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18 February 2022, Volume 26 Issue 5 Previous Issue    Next Issue

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Feasibility of ultrasound-guided intra-articular injection in rabbit hip joint Wang Shaoling, Wang Yanxue, Zheng Yaochao, Yu Shaojun, Ma Chao, Wu Shaoling 2022, 26 (5):  657-662.  doi: 10.12307/2022.107 Abstract ( 553 )   PDF (868KB) ( 167 )   Save BACKGROUND: In the past, fluoroscopy guidance was the first choice for guiding hip injections. Recently, ultrasound has become increasingly popular in intra-articular injections due to its portability, non-radiation, low cost, and high accuracy. OBJECTIVE: To compare the accuracy of ultrasound-guided intra-articular treatment and fluoroscopy-guided injection in rabbit hip joint and to determine whether ultrasound guidance is a suitable method for intra-articular injection. METHODS: High-resolution ultrasound and fluoroscopy were used for visualized injections. New Zealand rabbits (n=16, a total of 64 hip joints injected in two rounds) were randomly divided into two groups before each round. Injections were guided by the high-resolution ultrasound or by the fluoroscopy using an X-ray machine with wireless flat-panel detector. The distribution of iohexol was detected by computed tomography after injections. To determine whether ultrasound guidance can significantly improve the accuracy of rabbit hip injections, we compared the accuracy, number of puncture attempts, and procedure time between two groups. The study protocol was approved by the Experimental Animal Ethics Committee of Sun Yat-sen University. RESULTS AND CONCLUSION: A total of 32 hip joints were injected in each group, 29 of which were successfully injected in the ultrasound guidance group and 21 of which were successfully injected in the fluoroscopy guidance group. The accuracy rate of interventions in the ultrasound guidance group (90.6%) was significantly higher than that in the fluoroscopy guidance group (65.6%; P < 0.05). The number of puncture attempts in the ultrasound guidance group was significantly lower than that in the fluoroscopy guidance group (P < 0.05). There was no significant difference in the procedure time between two groups. Compared with fluoroscopy guidance, ultrasound-guided intra-articular treatment has a higher accuracy and no radiation, and needs fewer puncture attempts, which a suitable and feasible method for intra-articular injection in rabbit hip joint.  Figures and Tables | References | Related Articles | Metrics

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Effects of electroacupuncture at Zusanli acupoint on visceral hypersensitivity in rats with functional dyspepsia Fan Jianchao, Xu Paidi, Han Yongli, Wen Caiyuzhu, Zhang Hongxing, Pan Xiaoli 2022, 26 (5):  663-668.  doi: 10.12307/2022.108 Abstract ( 474 )   PDF (766KB) ( 199 )   Save BACKGROUND: The pathogenesis of functional dyspepsia is complex, and visceral hypersensitivity is one of the most important pathological mechanisms. However, there are few reports on electroacupuncture treatment of functional dyspepsia from the perspective of visceral hypersensitivity mechanism. OBJECTIVE: To observe the effects and its possible mechanism of electroacupuncture at Zusanli (ST36) on visceral hypersensitivity in rats with functional dyspepsia.  METHODS: Twenty-four 7-day-old male Sprague-Dawley rats were randomly divided into three groups: a control group, a model group, and an electroacupuncture group (n=8). The visceral hypersensitivity model of functional dyspepsia rats was prepared with multi-factor stress methods (intragastric administration of iodoacetamide+irregular feeding+Guo’s moderate clipping tail). In the electroacupuncture group, rats aged 8 weeks were treated with electroacupuncture intervention. A disposable sterile acupuncture needle was pierced into 7-10 mm at Zusanli acupoints of bilateral hind limbs of rats, which was connected with Hans-acupoint nerve stimulator (dilatational wave, 2/100 Hz, 1 mA). Electroacupuncture was performed 20 minutes per day, 5 consecutive days as one session with 2 days off, for 2 sessions in total. The average body mass of rats in different stages was computed. Mechanical pain threshold of the plantar was tested to detect visceral sensitivity of rats. Enzyme-linked immune sorbent assay (ELISA) was applied to detect the level of 5-hydroxytryptamine in serum and gastric fundus mucosa tissue. Real-time fluorescence quantitative PCR was used to assess the expression of exchange protein 1 directly activated by cAMP (EPAC1) and PIEZO2 mRNA in gastric fundus mucosa tissue.  RESULTS AND CONCLUSION: Compared with the control group, the average body mass and plantar mechanical pain threshold were significantly decreased in the model group, and the level of 5-hydroxytryptamine in serum and gastric fundus mucosa was significantly increased (all P < 0.01). The mRNA expression levels of EPAC1 and PIEZO2 in gastric fundus mucosa were significantly increased in the model group compared with the control group (P < 0.01). Compared with the model group, in the electroacupuncture group, the average body mass and plantar mechanical pain threshold were significantly increased after 7 and 14 days of treatment (P < 0.05, P < 0.01), while the mRNA expression levels of EPAC1 and PIEZO2 in gastric fundus mucosa were significantly decreased (P < 0.01). These findings indicate that electroacupuncture at Zusanli can significantly improve the visceral hypersensitivity of functional dyspepsia rats, which is possibly mediated by regulating the release of 5-hydroxytryptamine from enterochromaffin cells and the mRNA expression of EPAC1 and PIEZO2. Figures and Tables | References | Related Articles | Metrics

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Effects of aerobic and resistance exercises on brain-derived neurotrophic factor, nuclear factor-kappa B and inflammatory cytokines in skeletal muscle of type II diabetic rats Shui Xiaoping, Li Chunying, Li Shunchang, Sun Junzhi, Su Quansheng 2022, 26 (5):  669-675.  doi: 10.12307/2022.109 Abstract ( 485 )   PDF (1102KB) ( 448 )   Save BACKGROUND: Studies have suggested that intervention for the expression of brain-derived neurotrophic factor and nuclear factor-κB in the skeletal muscle is beneficial to improve the glucose and lipid metabolism of the skeletal muscle. Whether exercise has a positive intervention effect on the above indicators in the skeletal muscle of type 2 diabetic rats is rarely reported. OBJECTIVE: To observe the effects of aerobic and resistance exercises on the expression of brain-derived neurotrophic factor, nuclear factor-κB and inflammatory indexes in the skeletal muscle of type 2 diabetic rats.  METHODS: Type 2 diabetic rats were made through high-fat and high-sugar diet combined with low-dose streptozotocin and randomly divided into diabetic control group, diabetic aerobic exercise group and diabetic resistance exercise group. In the diabetic control group, the rats were randomly divided into a quiet control group, an aerobic exercise group, and a resistance exercise group. The aerobic and resistance exercise lasted for 8 weeks. After 8-week exercises, fasting blood glucose, insulin resistance index, triglyceride, total cholesterol, low density lipoprotein, wet weight of gastrocnemius muscle and mass fraction of gastrocnemius muscle were measured. Hematoxylin-eosin staining was used to observe the changes of gastrocnemius muscle structure, The changes of interleukin-1β, interleukin-10 and tumor necrosis factor-α in gastrocnemius muscle were detected by ELISA. The expression of brain-derived neurotrophic factor and nuclear factor-κB in gastrocnemius muscle were detected by western blot. RESULTS AND CONCLUSION: Compared with the quiet control group, fasting blood glucose, insulin resistance index, triglyceride, total cholesterol, low density lipoprotein of all diabetic rats increased; the wet weight of gastrocnemius muscle decreased, and microscopic examination indicated skeletal muscle atrophy and inflammatory lesions; the expression of nuclear factor-κB in skeletal muscle increased, and the level of tumor necrosis factor-α increased; and the expression of brain-derived neurotrophic factor protein in skeletal muscle increased significantly. After 8 weeks of exercise, compared with the diabetic control group, all the blood glucose and lipid indexes in the two diabetic exercise groups decreased, inflammatory cell infiltration, atrophy and degeneration of skeletal muscles were reduced, the wet weight and mass fraction of gastrocnemius muscle increased, the expression of nuclear factor-κB and tumor necrosis factor-α in skeletal muscle decreased, and the expression of brain-derived neurotrophic factor increased significantly in the diabetic aerobic exercise group. Compared with the diabetic aerobic exercise group, the fasting blood glucose and nuclear factor-κB expression in skeletal muscle were significantly reduced in the diabetic resistance exercise group (P < 0.05), the wet weight and mass fraction of gastrocnemius muscle increased significantly (P < 0.05); however, the blood lipid indexes were significantly lower in the diabetic aerobic exercise group than the diabetic resistance exercise group (P < 0.05, P < 0.01). To conclude, both aerobic exercise and resistance exercise can promote the expression of brain-derived neurotrophic factor in skeletal muscle of diabetic rats and improve blood lipid metabolism. Resistance exercise can reduce the expression of nuclear factor-κB protein, reduce the level of tumor necrosis factor-α, improve the inflammation of skeletal muscle, and improve blood glucose level in diabetic rats. Figures and Tables | References | Related Articles | Metrics

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Effect of xanthohumol on inflammatory factors and articular cartilage in a mouse mode of osteoarthritis Lin Xuchen, Zhu Hainian, Wang Zengshun, Qi Tengmin, Liu Limin, Suonan Angxiu 2022, 26 (5):  676-681.  doi: 10.12307/2022.110 Abstract ( 556 )   PDF (1097KB) ( 256 )   Save BACKGROUND: Studies have shown that xanthohumol has antioxidant and anti-inflammatory properties; however, there is no study regarding the precise effect of xanthohumol on osteoarthritis.  OBJECTIVE: To investigate the role of xanthohumol in the occurrence and development of osteoarthritis in vivo and in vitro. METHODS: (1) A mouse osteoarthritis model was constructed by interleukin 1β treatment, followed by intervention with 0-40 µmol/L xanthohumol. The level of chondrocyte inflammatory factors was detected by ELISA, and the chondrocyte synthesis and metabolism indicators were detected by RT-PCR. (2) Surgery for medial meniscus instability was used to construct the arthritis model in mice, followed by intervention with 50 mg/kg/d xanthohumol for 6 weeks. Histological staining was used to evaluate the severity of damage to the articular cartilage, and μCT scan was used to analyze the changes in subchondral bone mass in the knee joint. RESULTS AND CONCLUSION: The cytokines, such as nitric oxide, prostaglandin E2, tumor necrosis factor α and interleukin 6,  which were produced in response to interleukin 1β-induced chondrocyte inflammation, were inhibited by xanthohumol pretreatment. Xanthohumol prevented the degradation of the extracellular chondrocyte matrix caused by interleukin 1β by down-regulating metalloproteinase 13 matrix and by increasing the synthesis of type II collagen. Mice treated with xanthohumol dramatically postponed the development of osteoarthritis caused by surgery, and had better articular cartilage morphology and maintained subchondral bone density. Overall, these findings indicate that xanthohumol can inhibit the synthesis of chondrocyte inflammatory mediators, inhibit the degradation of the extracellular matrix of the cartilage, and maintain the metabolic equilibrium in the articular cartilage. Figures and Tables | References | Related Articles | Metrics

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Overexpression of miR-25 downregulates titanium particle-induced osteoclast differentiation through the NFATc1 signaling pathway Hu Weifan, Zheng Li, Li Dadi, Sun Yang, Zhao Fengchao 2022, 26 (5):  682-687.  doi: 10.12307/2022.111 Abstract ( 643 )   PDF (942KB) ( 681 )   Save BACKGROUND: Studies have found that the down-regulation of miR-25 is related to the excessive activation of nuclear factor of activated T cells c1 (NFATc1), and NFATc1 is the core transcription factor in osteoclasts differentiation and maturation, suggesting that the expression level of miR-25 can regulate osteoclasts differentiation. OBJECTIVE: To explore the effect of miR-25 overexpression on titanium (Ti) particles-induced osteoclasts differentiation and investigate the signaling pathways. METHODS: RAW264.7 cell line was cultured in vitro. Cell counting kit-8 was used to determine the effect of Ti particles on cell proliferation. miR-25 mimics were transfected into RAW264.7 cells, and cultured with Ti particles to induce osteoclasts differentiation. Immunofluorescence was used to detect the activation status of NFATc1, TRAP staining and counting were adopted to verify the differentiation of osteoclasts, and real-time PCR was employed to detect and analyze the differential expression of NFATc1, CaMKII, and CaMKIV mRNAs. RESULTS AND CONCLUSION: The low concentration of Ti particles (0.1 g/L) had no significant effect on cell proliferation. Compared with the negative control group, there was less production of osteoclasts (TRAP positive) in the miR-25 overexpression group (P < 0.05). After intracellular transfection with miR-25 mimic, immunofluorescence detection showed that the activation of NFATc1 decreased and the fluorescence intensity decreased. The expression of signaling pathway molecules NFATc1, CaMKII, and CaMKIV mRNAs decreased significantly after miR-25 overexpression (P < 0.05). These findings indicate that miR-25 overexpression can inhibit the differentiation of Ti particles-induced osteoclasts. This process may be achieved through the Ca2+/NFATc1 pathway. Figures and Tables | References | Related Articles | Metrics

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Ermiao san aqueous extract regulates proliferation, migration, and inflammatory factor expression of fibroblast-like synovial cells in collagen-induced arthritis rats Liu Jin, Li Zhen, Hao Huiqin, Wang Ze, Zhao Caihong, Lu Wenjing 2022, 26 (5):  688-693.  doi: 10.12307/2022.112 Abstract ( 512 )   PDF (1116KB) ( 106 )   Save BACKGROUND: The activation of nuclear factor -κB signaling pathway is closely related to the proliferation and inflammation of fibroblast-like synovial cells in rheumatoid arthritis. However, the mechanism by which Ermiao san aqueous extract interferes with fibroblast-like synoviocytes of collagen-induced arthritis rats (CIA-FLS) via the NF-κB signaling pathway has not been reported.  OBJECTIVE: To study the effects of different concentrations of Ermiao san aqueous extracts on the proliferation, migration and inflammatory factors expression of CIA-FLS, and to explore its mechanism based on the nuclear factor-κB signaling pathway.  METHODS: CIA-FLS cells were resuscitated and coped with different concentrations of Ermiao san aqueous extracts (200, 400, 800, 1600, 3 200 mg/L) after subculture. The proliferation and migration ability of CIA-FLS were detected by MTT method and Transwell chamber, and real-time fluorescent quantitative PCR (qRT-PCR) and western blot assay were used to detect the NF-κB signaling pathway related molecules interleukin-6, tumor necrosis factor-α, nuclear factor-κBp65 mRNA and protein expression levels in CIA-FLS.  RESULTS AND CONCLUSION: Different concentrations of Ermiao san aqueous extracts acted on CIA-FLS for 48 hours. Compared with the blank control group, Ermiao san aqueous extracts inhibited the proliferation of CIA-FLS in a dose-dependent manner (P < 0.05). 1 600 mg/L Ermiao san aqueous extract significantly inhibited the proliferation and migration of CIA-FLS (P < 0.01), and at the same time, it significantly inhibited the expression of interleukin-6, tumor necrosis factor-α, nuclear factor-κBp65 mRNA and protein in CIA-FLS (P < 0.01). Therefore, the optimal concentration of Ermiao san aqueous extract to inhibit the proliferation, migration and inflammatory factor expression of CIA-FLS is 1 600 mg/L. Ermiao san aqueous extract may inhibit the activation of nuclear factor-κB signaling pathway and the production of inflammatory factors, thereby reducing the proliferation and inflammation of CIA-FLS. It provides certain research experimental basis for further research on the mechanism of Ermiao san treatment of rheumatoid arthritis in the later period. Figures and Tables | References | Related Articles | Metrics

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Interventional effect of Yanghe Decoction on synovial inflammation in a rabbit model of early knee osteoarthritis He Junjun, Huang Zeling, Hong Zhenqiang 2022, 26 (5):  694-699.  doi: 10.12307/2022.113 Abstract ( 626 )   PDF (835KB) ( 195 )   Save BACKGROUND: Yanghe Decoction is an effective prescription for the clinical treatment of knee osteoarthritis. Our previous basic studies have shown that the mechanism of Yanghe Decoction to prevent and treat knee osteoarthritis is related to the protection of articular cartilage. It is still not unclear about the effect of Yanghe Decoction on early synovial inflammation of knee osteoarthritis.  OBJECTIVE: To investigate the effect of Yanghe Decoction on the pain and synovial inflammation in a rabbit model of early knee osteoarthritis, and to further clarify the efficacy and mechanism of Yanghe Decoction in the treatment of early osteoarthritis. METHODS: Twenty-four 4-month-old New Zealand rabbits were randomly divided into blank control group, model group, Yanghe Decoction group and positive control group, with six rabbits in each group. Except for the blank control group, the rabbits in the other groups were injected with papain into the joint cavity for modeling. Two weeks after modeling, the blank control and model groups were given the same amount of normal saline by gavage, the Yanghe Decoction group was given 6 g/kg/d Yanghe Decoction, and the positive control group was given 24 mg/kg/d Celebrex. Administration in each group lasted for 2 weeks. At 4 hours after final administration, the knee joint skin temperature and circumference were measured, and Lequesne MG score was used to evaluate knee joint function. At 2 days after final intragastric administration, ELISA was used to detect the levels of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and prostaglandin E2 in the synovial fluid. Synovial tissue morphology was observed using hematoxylin-eosin staining. Immunohistochemical detection was conducted to detect the expression of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2 proteins in synovial tissue.  RESULTS AND CONCLUSION: Compared with the blank control group, the knee joint circumference in the model group was widened (P < 0.05), and the local skin temperature, Lequesne MG score, and the levels of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and prostaglandin E2 in the synovial fluid were all increased (P < 0.05), synovial membrane morphology and inflammatory changes were obvious, and the expressions of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2 proteins in synovial tissue were all increased (P < 0.05). Compared with the model group, the knee joint circumference in the Yanghe Decoction group and positive control group decreased (P < 0.05), local skin temperature, Lequesne MG score, and the levels of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and prostaglandin E2 in the synovial fluid were all decreased (P < 0.05), synovial membrane morphology and inflammatory changes were alleviated, and the expressions of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2 proteins in synovial tissue were all downregulated (P < 0.05). In conclusion, Yanghe Decoction can inhibit the expression of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and prostaglandin E2, reduce synovial inflammation, and improve joint function, thereby delaying the progression of knee osteoarthritis. Figures and Tables | References | Related Articles | Metrics

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Implantation of Kirschner wire with Staphylococcus aureus biofilm establishes a traumatic osteomyelitis model in rats Feng Jianbo, Li Chencheng, Liu Jinyue, Wang Xiaomin, Peng Jiachen 2022, 26 (5):  700-705.  doi: 10.12307/2022.114 Abstract ( 732 )   PDF (976KB) ( 925 )   Save BACKGROUND: To establish an animal osteomyelitis model is the basis and key to explore the treatment of osteomyelitis. In the past, direct addition of bacteria was used to make the osteomyelitis model, which is significantly different from clinical pathogenic factors. Moreover, it is difficult to control the amount of bacterial suspension dripped, which can easily lead to the death of model animals. Osteomyelitis caused by bacterial biofilms is the most common in clinical practice.  OBJECTIVE: To prepare a rat model of osteomyelitis by inserting Kirschner wires with bacterial biofilms into the rat bone marrow cavity. METHOD: Bacterium-bearing Kirschner wires were prepared using Staphylococcus aureus. Eighteen healthy Sprague-Dawley rats were enrolled. Kirschner wires with Staphylococcus aureus biofilms were inserted into the rat tibia, and the borehole was sealed with sterile paraffin. Rats’ behaviors and incision healing were observed after modeling. Bone infection was observed through imaging and pathological examinations at 4 weeks after modeling. Secretions at the model site were aseptically taken for bacterial culture, and mass spectrometry was used to identify whether they were the bacteria inoculated during the production of bacterial biofilms, and the serum inflammatory factors of rats before and after modeling were detected as indicators for evaluating the success of the osteomyelitis model. RESULTS AND CONCLUSION: All the 18 rats presented with the characteristics of osteomyelitis. They all showed different degrees of pus, dead bone, dead space and new bone formation. After modeling, the levels of serum inflammatory factors, such as procalcitonin, tumor necrosis factor alpha and interleukin-10, increased significantly (P < 0.05). The bacteria that formed after secretion culture were identified as Staphylococcus aureus. To conclude, the rat osteomyelitis model can be successfully made by inserting the Kirschner wire into the rat tibia through the Staphylococcus aureus biofilm, which is closer to osteomyelitis in clinic. Figures and Tables | Related Articles | Metrics

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Effect of arc edge needle-scalpel therapy on inflammatory factors and histomorphology of the frozen shoulder in rabbit models Wang Shihui, Cheng Yang, Zhu Yunjie, Cheng Shaodan, Mao Jianying 2022, 26 (5):  706-711.  doi: 10.12307/2022.115 Abstract ( 467 )   PDF (1286KB) ( 291 )   Save BACKGROUND: Arc edge needle-scalpel therapy has a significant clinical effect in the treatment of frozen shoulder; however, there is still a lack of basic research on the therapeutic mechanism. OBJECTIVE: To observe the effect of arc edge needle-scalpel therapy on serum inflammatory factors and the morphology and structure of tendon and synovium in a rabbit frozen shoulder model, and to explore the possible mechanism of arc-edge needle knife therapy in the intervention of frozen shoulder.   METHODS: Forty-eight male New Zealand rabbits were randomly divided into blank group (n=8), model group (n=8), electroacupuncture group (n=8), and arc edge needle-scalpel groups I, II, III (n=8 per group). The rabbit frozen shoulder model was made by the method of continuous mechanical strain and ice compress in all groups except for the blank group. After the establishment of the model, the electroacupuncture group was treated with electroacupuncture at Jianyu and Quchi, 3 times a week for 4 continuous weeks. Arc edge needle-scalpel groups I, II, III were treated with arc edge needle-scalpel at internodular groove, the beginning of teres major, and junction between supraspinatus tendon and muscle belly, once a week: four sessions in arc edge needle-scalpel group III, first two sessions in arc edge needle-scalpel group I, and latter two sessions in arc edge needle-scalpel group II. At 3 days after intervention termination, the width of effusion in the posterior recess of the right shoulder joint was detected by ultrasound, the contents of interleukin-1β, NLRP3 and caspase-1 in serum were detected by ELISA method, the histomorphology of long head tendon and synovium of biceps brachii was observed using hematoxylin-eosin and Masson staining, and the expression of interleukin-1β protein in synovium was observed by immunohistochemical method. The study was approved by the Animal Experimental Ethics Committee (approval No. 191213015). RESULTS AND CONCLUSION: Compared with the blank group, after modeling, a large amount of fluid was observed on the posterior recess side of the shoulder cavity in the model group. After intervention, the width of effusion in the arc edge needle-scalpel groups I and III was significantly smaller than that in the electroacupuncture group and arc edge needle-scalpel group II. Compared with the model group, the levels of interleukin-1β, NLRP3 and caspase-1 in the serum were significantly lower in the electroacupuncture group and arc edge needle-scalpel groups I, II, III (P < 0.01). The levels of interleukin-1 β and NLRP3 in the serum of the arc edge needle-scalpel group I were significantly lower than those of the arc edge needle-scalpel group II (P < 0.05). Under hematoxylin-eosin and Masson staining, electroacupuncture group and arc edge needle-scalpel group II showed partial tendon fiber hyperplasia and rupture, synovium thickening and fibrosis; arc edge needle-scalpel groups I and III showed reduced tendon fiber proliferation and synovium thickening, and improved pathological state of tissue inflammation and fibrosis. Compared with the model group, the expression of interleukin-1β in synovium was significantly lowered in the electroacupuncture group and arc edge needle-scalpel groups I, II, III (P < 0.01), while the expression of interleukin-1β in synovium in the arc edge needle-scalpel groups I, III was significantly lower than that in the arc edge needle-scalpel groups II (P < 0.01). To conclude, arc edge needle-scalpel therapy can reduce the levels of interleukin-1β, NLRP3 and caspase-1 in serum and the expression of interleukin-1β protein in synovium, and promote the repair of damaged tissue in the rabbit frozen shoulder model, so as to inhibit local aseptic inflammation of the frozen shoulder. Figures and Tables | References | Related Articles | Metrics

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Relationship between tacrolimus metabolic rate and early BK virus infection after kidney transplantation Yang Zhiwei, Liu Junchang, Gao Xiaolin, Jiang Taimao 2022, 26 (5):  712-716.  doi: 10.12307/2022.116 Abstract ( 646 )   PDF (908KB) ( 542 )   Save BACKGROUND: BK virus is a kind of polyomavirus. In recent years, with the widely application of new powerful immunosuppressants, BK virus infection rate is continuously rising after renal transplantation. Kidney diseases caused by BK virus nephropathy have become one of the important reasons for renal allograft loss. However, there is a lack of effective antiviral drugs to prevent or treat BK virus nephropathy. Identifying the high-risk population of BK virus infection after kidney transplantation will help in the timely detection and early prevention and control of BK virus nephropathy. OBJECTIVE: To study the relationship between the metabolic rate of tacrolimus and early BK virus infection after kidney transplantation.  METHODS: A total of 62 kidney transplant recipients from January 2017 to December 2018 in Air Force Hospital of PLA Northern Theater Command were selected for detection of CYP3A5 gene polymorphism by gene sequencing, and then were divided into fast metabolites (CYP3A5*1/*1 or *1/*3 genotype; n=28) and slow metabolites (CYP3A5*3/*3 genotype; n=34), according to the gene detection results. All surgeries were approved by the Ethics Committee of the Air Force Hospital of PLA Northern Theater Command. The study protocol was also approved by the Ethics Committee of Air Force Hospital of Northern Theater Command. RESULTS AND CONCLUSION: The tacrolimus metabolic rates at 1, 3, 6 and 12 months after surgery were significantly lower in the fast metabolite group than the slow metabolite group, and the incidence rates of BK viruria and BK virus nephropathy were similar between the two groups. These findings suggest that kidney transplant recipients with CYP3A5*1/*1 and *1/*3 genotypes have a higher risk of early BK viremia after kidney transplantation than those with CYP3A5*3/*3 genotypes. Figures and Tables | References | Related Articles | Metrics

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Effects of exercise preconditioning on myocardial protection and apoptosis in a mouse model of myocardial remodeling due to early stress overload Deng Shuang, Pu Rui, Chen Ziyang, Zhang Jianchao, Yuan Lingyan 2022, 26 (5):  717-723.  doi: 10.12307/2022.117 Abstract ( 557 )   PDF (965KB) ( 114 )   Save BACKGROUND: Studies have shown that long-term regular aerobic exercises can lower blood pressure and improve ventricular remodeling caused by hypertensive myocardial hypertrophy and myocardial fibrosis. OBJECTIVE: To investigate the effects of swimming exercise preconditioning on myocardial apoptosis and remodeling in mice during pressure overload compensatory period. METHODS: Male C57B/L6 mice aged 6-7 weeks were randomly divided into control group, exercise group, operation group and operation+exercise group. Mice in the exercise and operation+exercise groups were subjected to 4-week swimming exercises (90 minutes per session, twice per day, and 7 days per week). Transverse aorta constriction was then used to construct a model of myocardial remodeling in the operation and operation+exercise groups. The aorta was ligated with a 27G needle to make the aorta constricted by more than 70%. Two weeks later, cardiac ultrasonography was performed and myocardial samples were collected to observe the apoptosis of myocardial cells. The expression levels of heat shock protein 70 and P53 proteins in mouse myocardial tissue were detected by western blot. The expression levels of P53, Bcl-2 and Bax in mice were detected by RT-PCR. RESULTS AND CONCLUSION: The heart was in the compensatory stage at 2 weeks after TAC surgery. Compared with the control group, the heart weight index and left ventricular shorting rate were significantly increased in the operation group (P < 0.01), the ventricular wall thickness and myocardial fibrosis were significantly increased (P < 0.01), but the heart function was not significantly decreased. Compared with the operation group, the ventricular wall thickness was significantly lower in the operation+exercise group (P < 0.05), and the level of myocardial fibrosis and apoptosis cell count were significantly decreased (P < 0.01). Western blot results showed that compared with the control group, the protein expression of P53 in the operation group was significantly increased (P < 0.01), and the protein expression of heat shock protein 70 was significantly decreased (P < 0.01). Compared with the operation group, the protein expression of P53 in the operation+exercise group was decreased (P < 0.05), and the protein expression of heat shock protein 70 was increased (P < 0.05). RT-PCR results showed that compared with the control group, the expression of Bax mRNA and P53 mRNA in the operation group was increased (P < 0.01), while the expression of Bcl-2 mRNA and Bcl-2/Bax value decreased (P < 0.01). Compared with the operation group, the expression level of Bax mRNA was decreased (P < 0.05), the expression level of P53 mRNA was decreased (P < 0.01), the expression level of Bcl-2 mRNA was increased (P < 0.01), and the ratio of Bcl-2/Bax was significantly increased (P < 0.01). To conclude, the mouse heart is in the compensatory phase of pathological myocardial hypertrophy after 2 weeks of aortic constriction surgery. A 4-week exercise preconditioning can enhance the mouse heart function in the early stage of pressure overload, and maintain and delay the pathological development of compensatory myocardial remodeling in the early stage. The myocardial protection induced by exercise preconditioning may be related to the up-regulation of heat shock protein 70 and Bcl-2 expression and the inhibition of P53 and Bax expression, thereby inhibiting myocardial cell apoptosis. Figures and Tables | References | Related Articles | Metrics

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Deep seawater promotes wound healing in diabetic mice by activating PI3K/Akt pathway Li Weiming, Xu Qingwen, Li Yijun, Sun Yanbo, Cui Jin, Xu Pengyuan 2022, 26 (5):  724-729.  doi: 10.12307/2022.118 Abstract ( 676 )   PDF (1235KB) ( 1157 )   Save BACKGROUND: Preliminary studies have confirmed that deep seawater not only affects the tolerance and immunity of mice, but also has an important regulatory effect on wound repair. OBJECTIVE: To explore the effect of deep seawater on the PI3K/Akt pathway in the process of wound repair in diabetic mice. METHODS: Forty-eight Kunming mice were enrolled to establish a diabetes model. A 1 cm2 wound was made on the back after successful modeling, and all the mouse models were randomized into four groups for corresponding treatments, including drinking purified water (control), tap water, deep seawater and deep seawater+LY294002, with 12 rats in each group. On the 3rd, 7th, and 10th days after wound modeling, the wound healing was observed, and western blot was used to detect the expression levels of vascular endothelial growth factor, basic fibroblast growth factor, hypoxia-inducible factor 1α, p-PI3K, p-Akt, PI3K and Akt in the wound tissue. qRT-PCR and western blot were used to detect the expression levels of collagen type I, collagen type III, interleukin-1β, tumor necrosis factor-α and transforming growth factor-β1 mRNA. On the 3rd and 10th days after wound modeling, hematoxylin-eosin staining was used to observe the morphological changes of the wound. The study protocol was approved by the Animal Ethic Committee of Kunming Institute of Zoology, Chinese Academy of Science with an approval No. KPRC-2017091. RESULTS AND CONCLUSION: The wound healing rate of the deep seawater group was higher than that of the control group and the tap water group (P < 0.01), while there was no significant difference in the wound healing rate between the tap water group and deep seawater+LY294002 group (P > 0.05). Hematoxylin-eosin staining showed that there were a large number of inflammatory cells infiltrated and a few fibroblasts on the wound surface in the control group, tap water group, and deep seawater+LY294002 group on the 3rd day, and granulation tissue, capillaries and fibroblasts were visible on the 10th day. In the deep seawater group, fibroblasts, capillaries and a few inflammatory cells were seen on the 3rd day, and new granulation tissue, more collagen fibers and a few capillaries were seen on the 10th day. Western blot analysis showed that the expressions of vascular endothelial growth factor, basic fibroblast growth factor, hypoxia-inducible factor 1α, p-PI3K and p-Akt in the deep seawater group were higher than those in the control group and the tap water group on each observational time point (P < 0.01). qRT-PCR and western blot results showed that the expressions of collagen type I, collagen type III and transforming growth factor-β1 in the deep seawater group were higher than those in the control group and deep seawater+LY294002 group on each observational time point (P < 0.05 or P < 0.01), while the expression levels of interleukin-1β and tumor necrosis factor-α were lower than those in the control group and deep seawater+LY294002 group (P < 0.05 or  P < 0.01). To conclude, deep seawater can promote wound healing in diabetic mice via activating the PI3K/Akt pathway. Figures and Tables | References | Related Articles | Metrics

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Granulocyte colony-stimulating factors improve myocardial fibrosis in rats with myocardial infarction Yin Tingting, Du Dayong, Jiang Zhixin, Liu Yang, Liu Qilin, Li Yuntian 2022, 26 (5):  730-735.  doi: 10.12307/2022.119 Abstract ( 488 )   PDF (1378KB) ( 241 )   Save BACKGROUND: As a powerful stem cell mobilization agent, granulocyte colony-stimulating factor can mobilize bone marrow mesenchymal stem cells to the ischemic area in the early stage of myocardial infarction, regulate extracellular matrix metabolism and inhibit myocardial fibrosis in the early stage of myocardial infarction. OBJECTIVE: To observe the effect of granulocyte colony-stimulating factor on myocardial fibrosis in rats with acute myocardial infarction. METHODS: Animal models of acute myocardial infarction were established in rats by coronary artery ligation. After successful modeling, the rats were randomly divided into two groups: model group (n=7) and treatment group (n=7). Another seven rats were randomly selected as blank control group without ligation. At 24 hours after modeling, the treatment group was subcutaneously injected with granulocyte colony-stimulating factor (50 μg/kg/d). Both the model group and the blank control group were injected with the corresponding volume of normal saline at the same site, once a day for 5 days. After 4 weeks, the morphological changes of myocardial tissue were observed by hematoxylin-eosin staining, and the collagen volume fraction was calculated by Masson staining. The levels of serum type I procollagen carboxyl terminal peptide and type III procollagen N-terminal peptide were detected by ELISA assay. The protein expressions of matrix metalloproteinase inducer (CD147), matrix metalloproteinase 2 and matrix metalloproteinase inhibitor 2 in the marginal zone of myocardial infarction were detected by immunohistochemistry and western blot.  RESULTS AND CONCLUSION: After 4 weeks, the volume fraction of collagen was significantly higher in the model group than in the blank control group (P < 0.001), the protein levels of CD147 and matrix metalloproteinase 2 were significantly increased (P < 0.001), and the level of matrix metalloproteinase inhibitor 2 protein was significantly decreased. Compared with the model group, the collagen volume fraction in the treatment group decreased significantly (P < 0.001), the protein levels of CD147 and matrix metalloproteinase 2 decreased (P < 0.001), and the level of matrix metalloproteinase inhibitor 2 protein increased significantly (P < 0.001). Compared with the blank control group, the expression levels of serum type I procollagen carboxyl terminal peptide and type III procollagen N-terminal peptide significantly increased in the treatment group (P < 0.001). Compared with the model group, the expression levels of serum type I procollagen carboxyl terminal peptide and type III procollagen N-terminal peptide reduced significantly in the treatment group (P < 0.001). To conclude, granulocyte colony-stimulating factor can improve myocardial fibrosis in rats with acute myocardial infarction, probably by down-regulating the expression of CD147 protein, directly or indirectly regulating the balance of matrix metalloproteinase 2/matrix metalloproteinase inhibitor 2 ratio, improving extracellular matrix metabolism and inhibiting collagen deposition. Figures and Tables | References | Related Articles | Metrics

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Effects of Pueraria lobata flavonoids on expressions of beta-catenin and glycogen synthase kinase 3beta in the brain of rats undergoing exhaustive exercise after long endurance exercise Mo Weibin, Huang Tianchang, Zeng Zhiwei, Yan Linbo 2022, 26 (5):  736-741.  doi: 10.12307/2022.120 Abstract ( 422 )   PDF (709KB) ( 146 )   Save BACKGROUND: Prolonged exhaustive exercise can easily cause ischemia and hypoxia in rats, leading to brain tissue damage. Pueraria lobata flavonoids can exert a series of roles, including cardiovascular and cerebrovascular protections, improvement of brain damage and anti-oxidation. However, whether supplementation of Pueraria lobata flavonoids prior to exercise can protect the brain tissue is still unclear. OBJECTIVE: To observe the effect of total flavonoids in Pueraria lobata on histopathological changes and expressions of β-catenin and glycogen synthase kinase 3β in rats undergoing exercises. METHODS: Fifty Sprague-Dawley male rats were randomly divided into five groups: a quiet control group, an exercise control group, and low-, medium-and high-dose groups of total flavonoids in Pueraria lobata. Except the quiet control group, the remaining groups were trained for 6 weeks, while the last training reached exhaustion on the 6th weekend. In the low-, middle- and high-dose groups, all the rats were given 50, 100, 200 mg/kg total flavonoids in Pueraria lobata by gavage at 20 minutes before the experiment once a day until the end of the experiment. In all the groups, hematoxylin-eosin staining was used to observe the histopathological changes of the brain, and immunohistochemistry, PCR and western blot were used to determine the expressions of β-catenin and glycogen synthase kinase 3β.  RESULTS AND CONCLUSION: Under the light microscope, in the exercise control group, some nerve cells in the cerebral cortex and hippocampus became swollen and contracted, and there were edema, hyperemia and bleeding in the meninges or ependymal membranes. The low-dose group appeared to have some mild symptoms, such as edema, congestion and hemorrhage. However, the pathological changes in the brain tissue of rats in the middle- and high-dose groups were not significantly different from those in the quiet control group. Immunohistochemical staining showed that the expression levels of β-catenin and glycogen synthase kinase 3β in the brain tissue of the exercise control group were higher than those in the quiet control group (P < 0.01). In the middle- and high-dose group, the expression levels of β-catenin and glycogen synthase kinase 3β in the brain tissue were lower than those of the exercise control group (P < 0.01). The mRNA and protein expressions of β-catenin and glycogen synthase kinase 3β in the brain tissue of the exercise control group were higher than those in the quiet control group (P < 0.05 or P < 0.01). The expressions of β-catenin and glycogen synthase kinase 3β mRNA and protein in the middle- and high-dose groups were lower than those in the exercise control group (P < 0.05 or P < 0.01). To conclude, exhaustive exercise could give rise to damage in the rat brain tissue, and upregulate the expressions of β-catenin and glycogen synthase kinase 3β, whereas the total flavonoids in Pueraria lobata may effectively reduce damage to the rat brain tissue by regulating the expressions of β-catenin and glycogen synthase kinase 3β, thereby protecting the brain tissue. Figures and Tables | References | Related Articles | Metrics

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Mechanism of Ermiao San in the treatment of rheumatoid arthritis Zhao Yuwei, Gao Yuting, Li Zhen, Hao Huiqin 2022, 26 (5):  742-748.  doi: 10.12307/2022.121 Abstract ( 678 )   PDF (2287KB) ( 1196 )   Save BACKGROUND: Ermiao San has a good effect in the treatment of rheumatoid arthritis. Studies have proved that Ermiao San can inhibit angiogenesis and delay the progression of the disease, but its mechanism is not clear.  OBJECTIVE: To analyze the pharmacological mechanism of Ermiao San in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking, so as to provide reference for studying the therapeutic mechanism and clinical application of classical prescriptions.  METHODS: The main chemical components and targets of Atractylodes macrocephala and Phellodendri were collected on the Systematic Pharmacological Platform of Traditional Chinese Medicine (TCMSP), and the active components of traditional Chinese medicine were screened according to ADME. The main targets of rheumatoid arthritis were obtained by GeneCards, OMIM, TTD and DRUGBANK databases, and the protein interaction was analyzed by String platform to construct the protein-protein interaction network and mine the potential protein functional modules in the network. The “drug-ingredient-target” and the relevant biological processes and signaling pathways were analyzed by Metascape platform, and then the “Ermiao San component-rheumatoid arthritis target-pathway” network was constructed by Cytoscape3.8.0 software. Finally, the molecular docking verification was carried out between the drug components with high value in the network and the core action target by Autodock software.  RESULTS AND CONCLUSION: The core active components of Ermiao San in the treatment of rheumatoid arthritis are quercetin, wogonin, β-sitosterol and so on, and the core targets are prostaglandin G/H synthetase 2, JUN proto-oncogene protein, and nuclear factor-κb/p65. The biological pathways of Ermiao San in the treatment of rheumatoid arthritis mainly include advanced glycation end product and receptor, mitogen-activated protein kinase, interleukin-17, and tumor necrosis factor signaling pathway, which are mainly related to immune regulation, apoptosis, inflammatory reaction and oxidative stress. The results of molecular docking showed that the key compounds such as quercetin, wogonin and β-sitosterol in Ermiao San have stable binding activity with key targets such as prostaglandin G/H synthetase 2, JUN proto-oncogene protein, and nuclear factor-κb/p65. This study preliminarily indicates that Ermiao San plays a role in the treatment of rheumatoid arthritis through multi-component, multi-target and multi-pathway regulations, which provides a basis for the study on the mechanism and clinical application of Ermiao San. Figures and Tables | References | Related Articles | Metrics

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Effect of electroacupuncture on expression of nucleotide binding oligomerization domain-like receptor protein 3/cysteinyl aspartate specific proteinase 1 in rats with cerebral ischemia/reperfusion injury Dong Miaomiao, Lai Han, Li Manling, Xu Xiuhong, Luo Meng, Wang Wenhao, Zhou Guoping 2022, 26 (5):  749-755.  doi: 10.12307/2022.122 Abstract ( 457 )   PDF (1222KB) ( 412 )   Save BACKGROUND: There is currently no effective treatment for cerebral ischemia/reperfusion injury, and for the exploration of treatments, it is crucial to mitigate cerebral ischemia/reperfusion injury cascade damage. Electroacupuncture can alleviate cerebral ischemia/reperfusion injury.  OBJECTIVE: To explore the neuroprotective effect of electroacupuncture on cerebral ischemia/reperfusion injury in rats based on nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase-1) pathway. METHODS: Forty-eight Sprague-Dawley rats were randomly divided into a sham group, a model group, an electroacupuncture group and an inhibitor group, with 12 rats in each group. Animal models of cerebral ischemia/reperfusion injury were made in the latter three groups using the suture-occluded method. Caspase-1 inhibitor was intervened with Z-YVAD-FMK, and acupoints were selected as “Hegu,” “Chize,” “Sanyinjiao” and “Zusanli.” Zea longa method was used to evaluate the neurological symptoms. 2,3,5-Triphenyltetrazolium chloride staining was used to observe the condition of cerebral infarction. Electron microscope was used to observe the pyroptosis of neurons. Fluorescence quantitative PCR and western blot were used to detect the expression of NLRP3 and Caspase-1. Immunofluorescence staining was used to observe the level of microglia. Enzyme linked immunosorbent assay was used to detect the levels of interleukin-1β, interleukin-18 and tumor necrosis factor-α. RESULTS AND CONCLUSION: (1) Compared with the model group, the neurological deficit score and infarct volume of brain tissue were decreased in the electroacupuncture group and inhibitor group (all P < 0.05). (2) Compared with the model group, pyroptosis of the cells was reduced in the electroacupuncture group and inhibitor group. (3) Compared with the model group, the number of microglia and the expression of interleukin-1β, interleukin-18 and tumor necrosis factor-α were decreased in the electroacupuncture group and inhibitor group (all P < 0.05). (4) Compared with the model group, the expression levels of NLRP3 and Caspase-1 were decreased in the electroacupuncture group and inhibitor group (all P < 0.05). In conclusion, electroacupuncture can reduce the level of microglia, reduce inflammatory reactions, and down-regulate the expression of NLRP3/Caspase-1, so as to reduce neuronal pyroptosis and exert a neuroprotective effect in rats with cerebral ischemia/reperfusion injury. Figures and Tables | References | Related Articles | Metrics

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miR-373 inhibits hepatic stellate cell activation by downregulating transforming growth factor beta type II receptor  Xu Jing, Yan Yongmin, Cai Mengjie 2022, 26 (5):  756-761.  doi: 10.12307/2022.123 Abstract ( 482 )   PDF (1007KB) ( 193 )   Save BACKGROUND: Activated hepatic stellate cells can secrete a large amount of collagen, which is the main factor in the progression of liver fibrosis. miRNA plays an important role in the activation and apoptosis of hepatic stellate cells. The role and mechanism of miR-373 in regulating collagen secretion from hepatic stellate cell are still unclear. OBJECTIVE: To investigate the role of miR-373 in the regulation of transforming growth factor beta type II receptor (TGFβR2) in collagen secretion from hepatic stellate cells. METHODS: Bal b/c mouse model of liver fibrosis was established by CCl4 injection. Masson staining was used to detect the collagen content of liver tissues. Serum samples from liver fibrosis mice were collected and total RNA was extracted by Trizol method. Quantitative reverse transcription PCR (qRT-PCR) was used to analyze the expression level of mouse mmu-miR-291a-3p (the homologous sequence of human hsa-miR-373-3p). The expression of TGFβR2 and α-smooth muscle actin in liver tissue was detected by immunohistochemistry. TargetScan software was used to predict the target gene of miR-373. The dual luciferase reporter gene assay was used to detect the activity of miR-373 regulating TGFβR2 promoter. Human hepatic stellate cells (LX-2) were transfected with miR-373 mimics (25 and 50 nmol/L) to overexpress miR-373. LX-2 cells transfected with random miRNA sequence served as a control. Western blot and immunofluorescence were used to investigate the effect of miR-373 on the expression of TGFβR2 and fibroblast activation protein. The study protocol was approved by the Experimental Animal Ethics Committee of Jiangsu University (approval No. UJS-IACUC-AP-2020033127). RESULTS AND CONCLUSION: Serum mmu-miR-291a-3plevel was significantly decreased in the fibrosis group compared with the health control group (P < 0.001), and collagen synthesis in the liver was significantly increased. Co-expression of TGFβR2 and α-smooth muscle actin in liver fibrosis tissue was obviously increased compared with the control group. miR-373 significantly inhibited the activity of TGFβR2 promoter in LX-2 cells (P < 0.01). The expression of TGFβR2 and fibroblast activation protein in LX-2 cells was significantly downregulated by miR-373 overexpression (P < 0.01). To conclude, miR-373 can inhibit the activation of hepatic stellate cells and collagen deposition in liver tissues by downregulating the expression of TGFβR2. Related Articles | Metrics

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Three-dimensional gait analysis of low-frequency repetitive transcranial magnetic stimulation for post-stroke hemiplegia Shan Sharui, Huang Xuming, Zhang Mingxing, Wang Xiukun, Zheng Xiang, Bao Sairong, Hong Feng 2022, 26 (5):  762-767.  doi: 10.12307/2022.124 Abstract ( 629 )   PDF (715KB) ( 482 )   Save BACKGROUND: At present, there are a large number of studies on contralateral low-frequency repetitive transcranial magnetic stimulation treatment or affected side high-frequency repetitive transcranial magnetic stimulation treatment, both of which can improve the upper limb motor function of stroke patients, whereas the effect on lower limb motor function is less reported. OBJECTIVE: To investigate the effect of low-frequency repetitive transcranial magnetic stimulation on hemiplegic gait by collecting gait parameters through three-dimensional gait analysis. METHODS: Thirty-six patients with hemiplegic stroke recovery were randomly divided into experimental group and pseudo stimulation group (n=18 per group), receiving both conventional drug and rehabilitation treatments. The experimental group on the basis of routine therapy received low-frequency repetitive transcranial magnetic stimulation using Magneuro100 transcranial magnetic stimulator. The 8-shaped coil was tangent to the brain surface of the first motor cortex corresponding to the healthy side of the patient’s skull. The stimulation frequency was set to 1 Hz, the stimulation intensity was 90% of the motor threshold, 20 pulses per sequence, 30 sequences once. The sequence interval was 2 seconds, and each treatment lasted for 20 minutes. The pseudo stimulation group was given false repetitive transcranial magnetic stimulation. Treatment in each group was performed once a day, 6 days per week, for 3 consecutive weeks. Gait Watch three-dimensional gait analyzer was used to collect the gait parameters of patients in the two groups to evaluate the efficacy. The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Guangdong Pharmaceutical University. RESULTS AND CONCLUSION: There was no significant difference in gait parameters between the two groups prior to the treatment (P > 0.05), whereas walking velocity, stride length, stride frequency, gait cycle, affected side to healthy side limb support phase ratio, and affected side to healthy side swing phase ratio in the experimental group were superior to those in the pseudo stimulation group after treatment (P < 0.05). No significant differences were found between the two groups in terms of stride width, double limb support phase, affected side limb support phase (%), affected side limb swing phase (%), contralateral support phase (%), and contralateral swing phase (%) (P > 0.05). To conclude, low-frequency repetitive transcranial magnetic stimulation improves walking velocity, stride frequency, stride length and gait symmetry parameters, but has no effect on balance related parameters such as double limb support phase and stride width. Low-frequency repetitive transcranial magnetic stimulation can improve the gait of patients with hemiplegia to some extent. Figures and Tables | References | Related Articles | Metrics

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Hyaluronic acid around articular chondrocytes: production, transformation and function characteristics Xu Lei, Han Xiaoqiang, Zhang Jintao, Sun Haibiao 2022, 26 (5):  768-773.  doi: 10.12307/2022.125 Abstract ( 809 )   PDF (709KB) ( 238 )   Save BACKGROUND: Up to date, there is still no review on the metabolism and function of hyaluronic acid around articular chondrocytes. OBJECTIVE: To summarize the latest definition and experimental results of hyaluronic acid, thereby providing theoretical basis for the clinical application of hyaluronic acid. METHODS: The relevant literatures in CNKI, WanFang, and PubMed databases were searched by computer from the establishment of the database to November 2020. The keywords were “hyaluronic acid, cartilage, sodium hyaluronate, osteoarthritis, cartilage, chondrocytes” in Chinese and English, respectively. Finally, 75 eligible articles were included for further analysis. RESULTS AND CONCLUSION: Hyaluronic acid plays a variety of roles in the joint, especially in chondrocytes and its surrounding matrix. Hyaluronic acid provides a basic scaffold for proteoglycan aggregates, which can bear part of the cartilage load-bearing function. The pathway formed by hyaluronic acid and CD44 can transmit the information between cells and the surrounding matrix. Continuous turnover and renewal of hyaluronic acid and aggrecan can increase the ability of cartilage to resist external damages. Exogenous hyaluronic acid can protect cartilage, treat osteoarthritis, relieve pain, and even treat bone metastases. Figures and Tables | References | Related Articles | Metrics

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Roles and values of blood flow restriction training in the rehabilitation of knee joint diseases Wei Xing, Liu Shufang, Mao Ning 2022, 26 (5):  774-779.  doi: 10.12307/2022.126 Abstract ( 779 )   PDF (666KB) ( 1333 )   Save BACKGROUND: As a new type of rehabilitation training, blood flow restriction training is gradually increasing in the application of knee joint disease rehabilitation. It can promote muscle strength growth and muscle hypertrophy with lower exercise intensity. However, current research lacks a plan for blood flow restriction training for different groups of people. The effect of training variables and blood flow restriction on the therapeutic efficacy is unknown, and improper use may also cause safety problems. OBJECTIVE: To explain the application status of blood flow restriction training in knee joint disease rehabilitation, attempt to summarize blood flow restriction training from the aspects of application status, application scheme and safety, and propose urgent problems to be solved, aiming to provide theoretical support and practice for the safe and effective application of this technology guide. METHODS: in PubMed, CNKI and other literature databases, literature search was conducted for related research on the application of blood flow restriction training in knee joint disease rehabilitation from inception to October 29, 2020. The Chinese search formula included “blood flow restriction training OR plus Compression training,” “blood flow restriction training OR compression training AND knee joint,” “knee osteoarthritis OR knee surgery OR patellofemoral joint pain OR anterior knee pain OR rheumatoid arthritis AND blood flow restriction training OR compression training.” The English search formula included “(((blood flow restriction training) OR (Occlusion Training)) OR (Kaatsu training)) AND (knee),” “((((((knee osteoarthritis) OR (Knee surgery)) OR (patellofemoral pain)) OR (anterior knee pain)) OR (rheumatoid arthritis)) AND (blood flow restriction training)) OR (Kaatsu training).” And according to the research needs, the corresponding selection criteria were established for the screening of final literatures. RESULTS AND CONCLUSION: A review of relevant literature worldwide found that in the rehabilitation of knee joint diseases, blood flow restriction training is mainly used for patients with anterior cruciate ligament reconstruction and knee arthroscopy, knee osteoarthritis, patellofemoral joint pain, rheumatoid arthritis and anterior knee pain. Currently, in this group of patients, blood flow restriction training with lower exercise intensity has been found to promote muscle strength growth and muscle hypertrophy. The use of blood flow restriction alone can effectively prevent disused muscle atrophy due to no-load state, which is conductive to accelerating the rehabilitation process after surgery on the knee joint. In current studies, there are rarely adverse events related to blood flow restriction, but when using blood flow restriction combined with resistance training, it is necessary to ensure that the cuff width and restriction pressure used are appropriate. Future studies should compare different blood flow restriction training programs in different populations. Figures and Tables | References | Related Articles | Metrics

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Molecular mechanism by which icariin regulates osteogenic signaling pathways in the treatment of steroid-induced avascular necrosis of the femoral head Li Jiajun, Xia Tian, Liu Jiamin, Chen Feng, Chen Haote, Zhuo Yinghong, Wu Weifeng 2022, 26 (5):  780-785.  doi: 10.12307/2022.127 Abstract ( 568 )   PDF (868KB) ( 202 )   Save BACKGROUND: Studies have confirmed that icariin can promote osteogenesis and prevent and treat steroid-induced avascular necrosis of the femoral head (SANFH). Understanding the drug-target-pathway regulation mechanism will be crucial for the effective treatment of SANFH. OBJECTIVE: To review the research progress of icariin in the prevention and treatment of SANFH based on the mechanism by which icariin regulates osteogenesis through Wnt, PI3K/AKT, mTOR and estrogen signaling pathways, in order to provide ideas and reference for the effective prevention and treatment of SANFH. METHODS: Relevant literatures published from 2014 to 2020 were retrieved from PubMed, Web of Science, CNKI, VIP and WanFang databases, using the keywords of “icariin, glucocorticoid, ONFH, osteonecrosis of the femoral head,  signaling pathways, pathogenesis, Wnt, Wnt/β-catenin, PI3K/AKT, mTOR, ERs.” The old and repeated literatures were excluded, and a total of 56 literatures were finally included for analysis and discussion. RESULTS AND CONCLUSION: Icariin can promote bone metabolism and improve blood circulation, and its mechanism of action in the treatment of SANFH has become the focus of research. Icariin can regulate Wnt, PI3K/AKT, mTOR, estrogen receptor and other related signaling pathways to play an osteogenic role in the treatment of SANFH. Icariin has a regulatory effect on the signaling pathways related to SANFH. However, relevant experimental studies have not yet been able to specify its mechanism of action, and there are also few relevant clinical studies. Therefore, explorations on icariin’s mechanism of action and its clinical application will be the focus and direction of research. Figures and Tables | References | Related Articles | Metrics

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Femoroacetabular impingement: strength trainings for nerve-muscle, peripheral muscle and core muscle Lu Qinxue, Xu Ning, Yang Yinglan, Han Qianqian, Duanmu Xianyu, Guo Yuwei, Han Qing 2022, 26 (5):  786-791.  doi: 10.12307/2022.128 Abstract ( 1422 )   PDF (723KB) ( 465 )   Save BACKGROUND: Femoroacetabular impingement is a common cause of hip pain in adolescents. With the development of rehabilitation medicine, rehabilitation therapy has become one of the important methods to treat femoroacetabular impingement. OBJECTIVE: To provide new ideas and clues for further research and treatment of the disease by summarizing the latest achievements in the rehabilitation treatment of femoroacetabular impingement. METHODS: We searched the articles from December 2010 to October 2020 in PubMed, Cochrane, Web of Science, EMbase, CNKI, WanFang, VIP, SinoMed databases with the key words of “femoroacetabular impingement, femoroacetabular impingement syndrome, femoro-acetabular impingement” AND “rehabilitation, physiotherapy” AND “preoperative and postoperative rehabilitation of femoroacetabular impingement syndrome” in Chinese and English, respectively. Repetitive literatures and those that were not closely related to the purpose of this study were eliminated, and finally 61 articles were included for review. RESULTS AND CONCLUSION: Femoroacetabular impingement has pathological changes such as decreased muscle strength around the hip joint, decreased proprioception, changed activation pattern and coordination of deep muscles around the hip joint, and decreased mobility of the lower back and pelvis. The rehabilitation treatment of femoroacetabular impingement mainly focuses on muscle strength training around the hip joint, nerve-muscle training, core muscle strength training, preoperative and postoperative rehabilitation of hip arthroscopy, traditional Chinese medicine rehabilitation therapy, physical factor therapy and injection therapy. For patients with femoroacetabular impingement, muscle strength training around the hip joint can effectively reduce hip pain, increase range of motion and improve joint stability. Neuromuscular training can increase local muscle strength of the hip joint, improve proprioceptive sensation of the hip joint, and improve deep muscle synergy. Core muscle strength training can stabilize the lumbar vertebra and pelvis, reduce compensatory movement of the lumbar vertebra and pelvis, and enhance the effect of muscle strength training around the hip joint. Preoperative and postoperative rehabilitation training of hip arthroscopy can alleviate postoperative pain, improve patient’s function, and improve the therapeutic effect of hip arthroscopy. Traditional rehabilitation therapy and physical factor therapy can effectively eliminate joint inflammation and swelling and alleviate joint pain. Intraarticular injection of corticosteroids and sodium hyaluronate can effectively reduce hip pain and improve hip function in patients with femoroacetabular impingement. Figures and Tables | References | Related Articles | Metrics

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Sarcopenia: age-related muscle mass loss and functional declines Zheng Zhenquan, Rong Jiesheng 2022, 26 (5):  792-797.  doi: 10.12307/2022.129 Abstract ( 784 )   PDF (679KB) ( 2035 )   Save BACKGROUND: Sarcopenia is defined as a syndrome of progressive reduction in age-related skeletal muscle mass, accompanied by declines in muscle strength and/or function, triggering a series of undesirable consequences such as accidental fractures.  OBJECTIVE: To review the progress in the definition, measurement methods, correlation with fractures, prevention and treatment of sarcopenia. METHODS: PubMed and CNKI were searched for literatures related to sarcopenia using the keywords of “sarcopenia/muscular atrophy/muscle/fracture/treatment/prevention.” Keywords were searched alone and in combination, followed by full-text reading.  RESULTS AND CONCLUSION: EWGSOP, IWGS, AWGS and other working groups have developed a standardized definition and diagnosis of sarcopenia. However, the criteria for defining sarcopenia vary slightly in literatures included in PubMed. Risk of fractures is increased in older adults with sarcopenia, and sarcopenia will have a worse effect in patients with osteoporosis. Animal experiments have verified that sarcopenia and osteoporotic fractures coexist in animal models, and sarcopenia can lead to delayed fracture healing. Exercise and nutrition intervention are currently used prevention and treatment programs. Osteocalcin, omega-3 polyunsaturated fatty acids, soluble activin IIB receptor and stem cell transplantation have great potential in the treatment of sarcopenia. Figures and Tables | References | Related Articles | Metrics

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Exercise regulates adult hippocampal neurogenesis in Alzheimer’s disease: mechanism and role Tang Jiping, Zhang Yeting 2022, 26 (5):  798-803.  doi: 10.12307/2022.130 Abstract ( 588 )   PDF (812KB) ( 210 )   Save BACKGROUND: Studies have found that exercise can regulate adult hippocampal neurogenesis and improve cognitive function in patients with Alzheimer’s disease. However, the mechanism by which exercise affects adult hippocampal neurogenesis and improves cognitive function in patients with Alzheimer’s disease is not clear. OBJECTIVE: To analyze and summarize how exercise affects adult hippocampal neurogenesis and the mechanism of adult hippocampal neurogenesis in improving Alzheimer’s disease. METHOD: Literature search (from inception to December 2020) was performed in CNKI and Web of Science databases (including WOS, DIIDW, INSPEC, KJD, MEDLINE, RSCI, SCIELO) using “exercise, neurogenesis, AHN, Alzheimer’s disease, aging, cognition” as keywords, to investigate the effects of exercise on Alzheimer’s disease and adult hippocampal neurogenesis. All enrolled literatures were analyzed and reviewed according to certain logic.  RESULTS AND CONCLUSION: Exercise can regulate the overall dynamic balance of neuronal niche by increasing the proliferation of astrocytes and enhancing the secretion of glucose transporter 1, vascular endothelial growth factor, and brain-derived neurotrophic factor, so as to promote adult hippocampal neurogenesis in patients with Alzheimer’s disease patients. However, this process is affected by mediators, growth factors or neurotrophic factors, such as glutamate, γ-aminobutyric acid, 5-hydroxytryptamine, vascular endothelial growth factor, N-methyl-d-aspartic acid, and brain-derived neurotrophic factor. Figures and Tables | References | Related Articles | Metrics

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Effect of resistance training on interleukin-6 and C-reactive protein in middle-age and elderly people: a Meta-analysis Liu Yiyi, Qiu Junqiang, Yi Longyan, Zhou Cailiang 2022, 26 (5):  804-812.  doi: 10.12307/2022.131 Abstract ( 608 )   PDF (932KB) ( 383 )   Save OBJECTIVE: Chronic low-grade inflammation which causes many chronic diseases caused by age is easy to occur in the middle-age and elderly people. In order to estimate the effect of resistance training on interleukin-6 and C-reactive protein in middle-aged and elderly people, and study the effects of different sexes, duration of intervention and mode, this study provided scientific theory for the application of resistance training in the middle-aged and elderly.  METHODS: CNKI, WanFang Data, PubMed, Web of Science, and EBSCO were searched for randomized controlled trials or self-controlled trials about the effect of resistance training on interleukin-6 and C-reactive protein levels in the middle-aged and elderly published before May 2020. Literature screening and data extraction were conducted according to the established literature inclusion and exclusion criteria. Enrolled literatures were evaluated using Cochrane Handbood 5.1.0 and ROBINS-I 2.0. Meta-analysis was conducted using RevMan 5.3. Subgroup analysis was carried out between different sexes, duration of intervention and interventional modes. RESULTS: There were 13 eligible articles with 246 subjects, all of which were assessed as low-risk bias. Meta-analysis results showed that resistance training significantly reduced interleukin-6 levels (mean difference [MD]=-0.30, 95% confidence interval [CI]: -0.48 to -0.11, P=0.002), but showed no significant reduction in C-reactive protein levels (MD=-0.26, 95%CI: -0.54 to -0.02, P=0.07) in the middle-aged and elderly. Subgroup analysis indicated resistance training effectively reduced interleukin-6 levels in middle-aged and elderly people, which showed less association with interventional subjects and duration of intervention (P < 0.05). Resistance training less than 12 weeks could effectively reduce the C-reactive protein level (P < 0.05), and resistance training (MD=-0.25, 95% CI: -0.54 to 0.04, P=0.05) had better effect on reducing the C-reactive protein level compared with elastic band resistance training (MD=-0.34, 95% CI: -1.39 to 0.71, P=0.87). CONCLUSION: Resistance training can effectively reduce the interleukin-6 level, but has no significant reduction in the C-reactive protein level in the middle-aged and elderly. The short-term resistance training (< 12 weeks) has obvious effect on reducing the levels of interleukin-6 and C-reactive protein inflammatory factors. Furthermore, mechanical resistance training may be more effective than elastic band resistance training. Further explorations on the effect of resistance training on C-reactive protein level in different research objects are required in future. Figures and Tables | References | Related Articles | Metrics

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Network Meta-analysis of different acupuncture methods for the treatment of lumbar disc herniation  Wang Nan, Qian Yuzhang, Xie Lin 2022, 26 (5):  813-820.  doi: 10.12307/2022.132 Abstract ( 636 )   PDF (943KB) ( 313 )   Save OBJECTIVE: Acupuncture treatment for lumbar disc herniation has good results. However, there are many acupuncture methods. Pairwise comparisons have been mostly used in existing clinical studies, and there is a lack of direct comparisons of the therapeutic effects of several common acupuncture methods. Various acupuncture methods have been used for the treatment of lumbar disc herniation, among which abdominal, floating, warm, electroacupuncture, balance and conventional acupuncture are the most popular and have been widely used in clinical practice. Therefore, we evaluated the efficacy and safety of six acupuncture methods in the treatment of lumbar disc herniation with network Meta-analysis.  METHODS: Seven databases including PubMed, EMbase, Cochrane Library, SinoMed, CNKI, WanFang and VIP were searched by computers. Two reviewers independently searched, screened and extracted the data, and randomized controlled trials regarding acupuncture for treating lumbar disc herniation were finally included. Quality of the literatures was assessed using the risk of bias tool in the Cochrane Handbook, and RevMan 5.3, Stata 14 and Gemtc 0.14.3 software were used for data analysis RESULTS: Forty-three randomized controlled trials involving 5 175 patients were finally included and the quality assessment of the literatures was acceptable. The results of network Meta-analysis showed that: (1) in terms of clinical efficiency, all the six acupuncture methods could achieve good curative effects, and the order of efficacy probability was ranked as follows: abdominal needle (0.97) > warm needle (0.47) > floating needle (0.44) > electroacupuncture (0.53) > balance needle (0.52) > conventional acupuncture (0.98). (2) In terms of reducing visual analog scale scores, the order of probability was: floating needle (0.4) > warm needle (0.4) > abdominal needle (0.26) > electroacupuncture (0.44) > balance needle (0.56) > conventional acupuncture (0.79). (3) In terms of safety, only eight of the included literatures mentioned adverse reactions, five of which had no obvious adverse reaction events, and three articles mentioned the occurrence of needle insertion point pain and subcutaneous hematoma, but no symptoms remained after treatment.  CONCLUSION: Six acupuncture methods, including abdominal, floating, warm, electroacupuncture, balance and conventional acupuncture, all have good advantages in the treatment of lumbar disc herniation, with no obvious serious adverse reactions. Abdominal needle ranks first in overall clinical efficacy. Floating needle has the first possibility in reducing low back and leg pain. When a severe pain occurs, floating needle can be clinically prioritized. However, high-quality, multicenter, large-sample, randomized double-blind controlled trials are required to verify the reliability of this conclusion. Figures and Tables | References | Related Articles | Metrics