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    18 October 2020, Volume 24 Issue 29 Previous Issue    Next Issue
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    Tumor necrosis factor alpha promotes apoptosis in long bone-like cells via ERK1/2 signaling pathway
    Shi Fangfu, Cui Hongwang, Sun Bo
    2020, 24 (29):  4593-4598.  doi: 10.3969/j.issn.2095-4344.2810
    Abstract ( 574 )   PDF (717KB) ( 177 )   Save

    BACKGROUND: Tumor necrosis factor α (TNF-α) is a pro-inflammatory factor that can induce osteoblast apoptosis and enhance osteoclast function, resulting in inflammatory bone destruction. However, the specific mechanism is unclear.

    OBJECTIVE: To investigate the effect of TNF-α on the proliferation and apoptosis of MLO-Y4 cells and the possible mechanism.

    METHODS: MLO-Y4 cells were divided into control group, TNF-α group and ERK1/2 inhibitor group, followed by incubation with α-MEM complete medium containing nothing, 50 μg/L TNF-α, and 50 μmol/L PD98059 for 24 hours, respectively. Cell proliferation was detected by MTT method, and cell apoptosis were detected by flow cytometry. To assess the level of oxidative stress, malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were detected. The protein levels of PCNA, cleaved Caspase-3, p-ERK1/2 and ERK1/2 were measured by western blot.

    RESULTS AND CONCLUSION: Compared with the control group, treatment with 50 μg/L TNF-α for 24 hours reduced the cell proliferation ability and increased the apoptosis rate increased; levels of lipid peroxidase and malondialdehyde increased significantly, whereas the activities of superoxide dismutase and glutathione peroxidase decreased significantly. Compared with the control group, significantly decreased PCNA and p-ERK1/2 as well as significantly up-regulated cleaved caspase-3 were observed in the TNF-α group; however, the expression of total protein ERK1/2 remained unchanged. There was no significant difference between the ERK1/2 inhibitor group and TNF-α group. To conclude, 50 μg/L TNF-α can decrease the proliferation and increase the apoptosis of MLO-Y4 cells. The mechanism may be related to the inhibition of ERK1/2 signaling pathway.

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    Mechanism of Achyranthes bidentata Bl.-Taxillus chinensis Danser in the treatment of osteoarthritis based on network pharmacology
    Huang Zeling, He Junjun, Shi Shanni, Gao Hongjian, Hong Zhenqiang
    2020, 24 (29):  4599-4604.  doi: 10.3969/j.issn.2095-4344.2785
    Abstract ( 535 )   PDF (850KB) ( 63 )   Save

    BACKGROUND: Achyranthes bidentata Bl.-Taxillus chinensis Danser is the most commonly used drug combination for clinical treatment of osteoarthritis, but its pharmacological mechanism is not clear.

    OBJECTIVE: To screen the main active chemical constituents of Achyranthes bidentata Bl.-Taxillus chinensis Danser based on the method of network pharmacology, collect the targets corresponding to the compounds, and build a drug-active ingredient-potential target network for treating osteoarthritis to treat bones and joints, and to systematically elucidate the pharmacological mechanism of inflammation.

    METHODS: The TCMSP database was used to obtain the active ingredients and targets of Achyranthes bidentata Bl.-Taxillus chinensis Danser, and the targets of osteoarthritis diseases obtained from the DisGeNET and GENE databases were intersected to screen out potential targets for the treatment of osteoarthritis by Achyranthes bidentata Bl.-Taxillus chinensis Danser. Using the String database and Cytoscape 3.6.1 software, we built a drug-active ingredient-therapeutic osteoarthritis potential target network and a protein-protein interaction network between potential targets. At the same time, the gene ontology (GO) biological function and Kyoto Encyclopedia of Genes and Gnomes (KEGG) pathway enrichment of potential targets were analyzed through the Omicshare cloud platform and DAVID database.

    RESULTS AND CONCLUSION: A total of 21 active ingredients and 48 potential targets for the prevention and treatment of osteoarthritis were screened from Achyranthes bidentata Bl.-Taxillus chinensis Danser. A total of 1 970 GO entries were obtained by GO enrichment analysis, of which 1 862 were biological processes, 29 were cellular components, and 79 were molecular functions (P < 0.01). KEGG pathway enrichment analysis screened out 76 potential signaling pathways for Achyranthes bidentata Bl.-Taxillus chinensis Danser to prevent osteoarthritis (P < 0.01). These findings indicate that Achyranthes bidentata Bl.-Taxillus chinensis Danser affects multiple metabolic pathways, affects different metabolic pathways that interacts and coordinates with each other, thereby preventing and curing osteoarthritis. This study tentatively explains the mechanism of the prevention and treatment of osteoarthritis by multi-component-multi-target-multi-pathway in Achyranthes bidentata Bl.-Taxillus chinensis Danser, which provides new ideas and clues for the prevention and treatment of osteoarthritis.

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    Beta-ecdysterone promotes in vitro proliferation and osteogenic differentiation of MC3T3-E1 cells
    Yan Caiping, Chen Lu, Deng Changgong, Chen Qian, Jiang Ke, Yi Yuanyuan, Li Yuling
    2020, 24 (29):  4605-4612.  doi: 10.3969/j.issn.2095-4344.2781
    Abstract ( 634 )   PDF (1198KB) ( 220 )   Save

    BACKGROUND: β-ecdysterone as a “phytoestrogen” has the ability to stimulate protein synthesis, promote carbohydrate and lipid metabolism, relieve hyperglycemia and hyperlipidemia, protect endothelial cells from apoptosis and induce their proliferation. Some scholars have reported that it also plays an important role in the treatment of osteoporosis, fractures and other bone inflammatory diseases.

    OBJECTIVE: To observe the effect of β-ecdystrone on the proliferation of mouse pre-osteoblasts (MC3T3-E1 cells) in vitro, and to explore whether β-ecdysterone can induce osteogenic differentiation of MC3T3-E1 at a safe dose.  

    METHODS: The fourth generation MC3T3-E1 cells were cultured in the osteogenic induction medium for 7, 10, 14, 21, and 28 days. The osteogenic differentiation proteins (alkaline phosphatase, type I collagen, osteopontin, and calcified nodules) were detected at different time points, to identify whether the cells have the ability of osteogenic differentiation. MC3T3-E1 cells were then seeded into the induction medium containing different final concentrations of β-ecdysterone (0.01, 0.1, 1, 10, 100 μmol/L). The proliferation activity of the cells was detected by cell counting kit-8 method at days 1, 2, 3, 4, 5, 6, and 7 after induction. The control group (general induction medium group) and the experimental group (general induction medium + β-ecdysterone) were cultured under the same conditions, and the expression levels of osteogenic marker proteins in each group of cells at different time periods were determined.

    RESULTS AND CONCLUSION: In the MC3T3-E1 cells stimulated by the osteogenic induction medium, alkaline phosphatase staining and type I collagen florescence staining showed higher expression at day 10 of induction, and this was also confirmed by detection of alkaline phosphatase activity (P < 0.05). At day 14 of induction, osteopontin immunocytochemical staining also indicated significant expression. Alizarin red staining results demonstrated that the number of calcified nodules increased significantly after osteogenic induction, and there were more calcified nodules with larger diameter and darker color at day 28 than at day 21. After treatment with β-ecdysterone, the proliferative activity of MC3T3-E1 cells reached the peak at day 5 after induction. The optimal concentrations of β-ecdysterone were 0.01 and 0.1 μmol/L. There was no significant difference between the two concentrations (P > 0.05). The expression of alkaline phosphatase and type I collagen was higher in the experimental group than in the control group at day 10 of induction. The expression of osteopontin and osteocalcin in the cells was higher at day 14 of induction, and there was no significant difference in the calcified nodule staining between the two groups at day 28 of induction. These findings indicate that β-ecdysterone can promote the proliferation of MC3T3-E1 cells in vitro and induce MC3T3-E1 cells to differentiate into osteoblasts at a safe dose.

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    Immunoinflammatory mechanism of Panax notoginseng in the treatment of osteonecrosis of the femoral head based on network pharmacology
    Nong Jiao, Zeng Ping, Li Juan, Liu Jinfu, Li Jinyi
    2020, 24 (29):  4613-4619.  doi: 10.3969/j.issn.2095-4344.2811
    Abstract ( 439 )   PDF (880KB) ( 706 )   Save

    BACKGROUND: In recent years, traditional Chinese medicine has obtained satisfactory results in the treatment of early and middle-stage osteonecrosis of the femoral head. Compared with western medicine, traditional Chinese medicine has complex components, unclear targets and mechanisms. Network pharmacology is a new and popular discipline, which is consistent with the traditional Chinese medicine in terms of holistic, systemic, and drug-focused characteristics, meeting the understanding of the nature of diseases in traditional Chinese medicine.

    OBJECTIVE: To screen the main active components of Panax notoginseng by network pharmacology, construct the active compound-target network, and elucidate the molecular mechanism of its therapeutic effect on osteonecrosis of the femoral head.

    METHODS: The targets of Panax notoginseng were screened by TCMSP database, and the targets related to osteonecrosis of the femoral head were screened by OMIM and GeneCards databases. The protein interaction network was analyzed by STRING database, the protein interaction network was constructed by Cytoscape, the compound-target network was constructed by Cytoscape software, and the network topology was analyzed. The target gene function and signal pathway were analyzed by biological information annotation database (DAVID), and the GO analysis and KEGG signal pathway enrichment analysis were carried out using the ClueGO plug-in.

    RESULTS AND CONCLUSION: There were 8 active components of Panax notoginseng, involving 98 targets related to osteonecrosis of the femoral head. Panax notoginseng was mainly involved in cell process, metabolic process, response to stress and other biological processes. Panax notoginseng played an anti-inflammatory role by regulating Toll-like receptor, PI3K-AKT, tumor necrosis factor, nuclear factor-κB, and JAK-STAT signal pathways. This study reflects the characteristics of components of Panax notoginseng-target-pathway, and provides new ideas and methods for further research on the anti-inflammatory mechanism of Panax notoginseng and even for disease treatment with compound Chinese medicine.

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    Effect of Rhizoma Drynariae on osteoclast differentiation is related to the concentration of drug-containing serum
    Xu Jinsong, Deng Na, Zhang Xiao
    2020, 24 (29):  4620-4625.  doi: 10.3969/j.issn.2095-4344.2777
    Abstract ( 379 )   PDF (810KB) ( 32 )   Save

    BACKGROUND: Total flavonoids of Rhizoma Drynariae can be used to prevent and treat osteoporosis, but its mechanism of action is mostly focused on osteoblasts rather than osteoclast differentiation.

    OBJECTIVE: To investigate the effect of Rhizoma Drynariae on osteoclast differentiation through T-cell nuclear factor 1 (NFATc1) signaling pathway.

    METHODS: Forty Sprague-Dawley rats were randomly divided into four groups. Total flavonoids of Rhizoma Drynariae were intragastrically administered at 0, 11.6, 34.8 and 104.4 g/kg, respectively. Control serum and low-, middle-, high-concentration drug-containing sera were obtained. Bone marrow macrophages were isolated from 5-week-old rats and the effects of different drug-containing sera on macrophage activity were detected by cell counting kit-8 method. The macrophages were divided into low-, middle- and high-concentration groups, negative control group and blank group, with 5 multiple holes in each well. The low, middle and high concentration of drug-containing serum, negative control serum culture medium and normal culture medium were added respectively. All culture media were used to induce osteoclast differentiation with 20 μg/L macrophage colony-stimulating factor and 100 μg/L receptor activator of nuclear factor kappa B ligand. The number of osteoclasts and fusion index were detected by tartrate-resistant acid phosphatase staining 7 days after induction of differentiation. The expressions of c-Fos, Fra-1, Fra-2, NFATc1 and cathepsin K were detected by real-time fluorescence quantitative PCR and western blot at 7 days after differentiation. The number of bone resorption lacunae and the proportion of lacunae area in osteoclasts after 14 days of differentiation were detected by bone fragment absorption lacunae test. The study protocol was approved by the Animal Experiment Ethics Committee of Anyang District Hospital of Puyang City with approval No. PYSAYDQ-2019096.

    RESULTS AND CONCLUSION: Cell counting kit-8 results showed that there was no significant change in macrophage activity after intervention with different concentration of sera containing Rhizoma Drynariae. The morphology of macrophages was regular before differentiation. After differentiation, osteoclasts were identified by tartrate-resistant acid phosphatase staining. Compared with the blank group and negative control group, the number of osteoclasts, fusion index, number of bone resorption lacunae and proportion of lacunae area and the relative expressions of c-Fos, Fra-1, Fra-2, NFATc1, cathepsin K mRNA and protein in the low-, middle- and high-concentration groups decreased significantly (P < 0.05). The above indicators showed a decreasing trend with the increase of serum concentration of Rhizoma Drynariae: low-concentration group > middle-concentration group > high-concentration group, and there were significant differences between different concentration groups (P < 0.05). In conclusion, Rhizoma Drynariae may inhibit the differentiation of rat macrophages into osteoclasts through NFATc1 signaling pathway, and the degree of differentiation inhibition is related to the serum concentration of Rhizoma Drynariae.

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    Protection of inflammatory osteoblasts in neonatal rats using catalpol from the root of Rehmannia glutinosa
    He Qiang, Qian Weiqing, Yao Nianwei, Zhou Mengling, Liu Yixin, Yin Hong
    2020, 24 (29):  4626-4631.  doi: 10.3969/j.issn.2095-4344.2791
    Abstract ( 287 )   PDF (842KB) ( 114 )   Save

    BACKGROUND: Studies have shown that abnormal osteoblast metabolism may cause abnormal subchondral bone mineralization in knee osteoarthritis.

    OBJECTIVE: To verify the effects of catalpol from the root of Rehmannia glutinosa on osteoblast proliferation and drug toxicity, and the anti-inflammatory protective effect on inflammatory osteoblasts induced by lipopolysaccharide.

    METHODS: (1) Osteoblasts from newborn Sprague-Dawley rats were primarily extracted, cultured, and passaged. The activity and proliferation of osteoblasts were determined by observing the morphology of osteoblasts alkaline phosphatase staining and staining of mineralized nodules. (2) Cell counting kit-8 (CCK-8) method was used to observe the effect of different concentrations of catalpol from the root of Rehmannia glutinosa on osteoblast activity. (3) Different concentrations of lipopolysaccharide (0, 10, 20, 40, 80, 160 mg/L) were used to induce inflammatory osteoblasts in fetal rats. CCK-8 method was used to verify the best concentration. (4) The experiment was divided into three groups: blank group, model group, low-, medium- and high-concentration catalpol groups. Inflammatory osteoblasts were induced by lipopolysaccharide at 80 mg/L, and then treated for 8 hours. CCK-8 method was used to observe the effect of different concentrations of catalpol on inflammatory osteoblasts. The study protocol was approved by the Medical Ethics Committee of Liuhe District People’s Hospital in Nanjing.

    RESULTS AND CONCLUSION: When osteoblasts were cultured to the fourth generation, followed by alkaline phosphatase staining, black grey granules were found in the cytoplasm of the positive cells, and the morphology of the cells was irregular. When the concentration of catalpol was lower than 1 mg/L, it had no significant effect on osteoblasts; when it was higher than 10 mg/L, it had a significant effect on the proliferation of osteoblasts but no drug toxicity (P < 0.05). When the concentration of lipopolysaccharide was higher than 80 mg/L, there was a significant trend of inflammatory damage to osteoblasts (P < 0.01). Therefore, 80 mg/L was selected as the best injury concentration in this experiment. When the concentration of catalpol from the root of Rehmannia glutinosa was lower than 1 mg/L, it had no significant protective effect on the inflammatory response of osteoblasts (P < 0.05); when it was higher than 10 mg/L, it had significant protective effect on the inflammatory response of osteoblasts (P < 0.05). Therefore, when the concentration of catalpol from the root of Rehmannia glutinosa reaches a certain level, it has no toxic effect on osteoblasts, promotes proliferation, and has anti-inflammatory protective effect on inflammatory osteoblasts induced by lipopolysaccharide.

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    L-arginine promotes the survival of extended dorsal perforator skin flap through activating L-arginine-nitric oxide pathway
    Li Wenbo, Shi Jie, Shi Peisheng, Xue Yun, Huang Qiang, Li Chuangbing, Gao Qiuming
    2020, 24 (29):  4632-4637.  doi: 10.3969/j.issn.2095-4344.2812
    Abstract ( 470 )   PDF (834KB) ( 65 )   Save

    BACKGROUND: Studies have shown that nitric oxide (NO) can effectively improve blood supply and promote flap survival, but the specific mechanism is still unclear.

    OBJECTIVE: To explore the effects of L-arginine (L-Arg) on the survival of extended dorsal perforator skin flap in rats by activating L-Arg-NO pathway.

    METHODS: Animal models of extended dorsal perforator skin flap were successfully established in 81 male Sprague Dawley rats, which were then divided into a L-Arg group, a blank group and a L-NAME group. L-Arg (400 mg/kg per day) and nitro-amino-methyl-L-arginine (L-NAME;     40 mg/kg per day) were injected intraperitoneally in the L-Arg group and L-NAME group immediately and 1-7 days after operation, respectively, while the same volume of isotonic sodium chloride solution was injected intraperitoneally in the blank group at the same time points. Flap survival rate was measured. Angiography was performed to observe appearance and distribution of blood vessels at 7 days after operation. NO concentration of choke II zone was detected immediately, 1, 3, 5, and 7 days after operation. Tissue samples were harvested from the choke II zone for detecting density and caliber of new blood vessels using hematoxylin-eosin staining and the expression of vascular endothelial growth factor and matrix metalloproteinase was detected by western blot, respectively. The study protocol was approved by the Animal Ethics Committee of the 94th Hospital of the PLA Joint Logistics Support Force (approval No. 2015KYLL046).

    RESULTS AND CONCLUSION: The highest survival rate of flap appeared in the L-Arg group, (89.47±3.17)%, which was significantly higher than that in the other groups (F=49.908, P < 0.001). At 7 days after operation, the vascular structure in the choke II zone of the L-Arg group was relatively complete with clear trajectory. The vessels that had expanded to achieve true anastomosis extended along the longitudinal axis of the flap to the end of the flap. In the blank group and L-NAME group, the vascular structure and vascular trajectory in the choke II zone were disordered. Moreover, the vascular structure at the end of flap in L-NAME group disappeared. NO concentration in L-Arg group was increased after surgery, peaked at 3 days after operation, and then decreased gradually. Microvessel density and caliber in the L-Arg group were significantly higher than those in the other groups at 7 days after operation (P < 0.001). Western blot showed that the expression of vascular endothelial growth factor and matrix metalloproteinase-2 were significantly higher in the L-Arg group than the other groups at 3 after operation (P < 0.05), while at 7 days after operation, the expression of vascular endothelial growth factor in the L-Arg group was significantly higher than that in the other groups (P < 0.05), but the expression of matrix metalloproteinase-2 showed no significant difference among the three groups. To conclude, NO could promote microvascular growth and dilatation in the choke II zone of extended dorsal three-vascular perforator flaps in rats; L-Arg could increase the NO concentration in tissue by activating the L-Arg-NO pathway, which is beneficial to the survival of skin flap.

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    Electroacupuncture combined with thunder-fire moxibustion in the treatment of cold-dampness knee osteoarthritis: a randomized controlled clinical trial
    Deng Kaifeng, Chen Rilan, Zhu Shengwang, Wei Xingcheng, Zhang Lijuan, Zhu Ying
    2020, 24 (29):  4638-4642.  doi: 10.3969/j.issn.2095-4344.2813
    Abstract ( 358 )   PDF (792KB) ( 89 )   Save

    BACKGROUND: Both thunder-fire moxibustion and electroacupuncture can effectively improve the related symptoms of knee osteoarthritis. At the same time, the two treatments have the advantages of simple operation, low cost, strong practicability and so on.

    OBJECTIVE: To observe the difference in curative effect between thunder-fire moxibustion combined with electro-acupuncture and celecoxib capsule in the treatment of cold-wet knee osteoarthritis.

    METHODS: Seventy-two patients with cold-wet knee osteoarthritis, including 35 males and 37 females, who were treated in Ruikang Hospital affiliated to Guangxi University of Chinese Medicine from June 2017 to December 2018, were randomly divided into two groups: observation group (n=35) received thunder-fire moxibustion (once a day) combined with electroacupuncture treatment (once a d); and control group (n=37) was given oral celecoxib capsule (once a day). Treatment in each group lasted for two sessions of 14 days each with a 2-day break. Visual analogue scale score, Western Ontario and McMaster Universities (WOMAC) score, and joint fluid related inflammatory index were detected before and after treatment. The effective rate of TCM syndrome was evaluated. A 1-month follow-up was carried out after treatment. The experimental protocol was approved by the Ethics Committee of Ruikang Hospital affiliated to Guangxi University of Chinese Medicine (KY2017-005).

    RESULTS AND CONCLUSION: There were no adverse reactions in the two groups. The visual analogue scale scores and WOMAC scores (pain, stiffness and function) in the observation group were significantly reduced after treatment and during the follow-up (P < 0.05). The visual analogue scale scores and WOMAC scores (pain and stiffness) in the control group were significantly reduced after treatment and at the end of the follow-up (P < 0.05). Compared with the control group, the visual analogue scale scores and WOMAC scores (pain, stiffness and function) were significantly lower in the observation group after treatment and during the follow-up (P < 0.05). The levels of interleukin-6 and tumor necrosis factor-α in the two groups were significantly lowered after treatment, and a more significant reduction was observed in the observation group (P < 0.05). The total effective rate of treatment in the observation group was higher than that in the control group (97.1% vs. 81.1%, P < 0.05). Therefore, electroacupuncture combined with thunder-fire moxibustion has favorable outcomes in the treatment of cold-wet knee osteoarthritis accompanied by less adverse reactions. Moreover, electroacupuncture combined with thunder-fire moxibustion is superior to celecoxib capsule in terms of curative effect persistence.

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    Platelet-rich plasma plays a protective role in chondrocytes by regulating synovitis
    Chen Wei, Zhang Guoru, He Jiandong, Huo Shaochuan
    2020, 24 (29):  4643-4649.  doi: 10.3969/j.issn.2095-4344.2814
    Abstract ( 423 )   PDF (955KB) ( 54 )   Save

    BACKGROUND: Studies have confirmed that inflammatory factors secreted by synovitis that accelerate the catabolism of articular cartilage have become the main cause of osteoarthritis. Matrix metalloproteinase 3 and matrix metalloproteinase 13 play a key role in osteoarthritis.

    OBJECTIVE: To study the effective mechanism of platelet-rich plasma (PRP) in the treatment of osteoarthritis.

    METHODS: The rat knee synovial cells and chondrocytes were isolated and extracted separately. The blood samples of rats were extracted to prepare PRP preparation. Then, synovial cells were divided into a control group and an E. coli lipopolysaccharide (LPS) treatment group, where synovial cells were stimulated with LPS to create a synovitis model. The synovitis cells were further divided into a PRP treatment group and an untreated group. The cells in each group were cultured for 24 hours. A portion of the medium was taken, in which the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-α was detected using ELISA. The other part of the medium was used to treat chondrocytes. After 48 hours of culture, the changes of type I, II collagens, matrix metalloproteinase 3 and matrix metalloproteinase 13 protein levels in chondrocytes were detected by western blot. The expression levels of matrix metalloproteinase 3 and matrix metalloproteinase 13 mRNA were detected by real-time PCR.

    RESULTS AND CONCLUSION: Determined by the ELISA, the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-α in the synovial cell culture medium of the LPS treatment group were significantly higher than those of the control group and the PRP treatment group (P < 0.01). The levels of interleukin-1β, interleukin-6 and tumor necrosis factor-α in the medium of PRP treatment group were significantly higher than those in the control group (P < 0.05). Western blot showed that the expression of type I and II collagens in the chondrocytes of the PRP treatment group were significantly higher than those in the control and LPS treatment groups (P < 0.01); the expression of type I and II collagens in the chondrocytes of the LPS treatment group was significantly lower than that in the control group (P < 0.05). The expression levels of matrix metalloproteinase 3 and matrix metalloproteinase 13 proteins in the LPS treatment group were significantly higher than those in the PRP treatment and control groups (P < 0.01). PCR analysis showed that the mRNA expression of matrix metalloproteinase 3 and matrix metalloproteinase 13 in the LPS treatment group was significantly higher than that in the PRP treatment and control groups. The findings of this study reveal that PRP treatment can reduce interleukin-1β, interleukin-6 and tumor necrosis factor-α levels in synovial cells, decrease matrix metalloproteinase 3 and matrix metalloproteinase 13 protein and mRNA levels in chondrocytes, and increase type I and II collagen expression, thereby protecting the cartilage.

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    Establishing a rat model of atrophic nonunion by using circular external fixator combined with periosteum cauterization
    Zhang Yan, Shen Zhen, Li Zige, Huang Minling, Feng Junming, Xie Lei, Gao Yijia, Zeng Zhanpeng, Jiang Ziwei
    2020, 24 (29):  4650-4655.  doi: 10.3969/j.issn.2095-4344.2788
    Abstract ( 393 )   PDF (766KB) ( 100 )   Save

    BACKGROUND: Establishment of a standard experimental animal model of atrophic nonunion is necessary for experimental study and related treatment of atrophic nonunion. However, the common modeling methods cannot accurately simulate atrophic nonunion in the clinical practice.

    OBJECTIVE: To construct a standard animal model of atrophic nonunion.

    METHODS: Thirty male Sprague-Dawley rats were randomly divided into experimental and control groups. All animals were subjected to bone cutting at the middle-lower segment of the right tibia and the circular external


    fixator was applied to keep a 4 mm defect interval. The animals in the experimental group were subjected to an additional cauterization of the periosteum at the fracture end of the tibia with a length of 1mm. The periosteum was not treated in the control group. The study protocol was approved by the Experimental Animal Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine on January 01, 2018, with approval No. TCMF1-2018002.

    RESULTS AND CONCLUSION: After modeling, there was one case of loose external fixation in each group, and no infection occurred in both groups. Imaging examination showed no bone connection and no sign of healing between the fractures of the tibia in the two groups at 6 weeks after modeling. Imaging and histological findings showed no healing at the end of fracture but typical atrophic nonunion in the experimental group at 12 weeks after modeling. By contrast, six animals had atrophic nonunion, and eight had hypertrophic nonunion in the control group. Overall, the animal model of atrophic tibial nonunion can be successfully constructed using circular external fixator combined with periosteal cauterization at the fracture end.

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    Effect of catalpol from the root of Rehmannia glutinosa on the expression of inflammatory proteins in synovium of the knee joint in rats with early osteoarthritis
    Zhang Bin, Dai Fenglei, Yin Hong, Zeng Yi, He Qiang, Qian Jianji, Ou Xianfeng
    2020, 24 (29):  4656-4661.  doi: 10.3969/j.issn.2095-4344.2815
    Abstract ( 409 )   PDF (765KB) ( 72 )   Save

    BACKGROUND: Inflammatory transmitters secreted from the synovium may be one of the important factors inducing the onset of knee osteoarthritis, and further exacerbate knee osteoarthritis.

    OBJECTIVE: To observe the effect of different concentrations of catalpol from the root of Rehmannia glutinosa on the expression of interleukin-1β, galectin 3 and S100A12 in the synovium of the knee joint in rats with early knee osteoarthritis, and to explore the mechanism of catalpol from the root of Rehmannia glutinosa in the treatment of early knee osteoarthritis.

    METHODS: The 14 of 48 adult male Wistar rats were randomly selected as a normal control group, and the remaining 34 rats were injected with 4% papain and 0.03 mol/L cysteine solution (0.2 mL) into the right knee joint cavity at 1, 4, 7 days after the initialization of the experiment to duplicate the model of early knee osteoarthritis. At 10 days after the initialization of the experiment, 4 rats in each group were randomly selected for histological observation using hematoxylin-eosin staining and validation of the model using Mankin and OARSI grading evaluation. After the model was successfully verified, the remaining 30 rats in the model group were randomly divided into model control group, low-dose group and high-dose group. At 2 days after successful modeling, each treatment group was infused with corresponding drugs at a dose of  0.2 mL/kg, and normal control group and model control group were infused with normal saline, once a day for 28 consecutive days. The synovium of the right knee joint was then taken from rats in each group, and the expression of interleukin-1β, galectin 3 and S100A12 in the rat synovium was detected by ELISA.

    RESULTS AND CONCLUSION: Mankin score and OARSI grading were significantly higher in the model control group than the normal control group (P < 0.05). The levels of S100A12, interleukin-1β and galectin 3 in the synovium were significantly higher in the model control group than the normal control group (P < 0.01). Compared with the model control group, the levels of S100A12, interleukin-1β and galectin 3 in the synovium was decreased somewhat in the low-dose group (P < 0.05), but significantly decreased in the high-dose group (P < 0.01). Therefore, catalpol from the root of Rehmannia glutinosa can delay the progression of knee osteoarthritis by reducing the level of inflammatory factors in the synovium.

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    Anatomical etiology and clinical significance of three-dimensional digital measurement of kidney stones
    Wu Libing, Xu Yangyang, He Yujie, Wang Haiyan, Gao Shang, Enhejirigala, Li Xiaohe, Li Zhijun
    2020, 24 (29):  4662-4666.  doi: 10.3969/j.issn.2095-4344.2779
    Abstract ( 535 )   PDF (990KB) ( 122 )   Save

    BACKGROUND: There are many causes of kidney stones, but there is no clear answer to whether kidney

    anatomy and morphology studies affect the generation of stones.

    OBJECTIVE: To reconstruct a three-dimensional model of the kidney and to measure and analyze anatomical data related to the etiology of kidney stones.

    METHODS: Thirty patients with kidney stones treated at Liangxiang Hospital in Fangshan District, Beijing from December 2017 to February 2019 were randomly selected as the study group, and the control group was 30 normal people who underwent physical examination during the same period. After collecting renal CT scan data from two groups of patients, the three-dimensional model of the kidney was reconstructed by image segmentation and fusion using Mimics 16.0. The length and width of the kidney, the length and width of the renal sinus, diameter of the junction between the renal pelvis and ureter, the distance from the upper edge of the kidney to the longitudinal line of the spinous process, the distance from the lower edge of the kidney to the longitudinal line of the spinous process, and the distance from the hilum to the longitudinal line of the spinous process. Multi-parameter Logistic regression analysis was performed on kidney anatomy parameters of patients with kidney stones.

    RESULTS AND CONCLUSION: There were no significant differences in the three-dimensional digital measurement results between patients with kidney stones and healthy people in the following aspects: the length and width of the kidney, length and width of the renal sinus, diameter of the junction between the renal pelvis and ureter, distance from the upper edge of the kidney to the longitudinal line of the spinous process, distance from the lower edge of the kidney to the longitudinal line of the spinous process, and distance from the hilum to the longitudinal line of the spinous process (P > 0.05). Multi-parameter Logistic regression analysis results of the kidney of patients with kidney stones indicated that there was no significant correlation among the length and width of the kidney, length and width of the renal sinus, diameter of the junction between the renal pelvis and ureter, distance from the upper edge of the kidney to the longitudinal line of the spinous process, distance from the lower edge of the kidney to the longitudinal line of the spinous process, and distance from the hilum to the longitudinal line of the spinous process (P > 0.05). These findings reveal that the difference in kidney morphology has nothing to do with the formation of stones.

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    Therapeutic effect of methotrexate combined with electroacupuncture in rheumatoid arthritis rats
    Zhang Guanghui, Zhang Chao, Guo Zhanfei, Hou Xiaodong
    2020, 24 (29):  4667-4672.  doi: 10.3969/j.issn.2095-4344.2816
    Abstract ( 480 )   PDF (799KB) ( 158 )   Save

    BACKGROUND: Currently, methotrexate for rheumatoid arthritis has been explored; however, there are still some problems such as unsatisfactory treatment effects.

    OBJECTIVE: To investigate the therapeutic effect and mechanism of methotrexate combined with electroacupuncture in rheumatoid arthritis rats.

    METHODS: A total of 100 Wistar rats were selected, 80 of which were injected type II collagenase to induce rheumatoid arthritis models. After successful modeling, the model rats were randomly divided into model group, methotrexate group, electroacupuncture group, and methotrexate+electroacupuncture group. The remaining 20 normal animals untreated were used as the normal control group. The arthritis index was evaluated at 1, 6, and 12 weeks of treatment. Hematological changes in the ankle were observed with hematoxylin-eosin staining at 12 weeks after treatment. RT-PCR and western blot were used to detect changes in tumor necrosis factor α, JAK3, and STAT3 expression levels. Flow cytometry was used to detect the apoptotic rate of chondrocytes.

    RESULTS AND CONCLUSION: Compared with the model group, methotrexate and electroacupuncture alone or in combination could significantly reduce the arthritis index of rheumatoid arthritis rats at 1, 6, and 12 weeks after administration (P < 0.05), and the reduction tendency was more significant in the methotrexate+electroacupuncture group. There was no synovial tissue lesion and joint capsule hyperplasia in the normal control group. In the model group, synovial tissue was infiltrated by extensive inflammatory cells; vasodilation and vascular hyperplasia in the synovium triggered the formation of vascular pannus; and intrathecal ligament nerve injury and proliferation of synovial and fibrous tissues were observed. Histological changes in the synovium were less after treatment with methotrexate and electroacupuncture alone than in combination. Treatment with methotrexate plus electroacupuncture obviously decreased inflammatory cell infiltration and synovial hyperplasia. Compared with the model group, the levels of tumor necrosis factor-α, JAK3 and STAT3 mRNA and protein were significantly reduced in the methotrexate group, electroacupuncture group, and methotrexate+electroacupuncture group (P < 0.05), and the reduction was more significant in the methotrexate+electroacupuncture group (P < 0.05). The apoptotic rate of chondrocytes was highest in the model group, followed by the methotrexate group, electroacupuncture group, and methotrexate+electroacupuncture group (P < 0.05). However, the apoptotic rate of chondrocytes in the methotrexate+electroacupuncture group was still higher than that in the normal control group (P < 0.05). To conclude, the combination of methotrexate and electroacupuncture for rheumatoid arthritis can inhibit the activity of tumor necrosis factor and JAK-STAT pathways, reduce the apoptosis of chondrocytes, and protect the articular cartilage.

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    Protective effect of crocin in ulcerative colitis rats and its related mechanism
    Yang Minjie, Liu Wei, Tu Hongfei, Li Li, Fei Sujuan
    2020, 24 (29):  4673-4679.  doi: 10.3969/j.issn.2095-4344.2817
    Abstract ( 516 )   PDF (1007KB) ( 225 )   Save

    BACKGROUND: Crocin has anti-inflammatory and anti-oxidative stress effects. The therapeutic effects of crocin on ulcerative colitis and related mechanisms are still unclear.

    OBJECTIVE: To explore the protective effect of crocin in ulcerative colitis rats and its related mechanism.

    METHODS: Thirty Sprague-Dawley rats were randomly divided into five groups: normal group, model group, low-dose crocin group, high-dose crocin group, and positive control group. Experimental rat model of ulcerative colitis was induced by dextran sodium sulfate. Starting on the first day of modeling, rats were routinely fed in the normal group, were given sulfasalazine by gavage in the positive drug group, and were gavaged with 0.05 and 0.1 g/kg crocin in the low- and high-dose crocin groups, respectively.

    RESULTS AND CONCLUSION: One week after intervention, the crocin-treated rats had significantly decreased scores on colon tissue injury and Crohn’s disease activity index (P < 0.05). Compared with the model group, crocin groups had a decrease in the content of malondialdehyde and activity of myeloperoxidase (P < 0.05), and an increase in the activity of superoxide dismutase in the colon tissue (P < 0.05). Shown by immunohistochemical staining, compared with the model group, treatment with crocin significantly reduced immune responses of tumor necrosis factor α and interleukin 23 proteins after 1 week of intervention (P < 0.05). Compared with the model group, treatment with crocin downregulated the expression levels of total protein Bax, Caspase-3, Toll-like receptor 4 and MyD88 (P < 0.05), and upregulated the expression of Bcl-2 in the intestinal tissue of rats (P < 0.05). These results indicate that crocin has a certain therapeutic effect in ulcerative colitis rats and its mechanism may be related to down-regulation of the Toll-like receptor 4/MyD88 signaling pathway and inhibition of oxidative stress, inflammation and apoptosis in the colon.

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    Whole body application of nerve growth factor promotes early healing of tibial shaft fracture and improves expression of bone morphogenetic protein-2 and vascular endothelial growth factor in rats
    Liu Guoming, Wang Qinfen, Lin Kefeng, Zhou Shiguo, Chen Zuxing, Lin Shishui
    2020, 24 (29):  4680-4685.  doi: 10.3969/j.issn.2095-4344.2780
    Abstract ( 314 )   PDF (723KB) ( 94 )   Save

    BACKGROUND: Fracture healing is a very complex, multi-stage physiological process with the coordinated participation of multiple cells. The influence of neurological factors on fracture healing has attracted increasing attention. Nerve growth factor is a bioactive complex protein that promotes cell growth. The mechanism of its role in promoting fracture healing is not clear.

    OBJECTIVE: To observe the effect of nerve growth factor on the healing of tibial fracture in rats and the mechanism.

    METHODS: Seventy-two male Sprague-Dawley rats were randomly divided into model group and treatment group. The model of tibial shaft closed fracture was established followed by intramedullary fixation. The treatment group was given intramuscular injection of nerve growth factor; the model group was given intramuscular injection of normal saline. The study was approved by the Experimental Animal Ethics Committee of Fujian Medical University on May 30, 2018, with approval No. FJYKDX-2018-035.

    RESULTS AND CONCLUSION: The callus volume in the treatment group was significantly higher than that in the model group at 2 and 4 weeks of intervention. At 6 weeks of intervention, the fracture line disappeared, the medullary cavity was recanalized, and the fracture in the treatment group healed earlier than that in the control group. Hematoxylin-eosin staining showed that the trabeculae grew densely and a large number of osteoblasts were observed in the treatment group at 2 and 4 weeks after intervention. The serum alkaline phosphatase level in the treatment group was significantly higher than that in the model group at 2 and 4 weeks of intervention. Immunohistochemical results showed that the positive expression of bone morphogenetic protein 2 and vascular endothelial growth factor in the callus of treatment group was significantly higher than that of model group at 2 and 4 weeks after intervention. The results of quantitative PCR showed that the mRNA expression of bone morphogenetic protein 2 and vascular endothelial growth factor in the treatment group was higher than that in the model group at 2 and 4 weeks after intervention. To conclude, the whole body application of nerve growth factor can enhance the osteogenesis of tibial fracture end and promote the early healing of tibial fracture in rats. At the same time, nerve growth factor can promote the expression of bone morphogenetic protein 2 and vascular endothelial growth factor, which shows certain regularity in different periods, and in turn induces the differentiation and proliferation of osteoblasts as well as formation and calcification of extracellular matrix to promote bone formation and bone healing.

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    Fibrotic changes in rat dorsal root ganglion following chronic sciatic nerve compression
    Li Qinwen, Liang Jie, Wang Dongmei, Shang Zhenghui
    2020, 24 (29):  4686-4691.  doi: 10.3969/j.issn.2095-4344.2741
    Abstract ( 484 )   PDF (749KB) ( 93 )   Save

    BACKGROUND: Chronic nerve compression leads to muscle atrophy and fibrosis. Previous studies mainly focus on its pathogenesis. However, little is known about the dorsal root ganglia (DRG) responses to chronic nerve compression injury.

    OBJECTIVE: To investigate the effect of chronic sciatic nerve compression on fibrosis of the DRG.

    METHODS: Animal models of chronic sciatic nerve compression were made in rats according to the method described by Mackinnon. L4-6 ipsilateral and contralateral DRG were harvested 3 weeks post injury. Real-time



    RT-PCR, immunofluorescence and western blot were performed to determine the expression levels of transforming growth factor-β, connective tissue growth factor, and collagen type I in ipsilateral and contralateral DRG.

    RESULTS AND CONCLUSION: Three weeks after injury, the mRNA and protein expression of transforming growth factor-β, connective tissue growth factor and collagen type I were increased significantly in the ipsilateral DRG as compared with the contralateral DRG (P < 0.05). Transforming growth factor-β and connective tissue growth factor mainly expressed in DRG neurons and axons, while collagen type I formed a net structure that surrounded DRG neurons and axons. These findings indicate that chronic sciatic nerve compression can induce fibrotic changes in the DRG that appears to be associated with an increase in transforming growth factor-β and connective tissue growth factor expression in DRG neurons.

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    Relationship between proprioception and postural stability of lower limbs in healthy adults
    Chen Zehua, Ye Xiangling, Chen Weijian, Xu Xuemeng
    2020, 24 (29):  4692-4696.  doi: 10.3969/j.issn.2095-4344.2818
    Abstract ( 456 )   PDF (602KB) ( 152 )   Save

    BACKGROUND: Proprioception is one of the many factors affecting posture stability, but the relationship and

    differences between proprioception and stability of the lower extremities remain unclear.

    OBJECTIVE: To investigate the differences of static stability and proprioception between dominant and non-dominant legs and the correlation between proprioception and stability in healthy adults without the influence of foot posture.

    METHODS: Sway length (SL) and sway area (SA) of the center of pressure (COP) were measured in 30 healthy adults with neutral feet standing on both legs and one leg, and the mean trajectory error (ATE) and completion time (CT) of lower limbs were recorded during proprioception evaluation. The study was approved by the Ethics Committee of Guangdong Second Traditional Chinese Medicine Hospital [No. (2019)50], and all participants voluntarily signed informed consent before the initiation of the study.

    RESULTS AND CONCLUSION: The ATE of the dominant leg was larger than that of the non-dominant leg (P < 0.05). There were significant correlations between left and right legs in proprioception and stability (P < 0.05 or 0.01). The associations between SL in left legs and ATE in right legs and between SL in right legs and ATE in left legs (P < 0.05) were significantly adjusted for the intrinsic differences of proprioception and stability. There was a significant correlation between SL standing with dominant legs and SL in two legs static standing (P < 0.05). Therefore, the proprioception of the dominant legs was significantly worse than that of the non-dominant legs, but there was no difference in their stability. To conclude, the stability of the lower limbs is not only related to the proprioception at the same side, but also to the proprioception at the opposite side. In the process of training and clinical rehabilitation therapy, if we hope to improve stability and proprioception of the lower limbs, we should not only strengthen training of the ipsilateral limb, but also pay attention to the contralateral proprioception.

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    Functional patch combined with surface electromyographic biofeedback for post-stroke dysphagia
    Wang Wei, Jia Yujie, Cai Hongmei, Wang Wenjuan, Sun Cuicui
    2020, 24 (29):  4697-4701.  doi: 10.3969/j.issn.2095-4344.2819
    Abstract ( 435 )   PDF (644KB) ( 277 )   Save

    BACKGROUND: Studies have shown that functional patch has a long-lasting effect on the treatment of dysphagia, and surface electromyographic biofeedback has also been confirmed to relieve dysphagia.

    OBJECTIVE: To analyze the clinical efficacy of functional patch combined with surface electromyographic biofeedback in patients with dysphagia after stroke.

    METHODS: One hundred patients with dysphagia after stroke were randomly divided into a control group, a functional patch group, a surface electromyographic biofeedback group and a combined treatment group (functional patch plus surface electromyographic biofeedback), each group containing 25 patients. The therapeutic effects were compared between groups by repetitive saliva swallowing test, video fluoroscopic swallow study and clinical efficacy evaluation before, 1 and 2 months after treatment. The implementation of the study protocol complied with the relevant ethical requirements of the First Affiliated Hospital of Jinzhou Medical University (approval No. 201918), and informed consent was obtained from all patients and their families prior to the initialization of the study.

    RESULTS AND CONCLUSION: After treatment, there was an increasing trend in the repetitive saliva swallowing test, a decreasing trend in the video fluoroscopic swallow study, and a significant improvement in the clinical efficacy in each group (P < 0.05). Compared with the control group, significantly increased frequency of saliva swallowing, significantly shortened time of epiglottis movement during swallowing and significantly improved clinical benefit rate were observed in the functional patch, surface electromyographic biofeedback group and combined treatment groups (all P < 0.05). More significant improvements in the above-mentioned indexes were observed in the combined treatment group (P < 0.05). These findings indicate that both functional patch and surface electromyographic biofeedback have certain curative effect on dysphagia after stroke, and the combination of the two therapies has better clinical effect.

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    Morphological traits in the head and face of Kazakh adults in Yili, Xinjiang
    Chen Shengguo, Yang Wenqing, Jia Long, Maerhaba•Tuerdihuojia, Wang Shuiquan, Bai Xin, Dong Jianjiang, Kaisaierjiang • Duolaiti, Nuermaimaiti • Bahaxiaer
    2020, 24 (29):  4702-4708.  doi: 10.3969/j.issn.2095-4344.2784
    Abstract ( 812 )   PDF (928KB) ( 117 )   Save

    BACKGROUND: The Kazakhs mainly live in the Yili Kazakh Autonomous Prefecture in northwestern Xinjiang. About 80% of the Kazakhs live in the areas of Yili, Tacheng, and Altay. To fully understand the physical characteristics of Kazakhs, a viviperception and head and face measurements of Kazakhs at the age of 20 and 86 were performed in Gilgelang Township, Gongliu County, Xinjiang.

    OBJECTIVE: To grasp the morphological traits in the head and face of Kazakh adults in Xinjiang.

    METHODS: Thirty-one head-face indexes of 422 Kazakh adults (219 males and 203 females) from Jiergelang county, Xinjiang were investigated. Twelve physical indices of the head and face were calculated.

    RESULTS AND CONCLUSION: In the Kazakh group, the incidence of eye fold of the upper eyelid was 92.7%; the rate of mongoloid fold was 9.9%; the appearance rates of flat and vertical types was 6.6% and 93.4%, respectively; the appearance rates of convex, concave and straight nasal profiles were 7.8%, 36.5% and 55.7%, respectively; the appearance rates of oblique, vertical and horizontal nostril shapes were 69.5%, 20.8% and 9.7%, respectively; the appearance rates of the chin of straight type and convex type were 68.2% and 31.8%, respectively; the appearance rates of earlobe type and non-earlobe type were 96.7% and 3.3%, respectively; the appearance rates of forehead hairline and non-forehead hairline were 72% and 28%, respectively; the appearance rates of straight hair and curly hair were 99.1% and 0.9%, respectively. Most of Kazakh males have dolichocephaly and hyperdolichocephaly (81.7%, 52.5%), hypsicephaly (93.6%), aerocephaly (84%), hyrerleptorrhiny (98.2%), and hypercuryen (74%). Kazak females most have dolichocephaly and hyperdolichocephaly (76.4%, 55.7%), hypsicephaly (97%), aerocephaly (84%), hyrerleptorrhiny (98.2%), and hypercuryen (74%). The head-face characteristics of Kazak population belongs to the North Asian type of Mongoloid

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    Advantages in instrument-assisted soft tissue mobilization for chronic soft tissue injury
    Lu Shuqing, Li Xin, Guo Jin, Liu Shiyu, Yang Shunbo, Feng Yuxia, Pang Wei
    2020, 24 (29):  4709-4716.  doi: 10.3969/j.issn.2095-4344.2786
    Abstract ( 480 )   PDF (45811KB) ( 286 )   Save

    BACKGROUND: Chronic soft tissue injury is easy to occur during daily living, sports training, treatment and rehabilitation of various acute and chronic diseases. Chronic soft tissue injury can cause pain. If there is no good treatment for the injured soft tissue, it is easy to develop limb dysfunctions (such as limited joint movements) due to have cicatricial contraction and adhesion, limited human activity and participation ability, affecting the quality of daily life activities. It can also reduce the effect of sports training or rehabilitation treatment for athletes and patients with various acute and chronic diseases. In recent years, the treatment of chronic soft tissue injury by instrument-assisted soft tissue mobilization has been widely concerned, which has a positive effect on pain relief after chronic soft tissue injury. This technology has been widely studied abroad, but less in China.

    OBJECTIVE: To summarize the progress of instrument-assisted soft tissue mobilization in the treatment of chronic soft tissue injury.

    METHODS: PubMed, WanFang, and CNKI were searched. Relevant literature concerning instrument-assisted soft tissue mobilization, chronic soft tissue injury and pain was retrieved and summarized.  

    RESULTS AND CONCLUSION: Instrument-assisted soft tissue mobilization has a positive effect on the improvement of pain and joint limitation caused by chronic soft tissue injury. It has been proved that instrument-assisted soft tissue mobilization can also improve the soft tissue function of healthy people. Instrument-assisted soft tissue mobilization is suggested to be used in clinical treatment and sports training as a means of treatment and prevention. Current basic research on this technology is still insufficient. In the future, in addition to a large number of clinical randomized controlled studies, we should deeply explore its action mechanism to provide theoretical support for clinical application.

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    Organs-on-a-chip and engineered human tissues in drug development
    Chen Peishan, Zhang Haiyan
    2020, 24 (29):  4717-4723.  doi: 10.3969/j.issn.2095-4344.2711
    Abstract ( 529 )   PDF (844KB) ( 86 )   Save

    BACKGROUND: Organs-on-a-chip (OOC) is a chip that miniatures tissues or organs in vitro to simulate human physiological or pathological activities.

    OBJECTIVE: To review the design considerations of single and multi-OOCs, expound its achievements, potential and application prospect in drug development and precision medicine, as well as the remaining challenges.

    METHODS: We searched relevant articles in PubMed and CNKI databases with the keywords of “organs-on-a-chip, liver, blood-brain barrier, tumor” in Chinese and “organs-on-a-chip, drug development, cell culture, organoids, microfluidic systems, induced pluripotent stem cells, liver” in English, respectively. Finally, 68 articles were analyzed in this review.

    RESULTS AND CONCLUSION: OOC is a breakthrough technology that benefits from progresses in engineered human tissue engineering, semiconductor fabrication and adult somatic cell culture, exceeding the limitations of current cell and animal models. The activities, mechanical properties and physiological reactions of the whole organ or human system can be embodied in the 3D microfluidic OOC. As it can simulate physiological or pathological states in vitro by integrating human cells with physiology-related microenvironments, OOCs are expected to supplement and reduce the pre-clinical trials of drugs, medical devices and biological materials, offering a favorable in vitro platform for screening drug-related adverse reactions. 

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    Wnt/beta-catenin signaling pathway in the treatment of osteoarthritis: new advances and application prospects
    Bei Tao, Liu Junting, Huang Qiulin, Su Wei, Zhao Jinmin
    2020, 24 (29):  4724-4730.  doi: 10.3969/j.issn.2095-4344.2714
    Abstract ( 697 )   PDF (38304KB) ( 62 )   Save

    BACKGROUND: Wnt/β-catenin signaling pathway plays a vital role in the development of osteoarthritis. OBJECTIVE: To review the recent progress of treating osteoarthritis based on the Wnt/β-catenin signaling pathway.

    METHODS: An electronical literature retrieval of PubMed, CNKI and WanFang databases was performed to search the literatures concerning the Wnt/β-catenin pathway in the treatment of osteoarthritis. The keywords

    were “catenin; wnt; osteoarthritis;arthritis; degenerative; arthritides; deformans; pathway; wnt signaling; signaling pathway; wnt signaling pathways; wnt beta catenin signaling pathway; canonical wnt pathway; canonical wnt” in English and Chinese, respectively. Finally, 74 articles were included in result analysis.

    RESULTS AND CONCLUSION: The potential treatments of osteoarthritis based on the Wnt/β-Catenin signal pathway include natural antagonists, small molecule inhibitors, agonists, traditional Chinese medicine and drug reposition. These drug pathways provide chondroprotective effect via activating or inhibiting the Wnt/β-catenin signaling pathway. The treatment of osteoarthritis based on the Wnt/β-catenin signaling pathway is currently in the laboratory stage, but it has a great application prospect. How to accurately regulate the pathway and better transfer the research results into the application will become a hotspot in the future.

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    Synovial macrophages in osteoarthritis: roles and features
    Cao Jiangang, Chen Desheng
    2020, 24 (29):  4731-4736.  doi: 10.3969/j.issn.2095-4344.2790
    Abstract ( 761 )   PDF (801KB) ( 86 )   Save

    BACKGROUND: The exact pathogenesis of osteoarthritis is unclear. Studies have shown that macrophages in synovial tissue are involved in sliding-inflammation response and the production of cartilage matrix degradation enzyme.

    OBJECTIVE: Based on the important role of synovial macrophages in osteoarthritis, to review and summarize the major research achievements and important research methods in this field, laying a foundation for future research on synovial macrophages.

    METHODS: The first author used computer to search relevant literatures included in PubMed and VIP from 1999 to 2019. The search terms were “osteoarthritis, synovitis, synovial macrophages” in English and Chinese, respectively. Manual screening was conducted according to the inclusion criteria, and irrelevant, repetitive and obsolete articles were excluded. Finally, 46 eligible articles were included.

    RESULTS AND CONCLUSION: There is an inflammatory response in the synovial tissue, and the severity of synovitis is closely related to osteoarthritis symptoms and progression. A large number of macrophages with different activation states are infiltrated in the synovial tissues of osteoarthritis patients at different stages. M1 macrophages are the main subgroup of macrophages involved in the production, cartilage degradation and osteophyte formation of osteoarthritis inflammatory factors, while M2 macrophages have a protective effect on osteoarthritis by secreting anti-inflammatory factors. Inhibiting the differentiation of macrophages into M1 type and promoting their M2 type differentiation can alleviate the pathological changes of osteoarthritis and delay the progression of osteoarthritis. It may be an effective method to treat osteoarthritis by regulating the polarization state of synovial macrophages.

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    Efficacy of platelet-rich plasma in arthroscopic anterior cruciate ligament reconstruction: a meta-analysis
    Huang Junhan, Chen Ping, Liu Jun, Chen Haiyun, Pan Jianke, Lü Yang, He Xiangzhong
    2020, 24 (29):  4737-4743.  doi: 10.3969/j.issn.2095-4344.2820
    Abstract ( 407 )   PDF (798KB) ( 64 )   Save

    BACKGROUND: Platelet-rich plasma has a favorable effect in the treatment of articular cartilage defects and bone defects. But there is still no consensus in its use for arthroscopic anterior cruciate ligament reconstruction.

    OBJECTIVE: To evaluate the clinical efficacy of platelet-rich plasma in arthroscopic anterior cruciate ligament reconstruction by a meta-analysis.

    METHODS: The randomized controlled trials concerning arthroscopic anterior cruciate ligament reconstruction with or without the use of platelet-rich plasma were retrieved in PubMed, EMbase, the Cochrane Library, CNKI, WanFang, VIP and CBM from inception to September 2019. According to inclusion and exclusion criteria, two searchers screened the literature, extracted the data and evaluated the quality independently, using RevMan 5.3 software for the meta-analysis. A total of 595 patients were enrolled in 10 randomized controlled trials. Both groups received arthroscopic anterior cruciate ligament reconstruction. The trial group was treated with platelet-rich plasma, while the control group was blank control or treated with normal saline.

    RESULTS AND CONCLUSION: Meta-analysis results showed that in the Lysholm score, the trial group was superior to the control group at 3 and 6 months after surgery [mean difference (MD)=9.26, 95% confidence interval (CI) (6.58, 11.94), P < 0.000 01; MD=5.14, 95%CI (3.04, 7.23), P < 0.000 01]. There was no significant difference between the two groups at 12 months after surgery [MD=2.17, 95%CI (-0.09, 4.42), P=0.06]. In the International Knee Documentation Committee (IKDC) score, the trial group was superior to the control group at 3 and 6 months after surgery [MD=6.29, 95%CI (3.74, 8.85), P < 0.000 01; MD=1.86, 95%CI (0.25, 3.47), P=0.02]. There was no significant difference in the proportion of normal, nearly normal and abnormal IKDC scores between the two groups [odds ratio (OR)=1.11, 95%CI (0.59, 2.08), P=0.75; OR=1.06, 95%CI (0.55, 2.05), P=0.87; OR=0.43, 95%CI (0.09, 2.02), P=0.28]. In the KT-1000/2000 arthrometer measurement, the trial group was better than the control group [MD=-1.08, 95%CI (-2.02, 0.15), P=0.02]. In the Visual Analogue Scale score, there was no significant difference between the two groups at 3 and 12 months after surgery [MD=-0.99, 95%CI (-2.06, 0.07), P=0.07; MD=-0.08, 95%CI (-0.99, 0.84), P=0.87]. The methods used to measure the width of bone tunnel were different among the studies. Therefore, descriptive analysis was carried out and it was concluded from limited evidence that the two groups had similar results. To conclude, in the arthroscopic anterior cruciate ligament reconstruction, platelet-rich plasma could improve the function of the knee joint in the short and medium term after surgery, as well as the stability of the knee joint. However, there was no significant difference in short-term or long-term pain relief and prevention of bone tunnel widening between the two groups. Due to the limitation of current literature quality and sample size, more high-quality studies are needed to verify the above conclusions.

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    Botulinum toxin A injection in the prevention of facial trauma or postoperative hypertrophic scar: a systemic review of effectiveness and safety
    Song Li, Ye Junru, Lu Mao, Tang Yi, Liu Yanlin, Chen Ximao
    2020, 24 (29):  4744-4750.  doi: 10.3969/j.issn.2095-4344.2778
    Abstract ( 441 )   PDF (820KB) ( 121 )   Save

    BACKGROUND: Facial scars are mainly caused by trauma or surgery, which greatly affect the appearance. Dermatologists and plastic surgeons have tried many ways to change the appearance of scars. Botulinum toxin A injection is widely used in clinical practice for prevention of scars, but the efficacy and safety are not proved.

    OBJECTIVE: To evaluate the effectiveness and safety of botulinum toxin A injection in the prevention of facial trauma or postoperative hypertrophic scar.

    METHODS: PubMed, EMbase, the Cochrane library, CNKI, CBM, WanFang, and VIP were searched for randomized controlled trials regarding botulinum toxin A injection in the prevention of facial scars. Manual retrieval was done for supplement of incomplete data. Two doctors were responsible for literature screen and evaluation. Finally, 11 randomized controlled clinical trials were included. The experimental group was injected with botulinum toxin A, and the control group was given saline or nothing. Part of the data was analyzed using Revman 5.3 software for meta-analysis, and the data that could not be analyzed using software were subjected to a descriptive analysis.

    RESULTS AND CONCLUSION: Eleven randomized controlled trials were included, involving 436 patients with 518 wounds. Meta-analyses showed that Vancouver scar scale score, visual analogue scale score and width of scars in the botulinum toxin A group were significantly better than those in the control group (weighted mean difference (WMD)=-1.61, 95% confidence interval (CI)=-2.06 to -0.26, P = 0.02; WMD=1.7, 95%CI=0.38 to 3.02, P = 0.01; WMD=-0.17, 95%CI=-0.22 to -0.12, P < 0.000 1). Incidence of adverse reactions of botulinum toxin A group was higher than that in the control group (χ2=8.335, P=0.004), but they were all slight and easy to release. There were no serious adverse events in both groups. It seems that botulinum toxin A injection can reduce the width of scars, improve Vancouver scale and visual analogue scale scores. However, it is suggested to make clear communication before and after the operation and take measures to deal with various adverse reactions in advance. 

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    The best route and dose of dexamethasone for brachial plexus block: a systematic review and meta-analysis
    Zhang Qing, Fan Junbai, Zhao Xiaoyu
    2020, 24 (29):  4751-4756.  doi: 10.3969/j.issn.2095-4344.2787
    Abstract ( 360 )   PDF (828KB) ( 107 )   Save

    BACKGROUND: Dexamethasone has been widely used in brachial plexus block to enhance the block effect,

    but the best way (perineural or intravenous) and dose are still inconclusive.

    OBJECTIVE: To systematically evaluate the optimal approach and dose of dexamethasone for brachial plexus block.

    METHODS: Studies on dexamethasone and brachial plexus block were searched in PubMed, Embase, Cochrane Library, CNKI, WanFang and VIP. Two evaluators analyzed the literatures, evaluated the quality, extracted relevant research indicators according to the screening criteria, and completed the meta-analysis.

    RESULTS AND CONCLUSION: A total of 16 articles were finally included in the meta-analysis (1 260 patients). As suggested by the Meta-analysis, regardless of 1-4 mg or 5-10 mg of dexamethasone, the perineural group significantly prolonged the duration of analgesia compared with the intravenous group [weighted mean difference (WMD)=201.38, 95% confidence interval (CI) (68.22, 334.54), P=0.003; WMD=302.96, 95%CI (142.41, 463.50), P=0.000 2]. There were no significant differences in the duration of motor block between the perineural and intravenous groups [WMD=121.06, 95%CI(-62.31, 304.42), P=0.20, I2=95%]. Compared with the intravenous group, the perineural group significantly prolonged the duration of analgesia. However, similar duration of analgesia was found in 1-4 mg and 5-10 mg of dexamethasone and the analgesia effect did not increase with the increase of dose. There were no significant differences in the duration of motor block between the perineural and intravenous groups.

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