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    18 September 2021, Volume 25 Issue 26 Previous Issue    Next Issue
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    Low-intensity focused ultrasound and low-intensity pulsed ultrasound for mild traumatic knee osteoarthritis: differences in pain and function
    Yue Heng, Zhen Ping, Liang Xiaodi
    2021, 25 (26):  4101-4105.  doi: 10.12307/2021.105
    Abstract ( 572 )   PDF (644KB) ( 45 )   Save

    BACKGROUND: Current studies have shown that both focused and pulsed ultrasound can effectively improve the pathological performance of traumatic knee osteoarthritis, but it is not clear whether there is a difference between the two therapies.

    OBJECTIVE: To compare low-intensity focused ultrasound and low-intensity pulsed ultrasound in the treatment of mild traumatic knee osteoarthritis.
    METHODS: A retrospective study was conducted in 60 mild traumatic knee osteoarthritis patients treated with low-intensity focused ultrasound (n=30) or low-intensity pulsed ultrasound (n=30). Patients in both groups received drug treatments combined with low-intensity pulsed ultrasound or low-intensity focused ultrasound for 8 weeks. Assessments and measurements were conducted before treatment, on the day after treatment, and 3 months after treatment, including Visual Analogue Scale for assessing pain, the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index for assessing joint function of the affected knee, and ELISA kits for detecting serum levels of interleukin-1β, interleukin-6 and tumor necrosis factor α.
    RESULTS AND CONCLUSION: Compared with pre-treatment data, the Visual Analog Scale score, WOMAC score, and serum inflammatory factor levels were significantly decreased after treatment with low-intensity focused ultrasound and low-intensity pulsed ultrasound (P < 0.05). This therapeutic effect lasted for at least 3 months. Low-intensity focused ultrasound induced lower Visual Analogue Scale score, WOMAC score, and serum levels of interleukin-6 and tumor necrosis factor α as compared to the low-intensity focused ultrasound. It is suggested that both low-intensity focused ultrasound and low-intensity pulsed ultrasound can effectively treat mild traumatic knee osteoarthritis, and the low-intensity focused ultrasound has a better outcome than the low-intensity pulsed ultrasound.
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    Regulatory effects of LncRNA MEG3 on the proliferation and apoptosis of nucleus pulposus cells in rat intervertebral disc
    Cheng Ning, Zhang Zhizhong
    2021, 25 (26):  4106-4111.  doi: 10.12307/2021.118
    Abstract ( 314 )   PDF (793KB) ( 22 )   Save

    BACKGROUND: Injury of nucleus pulposus cells in the intervertebral disc is one of the important causes of degenerative disc disease. The mechanism of longchain non-coding RNA (LncRNA) in intervertebral disc degeneration has not been clarified.

    OBJECTIVE: To investigate the effect of LncRNA MEG3 on the proliferation and apoptosis of nucleus pulposus cells in rat intervertebral discs and its regulatory effect on phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.

    METHODS: Primary cultured rat nucleus pulposus cells were treated with interleukin 1β (IL-1β) to establish a cell model. There were five groups in this experiment, including control group, IL-1β group, IL-1β+pcDNA group, IL-1β+pcDNA-MEG3 group, and IL-1β+pcDNA-MEG3+LY294002 group. Real-time quantitative PCR was used to detect the expression of MEG3. MTT was used to measure cell proliferation. Flow cytometry was used to detect apoptosis rate.Western blot was used to detect the expression of Ki-67, proliferating cell nuclear antigen (PCNA), Bax, Cleaved Caspase-3, PI3K, p-PI3K, Akt, and p-Akt.
    RESULTS AND CONCLUSION: Compared with the control group, in the IL-1β group, the expression of MEG3 in the cells was significantly reduced (P < 0.05), the cell viability was significantly reduced (P < 0.05), the apoptosis rate was significantly increased (P < 0.05), the levels of Ki-67, PCNA, p-PI3K, and p-Akt proteins were significantly reduced (P < 0.05), and the levels of Bax and Cleaved Caspase-3 proteins were significantly increased (P<0.05). Compared with the IL-1β+pcDNA group, in the IL-1β+pcDNA-MEG3 group, the cell viability was significantly increased (P < 0.05), the levels of Ki-67, PCNA, p-PI3K, and p-Akt proteins were significantly increased (P < 0.05), the apoptosis rate was significantly reduced (P < 0.05), and the levels of Bax and Cleaved Caspase-3 proteins were significantly reduced (P < 0.05). Compared with the IL-1β+pcDNA-MEG3 group, in the IL-1β+pcDNA-MEG3+LY294002 group, the cell viability was significantly reduced (P < 0.05), the apoptosis rate was significantly increased (P < 0.05), the levels of Ki-67 and PCNA proteins were significantly reduced (P < 0.05), and the levels of Bax and Cleaved Caspase-3 proteins were significantly increased (P < 0.05). To conclude, overexpression of MEG3 may promote IL-1β-induced proliferation and inhibit apoptosis in rat nucleus pulposus cells by activating the PI3K/Akt signaling pathway.

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    MicroRNA-98-5p promotes osteoblast proliferation and differentiation: possibilities and mechanisms
    Zheng Feng, Zhang Fucai, Xu Zhe
    2021, 25 (26):  4112-4117.  doi: 10.12307/2021.107
    Abstract ( 339 )   PDF (1003KB) ( 36 )   Save

    BACKGROUND: MicroRNA-98-5p (miR-98-5p) can inhibit the high mobility group AT-HOOK 2 (HMGA2). The phosphatidylinositol 3-kinase/alkaline phosphatase/glycogen synthase kinase-3β (PI3K/AKT/GSK-3β) signaling pathway is involved in cell proliferation. During the fracture healing process, it is unclear whether miR-98-5p can act on the PI3K/Akt/GSK-3β pathway by activating HMGA2 to promote the proliferation of osteoblasts.

    OBJECTIVE: To investigate the mechanisms of microRNA-98-5p (miR-98-5p) in promoting osteoblast proliferation and differentiation by regulating HMGA2 and PI3K/Akt/GSK-3β pathway. 
    METHODS: MC3T3-E1 cells transfected with miR-98-5p mimics and HMGA2 plasmid by Lipofectamine 2000 were divided into a miR-98-5p mimics group and a HMGA2 overexpression group, respectively. MC3T3-E1 cells transfected with dimethyl sulfoxide and scrambled plasmids were divided into a mimic control group and a scramble group. Cells transiently transfected with miR-98-5p inhibitor using liposomes were as a miR-98-5p inhibitor group. Normal MC3T3-E1 cells without treatment were used as a blank control group. 
    RESULTS AND CONCLUSION: There were no significant differences in HMGA2, PI3K/Akt/GSK-3β, alkaline phosphatase activity and mRNA level between the blank control group and the mimic control group. Compared with the mimic control group, the HMGA2 and PI3K/Akt/GSK-3β protein expression, cell differentiation and proliferation, alkaline phosphatase activity and mRNA level were significantly reduced in the miR-98-5p mimics group. The interaction between miR-98-5p and HMGA2 predicted by Targetscan7.1 showed that compared with the mimic control group, the HMGA2 protein and mRNA were reduced in the miR-98-5p mimic group, while compared with the miR-98-5p mimic group, the HMGA2 protein and mRNA had an increase in the miR-98-5p inhibitor group. There were no significant differences in osteoblast proliferation, alkaline phosphatase activity and mRNA between the blank control group and the scramble group. Compared with the scramble group, the PI3K/Akt/GSK-3β expression, cell differentiation and proliferation, alkaline phosphatase activity and mRNA in the HMGA2 overexpression group were significantly increased. To conclude, miR-98-5p can inhibit the HMGA2 and PI3K/Akt/GSK-3β expressions in MC3T3-E1 cells, inhibit cell proliferation and differentiation. HMGA2 is possible the direct target of miR-98-5p.
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    Changes in bone morphology, bone mineral density and bone metabolism in different parts of natural aging rats
    You Bin, Huang Xiuzhu, Lin Yu, Huang Xi
    2021, 25 (26):  4118-4122.  doi: 10.12307/2021.108
    Abstract ( 278 )   PDF (1019KB) ( 105 )   Save

    BACKGROUND: Rats are a kind of quadruped rodents, with the bone weight being different from that of humans who walk upright, and the time course of bone homeostasis damage within the maximum life span of rats is also inconsistent with that of humans.

    OBJECTIVE: To explore the changes inbone metabolism in different rats during natural aging. 
    METHODS: A total of 80 Sprague-Dawley (SD) rats (male and female half) were randomly assigned into  7-,10-,15-,20-month groups according to their sex (n=10 per group). The study protocol was approved by the Animal Ethics Committee of Fuzhou Second Hospital Affiliated to Xiamen University with an approval No. 20160012 in June 2016.
    RESULTS AND CONCLUSION: The bone trabeculae of female and male SD rats at 7 to 10 months of age arranged regularly and formed a uniform dense network.The bone trabeculae of femaleSD rats at 15 to 20 months of age were fine, the spacing was widened, the arrangement was scattered and sparse, and there were many discontinuities.The bone trabeculae of male SD rats at 15 months of age were slightly smaller, the spacing was widened, and the arrangement was still orderly, and the bone trabeculae of male SD rats at 20 months of age were partially interrupted.The percentage of bone trabecular area in all parts of female and male SD rats began to decrease at 10 months of age, and reached the lowest value at 20 months of age.The bone mineral density also showed the same trend.The bone alkaline phosphatase level of female and male SD rats decreased gradually with the increase of month age.The level oftype 1 collagen carboxy terminal peptide in female SD rats increased gradually with the increase of month age, while that of male SD rats began to decrease gradually at 10 months of age with the increase of month age.To conclude, 7, 10, 15, and 20 months old can represent four different stages: bone growth balance, beginning to decline, decline accelerated, and complete decline, respectively.Female SD rats at 15-20 months of agewere in a high-transition state of bone metabolism. Male SD rats at 15-20 months of agewere in a low-transition state.
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    The difference between autologous and allogeneic purified platelet-rich plasma in the treatment of rabbit knee osteoarthritis
    Zhao Luting, Fang Qilin, Tang Haiyan, Xu Fangyuan
    2021, 25 (26):  4123-4129.  doi: 10.12307/2021.109
    Abstract ( 279 )   PDF (1174KB) ( 72 )   Save

    BACKGROUND: Purified platelet-rich plasma after activation can promote the proliferation of chondrocytes, regulate inflammation in the joints, and effectively treat knee osteoarthritis.

    OBJECTIVE: To compare the effects of autologous and allogeneic purified platelet-rich plasma in repairing knee osteoarthritis.
    METHODS: Thirty-two 3-month-old New Zealand big-eared rabbits were divided into four groups using a random number table method, with eight rabbits in each group: the normal group was treated without any treatment; in the model, autologous, and allogeneic groups, a knee osteoarthritis model was prepared by intra-articular injection of a mixed solution of papain and L-cysteine. After 2 weeks of modeling, the autologous group and allogeneic group were injected intra-articularly with autologous and allogeneic purified platelet-rich plasma, respectively. Platelet-rich plasma was injected once every 2 weeks for a total of three injections. Two weeks after the last injection, gross observation, histological observation and immunohistochemical observation of the articular cartilage were performed. The experiment was approved by the Laboratory Animal Management Committee of Southwest Medical University.
    RESULTS AND CONCLUSION: General observation: The surface of the articular cartilage of the model group was rough, cartilage defects, erosions, ulcers, joint osteophytes were formed, and there was a large amount of joint cavity effusion. Articular cartilage damage and osteophytes formation in the autologous group were lighter than those in the model group. Compared with the model group, the articular cartilage injury and osteophyte formation in the allogeneic group were not significantly improved. Histological observation: Compared with the model group, the cartilage structure, matrix staining, cells, and tide lines of the autologous group were significantly improved (P < 0.05); the cartilage structure of the allogeneic group was improved (P < 0.05), but there was no obvious improvement in cell arrangement, matrix staining, and tide line. Immunohistochemical observation: The expression of bone morphogenetic protein 2 and Sox9 in the autologous group and the allogeneic group was higher than that of the model group (P < 0.05), and the expression of bone morphogenetic protein 2 in the autologous group was higher than that of the allogeneic group (P < 0.05). To conclude, both autologous and allogeneic purified platelet-rich plasma can improve the proliferation of knee osteoarthritis chondrocytes and promote chondrocyte repair to a certain extent, but the therapeutic effect of autologous purified platelet-rich plasma is more obvious.
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    Effect of proanthocyanidins on proliferation and differentiation of skeletal muscle satellite cells under hypoxic-ischemic condition
    Chen Shi, Du Chao, He Xuemei, Zhou Xiangyu
    2021, 25 (26):  4130-4136.  doi: 10.12307/2021.110
    Abstract ( 431 )   PDF (862KB) ( 59 )   Save

    BACKGROUND: Limb ischemic injury is mainly caused by peripheral arterial disease. Surgical treatments can restore blood supply to the limbs, but ischemia-reperfusion can still aggravate tissue damage. Reducing oxidative stress and promoting regeneration of impaired skeletal muscle may offer a novel treatment opportunity for the ischemic limb.

    OBJECTIVE: To investigate the effect of proanthocyanidins on proliferation and differentiation of skeletal muscle satellite cells under hypoxic-ischemic condition.
    METHODS: The primary cultured skeletal muscle cells were purchased and the passage 2 cells were used for subsequent experiment. There was a control group treated with normal saline and two experimental groups treated with 2.5 or 5 mg/L procyanidins. The cells in each groups were cultured in an environment of low oxygen (1% O2) and low serum (1% fetal bovine serum), and were observed at different time points. Cell proliferation was detected by cell counting kit-8 method at 1, 2, 3 and 4 days of culture. The cells were collected at 1 day of culture. Cell cycle was detected by flow cytometry. Total proteins were extracted and the expression of proliferation-related proteins, myogenic marker genes and pathway-related proteins were detected by western blot assay. The morphology of myotubes was detected using laser scanning confocal microscope. To further clarify the role of the P38-MAPK signaling pathway, four groups were set up, namely a normal saline group (control group), a proanthocyanidin group, a normal saline+P38-MAPK pathway inhibitor group, and a proanthocyanidin+P38-MAPK pathway inhibitor group. The expressions of myogenic marker genes and related pathway proteins in the cells were detected. The animal experiment was approved by the Animal Experiment Ethics Committee of Southwest Medical University. The mice were randomly treated with saline (n=12) or 20 mg/kg proanthocyanidin (n=12) via intraperitoneal injection after hind limb ischemia modeling. Gastrocnemius was taken from the mice at 7 days after intervention, and muscle regeneration was observed by hematoxylin-eosin staining. 
    RESULTS AND CONCLUSION: (1) Cell experiment: Under hypoxic-ischemic condition for 1, 2, 3 and 4 days, the proliferation ability of cells in the proanthocyanidin groups were significantly higher than that of the control group (P < 0.05).Under hypoxic-ischemic condition for 1 day, the expression levels of proliferating cell nuclear antigen protein in the proanthocyanidin groups were significantly higher than that in the control group (P < 0.05).Under hypoxic-ischemic condition for 1 day, the number of S-phase cells in the proanthocyanidin groups was significantly higher than that in the control group (P < 0.05).Under hypoxic-ischemic condition for 3 or 5 days, the expression of myogenic marker gene and the formation of myotubes in the proanthocyanidin groups were significantly higher than those in the control group (P < 0.05). The above-mentioned indexes showed no significant difference between the two proanthocyanidin groups (P > 0.05). Under hypoxic-ischemic condition for 3 days, p-P38-MAPK signaling pathway-related proteins were significantly highly expressed in the proanthocyanidin groups compared with the control group (P < 0.05). However, there was no significant difference between saline+p38-mapk pathway inhibitor group and proanthocyanidin+p38-mapk pathway inhibitor group (P > 0.05). (2) Animal experiment: After lower extremity ischemia for 7 days, proanthocyanidin-treated mice contained a higher number of regenerating myofibers than that in the control group (P < 0.05). To conclude, proanthocyanidin can promotes the proliferation of skeletal muscle satellite cells under hypoxic-ischemic condition, and meanwhile induces the expression of myogenic marker genes and formation of muscle tube by activating p38-MAPK signaling pathway, so as to promote regeneration of ischemic damaged skeletal muscle and repair damaged myofibers, exerting an important protective role.

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    Changes of serum and liver bile acid profiles in a mouse model of metabolic associated fatty liver disease induced by a methionine-choline-deficient diet
    Yang Hailin, Zhang Dingqi, Chen Gaofeng, Zhang Congcong, Chen Jiamei, Wang Xiaoning, Liu Wei, Liu Ping
    2021, 25 (26):  4137-4144.  doi: 10.12307/2021.111
    Abstract ( 418 )   PDF (1307KB) ( 79 )   Save

    BACKGROUND: Methionine-choline-deficient (MCD) model is widely used to induce metabolic associated fatty liver disease. There are few dynamic changes of bile acid profiles reported in the existing relevant research; however, the regulation of bile acid is one of the important ways to intervene with the lipid metabolism of liver. Therefore, it is necessary to clarify the dynamic changes of bile acid profiles during model establishment.

    OBJECTIVE: To investigate the changes of bile acid profiles in serum and liver of mice with metabolic associated fatty liver disease induced by feeding a MCD diet. 
    METHODS: After 1 week of adaptive feeding, 60 male C57/BL6J mice were randomly divided into 2 groups, with 30 mice in each group. One group was fed with methionine-choline-sufficient diet (MCS), and the other group was fed with MCD diet, with free access to food and water. At the end of the 4th, 6th, and 8th week, 10 mice were randomly selected from each group, with serum and liver tissue samples of mice collected. The activities of alanine aminotransferase and aspartate aminotransferase in serum and the content of triglyceride in liver tissue were detected. Hematoxylin-eosin staining, oil red O staining and sirius red staining were used for pathological evaluation. The contents of 18 kinds of bile acids in serum and liver were measured by ultra-performance liquid chromatography-tandem mass spectrometry. 
    RESULTS AND CONCLUSION: The test results of animal samples with different modeling time showed that, compared with the MCS diet group, the activity of alanine aminotransferase and aspartate aminotransferase in serum and the content of triglyceride in liver tissue were significantly increased in the MCD diet group at each observational time (P < 0.05). Compared with the MCS diet group, extensive hepatocyte steatosis was found in liver tissue, collagen fibers around sinusoids increased, and non-alcoholic fatty liver disease activity score increased significantly in the MCD diet group at each observational time. Compared with the MCS diet group, the content of total free bile acids and total combined bile acids and the content of bile acids except taurodeoxycholic acid in the serum of the MCD diet group showed an upward trend, and the value of cholic acid/chenodeoxycholic acid increased significantly. Compared with the MCS diet group, the contents of total free bile acids, bile acids, glycocholic acid, glycochenodeoxycholic acid, and taurocholic acid in the liver of the MCD diet group showed an increasing trend, while the contents of chenodeoxycholic acid, ursodeoxycholic acid, hyodeoxycholic acid, tauroursodeoxycholic acid, taurolithocholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid in the liver decreased. The content of glycodeoxycholic acid decreased first and then increased with the extension of modeling time. The contents of deoxycholic acid and taurohyodeoxycholic acid remained basically unchanged, and the value of cholic acid/chenodeoxycholic acid increased significantly. All these findings show that the bile acid profiles in the serum and liver of mice with metabolic fatty liver disease induced by MCD diet change significantly, and especially the increase of cholic acid/chenodeoxycholic acid ratio may play a key role. It is suggested that the development of metabolic fatty liver disease in the MCD model may be closely related to the changes of bile acid profiles and its toxicity.
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    Epigallocatechin gallate alleviates skeletal muscle ischemia-reperfusion injury in rats
    Xue Qing, Tong Liangcheng, Yang Zhiwei, Wang Jianling, Zhao Lei, Zhou Sheng, Peng Sai, Li Ying
    2021, 25 (26):  4145-4149.  doi: 10.12307/2021.112
    Abstract ( 430 )   PDF (990KB) ( 43 )   Save


    BACKGROUND: Skeletal muscle ischemia-reperfusion (I/R) injury is a serious problem commonly encountered in clinical practice which seriously impacts the function and survival rate of replanted limbs. Epigallocatechin gallate (EGCG) has been proved to be antioxidant, anti-inflammatory and anti-apoptotic. 

    OBJECTIVE: To investigate the role of EGCG in I/R injury of rat skeletal muscle.
    METHODS: Thirty male Sprague-Dawley rats were randomly divided into five groups: sham operation group, I/R group, and three EGCG groups in which 10, 100 and 200 mg/kg EGCG was intraperitoneally injected 30 minutes before reperfusion respectively according to the weight of the rats. A lower limb I/R injury model was made in each group except for the sham operation group. The levels of tumor necrosis factor-α and interleukin-1β in serum were measured and the levels of superoxide dismutase and myeloperoxidasein gastrocnemius muscle tissue were detected. Morphological changes of gastrocnemius muscle tissue were observed by hematoxylin-eosin staining. Cell apoptosis in gastrocnemius muscle tissue was observed by the TUNEL assay.
    RESULTS AND CONCLUSION: In the 100 and 200 mg/kg EGCG groups compared to the I/R group, there were the decreased levels of tumor necrosis factor-α and interleukin-1β in serum and myeloperoxidase in gastrocnemius muscle tissue and the increased level of superoxide dismutase in gastrocnemius muscle tissue, which were positively correlated with the EGCG dose. Hematoxylin-eosin staining results suggested an evident improvement in pathological manifestations ofgastrocnemius muscle, such as the continuity and integrity of muscle fibers and the degree of interstitial edema, in 100 and 200 mg/kg EGCG groups. TUNEL assay showed that 100 and 200 mg/kg EGCG inhibited cell apoptosis in gastrocnemius muscle tissue. To conclude, EGCG protects rat skeletal muscle from I/R injury by reducing inflammatory reaction, antioxidant stress and inhibiting apoptosis.
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    Effect of Tongluo Shenggu Capsule on toll-like receptor 4 signaling pathway in rats with steroid-induced osteonecrosis of the femoral head
    Liu Jinfu, Zeng Ping, Nong Jiao, Fan Siqi, Qian Xiaofen, Feng Chengqin, Lei Zhiqiang, Luo Jun, Huang Jiaxing
    2021, 25 (26):  4150-4155. 
    Abstract ( 284 )   PDF (899KB) ( 44 )   Save

    BACKGROUND: Early pharmacological studies have found that Tongluo Shenggu Capsule has various mechanisms for repairing steroid-induced osteonecrosis of the femoral head (SANFH), but its influence on the toll-like receptor 4 (TLR4) signaling pathway has not been documented.
    OBJECTIVE: To investigate the molecular mechanism of Tongluo Shenggu Capsule in SANFH treatment based on the TLR4 signaling pathway.
    METHODS: A total of 60 female Sprague-Dawley rats were randomly divided into a normal group (20 rats) and a model group (40 rats). Endotoxin combined with methylprednisolone was used to establish the SANFH rat model. The normal group was injected with normal saline at the same volume. After modeling, 5 rats from the normal group and 10 rats from the model group were selected for observation under light microscope. The 30 rats successfully modeled were randomly divided into two groups: a hormone group and an intervention group with 15 rats in each group. The intervention group was given Tongluo Shenggu Capsule solution 0.4 g/kg once a day for 4 weeks. The hormone group and the normal group were given the same dose of normal saline for 4 weeks, once a day. The hormone and normal groups were given the same amount of normal saline once a day for 4 weeks. After the end of intervention, bilateral femoral heads of rats in each group were taken for morphological observation and pathological detection. Expressions of TLR4, MyD88, tumor necrosis factor-β and nuclear factor-κB proteins were detected by western blot.
    RESULTS AND CONCLUSION: The femoral head of rats in the normal group had a lustrous and smooth appearance without deformation or collapse. The femoral head of rats in the hormone group had a dull, purple appearance and a large area, while the femoral head of rats in the intervention group tended to be normal. Hematoxylin-eosin staining results showed that in the hormone group, trabeculae of the femoral head were sparse and even broken, bone nuclei were solidified, dissolved and disappeared, and the number of empty bone lacunae was the largest. Compared with the normal group and the intervention group, the difference in the rate of empty bone lacunae was significant (P < 0.05). In the intervention group, the bone trabeculae were large and regular, and the cell morphology was mostly normal, which was improved compared with the hormone group. Protein levels of nuclear factor-κB, tumor necrosis factor-β, MyD88 and TLR4 detected by western blot were significantly lower in the normal group and the intervention group than in the hormone group (P < 0.05). There was no significant difference in TLR4 and MyD88 expression between the intervention group and the normal group (P > 0.05). In conclusion, the mechanism of Tongluo Shenggu Capsule in SANFH treatment may be related to inhibition of MyD88-dependent TLR4 signaling pathway.
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    Piezo 1 mediates apoptosis of fibroblast-like synovial cells in rheumatoid arthritis via MAPK/ERK5 signaling pathway
    Qu Xiangyang, Song Qinyong
    2021, 25 (26):  4156-4161.  doi: 10.12307/2021.114
    Abstract ( 460 )   PDF (988KB) ( 43 )   Save


    BACKGROUND: Previous studies have mostly focused on immune factors involved in the pathogenesis of rheumatoid arthritis. Recently, increasing attention has been paid to the role of biomechanical factors in the occurrence and development of rheumatoid arthritis.
    OBJECTIVE: To explore the mechanism by which Piezo1 mediates apoptosis of fibroblast-like synovial cells in rheumatoid arthritis through MAPK/ERK5 signaling pathway.  
    METHODS: The tissue block method was used to culture synovial cells of rheumatoid arthritis. The stretch stress model of cells in vitro was constructed by Flexcell 5000T cell stretch stress system, and piezo1 siRNA gene interference vector and overexpression plasmid were constructed. According to the preliminary experimental results and treatment plan, fibroblast-like synovial cells of rheumatoid arthritis were divided into six groups: siRNA interference group, overexpression plasmid group, blank control group, siRNA interference+BIX02188 group, overexpression plasmid+BIX02188 group, and blank control+BIX02188 group. The expression of Piezo1, ERK5 and apoptosis-associated genes were detected by RT-PCR, the intracellular calcium content was detected by Fluo-3 AM probe, and the apoptotic level was detected by AV-PI kit.   
    RESULTS AND CONCLUSION: The intracellular Ca2+ content of the siRNA interference+BIX02188 group was significantly lower than that of the siRNA interference group (P < 0.05); the intracellular Ca2+content of the overexpression plasmid+BIX02188 group was significantly lower than that of the overexpression plasmid group (P < 0.05). The relative expression of Piezo1 and ERK5 mRNA in the siRNA interference group was significantly lower than that in the blank control group (P < 0.05), and that in the overexpression plasmid group was significantly higher than that in the blank control group (P < 0.05). The expression of Piezo1 mRNA did not change after BIX02188 inhibition; however, the relative expression of ERK5 mRNA in the siRNA interference+BIX02188 group was significantly lower than that in the siRNA interference group (P < 0.05), and the expression of ERK5 mRNA in the overexpression plasmid+BIX02188 group was significantly lower than that in the overexpression plasmid group (P < 0.05). The early apoptotic rate, the late apoptotic rate and the total apoptotic rate in the siRNA interference group were significantly lower than those in the blank control group (P < 0.05), whereas the early apoptotic rate, the late apoptotic rate and the total apoptotic rate in the overexpression plasmid group were significantly higher than those in the blank control group (P < 0.05). To conclude, the overexpression of Piezo 1 protein can promote the apoptosis of rheumatoid arthritis fibroblast-like synovial cells, and the apoptotic signal mediated by the MAPK/ERK5 signaling pathway can act as the potential target gene for treating rheumatoid arthritis.

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    Effect of GOLM1 gene knockout on renal fibrosis in mice with unilateral ureteral obstruction
    Qin Jianfang, Wang Huan, Wu Bingbing, Ma Xiaojing
    2021, 25 (26):  4162-4167.  doi: 10.12307/2021.115
    Abstract ( 362 )   PDF (780KB) ( 34 )   Save


    BACKGROUND: Golgi membrane protein 1 (GOLM1) is widespread in human tissues, and its abnormal expression is closely related to cancer, viral infections and other diseases. Studies have shown that GOLM1 can regulate some fibrotic cytokines, but its role in renal fibrosis is unclear.

    OBJECTIVE: To study the potential effects of GOLM1 on renal fibrosis in mice.
    METHODS: Twelve 6-8-week-old GOLM1 knockout mice and 12 C57BL/6 wild type mice were selected and received an operation with left ureteral obstruction. The right kidney served as a control. The mice were sacrificed on the 4th day after the operation. The kidneys of the mice were divided into four groups: WT-C, WT-UUO, KO-C and KO-UUO. Hematoxylin-eosin staining and Masson staining were used to observe the renal tissue pathology and the degree of renal fibrosis. The mRNA expression of extracellular matrix components such as type I collagen α1 and fibronectin were detected by qRT-PCR. Flow cytometry was used to detect the proportion of macrophages. The expressions of inflammatory factors were detected by qRT-PCR. The study protocol was approved by the Experimental Animal Ethics Committee of Shanghai Jiaotong University.
    RESULTS AND CONCLUSION: The kidneys of the WT-UUO and KO-UUO groups showed obvious kidney injury and renal interstitial fibrosis, and the expression of type I collagen α1 and fibronectin was remarkably increased. Compared with the WT-UUO group, the KO-UUO group had significantly severer renal damage, severer inflammatory cell infiltration and higher expression of extracellular matrix components (P < 0.05). There was no obvious renal injury, renal fibrosis, and extracellular matrix deposition in the kidneys of WT-C group and KO-C group. Compared with the WT-UUO group, the mRNA expression of interleukin-6, tumor necrosis factor α, interleukin 1β, C-C motif chemokine ligand 5 and monocyte chemotactic protein 1 increased significantly in the KO-UUO group (P < 0.05). Besides, the proportion of macrophage infiltration was also increased significantly in the KO-UUO group (P < 0.05). In the two control groups, there was less macrophage infiltration and low expression of inflammatory mediators in the renal tissue. To conclude, GOLM1 plays a protective role in the development of renal fibrosis. Its mechanism may be related to macrophage infiltration and the regulation of inflammatory mediators.
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    Extracellular matrix promotes fibroblast proliferation and post-operation knee arthrofibrosis through ERK signaling pathway
    Hou Jingzhao, Zhang Zhen
    2021, 25 (26):  4168-4174.  doi: 10.12307/2021.116
    Abstract ( 391 )   PDF (1333KB) ( 66 )   Save

    BACKGROUND: Osteoporosis and fracture type are two important reasons for the failure of internal fixation of proximal femoral nail antirotation. Type AO31-A3.3 interArthrofibrosis is one of the most serious complications. It is currently considered that extracellular matrix plays an important role in the occurrence of fibrosis; however, the mechanism of extracellular matrix is still unclear. 

    OBJECTIVE: To explore the effect of extracellular matrix on post-operation arthrofibrosis and fibroblast proliferation in vitro.  
    METHODS: (1) In vivo test: twelve New Zealand rabbit models of lower-lime knee arthrofibrosis were established; and the influence of the extracellular matrix on post-operation arthrofibrosis was studied by hematoxylin-eosin staining, Masson staining, Sirius red staining and proliferating cell nuclear antigen immunohistochemical staining at 2 and 4 weeks after surgery. (2) In vitro test: Fibroblast derived extracellular matrix and decellularized extracellular matrix were constructed, and the thickness of extracellular matrix was measured by confocal three-dimensional imaging. Fibroblasts were cultured in three-dimensional and two-dimensional extracellular matrix. The function of extracellular matrix was evaluated by cell membrane staining and rapid cell attachment test. Cell count, EdU test, cell cycle and western blot assay were used to evaluate the effect of extracellular matrix on cell proliferation, and the expression of ERK signaling pathway protein was detected.
    RESULTS AND CONCLUSION: In vivo test: hematoxylin-eosin staining, Masson trichrome staining and Sirius red staining results showed that the degree of fibrosis was serious at 4 weeks; and the collagen synthesis of extracellular matrix in arthrofibrosis tissue increased obviously. Sirius red staining results showed that the collagen was mainly composited of collagen type I and III. Immunohistochemical staining showed that number of fibroblasts and the level of PCNA protein in fibrotic tissue increased 4 weeks after operation. In vitro test: The thickness of the outer matrix was more than 10 μm. Cell membrane staining showed that fibroblasts in three-dimensional culture were spindle shaped, while those in two-dimensional culture were irregular. rapid cell attachment test demonstrated that the number of cell adhesion in three-dimensional culture was 6 times that in two-dimensional culture (P < 0.05). Cell count, EdU test, and cell cycle analysis showed that the proliferation of fibroblasts in three-dimensional culture was faster than that in two-dimensional culture (P < 0.05). Western blot assay showed that the expression of PCNA, Cyclin D1, p-MEK and p-ERK in three-dimensional culture was higher than that in two-dimensional culture            (P < 0.05). In summary, extracellular matrix promotes the occurrence of post-operation arthrofibrosis and fibroblast proliferation possibly through ERK signaling pathway.
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    Lipoxanthin A4 plays a neuroprotective role against spinal cord ischemia-reperfusion injury in rats
    Lu Tan, Chang Yaohui, Wei Na
    2021, 25 (26):  4175-4179.  doi: 10.12307/2021.117
    Abstract ( 377 )   PDF (807KB) ( 59 )   Save

    BACKGROUND: Previous studies have indicated that lipoxin A4 has a neuroprotective effect against spinal cord injury in rats, but its mechanism of action in spinal cord ischemia-reperfusion injury is still unclear.

    OBJECTIVE: To investigate the neuroprotective effect of lipoxin A4 in rats with spinal cord ischemia-reperfusion injury. 
    METHODS: Forty-eight Sprague-Dawley rats were randomized into three groups (n=16 per group): Spinal cord ischemia-reperfusion injury models were built in control and experimental groups followed by intrathecal injection of normal saline and lipoxin A4 respectively, and no treatment was given in blank control group. Basso-Beattie-Bresnahan (BBB) score was used to evaluate motor nerve function in rats at 6, 12, 24, and 48 hours after modeling. At 24 hours after reperfusion, TUNEL assay was used to detect cell apoptosis in the rat spinal cord; ELISA was used to detect the levels of Bcl-2 and Bax in the rat spinal cord, and western blot assay was used to detect the levels of cleaved-caspase-3, p-IKKβ and p-NF-κB proteins in the rat spinal cord. This experiment was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical University (approval No. 2018038).
    RESULTS AND CONCLUSION: Compared with the blank control group, the BBB scores were lower in the control group at different observation time points 
    (P < 0.05), while compared with the control group, the BBB score was higher in the experimental group at 12, 24, and 48 hours after modeling (P < 0.05). There were more apoptotic cells in the control group than the blank control group (P < 0.05), while the number of apoptotic cells in the experimental group was lower than that in the control group (P < 0.05). The levels of Bcl-2 and Bax in the spinal cord were significantly higher in the control group than the blank control group, while compared with the control group, the experimental group showed a higher Bcl-2 level and a lower Bax level (P < 0.05). Compared with the blank control group, the expressions of cleaved-caspase-3 and p-NF-κB proteins were strongly higher in the control group, while the protein expression of p-IKKβ was weaker in the control group. Compared with the control group, the expressions of cleaved-caspase-3 and p-NF-κB proteins were lower in the experimental group, while the protein expression of p-IKKβ was higher in the experimental group. These findings indicate that lipoxin A4, as a therapeutic agent for spinal cord ischemia-reperfusion injury, can inhibit cell apoptosis by activating the Caspase-3/IKKβ/NF-κB pathway in the cytoplasm.

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    Transcranial direct current stimulations at bilateral brain motor areas elevate maximum output power of both lower limbs
    Hu Huili, Li Danyang, Nie Qiu, Ni Lili, Chen Yiyi
    2021, 25 (26):  4180-4185.  doi: 10.12307/2021.106
    Abstract ( 346 )   PDF (710KB) ( 65 )   Save

    BACKGROUND: Transcranial direct current stimulation technology is a new type of brain stimulation technique that has been proved to improve muscle strength, aerobic endurance, and cognitive ability. However, whether transcranial direct current stimulation can improve the ability of lower limb power output or not is less researched.

    OBJECTIVE: To investigate the effect of single-session anodal transcranial direct current stimulation at bilateral brain motor areas on countermovement jump performance.
    METHODS: Twelve healthy male college students, (24.25±1.21) years old, height: (175.91±4.60) cm, weight: (76.56±8.72) kg, were recruited. Randomized crossover design was used, and the subjects were randomly assigned to anode stimulating group or sham stimulating group. The experiment was conducted twice, with an departing interval of 7 days. All the subjects were given 2 mA anodal or sham stimulation for 20 minutes targeting the bilateral motor cortex.  A countermovement jump test was conducted before each stimulation. Jump height and relative maximum power were recorded immediately after stimulation and every 10-minute intervals during 1 hour after stimulation, in order to analyze the effect of anodal stimulation on the countermovement jump of healthy men. Pearson’s correlation analysis was used to judge the test-retest reliability of the experiment, and repeated measurement variance analysis was used to compare the jump height and relative maximum power of the countermovement jump test between the two groups at different time periods. The implementation of the study complied with the relevant ethical requirements of Wuhan Sports University with an approval No. 2019006. All the subjects voluntarily participated in the trial and signed an informed consent form.
    RESULTS AND CONCLUSION: For the test-retest reliability, the correlation coefficient of jump height was 0.921 (P < 0.001), and the correlation coefficient of relative maximum power was 0.938 (P < 0.001). For the relative maximum power, the main effect of the group was significant(P < 0.05, pη2=0.557). The relative maximum power of the stimulating group (4.9%) was significantly higher than that of the sham stimulating group. There were no significant differences in the interaction of group × time and the main effect of the time on the relative maximum power (P > 0.05, pη2=0.072 and 0.062). For the jump height, the interaction of group × time and the main effect of group and time had no significant difference (P > 0.05, pη2=0.088, 0.196 and 0.069). These findings indicate that the maximum output power of lower extremities of healthy adult males is increased within 1 hour after anodal transcranial direct current stimulation (2 mA, 20 minutes) at bilateral motor areas of the brain.
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    An overview of modeling and evaluation indexes of experimental animals with sciatic nerve injury
    Su Jing, Ling Chunyan, Lei Longming
    2021, 25 (26):  4186-4191.  doi: 10.12307/2021.119
    Abstract ( 402 )   PDF (720KB) ( 37 )   Save

    BACKGROUND: There are various limitations for in vitro research regarding nerve repair and regeneration following sciatic nerve injury. Therefore, it is particularly important to seek animal models that are more suitable for research on human sciatic nerve injury and to develop practical evaluation methods or indicators.

    OBJECTIVE: To review the research progress on the establishment and evaluation indexes of sciatic nerve injury in animal models in the past 10 years by retrieving the relevant literature on sciatic nerve injury, so as to provide a theoretical basis for the research on the pathogenesis of sciatic nerve injury and for the exploration on new treatment methods.

    METHODS: Databases of CNKI, WanFang, VIP, Sinomed, PubMed and Web of Science were searched for relevant literature published from 2010 to 2020. The search words were “sciatic nerve injury” and “animal models” in Chinese and English, respectively. Authoritative journal articles were preferred, and finally 58 articles were included.

    RESULTS AND CONCLUSION: The establishment methods of sciatic nerve injury animal models include physical injury and chemical injury. The animal model prepared using the clamp pressure injury method is more suitable for observing the morphology and behavior of the nerve because the continuity of the nerve is not interrupted. The animal model prepared using the transverse injury method is more suitable for observing neurotrophic factors and related proteins that promote nerve regeneration. The animal model prepared using the entrapment method is suitable for the observation of inflammatory factors. According to the experimental purposes and clinical research needs, selecting the appropriate animal model, optimizing and summarizing the animal model,and carrying out relevant research on practical indicators are the key to the in-depth experimental study on the pathology and pathogenesis of this disease.

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    Autophagy regulates osteoclast proliferation, differentiation and function through mitogen-activated protein kinase signaling pathway
    Yang Yuchen, Yang Peipei, Huang Biying, Zhang Qiang
    2021, 25 (26):  4192-4197.  doi: 10.12307/2021.120
    Abstract ( 270 )   PDF (567KB) ( 43 )   Save

    BACKGROUND: Bone homeostasis is mainly kept relying on the synergistic effect between osteoclasts and osteoblasts. Mitogen-activated protein kinase-mediated autophagy exerts some effects on proliferation, differentiation and function of osteoclasts, which is likely to disrupt the bone homeostasis, thus affecting bone reconstruction in tissue engineering.

    OBJECTIVE: To analyze the effects of mitogen-activated protein kinase-mediated autophagy on osteoclasts based on existing experimental and clinical data.
    METHODS: The relevant literatures in CNKI, WanFang, and PubMed database were searched by computer. The retrieval time was from inception to June 31, 2020. The keywords were “mitogen activated protein kinase, osteoclast, autophagy” in Chinese and “mitogen-activated protein kinase, ERK, P38, JNK, osteoclast, autophagy” in English.
    RESULTS AND CONCLUSION: Mitogen-activated protein kinase cannot only mediate autophagy and affect osteoclasts, but also activate other signaling pathways to mediate autophagy together. Autophagy mediated by extracellular signal-regulated kinase pathway is often accompanied by Ca2+ involvement, which mainly affects osteoclast differentiation and function. c-Jun N-terminal kinase influences osteoclast maturation and differentiation mainly through the co-action of Beclin-1. p38 kinase-mediated autophagy has a two-way effect on promotion and inhibition, thus affecting the proliferation and differentiation of osteoclasts.
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    MicroRNA-21 — an important regulator of bone regeneration and various bone diseases
    Peng Hongcheng, Hua Zhen, Wang Jianwei
    2021, 25 (26):  4198-4203.  doi: 10.12307/2021.121
    Abstract ( 446 )   PDF (623KB) ( 36 )   Save

    BACKGROUND: As a non-coding RNA processed by primary transcription, microRNA-21 (miR-21) plays an important role in biological functions such as growth and development, cancer diagnosis and treatment, immune response, osteogenic differentiation and bone regeneration.

    OBJECTIVE: To review the cellular targets of miR-21 in bone, the molecular mechanisms that regulate bone regeneration, and the role of miR-21 in bone disease.
    METHODS: With the keywords of “mir-21, bone, osteogenic differentiation of osteoclast differentiation, skeletal muscle, bone regeneration” in English and “miR-21, bone, skeletal muscle, bone regeneration” in Chinese, PubMed, CNKI, and WanFang databases were retrieved by the first author for articles regarding miR-21 published from 2000 to April 2020. Finally 50 articles were retained for review.
    RESULTS AND CONCLUSION: In recent years, miR-21 has not only been deeply studied as an oncogene, but also received extensive attention in the proliferation, differentiation, metabolism and other aspects of bone cells. Specifically, miR-21 can mediate the growth and development of skeletal muscle by regulating the expression of transforming growth factor β induced gene and other genes. MiR-21 can promote the osteogenesis of bone marrow mesenchymal stem cells by targeting specific signaling pathways and related gene expression. It can also regulate the positive feedback of osteoclast differentiation through c-Fos/tumor suppressor gene programmed death factor 4, and promote the formation of osteoclasts induced by RANKL. It also regulates the differentiation of dendritic cells and indirectly regulates the expression of hypoxia inducible factor 1α and vascular endothelial growth, which mediates the angiogenesis of stem cells. In addition, miR-21 is closely associated with osteoporosis, osteosarcoma, multiple myeloma, knee osteoarthritis and ankylosing spondylitis.

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    Application of single-cell RNA sequencing technology in the study of skeletal system biology
    Zhu Bin, Yan Yiguo
    2021, 25 (26):  4204-4210.  doi: 10.12307/2021.122
    Abstract ( 332 )   PDF (653KB) ( 118 )   Save

    BACKGROUND: Single-cell RNA sequencing technology can obtain gene expression profile from single cell level, understand the heterogeneity of cells in tissue samples, discover new cell types and related cell-specific markers, and gain a deeper understanding of the skeletal system.

    OBJECTIVE: To introduce the basic principles of single-cell RNA sequencing technology and review the application of single cell RNA sequencing technology in skeletal system biology in recent years, and further discuss the normal physiology of bone system and pathophysiology and pathogenesis of related diseases.
    METHODS: The first author searched PubMed, CNKI and WanFang databases with the key words of “single cell RNA sequencing technology, bone/skeletal, tendons, ligaments, bone/skeletal diseases” in English and Chinese, respectively. And finally 75 literatures were included for review.
    RESULTS AND CONCLUSION: Single-cell RNA sequencing technology as a new research method has shown its good development prospects. Novel cell types, related cell specific markers and potential functions of novel cells can be found in skeletal system biology. However, there are still some shortcomings in the separation of special samples and high cost. Therefore, it is still necessary to further improve the sequencing technology and expand its development space.
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    Animal models of femoral head necrosis: classification and application
    Wei Wei, Lou Pengqiang, Hou Decai
    2021, 25 (26):  4211-4216.  doi: 10.12307/2021.123
    Abstract ( 360 )   PDF (623KB) ( 30 )   Save

    BACKGROUND: The development of a model of femoral head necrosis has been slow, and most studies have not elaborated the advantages and disadvantages of various animal models and optimal selection methods

    OBJECTIVE: To explore the most suitable animal modeling methods and modeling ideas, summarize the advantages and disadvantages of each model, and point out the existing problems and solutions, providing basis and ideas for the subsequent research on femoral head necrosis.
    METHODS: A search of CNKI, PubMed, and WanFang databases was performed for relevant articles published from 2009 to 2020 using the keywords of “osteonecrosis of the femoral head, animal model, osteoarthritis, collapse of the femoral head, trauma, corticosteroid, alcohol, liquid nitrogen” in Chinese and English, respectively. Finally, 55 eligible articles were included for review.
    RESULTS AND CONCLUSION: Common causes of femoral head necrosis include alcohol, hormones, and mechanical trauma. Among them, there is no vomiting reflex center in rats, which is more commonly used in alcohol-based modeling. The mechanism of hormone-induced osteonecrosis of the femoral head is still unclear, mainly including three hypotheses: fat metabolism disorder, intravascular coagulation and osteoporosis. The pathogenesis of hormone-induced modeling in animal experiments is similar to humans, and it can also reflect the pathological changes of femoral head necrosis in the advanced stage. After the trauma, the femoral head suffers subchondral fracture and local collapse caused blood circulation disorder, which causes ischemic necrosis of the femoral head. But in animal experiments, the pathogenesis of trauma in animals is different from that of humans. However, there are certain problems in various animal studies: (1) In the modeling of hormone-induced models, there is no unified standard for the selection and dosage of hormones, and the uncertainty of the site of model necrosis. (2) The freezing dog model is more popular in recent years, but it lacks mature and accurate operation methods. The uncertainty of the freezing range has a certain impact on the later stage of modeling. (3) The pathogenesis in most trauma models is different from human pathogenesis.
    Key words: bone; femoral head necrosis; animal; model; alcohol; hormone; trauma; review

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    Reconstruction of medial patellofemoral ligament: selection of single- and double-bundle graft and fixation technique of patellar and femoral insertion point
    Lin Chaosheng, Liu Yuwei, Zhu Weimin, Xiong Jianyi
    2021, 25 (26):  4217-4222.  doi: 10.12307/2021.124
    Abstract ( 316 )   PDF (628KB) ( 47 )   Save

    BACKGROUND:  Acute dislocation of the patella is a common knee joint injury, accounting for 2%-3% of all knee joint injuries. It is more common in young women, with complicated causes. Various therapeutic methods for patellar dislocation have been developed. 

    OBJECTIVE: To review the progress in medial patellofemoral ligament reconstruction, providing clinical guidance for surgeons.
    METHODS: PubMed database was retrieved with the search strategy of “((MPFL reconstruction)) OR (reconstruction of the medial patellofemoral ligament)” for the literature related to medial patellofemoral ligament reconstruction from 2000 to 2020. 
    RESULTS AND CONCLUSION: There is no significant difference in the rate of re-dislocation among bone tunnel fixation, suture anchor fixation and soft tissue fixation. Bone tunnel technology is more likely to lead to patella fracture. The reconstruction of medial patellofemoral ligament with suture anchor fixation and soft tissue fixation can better simulate the motion pattern of the patellofemoral joint under physiological conditions.
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    Molecular mechanism of osteoarthritis by multi-chip combination analysis
    Rong Weiming, Yuan Changshen, Duan Kan, Lu Zhixian, Mei Qijie, Guo Jinrong
    2021, 25 (26):  4223-4229.  doi: 10.12307/2021.125
    Abstract ( 429 )   PDF (1801KB) ( 41 )   Save

    BACKGROUND: Osteoarthritis is the most common chronic joint disease. Its pathogenesis is closely related to the complex gene regulatory network, but its underlying network has not been fully clarified.

    OBJECTIVE: To identify hub genes, important pathways, miRNA-mRNA regulatory network and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis, with fully clarifying the pathogenesis of osteoarthritis. 
    METHODS: The gene expression microarrays of GSE1919, GSE55235 and GSE12021 were obtained from GEO database, with differentially expressed genes screened out and enriched by R software. Then, protein-protein interaction network and miRNA-mRNA network were constructed based on upstream regulatory miRNAs of predicted differentially expressed genes to screen out hub genes and miRNAs. Finally, immune infiltration of synovial tissue in osteoarthritis and normal control groups was analyzed by CIBERSORT. 
    RESULTS AND CONCLUSION: In total 64 up-regulated genes and 23 down-regulated genes were obtained, which were mainly involved in response to steroid hormone, response to corticosteroid, response to lipopolysaccharide and leukocyte migration. The important pathways closely related to osteoarthritis mainly included interleukin-17 signaling pathway, nuclear factor-κB signaling pathway, tumor necrosis factor signaling pathway and mitogen-activated protein kinase signaling pathway. MiRNA-mRNA network analysis showed that 10 hub genes, such as interleukin-6, VEGFA, MYC and miR-21-5p and miR-142-3p, were identified in osteoarthritis. Results of immune infiltration showed that there were significant differences in six kinds of immune cells, such as naïve B cells, plasma cells and regulatory T cells, between osteoarthritic synovium and normal synovium. The study constructed miRNA-mRNA regulatory network and investigated the difference of immune infiltration in synovial tissues, providing a theoretical basis for understanding the pathogenesis of osteoarthritis from the perspective of synovial tissue.

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    The role of signal pathways and receptors in various layers of mucosa in overactive bladder
    Li Wen, Chen Yuelai
    2021, 25 (26):  4230-4235.  doi: 10.12307/2021.126
    Abstract ( 507 )   PDF (552KB) ( 23 )   Save

    BACKGROUND: Evidence has shown that the treatment of overactive bladder at the level of mucosal structure has a certain advantage, so the study on the possible involvement of mucosa in regulating bladder afferent signal transduction and improving the symptoms associated with overactive bladder has gradually become a hot spot.

    OBJECTIVE: To review the role of signal pathways and receptors in various layers of mucosa in the pathogenesis of overactive bladder.
    METHODS: With the key words of “overactive bladder, mucosa, urothelium, lamina propria, mechanisms" in both English and Chinese, CNKI, WanFang and PubMed were searched for relevant literature published from 2000 to 2020, and eventually 49 articles meeting the requirements were reviewed.
    RESULTS AND CONCLUSION: The pathogenesis of overactive bladder is very complex. At present, there are few reports on whether the myogenic hypothesis and the neurogenic hypothesis interact with the mucosal signaling mechanism. Urothelial signaling pathway is the key of the current research, but the basement membrane layer and the lamina propria related signaling pathways are less reported. The various types of cells in the lamina propria and their functions have not been clear, and the relationship of mucosal signal with spinal cord center and senior center has not been fully research. Therefore, a horizontal study will be done on the relationship between the three types of pathogenesis of overactive bladder, and deeply and vertically explore the upstream or downstream of one of the three signal pathways, so as to provide a clearer target for the treatment of overactive bladder.

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    N6-methyladenosine RNA methylation is involved in orthopedic related diseases
    Chen Weijian, Zhang Gangyu, Lin Tianye, Liang Du, Wang Haibin
    2021, 25 (26):  4236-4242.  doi: 10.12307/2021.127
    Abstract ( 419 )   PDF (666KB) ( 114 )   Save

    BACKGROUND:  With the development of high-throughput sequencing technology, recent studies have found that the presence of N6-methyladenosine (m6A) modification can be detected in bone marrow mesenchymal stem cells, osteoblasts, adipocytes, osteoclasts, chondrocytes, and osteosarcoma cells. It can affect the translation of mRNA and/or non-coding RNA of related genes by regulating the methylation of RNA in cells, which can activate cell signal transduction pathways, regulating cell proliferation, differentiation, migration, invasion, apoptosis and DNA damage repair. In turn, it can regulate the physiological and pathological processes such as bone development, joint degeneration, fracture healing, and the occurrence and development of bone tumors.

    OBJECTIVE: To summarize the latest research results and specific mechanisms of m6A modification in osteoporosis, osteoarthritis and other orthopedic diseases in recent years, and to offer inspiration for the development of new treatment strategies for orthopedic diseases.
    METHODS: CNKI and PubMed were searched with the keywords of “N-6 methyladenine, osteoporosis, osteoarthritis, orthopedic diseases” for literatures regarding m6A methylation modification in orthopedic diseases from their inception date to June 2020. According to the established inclusion and exclusion criteria, 61 articles were finally included for review.
    RESULTS AND CONCLUSION: During the accelerated development of osteoporosis, METTL3-mediated m6A methylation and FTO-mediated m6A demethylation affect the expression of related genes and further regulate the bone formation and adipogenic differentiation of bone marrow mesenchymal stem cells. METTL3-mediated m6A methylation plays an important role in the development of osteoarthritis by regulating nuclear-κB signaling in chondrocytes and extracellular matrix synthesis. METTL3/m6A inhibits the osteogenic mechanism in the fracture healing process by targeting the regulation of osteoblast-related miR-7212-5p. METTL3 activates Wnt/β-catenin signals by regulating the m6A level of lymphoid enhancer binding factor 1 and accelerates the progression of osteosarcoma by regulating the m6A methylation of ATAD2 gene. Therefore, m6A modification is involved in the pathological progresses of osteoporosis, osteoarthritis and other orthopedic diseases. The in-depth study of m6A modification provides a theoretical basis for further understanding the pathogenesis of orthopedic related diseases, and provides therapeutic thoughts and references for orthopedic diseases based on epigenetics.
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    Hypertrophic fibrosis of the ligamentum flavum: signaling pathways and molecular level characteristics
    Fan Xiaoqian, Chen Feng, Liang Xiongqin, Gao Sen, Yang Xinqiang
    2021, 25 (26):  4243-4248.  doi: 10.12307/2021.128
    Abstract ( 310 )   PDF (611KB) ( 32 )   Save

    BACKGROUND:  Ligamentum flavum hypertrophy is considered to be the main cause of lumbar spinal stenosis. In recent years, it has been reported that hypertrophy of the ligamentum flavum is related to growth factors, microRNAs and key signaling pathways.

    OBJECTIVE: To make a systematic review on the molecular level and signaling pathway of hypertrophic fibrosis of the ligamentum flavum.
    METHODS: Chinese and foreign databases, including CNKI, VIP, WanFang, PubMed, Biosos Preview, and Web of Science, were searched for relevant articles, and the basic experiments of hypertrophic fibrosis of the ligamentum flavum were collected by hand. The search terms included “lumbar spinal stenosis; hypertrophy of ligamentum flavum; ligamentum flavum hyperplasia; fibrosis of ligamentum flavum; cell factor; protein; signal path; microRNA” in Chinese and English, respectively. The retrieval time limit was set as June 30, 2020. The retrieved articles were screened in strict accordance with the inclusion criteria, and finally 15 relevant basic experimental articles were reviewed.
    RESULTS AND CONCLUSION: In the process of hypertrophic fibrosis, the ligamentum flavum can be affected by a variety of growth factors, miRNAs and multiple signaling pathways. Therefore, it is rational to speculate that the proliferation and fibrosis of the ligamentum flavum is a consequence of multi-dimensional coordination by multiple biological processes. However, the degree of fibrosis has not been determined yet, and further basic research is still needed in the future.

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    Arthroscopic debridement combined with sodium hyaluronate injection for the treatment of senile knee osteoarthritis: a Meta-analysis of changes in pain, inflammatory factor, and joint function
    Huang Linfeng, Gu Yingxuan, Quan Xiaoming, He Wei, Chen Leilei
    2021, 25 (26):  4249-4256.  doi: 10.12307/2021.129
    Abstract ( 300 )   PDF (794KB) ( 56 )   Save

    OBJECTIVE: Relevant clinical studies have shown that arthroscopic debridement combined with sodium hyaluronate plays a positive role in the treatment of senile knee osteoarthritis, but its efficacy and safety are not completely clear, lack of sufficient evidence-based basis. Herein, we conducted a Meta-analysis on the clinical efficacy of arthroscopic debridement combined with sodium hyaluronate in the treatment of senile knee osteoarthritis. 

    METHODS: A systematic search of relevant literatures in PubMed, Cochrane library, EMbase, Web of Science, CNKI, CBM, WanFang and Baidu Scholar from January 1, 2016 to October 30, 2020 was performed. We collected all the randomized controlled trials of arthroscopic debridement combined with sodium hyaluronate injection in the treatment of senile knee osteoarthritis. Two researchers screened the study strictly according to the inclusion and exclusion criteria, and extracted data and evaluated the quality of the literature. Meta-analysis of the included literatures was processed by Revman5.3 software. 
    RESULTS: A total of 12 randomized controlled trials were collected in this meta-analysis, including 1 072 knees in the experimental group and 532 in the control group. The results of Meta-analysis showed that arthroscopic debridement combined with sodium hyaluronate injection in the treatment of senile knee osteoarthritis was superior to arthroscopic debridement alone with regard to the total clinical effective rate (relative risk (RR)=1.24, 95% confidence interval (CI): 1.15 to 1.33, P < 0.000 01), Lysholm score (standardized mean difference (SMD)=9.80, 95%CI: 8.09 to 11.51, P < 0.000 01), and Visual Analogue Scale score (MD=
    -1.19, 95%CI: -1.58 to -0.80, P < 0.000 01). Compared with the arthroscopic debridement alone, the combination therapy showed a significant decrease in the levels of intra-articular interleukin-1 (MD=-9.95, 95%CI: -11.31 to -8.59, P < 0.000 01), interleukin-6 (MD=-33.68, 95%CI: -42.42 to -24.93, P < 0.000 01) and tumor necrosis factor-α (MD=-84.72, 95%CI: -91.49 to -77.95, P < 0.000 01). There was no significant difference in the incidence of complications between the two groups (RR=0.60, 95%CI: 0.30 to 1.18, P=0.14]. 
    CONCLUSION: Compared with arthroscopic debridement alone, arthroscopic debridement combined with sodium hyaluronate is more effective in the treatment of senile knee osteoarthritis, which is embodied in relieving joint pain, improving knee joint function and reducing the level of inflammatory factors. However, more randomized controlled trials with high quality and large sample size are still needed in the future.

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    A Meta-analysis regarding the effect of lower limb resistance training on walking ability and balance ability in the elderly
    Wu Chaoming, Sun Junzhi
    2021, 25 (26):  4257-4264.  doi: 10.12307/2021.130
    Abstract ( 417 )   PDF (671KB) ( 50 )   Save

    OBJECTIVE: A large number of studies have confirmed that lower limb resistance training has a significant effect on increasing skeletal muscle content and reducing the incidence of myopenia in the elderly. At present, there is a great controversy about whether lower limb resistance training can have a positive impact on the walking ability and balance ability of the elderly. Therefore, this Meta-analysis focuses on the intervention effect of lower limb resistance training on walking ability and balance ability of the elderly, so as to provide a theoretical basis for the formulation of standardized exercise prescription for the elderly.

    METHODS: A computer-based search was conducted in the English databases of Cochrane Library, PubMed, Web of Science, EBSCO Host, and the Chinese databases of WanFang and CNKI. Randomized controlled trials addressing the effect of lower limb resistance training on walking ability and balance ability in the elderly were collected. Two researchers independently evaluated the methodological quality of the included articles according to the Cochrane system evaluation manual, and extracted the main outcome indicators, including time up-and-go (TUG) test, routine walking speed, functional extension test (FET), one-leg stand with eyes open (OLSO) test, and secondary outcome index, maximum walking speed. The included articles were analyzed using RevMan 5.3 software for a Meta-analysis. 
    RESULTS: Fourteen randomized controlled trials were finally included. After the quality evaluation, except for selective reports and other bias risks that were unclear, the overall quality of the articles included was good. A total of 551 subjects were included in these 14 trials, including 285 in experimental group and 266 in the control group. Compared with the control group, lower limb resistance training could significantly improve the TUG time of the elderly under 80 years old [for 60-69 years old, mean difference (MD)=-0.99, 95% confidence interval: -1.90 to -0.08, P < 0.05; for 70-79 years old, MD=-1.17, 95%CI: -2.50  to -0.08, P < 0.01], OLSO time (MD=3.92, 95%CI: 2.46 to 5.38, P < 0.01], FET distance (MD=4.85, 95%CI: 1.93 to 6.63, P < 0.01], and the heterogeneity of TUG time was smaller after more than 12 weeks of training (I2=0). However, the lower limb resistance training had no significant effect on normal walking speed (MD=0.03, 95%CI: -0.05 to 0.10, P=0.46] and maximum walking speed (MD=0.08, 95%CI: -0.02 to 0.17, P=0.11] in all the subjects as well as on TUG time (MD=-4.92, 95%CI: -15.65 to 5.81, P=0.37] in people over 80 years old. 
    CONCLUSION: Lower limb resistance training can effectively improve the balance ability of the elderly and the TUG level of the elderly under 80 years old, but there is no significant change in normal walking speed and maximum walking speed. In the future, the formulation of exercise prescription for the elderly should be more standardized and improved and verified. Importantly, the physical characteristics of the elderly at different ages should be distinguished in the formulation of exercise prescriptions, so as to ensure the scientificity and effectiveness of exercise prescriptions in the implementation of different age groups.

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