208KB) ( 41 )   Save BACKGROUND: Diabetes can cause dysfunction of the whole body tissues and organs. 6-Phosphofructokinase-2/fructose bisphosphatase-2 isoenzyme 3 (PFKFB3) and sphingosine 1-phosphate receptor 2 (S1P2) may be related to the complications of diabetes. Tertiary butylhydroquinone has a certain protective effect on the complications of diabetes. OBJECTIVE: To study the expression of PFKFB3 and S1P2 in various organs (heart, retina, kidney, and aorta) of type 2 diabetic rats and to explore the relationship between tertiary butylhydroquinone and PFKFB3 and S1P2.  METHODS: Twenty-four male Sprague-Dawley rats were divided into normal control group, diabetic group and tertiary butylhydroquinone group. Diabetic models were made in the latter two groups. At 7 days after modeling, the rats in the tertiary butylhydroquinone group were fed with high-fat and high-sugar diet containing 1% tertiary butylhydroquinone, while those in the diabetic group continued to be fed with high-fat and high-sugar diet. After 12 weeks of intervention, the blood glucose and insulin levels were detected; immunohistochemistry and qRT-PCR were used to detect the distribution and expression of PFKFB3 and S1P2 at protein and mRNA levels, respectively; and TUNEL method was used to detect the apoptosis index in different rat organ cells. RESULTS AND CONCLUSION: There was an overall significant difference in the blood glucose and insulin levels between groups (P=0.000, P=0.000). PFKFB3 and S1P2 were mainly distributed in the retinal ganglion cell layer, the inner nuclear layer, aortic intima endothelial cells, cardiomyocytes, interstitial myocardial endothelial cells, and renal tubular cells. The relative protein and mRNA levels of PFKFB3 and S1P2 were significantly different in the retina, aortic intimal endothelial cells, cardiomyocytes, interstitial myocardial endothelial cells, and renal tubular cells (all P < 0.05). The overall difference in the relative expression of S1P2 protein and mRNA in the glomerulus was statistically significant (all P < 0.05). Compared with the normal control group, the expression of PFKFB3 and S1P2 was significantly increased in the diabetic group (P < 0.05), while compared with the diabetic group, the expression of PFKFB3 and S1P2 was significantly decreased in the tertiary butylhydroquinone group (P < 0.05). TUNEL results indicated that there was an overall significant difference in the apoptotic index of rat retinal ganglion cells, cardiomyocytes, renal tubular cells, and aortic full-thickness cells between groups (all P < 0.05). The overall apoptotic index of various organs in the diabetic group was significantly higher than that in the normal control group (P < 0.05), while compared with the diabetic group, the overall apoptotic index was significantly reduced in the tertiary butylhydroquinone group (P < 0.05). To conclude, PFKFB3 and S1P2 are the metabolites involved in the pathological process of various organs in diabetic rats and may be related to the apoptosis of cells in various organs of diabetic rats. Tertiary butylhydroquinone can reduce the expression of PFKFB3 and S1P2 and reduce cell apoptosis in various organs, indicating that tertiary butylhydroquinone has a certain protective effect on various organs of type 2 diabetic rats. Figures and Tables | References | Related Articles | Metrics

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Protective effect of Ganoderma lucidum spores on epididymis and authophage in diabetic rats Zhang Xin, Ma Xiaoru, Xue Jingwen, Wang Fangfang, Wu Lan, Li Yue 2022, 26 (29):  4632-4637.  doi: 10.12307/2022.851 Abstract ( 529 )   PDF (1335KB) ( 50 )   Save BACKGROUND: Hyperglycemia caused by diabetes are closely related to male infertility, and Ganoderma lucidum spores are considered to be anti-aging and improve blood glucose levels. However, the protective effect of Ganoderma lucidum spores on diabetic epididymis remains unclear. OBJECTIVE: To investigate the protective effects of Ganoderma lucidum spores on diabetic epididymis. METHODS: Male Sprague-Dawley rats were randomly divided into normal group (n=10), high fat/high glucose group (n=10), and model group (n=20). Rats in the normal group were fed with normal diet, while those in the high fat/high glucose group and model group were fed with high fat and high glucose diet. The rats in the model group were then intraperitoneally injected with streptozotocin (30 mg/kg) to induce diabetes mellitus. Model rats were randomly divided into diabetes mellitus group (n=10) and Ganoderma lucidum spores group (GLS, n=10). The rats in the GLS group were treated with Ganoderma lucidum spores  (300 mg/kg per day) by gavage, and the rats in the high fat/high glucose group and diabetes mellitus group were gavaged with the equal volume of normal saline and fed with high fat and high glucose diet for 12 weeks. Body mass, fasting blood glucose, superoxide dismutase activity, malondialdehyde level and sperm deformity rate were measured in each group. Structural changes in the epididymis in diabetic rats were observed by hematoxylin-eosin staining. The protein expression levels of cleaved caspase-3, beclin1, p62, and LC3 in the rat epididymal tissue were detected by western blot and immunohistochemical staining.  RESULTS AND CONCLUSION: Ganoderma lucidum spores could significantly recovery epididymal function, improve the epididymal histopathology, and promote cell autophagy and antioxidant capacity. Immunohistochemical staining results showed that the immune intensity of p62 and cleaved caspase-3 decreased significantly. Western blot analysis showed that Ganoderma lucidum spores obviously upregulated beclin1 and LC3 protein expression levels and decreased p62 and Cleaved caspase-3 protein expression levels when compared with the diabetes mellitus group. To conclude, Ganoderma lucidum spores may induce autophagy, increase antioxidant capacity and inhibit apoptosis to protect against epididymal injury in diabetic rats. Figures and Tables | References | Related Articles | Metrics

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Effects of metformin on cognitive dysfunction in preeclampsia rats Zhao Junguo, Chen Xin, Jiang Ruohan, Guo Ying, Gao Bo 2022, 26 (29):  4651-4657.  doi: 10.12307/2022.850 Abstract ( 487 )   PDF (1159KB) ( 85 )   Save BACKGROUND: Preeclampsia is a unique syndrome of pregnancy involving multiple organ systems, with no final conclusion in its pathogenesis. Endothelial dysfunction is a mechanism that has been widely used in basic research. Therefore, NG-nitro-L-arginine methyl ester was used in this study for preeclampsia modeling, followed by treatment with metformin. OBJECTIVE: To establish the model of preeclampsia in rats by intraperitoneal injection of NG-nitro-L-arginine methyl ester, and to explore the effects of metformin on preeclampsia and cognitive function in rats. METHODS: Pregnant rats were randomly divided into control group, model group, and metformin group. The model group was intraperitoneally injected with NG-nitro-L-arginine methyl ester in the middle and late pregnancy, and the metformin group was intraperitoneally injected with the same dose of NG-nitro-L-arginine methyl ester and metformin in the middle and late pregnancy. Body mass of each pregnant rat was recorded and corresponding drug dose was calculated every day. Caudal artery blood pressure was measured, and soluble endothelin and placental growth factor levels were quantified on day 19 of gestation and on days 10 and 30 after delivery. On the 19th day of gestation, urine was collected for 24 hours for urinary albumin and creatinine quantification. The Morris water maze test was conducted on the 10th and 30th days after delivery to obtain the escape latency, number of platform crossings and the average time spent in the target site where the platform was located. RESULTS AND CONCLUSION: Intraperitoneal injection of NG-nitro-L-arginine methyl ester could successfully establish the preeclampsia model in rats, resulting in hypertension, proteinuria and intrauterine growth restriction and endothelial dysfunction. Metformin could improve the preeclampsia-like performance induced by NG-nitro-L-arginine methyl ester. NG-nitro-L-arginine methyl ester-induced preeclampsia rats presented with impaired cognitive function 10 and 30 days after delivery, and metformin treatment could improve the above performance to a certain extent. Therefore, metformin has certain potential in the treatment and prevention of preeclampsia, and its mechanism of action needs to be further studied.  Figures and Tables | References | Related Articles | Metrics

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Aerobic and resistance exercises can alleviate liver inflammation in type 2 diabetic rats Fu Yu, Shang Huayu, Li Shunchang 2022, 26 (29):  4666-4671.  doi: 10.12307/2022.882 Abstract ( 435 )   PDF (998KB) ( 105 )   Save BACKGROUND: Type 2 diabetes mellitus can induce liver inflammation, and exercises have been proved to improve type 2 diabetes mellitus, but the mechanism is unclear. OBJECTIVE: To explore the effects of aerobic and resistance exercises on liver inflammation in type 2 diabetic rats. METHODS: Sprague-Dawley male rats were randomly divided into six groups (n=8 per group), which were blank control group, aerobic exercise group, resistance exercise group, diabetic model group, diabetic aerobic exercise group, and diabetic resistance exercise group. Animal models of type 2 diabetes mellitus were established with high-sugar and high-fat diet combined with low-dose streptozotocin. The aerobic exercise was carried out on a non-weight-bearing treadmill, 20 m/min, 60 min/d, 5 days per week, for 8 weeks in total. The resistance exercise was set to be a weight-bearing ladder exercise, during which the load was progressively increased to 100% of the maximum load. The weight-bearing ladder exercise was repeated three times under the same load, a session per day, 5 days a week, for 8 weeks in total. Fasting blood glucose was measured by Johnson & Johnson blood glucose meter, and glucose tolerance test was performed by intraperitoneal injection, and the area under the blood glucose line (AUC) was calculated. Fasting insulin, nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, caspase-1, and interleukin-1β were tested by enzyme-linked immunosorbent assay. The morphological changes of liver tissue were observed by hematoxylin-eosin staining. RESULTS AND CONCLUSION: Compared with the blank control group, fasting blood glucose and AUC increased significantly in the diabetic model group (P < 0.01). After exercise intervention, fasting blood glucose and AUC in the diabetic aerobic exercise group and diabetic resistance exercise group were still significantly higher than those in the blank control group (P < 0.01, P < 0.05). However, compared with the diabetic model group, fasting blood glucose and AUC were significantly decreased in the diabetic aerobic exercise group and diabetic resistance exercise group (all P < 0.01), and fasting blood glucose and AUC in the diabetic resistance exercise group were significantly lower than those in the diabetic aerobic exercise group (P < 0.05). Compared with the blank control group, the structure of hepatic lobules was unclear and the arrangement of hepatocyte cords was disordered in the diabetic model group, accompanied by enlarged hepatocytes and inflammatory cell infiltration to varying degrees; the arrangement of hepatocytes was more regular, hepatocyte swelling was improved, and the number of inflammatory cells decreased in the diabetic aerobic exercise group; the arrangement of hepatocytes was irregular, hepatocyte swelling was slightly improved, and the number of inflammatory cells decreased in the diabetic resistance exercise group. The expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD, caspase-1, and interleukin-1β in the liver of rats in the diabetic model group were significantly higher than those in the blank control group (P < 0.01), while the expression levels of these indicators in the diabetic aerobic exercise group were significantly lower than those in the diabetic model group (P < 0.05). Compared with the diabetic model group, the expression of the above-mentioned indicators showed a downward trend but did not change significantly in the diabetic resistance exercise group (P > 0.05), and there was also no significant difference between diabetic aerobic exercise group and diabetic resistance exercise group (P > 0.05). To conclude, aerobic exercise can effectively alleviate liver inflammations induced by diabetes, maybe because the aerobic exercise can reduce the activation of NLRP3 inflammasome and inhibit interleukin-1β expression, while the resistance exercise that can significantly improve hyperglycemia and insulin resistance has no obvious effect on liver inflammations induced by diabetes. Figures and Tables | References | Related Articles | Metrics

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Classification of vertigo state based on machine learning and electroencephalogram signal analysis Geng Yuehua, Shi Jinxiang 2022, 26 (29):  4624-4631.  doi: 10.12307/2022.844 Abstract ( 551 )   PDF (1563KB) ( 110 )   Save BACKGROUND: Electroencephalogram (EEG) is a common means to detect and analyze vertigo in clinic. Currently, unipolar or multistage lead tracing is mostly used to record and analyze whether the EEG frequency is abnormal. However, the EEG process of vertigo is extremely complex. It is difficult to accurately classify and detect the vertigo state only using a frequency speed analysis.  OBJECTIVE: To classify the types of vertigo based on the combination of machine learning and EEG signal analysis, which has certain research significance and clinical application value for the diagnosis of vertigo. METHODS: The non-invasive vestibular function regulation technology for vestibular electrical stimulation was used to create a reversible vertigo state. The stimulation current intensity was 1, 2, and 4 times that of the skin perception threshold. All subjects were required to fill in a dizziness handicap inventory after different intensity current stimulations. The vertigo symptoms were divided into different grades according to the evaluation results of the dizziness handicap inventory, which was used as the data label for supervised learning of EEG classification. The stimulated EEG signals were collected, the wavelet energy and wavelet entropy sample features of EEG signals were extracted by wavelet transform, and a variety of machine learning classification models were used to classify the features of samples with or without vertigo and with different levels of vertigo. RESULTS AND CONCLUSION: By comparing the classification results of various classification models, we found that the supervised learning classification based on the wavelet transform characteristics of EEG signals could realize the binary classification and multi-classification of vertigo and vertigo level. Compared with logistic regression model, support vector machine model, back propagation neural network model, and random forest classification model showed higher accuracy in the binary classification and multi-classification of vertigo detection. The accuracy of the binary classification was up to 82.5% and the operating characteristic curve area was 0.913; the accuracy of the three-way classification was up to 75.8% and the operating characteristic curve area was 0.927. All these findings indicate that the random forest model has a relatively higher accuracy in the classification of EEG features with or without vertigo and vertigo level. This method provides a feasible supplementary scheme for the classification and detection of vertigo symptoms and offers a new perspective on the diagnosis of vertigo. Figures and Tables | References | Related Articles | Metrics

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Exploring peripheral blood biomarkers and therapeutic drugs for osteoarthritis based on bioinformatics Yang Wei, Han Qingmin 2022, 26 (29):  4672-4679.  doi: 10.12307/2022.883 Abstract ( 479 )   PDF (2206KB) ( 131 )   Save BACKGROUND: There are still no sensitive markers for monitoring the occurrence or progression of osteoarthritis. The detection of changes in peripheral blood gene expression profiles during the active period of osteoarthritis is helpful to explore the precise targets for diagnosis and treatment in the blood and explain the pathogenesis.  OBJECTIVE: To simultaneously analyze the differences in gene expression profiles of peripheral blood mononuclear cells and synovium between osteoarthritis and normal human using bioinformatics methods, to explore the diagnosis and treatment targets and therapeutic drugs of osteoarthritis in the blood from the molecular level, and to provide a new perspective on the study of osteoarthritis. METHODS: We found GSE48556 and GSE55235 data sets from GEO and ArrayExpress databases. Blood samples from 105 patients with osteoarthritis and 24 normal controls and synovial samples from 10 patients with osteoarthritis and 10 normal controls were included. We used the R language limma package to screen differentially expressed genes in blood and synovium between osteoarthritis and normal controls and to identify the intersected genes. The gene ontology and KEGG pathways of differentially expressed genes were analyzed by DAVID. We used STRING and Cytoscape software to construct a protein-protein interaction network, used Mcode plug-in for module analysis, and used Cytohubba to screen out key genes. We imported differentially expressed genes into the online platform of Connectivity Map to screen out the top 10 small molecule drugs that are negatively related. RESULTS AND CONCLUSION: A total of 142 differentially expressed genes were obtained, of which 75 were up-regulated genes and 67 were down-regulated genes. The gene ontology enrichment analysis of all differentially expressed genes mainly focused on T cell activation, leukocyte migration, leukocyte-cell adhesion, positive regulation of cell adhesion, and regulation of lymphocyte activation. The kyotoencyclopedia of genes and genomes was mainly enriched in the MAPK signaling pathway, Rap1 signaling pathway, Ras signaling pathway, B cell receptor signaling pathway, and chemokine signaling pathway. The protein-protein interaction network and related plug-ins were used to screen out 10 genes including mitogen-activated protein kinase 1, vascular endothelial growth factor A, growth factor receptor binding protein 2, early growth response protein 1 and ras-related c3 botulinum toxin substrate 2, which were highly related to cell apoptosis and immune inflammation in osteoarthritis. Connectivity Map screened out some small molecules with potential therapeutic effects, such as indirubin and beclomethasone. To conclude, the bioinformatics analysis can indicate that the differences of gene expression in peripheral blood mononuclear cells and synovium between osteoarthritis patients and normal controls are concentrated in the biological events of apoptosis and inflammation, so that the blood expression profile becomes an effective breakthrough for monitoring target markers of osteoarthritis and studying their potential molecules for drugs. Figures and Tables | References | Related Articles | Metrics

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Application enlightenment of exercise and fat oxidation kinetic characteristics Kong Fanming, Zhu Miaomiao, Mi Jing, Ma Jie 2022, 26 (29):  4709-4715.  doi: 10.12307/2022.843 Abstract ( 414 )   PDF (1131KB) ( 241 )   Save BACKGROUND: At present, reducing fat and losing weight has become an eternal topic. Exercise is an important means of lowering fat, and exploring the factors that affect fat metabolism during exercise has become a research hotspot.  OBJECTIVE: To explore the effects of exercise style, exercise intensity, and exercise time on the kinetic characteristics of fat oxidation, summarize the biological mechanism of exercise regulating fat oxidation, explore the application enlightenment of reasonable exercise prescriptions in the prevention and treatment of obesity and other metabolic diseases, and look forward to future research directions in the field.  METHODS: Literature retrieval was conducted in Chinese and English databases such as China Knowledge Network (CNKI), Bailian Cloud Library, PubMed and EBSCO Sports Science Full Text and Researcher and ResearchGate academic social platforms. The search terms included “exercise; fat metabolism; fat energy ratio; fat oxidation rate” in Chinese and English. After initial search, relevant documents were classified, summarized, and refined. RESULTS AND CONCLUSION: Fat oxidation kinetics is a complex non-linear process, which mainly includes two aspects - fat energy supply ratio and fat oxidation rate, and is affected by exercise intensity, exercise time, exercise mode, exercise level, exercise habits, and body composition. The above-mentioned factors are interrelated and interacted, which experience changes in stages. The molecular biological mechanism of exercise regulating fat oxidation is relatively mature, but the biological mechanism of lactic acid inhibiting fat oxidation is not fully understood. To strengthen the weight loss effect, it is recommended to increase the amount of daily exercise. However, due to the influence of energy protection mechanism, a longer exercise does not indicate a better effect on weight loss. Further studies should be strengthened on the basic application of exercise to control fat oxidation. With the help of proteomics, genomics, and immunoomics tools, we can search for scientific evidence and explore relevant biological mechanisms at the organ system and cell molecular levels, in terms of neuromodulation, immune system control, skeletal muscle metabolism, mitochondrial adaptation, intestinal flora activity and exosomal release. Figures and Tables | References | Related Articles | Metrics

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Aerobic exercise improves the cognitive function of elderly patients with mild cognitive impairment Yang Yi, Wang Kun, Liu Hengxu, Zhang Tingran, Lu Wenyun, Chen Peijie, Luo Jiong 2022, 26 (29):  4716-4722.  doi: 10.12307/2022.842 Abstract ( 479 )   PDF (963KB) ( 481 )   Save BACKGROUND: Considering the current growing trend of the population base of the elderly, extensive attention has been paid to the living standards and quality of life of the elderly.  OBJECTIVE: To introduce the effects of aerobic exercise on the cognitive abilities of elderly patients with mild cognitive impairment, and to explore the effects of different cycles of aerobic exercise on the cognitive abilities of elderly patients with mild cognitive impairment and the possible mechanisms. METHODS: Elsevier, Springer, Web of Science, PubMed, CNKI, WanFang, VIP, and Taiwan academic literature database were searched for relevant articles published before September 2021. The search terms included “mild cognitive impairment in the elderly, aerobic exercise, the elderly, cognitive ability, cognitive decline, acute aerobic exercise” in English and Chinese. Appropriate criteria were established as per the research needs, by which all the retrieved articles were screened.  RESULTS AND CONCLUSION: Aerobic exercise plays a positive role in intervening the cognitive function of elderly patients with mild cognitive impairment. Acute aerobic exercise increases the level of brain-derived nerve growth factor, while short- and mid-to-long-term aerobic exercises improve physical fitness, increase cerebral blood flow, enhance cognitive and coordination abilities in the elderly with mild cognitive impairment, all of which help improve the health and quality of life of the elderly. Acute aerobic exercises improve patient’s attention and inhibition control, and short-term and mid-to-long-term aerobic exercises positively act on memory function and neural network. There are certain differences in the benefits of aerobic exercise in different periods on patient’s cognitive function. Overall, persistent aerobic exercises can improve the cognitive function of elderly patients with mild cognitive impairment, improve their cardiorespiratory fitness, and increase exercise participation. However, different aerobic exercise prescriptions are required for the improvement of specific cognitive areas. There is a dynamic variable process between aerobic exercise and mild cognitive impairment. Individual aerobic exercise prescriptions are necessary for patients with different types of cognitive impairment, such as single- and multi-domain mild cognitive impairment. Aerobic exercises can improve patient’s cognitive function, which may be related to delaying brain atrophy, promoting gene expression, and increasing cerebral blood flow, but there is no mechanism that is commonly accepted.  Figures and Tables | References | Related Articles | Metrics

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Citespace-based visual analysis of research literature related to cartilage repair using cartilage precursor cells He Qize, Meng Lin, Wang Jie, Weng Chenyi 2022, 26 (29):  4723-4728.  doi: 10.12307/2022.903 Abstract ( 388 )   PDF (1508KB) ( 79 )   Save BACKGROUND: Cartilage repair has always been a great challenge for orthopedic surgeons and also a hot issue in relevant fields. Recent studies have revealed the existence of cartilage progenitor cells with stem cell characteristics in the articular cartilage, providing a new entry point for cartilage repair. OBJECTIVE: By analyzing the trend of publications, author collaboration network, institutional collaboration network, co-occurrence analysis and clustering analysis of keywords in the cartilage progenitor cells-related literature, to explore the development status, research hotspots and difficulties in this field in the past 20 years, and to provide new ideas and directions for cartilage repair-related scientific research as well as clinical work. METHODS: The core ensemble database included in Web of Science 1999-2021 was used as the literature source, and Citespace 5.8.R1 was applied to visualize and analyze relevant literature and draw relevant visualization maps. RESULTS AND CONCLUSION: A total of 829 papers were included, and the analysis results showed that: the annual publication volume was basically stable at 30-50 articles with a slight downward trend; CHUANJU LIU had the most publications and the institution with the most publications was Harvard Univ; and there were 20 high-frequency keywords that formed 12 meaningful clusters. Mesenchymal stem cells, chondrocytes, osteoblasts, bone marrow stromal cells, and stromal cells are the current research hotspots. Cartilage precursor cells are currently of little research concern, and there is still great room for future exploration. Most of the current research on cartilage precursor cells focuses on the application of tissue engineering materials combined with the cells for cartilage defect repair. Current frontier hotspots in cartilage repair research include the sources of chondrocytes and cartilage precursor cells, application of exosomes, tissue-scaffold interactions and scaffold degradation, identification and application of new stimuli, understanding structural maturation, biomechanics and function, and improving implantation, fixation and rehabilitation methods. Figures and Tables | References | Related Articles | Metrics

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Mechanism and application of sterol regulatory element binding protein in wound healing Zhu Boheng, Peng Ying, Wang Hong 2022, 26 (29):  4729-4734.  doi: 10.12307/2022.841 Abstract ( 411 )   PDF (1024KB) ( 82 )   Save BACKGROUND: Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate lipid homeostasis by controlling the expression of a series of enzymes required for the synthesis of endogenous cholesterol, fatty acids, phospholipids, and triglycerides. Recent studies have shown that SREBPs can regulate wound healing through the involvement in wound inflammation, angiogenesis, and epidermal cell formation.  OBJECTIVE: To summarize the main mechanism and application of SREBPs in wound repair.   METHODS: English databases, including PubMed, Web of Science, and Cochrane Library, and Chinese databases, including CNKI, VIP, WanFang, and China Biomedical Literature Database, were searched for relevant literature published from database inception to August 31, 2021. The search terms were “sterol regulatory element binding proteins, wound, inflammation, angiogenesis, epidermis” in Chinese and English.  According to the inclusion and exclusion criteria, 48 documents were included for result analysis.   RESULTS AND CONCLUSION: SREBP transcription factors can promote wound healing by regulating inflammation, promoting angiogenesis, and reepithelialization. In this review, we list some methods to regulate the activity of SREBP transcription factors. SREBP can regulate human lipid homeostasis, inflammatory responses, angiogenesis, and reepithelialization during wound repair, providing a new research direction for wound repair. To date, there are few clinical trials on the application of SREBP in wound repair, and the specific safety and efficacy of SREBP cannot be fully guaranteed.   Figures and Tables | References | Related Articles | Metrics

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Gaze characteristics of emotional faces in depressed patients: a Meta-analysis based on eye movement studies Xia Haisha, Li Yuxi, Liu Xiaobo, Fan Jin, Zhang Jiaming, Gou Xinyun, Li Juan, Zheng Zhong, Jin Rongjiang 2022, 26 (29):  4735-4741.  doi: 10.12307/2022.836 Abstract ( 488 )   PDF (1075KB) ( 128 )   Save OBJECTIVE: Relevant Meta-analyses have reported that there is a significant negative fixation pattern in depressed patients, but it is unclear about the magnitude of this pattern and the difference in gaze indicators under different stimuli. To this end, the article systematically evaluates the gaze characteristics of eye tracking in patients with depression under different emotional tasks, providing a reference for clinical outcome and prognostic evaluation. METHODS: PubMed, The Cochrane Library, EMbase, Web of science, CBM, CNKI, WanFang Database, and VIP database were electronically searched to collect case-control studies on eye tracking in depressive patients from their inception to September 5th, 2021. Two researchers independently screened literature, extracted data and the Newcastle-Ottawa Scale was used to evaluate the quality of the included studies. Meta-analysis was performed by using RevMan5.4 software.   RESULTS: A total of 12 case-control studies were included, in which 231 subjects (depressed patients) were in the case group and 307 in the control group. The Newcastle-Ottawa Scale scores of the included studies were 5 and above, indicating a higher quality of the included studies. The results of Meta-analysis showed that: for different stimulus types, compared with the control group, the fixation duration of depressed patients was significantly reduced under the positive stimulus [Standardized mean difference (SMD)positive=-1.00, 95% confidence interval (CI) (-1.88, -0.12), P=0.03], and was significantly increased under the negative stimulus [SMDnegative=0.77, 95% CI (0.50, 1.04), P < 0.000 01]. There was no significant difference in fixation duration under the neutral stimulus [SMDneutral=-0.17, 95%CI (-0.48, 0.14), P=0.28]. There was no significant difference in the first fixation duration between the case and control groups [SMDpositive=0.18, 95% CI (-0.25, 0.61), P=0.42; SMDneutral=-0.19, 95% CI (-0.46, 0.08), P=0.17; SMDnegative=0.24, 95% CI (-0.04, 0.52), P=0.09]. Compared with the control group, depressed patients showed a significant reduction in the fixation counts under positive and neutral stimuli [SMDpositive=-3.65, 95% CI (-4.59, -2.71), P < 0.000 01; SMDneutral=-1.08, 95% CI (-1.61, -0.56), P < 0.000 1), while the fixation counts in depressed patients increased significantly under negative stimuli [SMDnegative=1.32, 95% CI (0.78, 1.86), P < 0.000 01].   CONCLUSION: There are significant differences in the fixation patterns between depression and healthy individuals, mainly in terms of fixation duration and fixation count. Future studies can explore more eye movement indicators and characteristics of fixation patterns in depressed patients. Figures and Tables | References | Related Articles | Metrics

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Electromyographic biofeedback for post-stroke limb spasticity: a Meta-analysis Zhang Tiantian, Li Jiamin, Ou Liang, Shang Yan, Xu Yaqian, Hu Guoheng 2022, 26 (29):  4742-4748.  doi: 10.12307/2022.899 Abstract ( 601 )   PDF (1747KB) ( 114 )   Save OBJECTIVE: Electromyographic biofeedback therapy has been widely used in post-stroke muscle rehabilitation training. The purpose of this paper is to systematically evaluate the efficacy of electromyographic biofeedback on treating post-stroke spasticity. METHODS: The randomized controlled trials addressing electromyographic biofeedback in the treatment of post-stroke spasticity were retrieved from PubMed, Cochrane Library, Embase, CNKI, VIP, Chinese BioMedical Literature Database, and WanFang Database. The retrieval time ranged from database inception to June 2021. The risk of bias was evaluated by the Cochrane Collaboration tool and modified Jadad scale. Meta-analysis was performed using RevMan 5.4 software. RESULTS: A total of 15 randomized controlled trials were included, and 878 samples were extracted. The results of Meta-analysis showed that treatment with electromyographic biofeedback ≤ 4 weeks or over 4 weeks showed a significantly lower modified Ashworth scale score [mean difference (MD)=-0.32, 95% confidence interval (CI): -0.45 to -0.19, P < 0.000 01; MD=-0.27, 95% CI: -0.37 to -0.17, P < 0.000 01] and significantly lower clinical spasticity index (MD=-2.05, 95% CI: -2.27 to -1.83, P < 0.000 01) compared with the control group. Compared with the control group, electromyographic biofeedback could significantly improve the motor function (upper limbs ≤ 4 weeks: MD=3.39, 95% CI: 2.02-4.77, P < 0.000 01; upper limbs > 4 weeks: MD=2.53, 95% CI: 2.04-3.02, P < 0.000 01; lower limbs > 4 weeks: MD=3.36, 95% CI: 2.90-3.83, P < 0.000 01; total score ≤ 4 weeks: MD=20.63, 95% CI: 19.38-21.88, P < 0.000 01; total score > 4 weeks: MD=8.08, 95% CI: 3.38-12.78, P=0.000 8), the active range of motion of the ankle joint (≤ 4 weeks: MD=4.87, 95% CI: 1.12-8.62, P=0.01; > 4 weeks: MD=3.69, 95% CI: 3.04-4.34, P < 0.000 01) and electrophysiological parameters (flexor group: MD=-16.80, 95% CI: -24.75 to -8.85, P < 0.000 1; extensor group: MD=17.88, 95% CI: 2.83-32.93, P=0.02) of the hemiplegic limbs. CONCLUSION: Electromyographic biofeedback can effectively improve post-stroke limb spasticity and function. However, more high-quality randomized controlled trials are still needed to further verify its efficacy and safety. Figures and Tables | References | Related Articles | Metrics

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Effect of eccentric strengthening on hamstring strength: a Meta-analysis Zheng Wei, Sun Libing, Xiong Yingzhe, Zhang Yichi, You Jing, Huang Wenqi, Guo Yanhua, Liu Hongjun 2022, 26 (29):  4749-4756.  doi: 10.12307/2022.900 Abstract ( 462 )   PDF (1430KB) ( 52 )   Save OBJECTIVE: The evaluation indexes for hamstring strength improved by eccentric strengthening are scattered and the results are not consistent. Herein, a Meta-analysis is conducted to analyze the influence of eccentric training on hamstring strength, aiming to provide an evidence-based basis for improving the effect of sports training and applying reasonable and effective strategies for injury protection. METHODS: Randomized controlled trials on hamstring strength improved by eccentric strengthening were searched from CNKI, WanFang, PubMed, Web of Science, and EBSCO databases. The retrieval period was from database building to September 2021. Review manager 5.3 and Stata 16.0 were used for quality assessment, Meta-analysis, subgroup analysis, sensitivity analysis, and publication bias analysis. RESULTS: A total of 14 articles involving 557 subjects were included, with 314 subjects in experimental group and 243 subjects in control group. The overall quality of literature was high. Eccentric strengthening can be used as an effective intervention to significantly improve the relative concentric contraction peak torque [standardized mean difference (SMD)=0.60, 95% confidence interval (CI): 0.18-1.02, P < 0.01] and eccentric contraction peak torque of the hamstrings (SMD=0.43, 95% CI: 0.18-0.67, P < 0.001) and functional H/Q ratio (SMD=0.69, 95% CI: 0.34-1.05, P=0.000 1), but it has no significant effect on isometric contraction peak torque and conventional H/Q ratio. The relative concentric contraction peak torque (SMD=0.86, 95% CI: 0.22-1.49, P < 0.01) and the relative eccentric contraction peak torque (SMD=0.46, 95% CI: 0.09-0.82, P < 0.05) in the experimental group were significantly different from those in the control group when a low angular velocity was selected. The 6-week eccentric strengthening was better than the 4- and 27-week eccentric strengthening to improve the functional H/Q ratio (SMD=0.71, 95% CI: 0.32-1.10, P < 0.001). CONCLUSION: Eccentric strengthening can improve hamstring strength, characterized by increasing hamstring concentric and eccentric contraction strength, correcting the strength imbalance of hamstring and quadriceps, and reducing initial or second injuries of the hamstring. Figures and Tables | References | Related Articles | Metrics