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18 September 2022, Volume 26 Issue 26 Previous Issue   

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Hyperbaric oxygen improves fracture healing by promoting osteoblast proliferation Yu Xue, Li Xiaofeng, Shu Kegang, Wu Liwei, Wang Yonglin, Lyu Dingkang, Zhou Anyuan, Liang Chaoxin, Yang Yuan 2022, 26 (26):  4136-4140.  doi: 10.12307/2022.833 Abstract ( 1142 )   PDF (2248KB) ( 238 )   Save BACKGROUND: Most fractures can be healed, 5%-10% of which will develop into nonunion. Clinical trials have confirmed that hyperbaric oxygen can accelerate fracture healing by significantly increasing the partial pressure of arterial oxygen via the blood circulation and promoting metabolism. OBJECTIVE: To explore the effect and mechanism of hyperbaric oxygen intervention for different time on the healing of femoral fractures in rabbits.  METHODS: Twelve New Zealand white rabbits were selected to make femoral fracture models and randomly divided into a hyperbaric oxygen treatment group for 1 month, a hyperbaric oxygen treatment group for 2 months, a normoxia treatment group for 1 month, and a normoxia treatment group for 2 months (3 rabbits per group). In the hyperbaric oxygen treatment groups, all animals were placed in a hyperbaric animal cabin for hyperbaric oxygen treatment on the 1st day after modeling. After 1 and 2 months of treatment, enzyme-linked immunosorbent assay was used to detect the levels of serum osteocalcin and type I collagen C-terminal peptide and hematoxylin-eosin staining was used to observe fracture healing. RESULTS AND CONCLUSION: After 1 month of treatment, expression levels of osteocalcin and type I collagen C-terminal peptide in serum showed no significant difference between the hyperbaric oxygen treatment groups and normoxia treatment groups (P > 0.05). After 2 months of treatment, the serum level of type I collagen C-terminal peptide was significantly decreased (P < 0.001) and the serum level of osteocalcin was significantly increased (P < 0.01) in the hyperbaric oxygen treatment group than the normoxia treatment group. After 1 month of treatment, there was no difference in the severity of pathological injury between the hyperbaric oxygen treatment group and normoxia treatment group. Whereas, after 2 months of treatment, pathological injuries were significantly reduced in the hyperbaric oxygen treatment group compared with the normoxia treatment group. To conclude, hyperbaric oxygen treatment for 2 months can effectively increase the expression of osteocalcin, suggesting that it may promote the formation of osteoblasts and accelerate fracture healing.  Figures and Tables | References | Related Articles | Metrics

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Bushen Jianpi Huoxue Recipe improves bone metabolism, oxidative stress, and autophagy in osteoporotic rats Mi Jianguo, Qiao Rongqin, Liu Shaojin 2022, 26 (26):  4147-4152.  doi: 10.12307/2022.816 Abstract ( 503 )   PDF (898KB) ( 164 )   Save BACKGROUND: Oxidative stress is considered to be one of the most important initiating factors for osteoporosis. In addition to directly activating classic mitochondrial and endoplasmic reticulum apoptosis pathways, oxidative stress can also activate an autophagy signaling pathway. The regulatory mechanism underlying the antioxidant function of osteoblasts in osteoporosis has not been clearly clarified. OBJECTIVE: To explore the effect and mechanism of Bushen Jianpi Huoxue Recipe on phosphatidylinositol 3-kinase, protein kinase B, and mammalian target of rapamycin in osteoporotic rats by improving oxidative stress and autophagy. METHODS: Seventy-two 6-month-old female Sprague-Dawley rats were randomly divided into a sham operation group (n=24) and an operation group (n=48), in which the rat ovaries were removed to make an ovariectomized model. After 3 months, 12 rats were taken from each group for detecting bone mineral density and serum osteocalcin, bone-specific alkaline phosphatase, type I procollagen N-terminal propeptide, and osteoprotegerin levels. The remaining 36 rats in the operation group were divided into model group, Bushen Jianpi Huoxue Recipe group, alendronate vitamin D3 (II) group, with 12 rats in each group. Drug groups were given intragastric administration of corresponding drugs. Sham operation and model groups were given an equal volume of normal saline. After 12 weeks, the rats in each group were sacrificed, and the bone mineral density of the lumbar spine and femur of the rats was detected by dual energy X-ray method. ELISA method was used to measure serum bone metabolism indexes and oxidative stress indexes. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of LC3, Beclin1, ATG5, and mammalian target of rapamycin in femoral tissue. Western blot assay was used to detect the protein expression of phosphatidylinositol 3-kinase, phosphorylated protein kinase B, and mammalian target of rapamycin. RESULTS AND CONCLUSION: Three months after modeling and drug treatment, compared with the sham operation group, the bone mineral density and osteoprotegerin of the model group were significantly reduced (P < 0.05), and the expression of osteocalcin, bone specific alkaline phosphatase, and type I procollagen N-terminal propeptide were significantly increased (P < 0.05). After 3 months of drug intervention, compared with the sham operation group, the expression levels of malondialdehyde and reactive oxygen species were significantly increased in the model group (P < 0.05), the mRNA expression of LC3, Beclin1 and ATG5 was significantly increased (P < 0.05), the mRNA levels of catalase, superoxide dismutase and mammalian target of rapamycin as well as the protein expression of phosphatidylinositol 3-kinase, phosphorylated protein kinase B, and mammalian target of rapamycin were significantly reduced (P < 0.05). After 3 months of drug interventions, compared with the model group, these indicators were all improved in the Bushen Jianpi Huoxue Recipe group and alendronate vitamin D3 (II) group (P < 0.05). To conclude, Bushen Jianpi Huoxue Recipe can improve postmenopausal osteoporotic bone metabolism, oxidative stress levels and inhibit autophagy, and its mechanism may be involved in the regulation of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Effects of suppressor of cytokine signaling 3 on osteogenic activity in the cartilage of adolescent idiopathic scoliosis Sun Jinpeng, Liu Jun, Bai Yunfeng, Hua Feng, Wang Haoran, Zheng Hongrui, Wu Tao 2022, 26 (26):  4160-4165.  doi: 10.12307/2022.818 Abstract ( 460 )   PDF (2341KB) ( 103 )   Save BACKGROUND: It has been reported that the abnormal expression of leptin and suppressor of cytokine signaling 3 (SOCS3) plays an important role in the pathogenesis of adolescent idiopathic scoliosis. OBJECTIVE: To investigate whether SOCS3 regulates the osteogenic activity of chondrocytes through the leptin signaling pathway. METHODS: Human spinous chondrocytes were stimulated with 0 (blank control group) and 100 µg/L leptin for 24 hours, and immunohistochemical staining was used to detect the expression of type II collagen. The human spinous chondrocytes were cultured in nine groups: a blank control group, a pcDNA3.1-NC transfected group, a pcDNA3.1-SOCS3 transfected group, a siRNA-NC transfected group, a siRNA-SOCS3 transfected group, a leptin+transfected pcDNA3.1-NC group, a leptin+transfected pcDNA3.1-SOCS3 group, a leptin+transfected siRNA-NC group, and a leptin+transfected siRNA-SOCS3 group. After being cultured in an incubator for 24 hours, real-time fluorescent quantitative PCR was used to detect the mRNA expression of SOCS3, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to detect the cell inhibition rate. RESULTS AND CONCLUSION: Results of immunohistochemical staining showed that the expression of type II collagen in chondrocytes s was higher in leptin-stimulated group than the blank control group. Results of real-time fluorescence quantitative PCR showed that transfection of pcDNA3.1-SOCS3 could significantly increase the mRNA expression of SOCS3 in chondrocytes, and transfection of siRNA-SOCS3 could significantly reduce the mRNA expression of SOCS3 in chondrocytes. In contrast, transfection of pcDNA3.1-NC and siRNA-NC had no effect on the mRNA expression of SOCS3 in chondrocytes. Leptin pre-stimulation could increase the mRNA expression of SOCS3 in chondrocytes transfected with pcDNA3.1-SOCS3 and siRNA-SOCS3, but it had no effect on the mRNA expression of SOCS3 in chondrocytes transfected with pcDNA3.1-NC and siRNA-NC. Results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that transfection of pcDNA3.1-SOCS3 could inhibit the osteogenic activity of chondrocytes, and transfection of siRNA-SOCS3 could enhance the osteogenic activity of chondrocytes. And leptin pre-stimulation could increase the osteogenic activity of chondrocytes transfected with pcDNA3.1-NC, pcDNA3.1-SOCS3, siRNA-NC, and siRNA-SOCS3. These findings indicate that leptin stimulation can increase the osteogenic activity of chondrocytes, and upregulating the expression of SOCS3 can inhibit the osteogenic activity of chondrocytes through leptin resistance. Figures and Tables | References | Related Articles | Metrics

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Regulating the expression of nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome-related molecules in dental pulp fibroblasts under inflammation Zhang Ansheng, Zhang Haiou, Ni Longxing 2022, 26 (26):  4107-4112.  doi: 10.12307/2022.810 Abstract ( 382 )   PDF (2375KB) ( 142 )   Save BACKGROUND: Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 inflammasome is an important inflammatory factor for cellular defense against various pathogens, which has been confirmed to be expressed in dental pulp fibroblasts. However, the mechanisms underlying the transcription regulation of NOD-like receptor protein 3 inflammasome in dental pulp fibroblasts under inflammation remains unclear. OBJECTIVE: To elucidate the mechanisms underlying the transcription regulation of NOD-like receptor protein 3 inflammasome in dental pulp fibroblasts under inflammation. METHODS: The 4th generation dental pulp fibroblasts were divided into six groups. Group A was cultured normally without any treatment. Group B was simulated with lipopolysaccharide for 6 hours. Group C was treated with a specific inhibitor of Toll-like receptor 4 for 1 hour, and then it was also treated with a mixed solution of Toll-like receptor 4 specific inhibitor and lipopolysaccharide for 6 hours. Group D was treated with a specific inhibitor of myeloid differentiation factor 88 for 1 hour, and then treated with a mixed solution of specific inhibitor of myeloid differentiation factor 88 and lipopolysaccharide for 6 hours. Group E was treated with a specific inhibitor of nuclear factor κB for 1 hour, and then treated with a mixture solution of specific inhibitor of nuclear factor κB and lipopolysaccharide for 6 hours. Group F was treated with a negative control of myeloid differentiation factor 88 specific inhibitor for 1 hour, and then treated with a mixed solution of myeloid differentiation factor 88 specific inhibitor negative control and lipopolysaccharide for 6 hours. Real-time polymerase chain reaction was used to detect the mRNA expression of NOD-like receptor protein 3, Caspase-1 and interleukin 1β. Western bolt was used to detect the expression of NOD-like receptor protein 3 and Caspase-1. And enzyme linked immunosorbent assay was used to detect the release level of interleukin 1β. RESULTS AND CONCLUSION: Compared with group A, the mRNA expression of NOD-like receptor protein 3, Caspase-1 and interleukin 1β was increased in group B (P < 0.05), while compared with group B, the mRNA expression of NOD-like receptor protein 3 and interleukin 1β was decreased in groups C-E (P < 0.05), and the mRNA expression of Caspase-1 was also decreased in group C (P < 0.05). Compared with group A, the protein expression of NOD-like receptor protein 3 and Caspase-1 was increased in group B (P < 0.05), while compared with group B, the protein expression of NOD-like receptor protein 3 was decreased in groups C-E (P < 0.05), and the protein expression of Caspase-1 was also decreased in group C (P < 0.05). Compared with group A, the level of interleukin 1β was increased in group B (P < 0.05), while compared with group B, the levels of interleukin 1β were decreased in groups C-E (P < 0.05). All these findings indicate that lipopolysaccharide upregulates the expression of NOD-like receptor protein 3 and interleukin 1β in dental pulp fibroblasts through the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Effects of interleukin-10 on alveolar bone remodeling under orthodontic force in a high glucose condition Han Yu, Li Wenjing, Wu Jie, Cui Zhanqin 2022, 26 (26):  4180-4185.  doi: 10.12307/2022.821 Abstract ( 435 )   PDF (2535KB) ( 196 )   Save BACKGROUND: Orthodontic treatment can change the levels of various cytokines in periodontal tissue, which promotes bone resorption on the tooth pressure side and bone formation on the tooth tension side. Changes in high glucose level and other inflammatory factor levels in diabetic patients induce an imbalance in bone metabolism where absorbed bone tissue is more than that formed. OBJECTIVE: To observe the effects of interleukin-10 and mechanical stimulation on the expressions of osteoprotegerin and receptor activator of nuclear factor kappa B ligand in human periodontal ligament cells under high glucose environment, and to explore the effect of interleukin-10 on bone remodeling of alveolar bone in diabetic patients under orthodontic force.  METHODS: Human periodontal ligament cells were cultured by tissue explant method. According to the mechanical stimulation the cells received, the cells were divided into stress group (A, B, C, D subgroups) and tension group (E, F, G, H subgroups). Both stress and tension groups included four subgroups (low-glucose DMEM group, low-glucose DMEM group+interleukin-10 group, high-glucose DMEM group, high-glucose DMEM+interleukin-10 group). Cell supernatant was collected at 0, 12, 24, 48, and 72 hours after culture. The expressions of osteoprotegerin and receptor activator of nuclear factor kappa B ligand in the supernatant were detected by ELISA.  RESULTS AND CONCLUSION: Pressure could decrease the expression of osteoprotegerin and increase the expression of receptor activator of nuclear factor kappa B ligand in human periodontal ligament cells, and decreased their ratio. High glucose could promote this process, while the effect of interleukin-10 was opposite to that of high glucose. Tension could increase the expression of osteoprotegerin, decrease the expression of receptor activator of nuclear factor kappa B ligand in human periodontal ligament cells, and increase their ratio. High glucose could inhibit this process, and interleukin-10 had an effect that was opposite to high glucose. To conclude, high glucose environment can reduce the expression of osteoprotegerin, increase the expression of receptor activator of nuclear factor kappa B ligand in human periodontal ligament cells, and decrease their ratio under mechanical stimulation. Whereas, interleukin-10 can antagonize the effect of high glucose.  Figures and Tables | References | Related Articles | Metrics

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Effect of electroacupuncture on glial fibrillary acidic protein expression at the injured site in a rat model of spinal cord injury Tang Fuyu, Zhou Binbin, Wei Weibing, Zhang Hongsheng 2022, 26 (26):  4113-4117.  doi: 10.12307/2022.811 Abstract ( 533 )   PDF (3964KB) ( 134 )   Save BACKGROUND: Glial fibrillary acidic protein is an intermediate filament overexpression protein, which is the most commonly used specific marker protein for astrocytes. Traditional Chinese medicine has a long history of treating spinal cord injury. Numerous studies have shown that acupuncture at Du Meridian and Stomach Meridian of Foot-Yangming has a certain therapeutic effect on nerve regeneration and repair after spinal cord injury.   OBJECTIVE: To observe the changes in the expression of glial fibrillary acidic protein in the injured part of spinal cord injury rats after electroacupuncture stimulation, and to further investigate the effect of electroacupuncture on nerve regeneration in rats with spinal cord injury. METHODS: A total of 120 Sprague-Dawley rats were randomly divided into 5 groups (n=24 per groups): a Du Meridian electroacupuncture group, a Stomach Meridian of Foot-Yangming electroacupuncture group, a mixed electroacupuncture group, a model control group, and a sham operation group. T10 spinal cord hemisection models were prepared in all the groups except for the sham operation group. After modeling, each group was randomly subdivided into four subgroups (n=6 per group): a 3-day group, a 7-day group, a 14-day group, and a 21-day group. The sham operation group and the model control group were not given an intervention, and the three electroacupuncture groups were given a corresponding electroacupuncture intervention. Immunohistochemical staining was used to detect the expression of glial fibrillary acidic protein positive cells in the injured area. PCR and western blot were used to detect the mRNA and protein expression of glial fibrillary acidic protein.   RESULTS AND CONCLUSION: Compared with the sham operation group, the expression of glial fibrillary acidic protein after injury was increased first and then decreased significantly in the model control group (P < 0.05). Compared with the model control group, the expression of glial fibrillary acidic protein was significantly reduced in the Du Meridian electroacupuncture group and the Stomach Meridian of Foot-Yangming electroacupuncture group (P < 0.05). The expression of glial fibrillary acidic protein in the mixed electroacupuncture group was lower than that in the Du Meridian electroacupuncture group and the Stomach Meridian of Foot-Yangming electroacupuncture group, but there was no significant difference (P > 0.05). To conclude, electroacupuncture stimulation can reduce the expression of glial fibrillary acidic protein and astrocytes in the injured area, thereby inhibiting the formation of glial scars. Figures and Tables | References | Related Articles | Metrics

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Effect of aging on the ultrastructure of common iliac artery in rats Dong Liping, Luo Jia, Li Guangyi, Yuan Heng 2022, 26 (26):  4123-4126.  doi: 10.12307/2022.813 Abstract ( 467 )   PDF (3143KB) ( 124 )   Save BACKGROUND: Aging is accompanied by a progressive decline in the structure and function of multiple organs. The structure and function of arterial vessels are impaired during the aging process.   OBJECTIVE: To observe the effect of aging on the ultrastructure of arterial wall.  METHODS: Five adult Sprague-Dawley rats and five aged Sprague-Dawley rats were selected. The common iliac artery of the rats was taken under anesthesia and fixed in glutaraldehyde, and the ultrasonography of the intima and media of the common iliac artery was observed using a transmission electron microscope.  RESULTS AND CONCLUSION: The connection between endothelial cells of the common iliac artery in adult rats was normal, while there was a relatively large gap between endothelial cells of the common iliac artery in aged rats. Smooth muscle cells of the common iliac artery in adult rats exhibited a contractile phenotype, and there were many elastic fibers in the extracellular matrix; in aged rats, smooth muscle cells presented with a synthetic phenotype, and the number of collagen fibers in the common iliac artery was significantly increased. Dead endothelial cells and smooth muscle cells, characterized by chromatin degradation and cell lysis, were observed in the common iliac artery of aged rats, whilst  no cell death was observed in adult rats. These findings indicate that the intima of the common iliac artery is thickened, smooth muscle cells present with a synthetic phenotype, the number of elastic fibers is reduced and the number of collagen fibers is increased in aged rats compared with adult rats. Figures and Tables | References | Related Articles | Metrics

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Effect of acupuncture and moxibustion at Zusanli on gastrointestinal motility in adjuvant arthritis rats Li Jia, Li Baicun, Cai Guowei, Li Jing 2022, 26 (26):  4141-4146.  doi: 10.12307/2022.815 Abstract ( 512 )   PDF (3288KB) ( 721 )   Save BACKGROUND: Insufficient gastrointestinal motility in patients with rheumatoid arthritis has been gradually concerned. As a treatment of rheumatoid arthritis, whether acupuncture can improve insufficient gastrointestinal motility is worthy of further exploration.  OBJECTIVE: To explore the effect of acupuncture and moxibustion treatment at Zusanli (ST 36) on gastrointestinal motility in a rat model of adjuvant arthritis.  METHODS: A total of 60 clean and healthy 3-month-old Sprague-Dawley rats were randomly divided into 5 groups: normal group, model group, acupuncture group, moxibustion group, and acupuncture plus moxibustion group, with 12 rats in each group. Adjuvant arthritis models were established in the latter four groups using Freund’s complete adjuvant. The acupuncture group, moxibustion group, and acupuncture plus moxibustion group were treated with acupuncture, moxibustion or both at Zusanli on the 1st day of modeling, for 15 minutes per day, for 14 continuous days. At the end of the corresponding treatment, all rats were measured for plantar circumference. Hematoxylin-eosin staining was used to observe the pathological changes of the knee joint. The number of peristaltic waves in the rat intestine was measured by the method of colonic peristaltic wave. The first black stool discharge time was observed after gavage with activated carbon suspension, to calculate the gastric emptying rate and intestinal propulsion rate. The contraction degree of jejunum smooth muscle strips of rats was detected by an in vitro perfusion device, and the distribution of jejunal nerve fibers were observed by immunofluorescence staining.  RESULTS AND CONCLUSION: After acupuncture and moxibustion at Zusanli, sacroiliac joint swelling in rats was significantly reduced, cartilage destruction and inflammatory cells decreased, the number of intestinal peristaltic waves was increased, the total gastrointestinal activated carbon discharge time was shortened, gastric emptying rate and intestinal propulsion rate were improved, the contraction of the jejunal smooth muscle strip increased, and the amount of jejunal nerve fibers decreased. The combination of acupuncture and moxibustion achieved the best results. To conclude, acupuncture and moxibustion at Zusanli can prevent and treat bowel dysfunction in adjuvant arthritis rats, and acupuncture combined with moxibustion method is better than acupuncture or moxibustion used alone. Figures and Tables | References | Related Articles | Metrics

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Exercise effects on myocardial type I, III collagen and angiotensin II/transforming growth factor beta1/Smad2 pathway in diabetic myocardial fibrosis rats Liu Ya, Liu Xia, Deng Penghui, Ji Wei, Li Jianping 2022, 26 (26):  4173-4179.  doi: 10.12307/2022.820 Abstract ( 644 )   PDF (2456KB) ( 396 )   Save BACKGROUND: Recent studies have found that exercise can improve myocardial fibrosis in type II diabetic rats. OBJECTIVE: To investigate the regulatory role of angiotensin II/transforming growth factor β1/Smad2 signaling pathway and its downstream factors in the process of diabetic myocardial fibrosis through swimming exercises in an animal model of diabetic myocardial fibrosis.  METHODS: Forty male Sprague-Dawley rats were randomly divided into two groups: a blank control group (n=10) and a diabetes model group (n=30). Rats in the blank control group were raised under a normal diet, and rats in the diabetes model group were fed with high-sugar and high-fat diet and treated with a single injection of 1% streptozotocin to establish a diabetic model. After successful modeling, 15 rats were randomly selected from the diabetes model group as a diabetes exercise group. Rats in the diabetes exercise group were subjected to non-weight bearing swimming, 60 minutes per day, 6 days per week. After training for 8 weeks, the fasting blood glucose and fasting insulin levels of rats were tested. Hematoxylin-eosin staining was used to observe the morphological changes of myocardial cells. Masson staining was used to observe the deposition of collagen fibers in the myocardial interstitium. Immunohistochemical staining was used to analyze the content of type I and III collagen fibers in myocardial tissue. Reverse transcription PCR was used to detect the mRNA expression of angiotensin II, type I collagen fiber, type III collagen fiber, transforming growth factor β1, and Smad2. RESULTS AND CONCLUSION: Compared with the blank control group, the fasting blood glucose level and insulin resistance index were increased in the diabetes model group (P < 0.01). Compared with the diabetes model group, the fasting blood glucose and insulin resistance index were decreased in the diabetes exercise group (P < 0.05). Results of hematoxylin-eosin staining and Masson staining showed that disordered arrangement of myocardial cells, widened intercellular space, inflammatory cell infiltration, and obvious myocardial fibrosis in the diabetic model group. Whereas the arrangement of myocardial cells was still in order, the intercellular space was basically normal, and myocardial fibrosis was significantly relieved in the diabetic exercise group compared with the diabetic model group. The content of type I collagen fibers in rat myocardial tissue was increased in the diabetic model group compared with the blank control group (P < 0.05). There was no significant difference in the content of type I and III collagen fibers in rat myocardial tissue between the diabetic model group and the diabetic exercise group (P > 0.05). Compared with the blank control group, the mRNA expression of type I collagen fibers and transforming growth factor β1 in rat myocardial tissue was increased in the diabetic model group (P < 0.05). Compared with the diabetic model group, the mRNA expression of type I and III collagen fibers and transforming growth factor β1 in rat myocardial tissue was decreased in the diabetic exercise group (P < 0.01). To conclude, swimming can effectively prevent the occurrence and development of diabetic myocardial fibrosis, which may be related to the inhibition of the angiotensin II/transforming growth factor β1/Smad2 pathway. Figures and Tables | References | Related Articles | Metrics

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Analgesic effect and mechanism of pivot meridian hyperthermia in a rat model of neuropathological pain Qin Qin, Xia Tian, Li Yuefa, Zhang Lingling, Qin Haixia 2022, 26 (26):  4199-4204.  doi: 10.12307/2022.824 Abstract ( 515 )   PDF (1928KB) ( 175 )   Save BACKGROUND: Pivot meridian hyperthermia is an external treatment method guided by the central meridian theory of traditional Chinese medicine (TCM). Studies have shown that it may have a better effect on neuropathic pain, but the specific efficacy evidence and mechanism of action are still unclear.  OBJECTIVE: To investigate the analgesic effect of pivot meridian hyperthermia in a rat model of neuropathological pain and its mechanism based on behavior indicators and molecular biological indicators.  METHODS: Eighty male healthy Sprague-Dawley rats were randomly divided into a blank control group, a model control group, a hyperthermia group, and a TCM hyperthermia group, with 20 rats in each group. In the last three groups, the L5 spinal nerve was ligated to prepare the rat model of neuropathic pain. In the hyperthermia group, cotton pads soaked in 45°C saline were used to heat the gall bladder meridian circulation parts of the rats’ bilateral feet. In the TCM hyperthermia group, cotton pads soaked in 45°C Chinese medicinal solution were applied to heat the gall bladder meridian circulation parts of the rats’ bilateral feet. Treatment in each group was performed once a day. Behavior testing was started after 15 minutes of each hot compress, to measure paw withdrawal mechanical threshold and paw withdrawal thermal latency. The expression levels of vesicular glutamate transporter 2 and Toll-like receptor 4 protein in rat spinal cord tissue were detected after 14 days of continuous treatment.  RESULTS AND CONCLUSION: Compared with the model control group, paw withdrawal mechanical threshold was significantly higher and paw withdrawal thermal latency was significantly lower in the hyperthermia and TCM hyperthermia groups at 7 and 14 days of treatment (P < 0.05). Moreover, the TCM hyperthermia group showed better efficacy than the hyperthermia group (P < 0.05). Compared with the model control group, the expression levels of vesicular glutamate transporter 2 and Toll-like receptor 4 protein were significantly lower in the hyperthermia and TCM hyperthermia groups (P < 0.05). However, there was no significant difference between the hyperthermia and TCM hyperthermia groups (P > 0.05). To conclude, pivot meridian hyperthermia has a significant analgesic effect in neuropathological pain rats, and its mechanism may be related to inhibiting vesicular glutamate transporter 2/Toll-like receptor 4 signaling pathways. Figures and Tables | References | Related Articles | Metrics

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Transcriptome sequencing of the uterine in a mouse model of vitamin D deficiency Chen Xia, Shang Yuwei, Wang Linxiao, Shi Yichao, Liu Huijun, Sun Huiting 2022, 26 (26):  4101-4106.  doi: 10.12307/2022.809 Abstract ( 537 )   PDF (1952KB) ( 182 )   Save BACKGROUND: It has been recently discovered that vitamin D receptor is widely distributed in the female reproductive system such as the ovary and uterus, which is closely related to adverse pregnancy outcomes such as spontaneous abortion and gestational diabetes mellitus, but its specific mechanism is still unclear.   OBJECTIVE: To investigate potential differentially expressed miRNAs and related regulatory networks via a whole transcriptome analysis of the uterine tissue of vitamin D-deficient mice. METHODS: Eighteen female C57BL/6J mice were randomly divided into two groups: a vitamin D deficiency group and a normal control group. Mice in the vitamin D deficiency group were fed with vitamin D deficiency diet, and mice in the normal control group were fed with vitamin D sufficiency diet. The body mass of the mice was recorded every week. After 8 weeks, the serum levels of 25,(OH)D3 and hormones in the mice were tested. Hematoxylin-eosin staining was used to detect mouse uterine tissue. Uterine tissue samples of two groups were collected for transcriptome sequencing, and bioinformatics analyses of gene ontology and Kyoto encyclopedia of genes and genomes.   RESULTS AND CONCLUSION: There was no difference in body mass between the two groups. Compared with the normal control group, the levels of 25,(OH)D3 and estradiol in mouse serum were significantly reduced, and the testosterone level was significantly increased in the vitamin D deficiency group. Hematoxylin-eosin staining of uterine tissue showed a reduction in the endometrial folds of mice in the vitamin D deficiency group. Twenty-five differentially expressed miRNAs were screened out by transcriptome sequencing, of which 9 were up-regulated (such as miR-541-5p and miR-205-5p) and 16 were down-regulated (such as miR-378d and miR-708-5p). At the same time, vitamin D deficient mice showed significantly differences in multiple gene ontology enrichment categories, such as developmental process, cell composition, tissue or biogenesis. In addition, the functional enrichment results of Kyoto genes and genomes encyclopedia showed that differentially expressed genes were mostly related to biochemical metabolic pathways and signal transduction pathways. Differentially expressed genes in these enrichment pathways mainly affected PI3K-Akt signaling pathway, MAPK signaling pathway, insulin signaling pathway, gonadotropin releasing hormone signaling pathway, and oocyte meiosis pathway, all of which were closely related to the regulation of the reproductive system. To conclude, vitamin D deficiency can lead to poor uterine implantation conditions in female mice, which is related to multiple signaling pathways, such as insulin regulation, in mouse reproductive system. Figures and Tables | References | Related Articles | Metrics

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Preventive and therapeutic effects of naringin on experimental autoimmune encephalomyelitis via regulating microglial polarization Zeng Chunrong, Liu Menglan, Xie Yang, Li Zuoxiao 2022, 26 (26):  4127-4135.  doi: 10.12307/2022.814 Abstract ( 644 )   PDF (2780KB) ( 251 )   Save BACKGROUND: Microglia M1/M2 phenotypic imbalance plays an important role in the progression of many neurodegenerative and autoimmune diseases, and regulating microglia phenotypic transformation is a target of immunotherapy. OBJECTIVE: To investigate the effect of naringin on microglial polarization in experimental autoimmune encephalomyelitis mice via STAT1 pathway and autophagy.  METHODS: Fifty female C57BL/6 mice were randomly divided into five groups: blank control group, model group and low-, medium- and high-dose naringin groups (n=10 per group). In the latter four groups, animal models of experimental autoimmune encephalomyelitis were established. The naringin groups were intraperitoneally injected with 10, 20, 40 mg/(kg·d) naringin for 10 consecutive days. Simultaneously, the blank control and model groups were intraperitoneally injected with the same amount of saline. Disease conditions in each mouse were observed. Hematoxylin-eosin staining and Lux fast blue staining were used to observe the pathological changes of spinal cord tissue. Immunofluorescence method was used to observe the expression of Iba-1 and LC3 protein in spinal cord tissue. Western blot assay was used to detect the protein levels of STAT1, Beclin1, p62, LC3, CD16, CD206, inducible nitric oxide synthase, and Arg-1 in the spinal cord. Real-time fluorescence quantitative PCR method was used to detect the mRNA level of STAT1 in spinal cord tissue.  RESULTS AND CONCLUSION: No mice in the blank control group had an attack, but mice in the other groups developed experimental autoimmune encephalomyelitis to different extents. Compared with the model group, the incubation period was prolonged (P < 0.01), the peak of onset was delayed (P < 0.01 or P < 0.05) and the neurological deficit scores (P < 0.01 or P < 0.05) were reduced in all naringin groups. The higher dose of naringin indicated milder symptoms in mice. Compared with the blank control group, the model group had a significant increase in inflammatory cell infiltration, demyelination, inflammation and demyelination scores in spinal cord tissue during the onset peak period (P < 0.01), while inflammatory cell infiltration and demyelination were alleviated and inflammation and demyelination scores were lower in all naringin groups (P < 0.01). The higher dose of naringin indicated the better effect (P < 0.01 or P < 0.05). Compared with the blank control group, the average absorbance value of positive Iba-1 and LC3 expression area in spinal cord tissue were increased in the model group (P < 0.01), while the average absorbance value of positive Iba-1 and LC3 expression area were decreased in all naringin groups (P < 0.01 or P < 0.05). The higher dose of naringin indicated the less reduction in the average absorbance value (P < 0.01 or P < 0.05). Compared with the blank control group, the LC3 II/LC3 I ratio and the levels of LC3, Beclin1, STAT1, STAT1 mRNA, CD16, and inducible nitric oxide synthase were increased (P < 0.01 or P < 0.05), while Arg-1, CD206, and P62 expressions were decreased (P < 0.01 or P < 0.05) in the model group. Compared with the model group, the LC3 II/LC3 I ratio and the levels of LC3, Beclin1, STAT1, STAT1 mRNA, CD16, and inducible nitric oxide synthase were decreased (P < 0.01 or P < 0.05), while  Arg-1, CD206, and P62 expressions were increased (P < 0.01 or P < 0.05) in all naringin groups. The higher dose of naringin indicated the better effect (P < 0.01 or P < 0.05). To conclude, naringin can prevent and treat experimental autoimmune encephalomyelitis in mice in a dose-dependent manner. Its mechanism may be related to the regulation of microglial polarization and the correction of M1/M2 microglia imbalance in experimental autoimmune encephalomyelitis mice by down-regulating STAT1 pathway and inhibiting autophagy. Figures and Tables | References | Related Articles | Metrics

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Bushen Yizhi Anti-aging Prescription improves cognitive function of APP/PS1 mice by regulating microglia and macrophage polarization Wang Yuyin, Wei Wenyue, Guo Minfang, Li Hongxia, Zhang Jing, Gu Qingfang, Liu Xiaoqin, Guo Xiaoping, Song Lijuan, Chai Zhi, Ma Cungen, Wei Jiezhong 2022, 26 (26):  4166-4172.  doi: 10.12307/2022.819 Abstract ( 523 )   PDF (49405KB) ( 100 )   Save BACKGROUND: Bushen Yizhi Anti-aging Prescription exerts different therapeutic effects on Alzheimer′s disease, and our previous studies have suggested that Bushen Yizhi anti-aging prescription can significantly improve the cognitive function of APP/PS1 Tg mice by simultaneously promoting the polarization of spleen macrophages and central microglia to M2 type.   OBJECTIVE: To explore the therapeutic effect and mechanisms of Bushen Yizhi Anti-aging Prescription on Alzheimer’s disease model mice (APP/PS1 Tg). METHODS: Totally 20 male APP/PS1 transgene mice aged 8 months were randomly assigned to APP/PS1 transgenic model group and Bushen Yizhi Anti-aging Prescription intervention group. Another age- and sex-matched wild-type male mice were used as wild-type control group. All mice were fed for 8 weeks. Morris Water Maze and Y-maze test were used to evaluate cognitive function of mice in the three groups. M1 microglial surface marker nitric oxide synthase, interleukin-6 and M2 microglial surface marker arginase-1 and interleukin-10 in mouse hippocampus were analyzed by immunohistochemistry. Expressions of Iba-1, inducible nitric oxide synthase, arginase-1, interleukin-6, interleukin-10, Toll-like receptor 4, myeloid differentiation factor 88 and nuclear factor-κB were examined by western blot. Flow cytometry was used to analyze the expression of M1 (CD16/32, interleukin-12) and M2-type mononuclear macrophages (CD206, interleukin-10) in mouse spleen. The study protocol was approved by the Animal Ethics Committee of Shanxi Datong Univerisity.  RESULTS AND CONCLUSION: Compared the wild-type control group, the model group showed decreased cognitive function and the microglia in the brain were activated and transformed into M1, while the mononuclear macrophages in the spleen also transformed into M1. After treatment with Bushen Yizhi Anti-aging Prescription, the cognitive function of APP/PS1 Tg mice was significantly improved (P < 0.05), the activation of microglia was inhibited (P < 0.01), the transformation from M1 microglia to M2 was promoted (P < 0.05), and the expressions of Toll-like receptor 4, myeloid differentiation factor 88 and nuclear factor-κB were down-regulated (P < 0.01). All these findings indicate that Bushen Yizhi Anti-aging Prescription reverses cognitive impairment and facilitates microglia M2 polarization via the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB signaling pathway in APP/PS1 transgenic mice. Figures and Tables | References | Related Articles | Metrics

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Effects of sodium arsenite on oxidative stress, apoptosis and Hippo signaling pathway in AML12 hepatocytes Zhao Zheyi, Wang Zhengrong, Fang Xingyan, Wang Tian, Xie Tingting 2022, 26 (26):  4186-4191.  doi: 10.12307/2022.822 Abstract ( 652 )   PDF (3065KB) ( 447 )   Save BACKGROUND: As the main target organ of arsenic toxicity, the liver has become the focus of research on the mechanism of arsenic toxicity. OBJECTIVE: To investigate the effects of sodium arsenite (NaAsO2) on oxidative stress and apoptosis of AML12 hepatocytes, as well as the influence on the expression of key molecules in the Hippo signaling pathway.  METHODS: AML12 hepatocytes were cultured in medium containing 0, 10, 15, 20, 25, 30 μmol/L NaAsO2 for 24 hours. The cell morphology was observed by phase-contrast microscopy and cell viability was assessed by cell counting kit-8 assay. The content of intracellular reactive oxygen species was detected by fluorescent probe technique combined with flow cytometry. The activity of caspase-3 was measured by colorimetry. The apoptotic rate of hepatocytes was detected by annexin V/propidium iodide double staining combined with flow cytometry. The mRNA expression level of Yes-associated protein was detected by real-time fluorescence quantitative PCR. The protein expression level of phosphorylated mammalian sterile20-like kinases1/2, phosphorylated Yes-associated protein and Yes-associated protein were detected by western blot assay.  RESULTS AND CONCLUSION: Compared with the control group, the viability of AML12 hepatocytes decreased gradually along with the increase of NaAsO2 concentration. With the increase of NaAsO2 concentration, the reactive oxygen species contents, the activity of caspase-3 and the apoptotic rate increased gradually in AML12 hepatocytes. There was no significant change in the mRNA expression of Yes-associated protein in NaAsO2 treated AML12 hepatocytes. NaAsO2 elevated the relative protein expression of phosphorylated mammalian sterile20-like kinases 1/2 and phosphorylated Yes-associated protein, while inhibited the relative protein expression of Yes-associated protein. Therefore, NaAsO2-induced oxidative stress and apoptosis injury in AML12 hepatocytes may be related to the activation of Hippo signaling pathway.  Figures and Tables | References | Related Articles | Metrics

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Up-regulating follicular regulatory T cells for treating antibody-mediated rejection after kidney transplantation Xu Yuan, Niu Yulin, Yuan Zhihui, Jia Lei, Pan Guanghui 2022, 26 (26):  4118-4122.  doi: 10.12307/2022.812 Abstract ( 477 )   PDF (1931KB) ( 87 )   Save BACKGROUND: There is currently no effective treatment for kidney transplant failure caused by antibody-mediated rejection. Studies have shown that the expression of plasma miR-4286 in kidney transplant patients is significantly up-regulated, and miR-4286 can down-regulate the expression of transforming growth factor β to activate an immune response. OBJECTIVE: To investigate the effect of miR-4286 silencing on up-regulating follicular regulatory T cells in the treatment of antibody-mediated rejection after kidney transplantation and its mechanism. METHODS: Patients who underwent kidney transplantation at the Affiliated Hospital of Guizhou Medical University from December 2018 to December 2020 were enrolled and assigned into two groups (n=20 per group): antibody-mediated rejection group and immune tolerance group. Hematoxylin-eosin staining and C4d immunohistochemistry were performed for biopsy of kidney tissues. The mRNA expression of miR-4286 in peripheral blood lymphocytes and the proportions of follicular helper and follicular regulatory T cells were detected. The lymphocytes of patients suffering rejection reaction were divided into a blank vector group, a miR-4286 overexpression group, a miR-4286 silence group, and a transforming growth factor β blocking group in which the cells were simultaneously transfected with miR-4286-inhibited lentiviral vector and transforming growth factor β neutralizing antibody). After 48 hours, we detected the proportions of B cells, plasma cells, and follicular regulatory T cells, as well as the levels of transforming growth factor β, interferon γ, interleukin 6, and interleukin 21 in the cell supernatant. RESULTS AND CONCLUSION: Hematoxylin-eosin staining results showed that the number of inflammatory cells infiltrated in the transplanted kidney tissue was higher in the antibody-mediated rejection group than the immune tolerance group (P < 0.05). Immunohistochemistry results showed that the antibody-mediated rejection group had a large number of C4d positive cells in the kidney tissue, while there were no C4d-positive cells in the immune tolerance group. The mRNA expression of miR-4286 and the proportion of follicular helper T cells in the antibody-mediated rejection group were higher than those in the immune tolerance group (P < 0.05). Spearman correlation analysis indicated that the expression of miR-4286 was positively correlated with the proportion of follicular helper T cells, while negatively correlated with the proportion of follicular regulatory T cells. Compared with the blank vector group, the level of transforming growth factor β was decreased in the miR-4286 overexpression group (P < 0.05), and the levels of interferon gamma, interleukin 6, and interleukin 21 were increased in the miR-4286 overexpression group (P < 0.05). Compared with the blank vector group, in the miR-4286 silence group, the level of transforming growth factor β was increased (P < 0.05), while the levels of interferon γ, interleukin 6, and interleukin 21 were decreased (P < 0.05). Compared with the miR-4286 silence group, the level of transforming growth factor beta was decreased in the transforming growth factor β blocking group (P < 0.05), and the levels of interferon γ, interleukin 6, and interleukin 21 was increased (P < 0.05). Compared with the blank vector group, the proportion of B cells and plasma cells was increased in the miR-4286 overexpression group (P < 0.05), and the proportion of follicular regulatory T cells was decreased (P < 0.05). Compared with the blank vector group, the proportion of B cells and plasma cells was decreased in the miR-4286 silence group (P < 0.05), and the proportion of follicular regulatory T cells was increased (P < 0.05). Compared with the miR-4286 silence group, the proportion of B cells and plasma cells was increased in the transforming growth factor β blocking group (P < 0.05), and the proportion of follicular regulatory T cells was decreased (P < 0.05). All these findings indicate that miR-4286 is highly expressed in peripheral blood lymphocytes of antibody-mediated rejection patients after kidney transplantation, and silencing of miR-4286 can up-regulate the proportion of follicular regulatory T cells in lymphocytes and inhibit humoral immunity through transforming growth factor β pathway.   Figures and Tables | References | Related Articles | Metrics

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Changing step frequency influences energy expenditure, surface electromyography, and gait characteristics when running at anaerobic threshold Li Qinlong, Zhou Yue, Wang Shuo 2022, 26 (26):  4153-4159.  doi: 10.12307/2022.817 Abstract ( 614 )   PDF (1566KB) ( 219 )   Save BACKGROUND: Running efficiency is considered to be improved by increasing step frequency, which is a popular idea in long-distance running. However, this requires scientific evaluation and research in many aspects.  OBJECTIVE: To compare the changes of heart rate, oxygen uptake, surface electromyography, and gait characteristics in individuals with preferred step frequency and varying step frequency under anaerobic threshold intensity, and to explore the effect of changing step frequency on runners, so as to provide scientific strategies for improving running efficiency. METHODS: Twelve male marathon runners were enrolled in this trial. Before the beginning of the trial, each runner was tested in an incremental exercise test on the treadmill to obtain the values of ventilatory anaerobic threshold and anaerobic threshold speed. After the beginning of the trial, a random crossover design was used. The runners ran on the treadmill at the anaerobic threshold with preferred step frequency, preferred step frequency ±5%, and preferred step frequency ±10%. Paired t-test and Pearson correlation analysis were used to statistically analyze heart rate, oxygen uptake, surface electromyography, and gait characteristics, and to explore the changing laws of each indicator after changing the step frequency. The implementation of this study complied with the relevant ethical requirements of Beijing Sport University, and the subjects were fully informed of the trial process.  RESULTS AND CONCLUSION: Heart rate and oxygen uptake: after changing the step frequency, the heart rate was increased significantly (P < 0.01), stride length changed significantly (P < 0.01), and oxygen uptake was increased significantly when preferred step frequency was -5% (P < 0.05) and ±10% (P < 0.01). There was a positive correlation between stride length and oxygen uptake (r=0.57, P < 0.01), and a negative correlation between step frequency/stride length and oxygen uptake (r=-0.42, P < 0.01). Surface electromyography: when preferred step frequency was +10%, the mean power frequency of biceps femoris, rectus femoris, and medial femoris was increased significantly (P < 0.05); when preferred step frequency was -5% and -10%, the mean power frequency of tibialis anterior muscle was increased (P < 0.05); and when preferred step frequency was +5%, the muscle contribution rate of rectus femoris was decreased significantly (P < 0.05). Gait characteristics: the ground contact time (P < 0.05) and the flight time (P < 0.01) were decreased while the ratio of ground contact time to flight time was increased (P < 0.05). When preferred step frequency was +5%, reduced knee joint extension range was 3o-4o (P < 0.05). When preferred step frequency was +10%, reduced knee joint extension range was 3o-4o (P < 0.05), reduced hip joint extension range was 3o (P < 0.05), and the range of the knee joint that swings forward was reduced by 4o (P < 0.01). As the step frequency was decreased, the ground contact time and the flight time were increased gradually, and the ratio of ground contact to flight time was decreased (P < 0.05). There was a negative correlation between ground contact time (r=-0.71, P < 0.01) and ground contact time/flight time ratio (r=-0.67, P < 0.01) and oxygen uptake, and a positive correlation between flight time and oxygen uptake (r=0.65, P < 0.01). Although no energy is saved immediately in individuals who increase the step frequency, which may require long-term training or adaptation, the energy expenditure is relatively lower in the study population when running with a shorter stride and at a larger ratio of step frequency/stride length. When running with a shortened stride, the ratio of ground contact to flight time is increased and the motion range of the hip and knee joint is reduced, which can make the body more stable and reduce the load on the knee joint. Figures and Tables | References | Related Articles | Metrics

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Effect of high-definition transcranial direct current stimulation on human dynamic balance Qiao Qiqi, Wu Yixin, Wang Xin, Xia Zhongliang 2022, 26 (26):  4192-4198.  doi: 10.12307/2022.823 Abstract ( 661 )   PDF (1828KB) ( 135 )   Save BACKGROUND: High-definition transcranial direct current stimulation has great potential in promoting the improvement of cognition and motor behavior, which can improve the body’s static balance ability.  OBJECTIVE: To investigate the effect of high-definition transcranial direct current stimulation on the body’s dynamic balance.  METHODS: A total of 36 healthy students from Shenyang Sport University were recruited as test subjects, including 24 males and 12 females. They were divided into three groups by a random number table method, followed by anodic high-definition transcranial direct current stimulation with different current intensities of 0  (sham stimulation), 1, and 2 mA for 20 minutes. The dynamic balance ability was tested before stimulation and immediately and 30 minutes after stimulation. The study protocol was approved by the Institutional Review Board of Shenyang Sport University (approval No. [2020]12).  RESULTS AND CONCLUSION: The subject’s bipedal dynamic stability index and right-foot dynamic stability index were significantly reduced immediately and 30 minutes after 1 mA stimulation (P < 0.05). The offset distance was significantly shortened at 30 minutes after 1 mA stimulation (P < 0.05). The subject’s bipedal dynamic stability index and right-foot dynamic stability index were significantly reduced 30 minutes after 2 mA stimulation (P < 0.05). The offset distance was significantly shortened immediately and 30 minutes after 2 mA stimulation (P < 0.05). Anodic high-definition transcranial direct current stimulation with different current intensities showed no different effects in improving the dynamic balance of the human body (P > 0.05). To conclude, high-definition transcranial direct current stimulation can temporarily improve the dynamic balance ability. It cannot only increase the dynamic stability when standing on single and both feet, but also promote gait stability during active exercises.  Figures and Tables | References | Related Articles | Metrics

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Arthroscopic repair of multiple ligament injuries after knee joint dislocation: a three-dimensional gait analysis He Lu, Liao Xinyu, Li Yanlin, Ruan Yanqin, Wang Xu, Wang Yang, Ning Ziwen, Shi Zhengliang, Wang Guoliang 2022, 26 (26):  4205-4210.  doi: 10.12307/2022.825 Abstract ( 578 )   PDF (3977KB) ( 189 )   Save BACKGROUND: Multiple ligament injuries of the knee are a complicated problem, which is prone to vascular and nerve damage, leading to severe dysfunction. However, for the current surgical treatment of knee dislocation and multiple ligament injuries, there is a lack of effective evaluation on the timing of surgery and postoperative gait.  OBJECTIVE: To investigate the clinical effect of stage I arthroscopic repair and reconstruction in patients with multiple ligament injuries of the knee joint, and provide a reference for clinical guidance of functional exercises after multiple ligament injuries of the knee joint through a three-dimensional gait analysis.  METHODS: The clinical data of 15 patients with multiple ligament injury of knee dislocation who were treated in the First Affiliated Hospital of Kunming Medical University from September 2014 to August 2018 were collected. All the cases were single knee injury, including 11 males and 4 females. Their age ranged from 18 to 40 years old, with an average of (28±8) years old. The time from injury to operation was 10-18 days, with an average of 14 days. At admission, the anterior and posterior drawer tests and the Lachman test were positive in all the patients. The knee varus stress test was positive in eight patients, and the knee valgus stress test was positive in five patients. Lysholm knee joint function score was (27.85±5.98) points, and joint range of motion was (49.15±13.47)°. Under arthroscopy, autologous hamstring tendons were taken to reconstruct the anterior cruciate ligament, posterior cruciate ligament, medial collateral ligament, and other injured knee joint structures. The range of knee joint motion and Lysholm score were evaluated, and three-dimensional gait analysis was conducted postoperatively. RESULTS AND CONCLUSION: Grade I/A healing was found in 15 patients. All patients were followed up for 11-24 months. During the postoperative follow-up, all patients had negative results in the anterior and posterior drawer tests and in the knee varus and valgus stress tests. Lysholm knee function score and joint range of motion of the affected limb were significantly improved at the last follow-up after repair, which were (85.3±6.65) points and (122.83±9.27)°, respectively, significantly different from the preoperative levels (t=24.879, P=0.000; t=17.452, P=0.000). Results of kinematic analysis showed that there were no significant differences in varus and valgus angles, internal and external displacements, internal and external rotations, flexion and extension angles, up and down displacements, and anteroposterior displacements between the healthy and affected limbs in the gait analysis at the last follow-up (P > 0.05). All these findings indicate that stage I arthroscopic repair of multiple ligament injuries of the knee joint can restore the stability of the knee joint, which is a safe, reliable, and effective treatment. Figures and Tables | References | Related Articles | Metrics

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Conventional versus marginal donor heart transplantation in patients with end-stage heart disease Duan Zhengwei, Liu Yunfei 2022, 26 (26):  4211-4215.  doi: 10.12307/2022.826 Abstract ( 487 )   PDF (853KB) ( 583 )   Save BACKGROUND: The lack of donor heart resources is a worldwide problem in heart transplantation. Broadening the inclusion criteria of donor heart and rationally applying marginal donor heart are effective ways to alleviate the lack of donor heart resources, and they are also the development direction of heart transplantation. OBJECTIVE: To compare the effect of conventional donor and marginal donor heart transplantation in patients with end-stage heart disease.  METHODS: Eighty patients with end-stage heart disease who underwent heart transplantation from April 2018 to March 2021 were divided into a conventional donor group (56 patients) and a marginal donor group (24 patients). All patients were given orthotopic heart transplantation. Then operative indicators, serum biochemical and prognostic were compared between the two groups.  RESULTS AND CONCLUSION: Compared with the conventional donor group, the operation time [(465.35±62.45) min vs. (423.42±58.23) min, t=2.888, P < 0.05] was longer and intraoperative blood loss [(1 235.36±203.4) mL vs. (678.65±123.21) mL, t=15.075, P < 0.01)] was higher in the marginal donor group. During the follow-up of 12 months, there were no significant differences in serum creatine kinase MB isoenzyme, cardiac troponin I, total bilirubin, alanine aminotransferase and left ventricular ejection fraction between the two groups (t=0.693, 1.322, 1.514, 1.348, 1.285, P > 0.05). Compared with the conventional donor group (2%, 9%), incidence rates of infection and renal insufficiency were also significantly higher in the marginal donor group (17%, 29%; x2=6.349, 5.397, P < 0.05). On the premise of strict heart donor protection and perioperative management, marginal donor transplantation can achieve the surgical effect similar to conventional donor heart transplantation. However, complications such as postoperative infection and renal insufficiency should be prevented.  Figures and Tables | References | Related Articles | Metrics

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Effects of aerobic exercise intervention on synaptic plasticity in Alzheimer’s disease patients Yang Jinxin, Wang Kun, Zhao Jing, Chen Peijie, Zhang Tingran, Lu Wenyun, Luo Jiong 2022, 26 (26):  4216-4223.  doi: 10.12307/2022.827 Abstract ( 848 )   PDF (2079KB) ( 209 )   Save BACKGROUND: Alzheimer’s disease is a degenerative disease of the central nervous system with the loss of brain cells and neurons, mainly manifested as cognitive dysfunction and memory decline. Abnormal synaptic plasticity is an important cause of cognitive decline in patients with Alzheimer’s disease. Numerous studies have shown that aerobic exercise can significantly improve patient’s cognitive decline due to Alzheimer’s disease; however, there is a lack of systematic and comprehensive understanding of the mechanism by which aerobic exercise improves synaptic plasticity as well as the effect of aerobic exercise on synaptic plasticity. OBJECTIVE: To comprehensively review the domestic and foreign literature on the synaptic plasticity induced by aerobic exercise stimulation and its alleviation of cognitive decline in Alzheimer’s disease patients, and to reveal the mechanism by which aerobic exercise improves cognitive function of Alzheimer’s disease patients, so as to provide theoretical basis and practical reference for the prevention and delay of Alzheimer’s disease progression by aerobic exercise. METHODS: The first author retrieved relevant literature in ELSEVIER, Web of Science, PubMed, CNKI, and WanFang using the keywords of “aerobic exercise, synaptic plasticity, cognitive function, exercise training, physical activity, cognitive neuroscience, Alzheimer’s disease” in English and Chinese, respectively. As per the inclusion criteria, 82 documents were finally selected and discussed. RESULTS AND CONCLUSION: Aerobic exercise can activate brain synaptic plasticity at molecular level to improve cognitive function in patients with Alzheimer’s disease. (1) Aerobic exercise can inhibit amyloid β deposition and aberrant phosphorylation of Tau protein, promote brain neurotrophic factor expression, regulate mitochondrial biogenesis, and reduce mitochondrial dysfunction through molecular signaling pathways, thereby improving brain microenvironment and stimulating the positive changes in synaptic plasticity. (2) Aerobic exercise intervention has a positive effect on to the cognitive function of patients with Alzheimer’s disease. Low-intensity aerobic exercise can improve the expression of synaptic plasticity-related proteins and reduce synaptic loss. High-frequency aerobic exercise can promote an increase in synaptic density. Mid-and-long-term can continuously up-regulate the level of synaptic-related proteins in the brain and maintain the changes in synaptic plasticity. (3) Aerobic exercise is a complex variable, and interventions for Alzheimer’s disease need to be individualized as per patient’s conditions, and appropriate exercise prescriptions should be taken according to the severity of the disease. Figures and Tables | References | Related Articles | Metrics

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Knowledge graph analysis of virtual reality technology in stroke treatment Zou Mengyao, Wang Junhua, Qin Pengfei, Zhong Weihua 2022, 26 (26):  4224-4233.  doi: 10.12307/2022.828 Abstract ( 831 )   PDF (13827KB) ( 83 )   Save BACKGROUND: Stroke has become one of the thorny diseases facing the world due to its high morbidity, high mortality, high disability rate, and high recurrence rate. However, traditional rehabilitation methods, characterized by slow effect, low efficiency, and dull training, elicit little effects in the treatment of stroke. With the development of science and technology, virtual reality technology which has the characteristics of simplicity, high efficiency, high security, strong interest, low price, and real-time feedback can solve the imbalance of doctor-patient ratio, promote the development of remote rehabilitation medicine, and has extremely important practical significance for the rehabilitation of stroke patients. OBJECTIVE: To study the research hotspots and progress of virtual reality technology in stroke treatment using Citespace V knowledge graph software, and to clarify the structural model of this field and predict the possible development trends of virtual reality technology worldwide in the future.  METHODS: A total of 1 374 core articles addressing virtual reality technology published since 2007 were retrieved from Web of ScienceTM, CNKI, CSSCI, and CSCD database and used as data sources. Citespace V knowledge graph software was used to analyze the research status of virtual reality technology in stroke treatment. In addition, the domestic and foreign differences in disciplines, countries, authors, institutions, and research hotspots were compared. Then, the possible development trend in the future was predicted. RESULTS AND CONCLUSION: The foreign countries have formed a multi-disciplinary and multi-domain comprehensive group, focusing on neuroscience, computer science, and biomedical engineering. Domestic disciplines are relatively monotonous, and no obvious discipline group has formed. There is a network of close exchanges and cooperation that has formed between foreign countries/regions, authors, and institutions, forming a high school mentality of countries, authors, and institutions. The cooperation among domestic authors, groups and institutions is poor, with geographical restrictions, and there is a lack of influential academic groups and institutions. There are differences in research contents at home and abroad, and there have been four development stages of this technology in foreign countries. The possible trends of future research abroad are the research, development and evaluation of remote rehabilitation medicine, robot-assisted therapy, and virtual rehabilitation system, highlighting the screening of virtual rehabilitation therapy. The possible future research topics in China may be the effect and evaluation of the combined treatment of specific parts with virtual reality technology and other methods, and the introduction and development of advanced technology. Figures and Tables | References | Related Articles | Metrics

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Visualization analysis of current research hotspots on rehabilitation treatment after anterior cruciate ligament reconstruction Li Zhishuai, Zhang Hongqian, Liu Jianquan, Zhang Hankun, Li Li 2022, 26 (26):  4234-4241.  doi: 10.12307/2022.829 Abstract ( 684 )   PDF (5019KB) ( 1921 )   Save BACKGROUND: The incidence of anterior cruciate ligament injury and the need for surgical reconstruction are increasing year by year. The safety and speed of activity and movement recovery after anterior cruciate ligament reconstruction mainly depend on a scientific rehabilitation program. OBJECTIVE: To explore the research status, hotspots and trends of rehabilitation therapy in anterior cruciate ligament reconstruction in the past 11 years based on the scientific knowledge mapping using the CiteSpace software, attempting to provide ideas and reference for the subsequent research and clinical treatment of anterior cruciate ligament reconstruction. METHODS: The Web of Science (SCI-Expanded, SSCI, CCR-Expanded, IC) core collection database was retrieved for the literature related to rehabilitation treatment and anterior cruciate ligament reconstruction published from 2010 to 2020. Scientific knowledge mapping and visualization analysis using CiteSpace were subsequently conducted.  RESULTS AND CONCLUSION: A total of 323 papers were included, and the number of published papers and total citation frequency in this field increased steadily in the past 11 years. A total of 101 journals have published articles related to this field. The research fields of the included journals are concentrated in sports science, rehabilitation, plastic surgery, and surgery, KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY is the journal that has the most publications. The top three countries with the most publications are the United States, Italy, and China, and the top three institutions with the most publications are Univ Delaware, Ohio State Univ, and Univ Groningen. Univ Delaware in the United States tops the list in terms of article amount and centrality. The team led by Lynn Snydermackler, a professor from the Department of Physical Therapy at the Univ Delaware, that has the most articles published in this field has a greater influence in this field. Literature co-citation analysis indicates the topics involved in the top five literatures include the timing of returning to sport level, evaluation indexes, knee joint function status and influencing factors, rehabilitation practice guidelines based on multidisciplinary consensus, risk rate of secondary injury after anterior cruciate ligament reconstruction and related interventions. Keywords analysis indicates that research on rehabilitation training plan, return to sport and secondary injury after anterior cruciate ligament reconstruction is a hot topic in this field. All these findings reveal that relevant research on rehabilitation training after anterior cruciate ligament reconstruction has been on the rise in recent 11 years. The focus in this field has been gradually shifted from local function of the knee joint to individual social participation. The research direction has gradually developed from the initial discussion of specific rehabilitation methods to guiding return to sport and avoiding secondary injury. Development of standards/guidelines for safe return to sport will be a future trend in this field. Figures and Tables | References | Related Articles | Metrics

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Osteoimmunological effect of tumor necrosis factor alpha in alveolar bone remodeling Gong Yuqing, Yao Wei, Li Ran 2022, 26 (26):  4242-4251.  doi: 10.12307/2022.830 Abstract ( 656 )   PDF (4790KB) ( 274 )   Save BACKGROUND: Osteoimmunology emphasizes the inseparable relationship between skeletal system and immune system, and its rise provides a new research direction for the treatment of alveolar bone remodeling related diseases. Tumor necrosis factor-α is an important cytokine in osteoimmunology, which participates in bone metabolism and bone remodeling related to osteoarthritis, chronic periodontitis and orthodontic tooth movement. OBJECTIVE: To review the osteoimmunological effect of tumor necrosis factor-α during alveolar bone remodeling and the latest progress. METHODS: The literatures related to tumor necrosis factor-α, bone remodeling, osteoimmunology were searched in PubMed, WanFang and CNKI databases, and finally 76 articles were included and summarized. RESULTS AND CONCLUSION: Alveolar bone is the most active part of bone remodeling, and alveolar bone remodeling is common in orthodontic treatment, periodontitis treatment and osseointegration of implants. The osteoimmunological effect of tumor necrosis factor-α on alveolar bone remodeling is that high concentration of tumor necrosis factor-α mainly promotes the expression of osteoclast genes such as nuclear factor κB receptor activator ligand through nuclear factor kappa-B signaling pathway, thus promoting the maturation and differentiation of osteoclasts leading to bone resorption. In the early stage, low concentration of tumor necrosis factor-α indirectly promotes the expression of osteogenic genes such as osteocalcin by activating Wnt/β-catenin and bone morphogenetic protein signaling pathways through the nuclear factor-κB pathway, which subsequently promotes osteoblast maturation and differentiation and leads to new bone formation. Therefore, tumor necrosis factor-α is one of the key cytokines regulating alveolar bone remodeling and plays a core role in the molecular mechanism network of this process. Tumor necrosis factor-α has a bi-directional regulatory role and the microenvironment in vivo is complex, so how to control the regulation of tumor necrosis factor-α is a difficult problem. This review may be expected to provide a new research direction and theoretical basis for monitoring the concentration of tumor necrosis factor-α and immediate feedback in clinical orthodontics, periodontitis and implant treatments to prevent iatrogenic alveolar bone resorption. Figures and Tables | References | Related Articles | Metrics

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Carvacrol: antibacterial activity, bone repair, and prevention and treatment in oral diseases Zhang Zihan, Wang Wenli, Li Jinnuo, Li Yourui 2022, 26 (26):  4252-4257.  doi: 10.12307/2022.831 Abstract ( 990 )   PDF (1523KB) ( 272 )   Save BACKGROUND: Carvacrol is a natural plant extract that acts as a substitute of antibiotics and has a good prospect because of its antibacterial activity, low drug resistance and low cytotoxicity.    OBJECTIVE: To review the antibacterial activity and clinical applications of carvacrol in the prevention and treatment of common oral diseases.   METHODS: PubMed and CNKI database were searched by computer using the keywords of “carvacrol, antibacterial, oral, osteogenesis” in English and Chinese, respectively. The retrieval period was from January 2011 to June 2021. Preliminary screening of literature was conducted through reading and analysis to exclude duplicate and low-correlation literature. Finally, 49 articles were included for result analysis.   RESULTS AND CONCLUSION: Experimental results have shown that carvacrol exerts significant antibacterial effects on the pathogens and bacterial biofilms of various common oral diseases, such as dental caries, oral candidiasis, periodontitis and peri-implantitis. The combined use of carvacrol and antibiotics produces a synergistic effect, which can enhance curative effect and reduce drug resistance. Even at high concentrations, carvacrol can still maintain low cytotoxicity and good safety. In addition, carvacrol can inhibit osteoclast differentiation, help repair bone defects and reduce bone destruction, which can be used in bone tissue engineering. Considering the above biological characteristics, carvacrol can be added into antibacterial drugs, biological barrier films and mouthwashes, which can be used in the clinical treatment of oral diseases.   Figures and Tables | References | Related Articles | Metrics

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Effects of concurrent aerobic and strength training on locomotor performance: a Meta-analysis Li Gaofeng, Wang Jun 2022, 26 (26):  4258-4264.  doi: 10.12307/2022.832 Abstract ( 724 )   PDF (3289KB) ( 325 )   Save OBJECTIVE: To conduct a Meta-analysis on the effects of endurance and strength training on maximum oxygen uptake (VO2 max), vertical jump and upper and lower limb strength (1RM) of different populations, so as to propose the optimal exercise intervention plan. METHODS: CNKI, PubMed, WanFang, and Web of Science were retrieved from their inception to October 2020. Review Manager 5.4 was used for analyzing the overall effect, heterogeneity, and publication bias using the fixed effect model and random effect model. Finally 15 foreign language documents involving 409 subjects were included and analyzed from different angles. RESULTS: Concurrent endurance and strength training could improve the maximum oxygen uptake, but was relatively inferior to the traditional endurance training. Concurrent endurance and strength training had no significant effect on the overall strength of the upper and lower limbs. The combined effect size of leg lift, leg flexion and extension, and squat and its 95% confidence interval were 8.47 [-3.95, 20.88], 2.46 [-11.34, 9.73], -0.81 [-2.72, 7.64] (P > 0.1). Concurrent endurance and strength training had certain but no significant effect on vertical jump (mean difference=0.44, 95% confidence interval [-0.97,1.85], P > 0.05). CONCLUSION: Concurrent endurance and strength training can improve the body’s maximum oxygen uptake. In sports training, compared with the traditional endurance or strength training alone, concurrent endurance and strength training can maintain the body strength level, while developing other basic qualities such as endurance. Therefore, concurrent endurance and strength training has better benefits for physical fitness compared with strength or endurance training alone. Moreover, concurrent endurance and strength training has less impact on explosive force and overall strength, which can achieve the best results based on an 8-12 week training cycle and 2-3 times per week. Figures and Tables | References | Related Articles | Metrics