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    18 May 2021, Volume 25 Issue 14 Previous Issue    Next Issue
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    Cone-beam CT measurement of alveolar bone thickness of the maxillary anterior area at implant anchorage site in different sexes
    Nie Jing, Shi Xiaoyu
    2021, 25 (14):  2133-2136.  doi: 10.3969/j.issn.2095-4344.3125
    Abstract ( 309 )   PDF (705KB) ( 18 )   Save
    BACKGROUND: At present, there are few studies on the bone thickness of the maxillary anterior teeth, and most domestic studies focus on the Han population in southern China. It is still unknown whether there are sex differences in the Uyghur population in Xinjiang.
    OBJECTIVE: To measure the thickness of alveolar bone in the maxillary anterior area of Uygur adults in Xinjiang and analyze the sex difference. 
    METHODS: Cone-beam CT data of 120 Uygur adults (60 males and 60 females) in Xinjiang were collected. The labiolingual thickness of the alveolar bone in the maxillary anterior area was selected at the height of 14, 17, and 20 mm from the reference plane in the sagittal plane between the incisors, between the central incisor and the lateral incisor, as well as between the lateral incisor and the canine. 
    RESULTS AND CONCLUSION: In the 14 and 17 mm height groups between the maxillary central incisors and between the central incisors and the lateral incisors, the bone thickness of Uygur men was significantly thicker than that of Uygur women; in the 14 mm height group between the maxillary lateral incisors and the canine, the bone thickness of Uygur men was significantly thicker than that of Uygur women. To conclude, there is a sex difference in the thickness of alveolar bone in the maxillary anterior teeth of Uygur adults, which provides a basis for the implantation of microscrew implants in orthodontic clinic.            

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    Effect of high-intensity interval training on fat reduction and irisin expression in obese rats
    Shi Xiaoyu, Feng Ziyang, Liu Ziming, Li Lin, Wang Zhen, Liu Xiaoran, Yu Liang
    2021, 25 (14):  2137-2141.  doi: 10.3969/j.issn.2095-4344.3091
    Abstract ( 244 )   PDF (813KB) ( 34 )   Save
    BACKGROUND: Studies have shown that high-intensity interval training is more time-saving than medium-intensity endurance training, which can effectively reduce visceral fat content.
    OBJECTIVE: To observe the changes of body fat, fibronectin type III domain containing protein 5 (FNDC5) expression of the soleus muscle and serum irisin level after high-intensity interval training in obese rats. 
    METHODS: Eighty healthy male Sprague-Dawley rats, 5 weeks old, were randomly divided into normal control group (n=20) and obesity group (n=60). The 30 rats were selected from the successful models and randomized into obesity quiet control group, moderate intensity exercise group and high-intensity intermittent training group (n=10 in each group), raising for 8 weeks. The change of the rat body mass was recorded, and samples were collected at quiet state after final exercise or at 12 hours after exercise. Body mass and body fat of the rats were measured, and the expression of FNDC5 in the soleus muscle was detected by immunoblotting, and the serum irisin level was determined. The experimental plan was approved by the Animal Experimental Ethics Committee of Beijing Sport University.
    RESULTS AND CONCLUSION: Compared with the obesity quiet control group, the body mass of rats decreased (P < 0.01), body fat composition decreased (P < 0.05), FNDC5 protein expression increased (P < 0.01), and serum irisin level increased (P < 0.01) in the two obese exercise groups. Compared with the moderate-intensity exercise group, the body mass of rats was significantly lowered (P < 0.01), the body fat composition was decreased (P < 0.05), and the protein expression level of FNDC5 and the serum irisin levels were significantly increased in the high-intensity interval training group (P < 0.01). To conclude, exercise training can reduce body fat in rats by increasing the serum expression of irisin and FNDC5. The body fat content of rats in the high-intensity interval training group was lower than that in the moderate-intensity training group, and the serum irisin content and soles muscle FNDC5 protein expression were higher, indicating that the high-intensity interval training has a better effect on fat reduction in obese rats. 

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    Effects of miR-335-5p on proliferation and apoptosis of osteoarthritic chondrocytes by targeting programmed cell death 5
    Zhang Yunqing, Wang Jian, Yang Chunhua, Li Cong
    2021, 25 (14):  2142-2147.  doi: 10.3969/j.issn.2095-4344.3133
    Abstract ( 226 )   PDF (924KB) ( 12 )   Save
    BACKGROUND: Studies have found that miR-335-5p is down-regulated in the synovial fluid of patients with osteoarthritis, which may be related to the occurrence and development of osteoarthritis. 
    OBJECTIVE: To investigate the effects of miR-335-5p on the proliferation and apoptosis of chondrocytes in osteoarthritis and the underlying mechanism.
    METHODS: Human primary articular chondrocytes were isolated and cultured, and the cells were then treated with 10 μg/L interleukin-1β to establish an osteoarthritis model. The treated cells were divided into normal group (normal culture medium), interleukin-1β group, miR-NC group, miR-335-5p group, si-NC group, si-programmed cell death 5 (PDCD5) group, miR-335-5p+pcDNA3.1 group, and miR-335-5p+pcDNA3.1-PDCD5 group. After 24, 48, and 72 hours of culture, the cell proliferation and apoptosis rate were detected by MTT and flow cytometry, respectively. The mRNA expression levels of miR-335-5p, PDCD5, ADAMTS-5 and matrix metalloproteinase-13 in chondrocytes were detected by qRT-PCR. The expression levels of PDCD5, Cyclin D1, p21, Bax and Bcl-2 proteins in chondrocytes were determined by western blot. The relationship between miR-335-5p and PDCD5 was verified by double luciferase reporting assay system. The study procedures were implemented in line with the relevant ethic requirements of the First Hospital of Changsha.
    RESULTS AND CONCLUSION: Compared with the control group, interleukin-1β inhibited the cell proliferation and promoted the apoptosis of chondrocytes, and inhibited the expression of miR-335-5p in chondrocytes. Over-expression of miR-335-5p promoted the proliferation and inhibited the apoptosis of chondrocytes induced by interleukin-1β. miR-335-5p targeted and negatively regulated the expression of PDCD5. Inhibition of PDCD5 promoted the proliferation of chondrocytes induced by interleukin-1β. Overexpression of PDCD5 reversed the effects of miR-335-5p up-regulation on the proliferation and apoptosis of chondrocytes induced by interleukin-1β. To conclude, miR-335-5p promotes cell proliferation and inhibits cell apoptosis by targeting PDCD5. miR-335-5p is a potential molecular target for osteoarthritis.

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    Tongdu Huoxue Decoction-medicated serum inhibits pyroptosis in annulus fibrosus cells of the intervertebral disc
    Wu Zijian, Hu Zhaoduan, Zhou Xiaohong, Li Jia, Li Bocun, Cai Guowei, Peng Rui
    2021, 25 (14):  2148-2153.  doi: 10.3969/j.issn.2095-4344.3517
    Abstract ( 192 )   PDF (1352KB) ( 22 )   Save
    BACKGROUND: Lumbar disc degeneration is the main pathological change of lumbar disc herniation, which is closely related to the programmed death of intervertebral disc annulus fibrosus cells. Previous clinical studies have shown that Tongdu Huoxue Decoction has a significant effect in the treatment of lumbar disc herniation, and it is worth further studying whether it can play a role by inhibiting the pyrolysis of annulus fibrosus cells. 
    OBJECTIVE: To investigate the inhibitory effect of Tongdu Huoxue Decoction-medicated serum on the pyroptosis of annulus fibrosus cells in the intervertebral disc induced by lipopolysaccharide/adenosine triphosphate (ATP), so as to explore the possible mechanism of Tongdu Huoxue Decoction in the treatment of lumbar disc herniation. 
    METHODS: Thirty-six 10-week-old Spraue-Dawley rats were gavaged with Tongdu Huoxue Decoction, and blood samples were taken from the abdominal aorta after 7-day continuous gavage to prepare drug-containing serum. Four-week-old Sprague-Dawley rats were taken to extract their lumbar intervertebral discs, and then the annulus fibrosus cells were extracted from the intervertebral disc tissues by mechanical-enzymatic digestion. The cells cultured to the second generation were identified by toluidine blue staining and type II collagen immunohistochemical staining. After that, the second-generation cells were randomly divided into blank group, model group, and low-, middle-, and high-dose serum-containing groups. Except for the blank group, the remaining four groups were given lipopolysaccharide/ATP to make the cell pyroptosis model. After modeling, 5%, 10%, and 20% of Tongdu Huoxue Decoction medicated serum were administrated in the low-, middle-, and high-dose serum-containing groups, respectively, and no intervention measures were taken in the blank group. We then used the MTT method to find the best concentration and time for the intervention of pyroptosis of annulus fibrosus cells with the drug-containing serum. Flow cytometry and Annexin V FIFT/PI double staining were used to measure the rate of cell pyroptosis. ELISA method was used to detect the expression of interleukin-1β and interleukin-18 in cell supernatant. qRT-PCR was used to detect the mRNA expression of Caspase-1, Gasdermin D, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). 
    RESULTS AND CONCLUSION: MTT showed that the best intervention concentration of Tongdu Huoxue Decoction medicated serum for the pyroptosis of annulus fibrosus cells was 10%, and the best intervention time was 24 hours. Flow cytometry results showed that compared with the blank group, the pyroptosis rate in the other four groups was significantly increased (P < 0.05). Compared with the model group, the pyroptosis rate in the three drug-containing serum groups was significantly decreased (P < 0.05). Compared with the low- and high-dose groups, the pyroptosis rate of the middle-dose group was significantly decreased (P < 0.05). Results from ELISA, qRT-PCR, and western blot assay indicated that compared with the blank group, the expression levels of interleukin-1β, interleukin-18, Caspase-1, Gasdermin D, NLRP3 mRNAs and proteins were significantly increased (P < 0.05), while compared with the model group, these expression levels were significantly decreased in the three drug-containing serum groups (P < 0.05). Moreover, the expression levels of interleukin-1β, interleukin-18, Caspase-1, Gasdermin D, NLRP3 in the middle-dose group were significantly lower than those in the low- and high-dose groups (P < 0.05). Therefore, Tongdu Huoxue Decoction-medicated serum can effectively relieve lipopolysaccharide/ATP induced pyroptosis of intervertebral disc annulus fibrosus cells and reduce inflammation. The middle-dose group has the best effect in delaying cell pyroptosis and reducing inflammation.

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    Effect of Tongluo Shenggu Capsule-containing serum on osteoclasts and Toll-like receptor 4/nuclear factor-kappa B signaling pathway
    Fan Siqi, Zeng Ping, Nong Jiao, Liu Jinfu, Qian Xiaofen
    2021, 25 (14):  2155-2160.  doi: 10.3969/j.issn.2095-4344.3134
    Abstract ( 252 )   PDF (1254KB) ( 28 )   Save
    BACKGROUND: Abnormal Toll-like receptor 4 (TLR4) signaling pathway plays an important role in the pathogenesis of steroid-induced necrosis of femoral head, and regulating TLR4 expression is expected to become a breakthrough point for effective treatment of hormonal femoral head necrosis.
    OBJECTIVE: To study the effect of Tongluo Shenggu Capsule on the TLR4 signal transduction pathway in the process of osteoclast differentiation, in order to understand the molecular biological mechanism by which Tongluo Shenggu Capsule inhibits osteoclast differentiation.
    METHODS: Twenty-eight 12-week-old C57BL/6 mice were randomly divided into Tongluo Shenggu Capsule high-dose, medium-dose, low-dose gavage group and normal saline gavage group. Medium dose was set to be 0.91 g/(kg·d), the high dose was 2 times up on the medium dose, and the low dose was 0.5 time up on the medium dose. The drug-containing serum was prepared by continuous gavage for 14 days. At 8 hours after the last administration, blood samples were taken from the abdominal aorta to prepare the serum containing the drug and the control serum. RAW264.7 cell line was induced by the combination of receptor activator of nuclear factor kappa B ligand and macrophage colony stimulating factor inducer. The cells were divided into five groups: normal group, normal saline group, high-, medium-, and low-dose drug-containing serum groups. Cell counting kit-8 method was used to observe the effect of drug-containing serum on cell proliferation. Then, the precursor of osteoclast was pretreated with 20% drug-containing serum on the 4th day of induction. Cell growth, morphology, and fusion were observed at 24, 48, 72, and 96 hours after induction. The number of osteoclasts was observed by TRAP staining on the 8th day. The expression of TLR4 and NF-κBp65 in cell supernatant was detected by western blot. The level of tumor necrosis factor α in cell supernatant was detected using ELISA. The study protocol was approved by the Animal Experimental Ethics Committee of Guangxi University of Chinese Medicine.
    RESULTS AND CONCLUSION: The level of tumor necrosis factor α in low-, medium- and high-dose drug-containing serum groups was lower than that in the normal group (P < 0.01), whereas there was no significant difference between the low-dose and medium-dose drug-containing serum groups. The protein expression of TLR4 in low-, medium- and high-dose drug-containing serum groups was significantly lower than that in the normal group (P < 0.05), whereas the protein expression of NF-κBp65 in the medium- and high-dose drug-containing serum groups was significantly lower than that in the normal group (P < 0.05). Moreover, inhibiting the protein expression of TLR4 and NF-κBp65 was most obvious in the medium-dose drug-containing serum group. Overall, one of the mechanisms underlying Tongluo Shenggu Capsule in the treatment of steroid-induced necrosis of femoral head may be to reduce the release of tumor necrosis factor α and improve the inflammatory environment by inhibiting TLR4/NF-κB signal pathway; on the other hand, it can inhibit the activity of osteoclasts, weaken bone absorption and improve the balance of bone metabolism after steroid-induced necrosis of femoral head.

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    Morphological characteristics of in vitro cultured articular chondrocytes from Sprague-Dawley rats at passage number from 0 to 3
    Yang Fan, Liu Baoyi, Liu Jiahe, Yang Jiahui, Qin Kairong, Zhao Dewei
    2021, 25 (14):  2161-2165.  doi: 10.3969/j.issn.2095-4344.3092
    Abstract ( 272 )   PDF (941KB) ( 16 )   Save
    BACKGROUND: Common methods for obtaining chondrocytes include mechanical-enzymatic digestion, sequential digestion of pronase and collagenase, sequential digestion of trypsin and type II collagenase, and simple type II collagenase digestion.
    OBJECTIVE: To investigate the isolation, extraction and identification of knee joint chondrocytes from Sprague-Dawley rats, and to observe the morphological characteristics of chondrocytes from primary to passages 3.
    METHODS: We used single-step digestive approach (type II collagenase digestion) to isolate and obtain chondrocytes from the knee joints of Sprague-Dawley rats in vitro, and then established a culture system in vitro. Cell proliferation assay and inverted phase contrast microscope were used to observe morphohistology of the cells. Toluidine blue staining, type II collagen as well as proteoglycan immunofluorescence staining were used to identify the characteristics of chondrocytes. The experimental protocol was approved by the Ethics Committee of Zhongshan Hospital of Dalian University.
    RESULTS AND CONCLUSION: Microscopic observation and cell proliferation assay both showed satisfactory cell morphology and proliferation at passages 2-3, and the capacity of the cells decreased gradually. Moreover, toluidine blue staining, type II collagen and proteoglycan immunofluorescence staining revealed superior characteristics of passage 3 chondrocytes cultured in vitro. These findings indicate that chondrocytes can successfully be isolated by the single-step type II collagenase digestion. Cell proliferation and passage cultivation can also be achieved. And dedifferentiation capacity of chondrocytes is improved gradually after the passages 3 cultured in vitro. Passage 3 cells cultured in vitro have superior characteristics for the use in experimental researches.
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    Effect of enhanced aryl hydrocarbon receptor expression on inflammatory response and healing of alveolar bone defects in diabetic rats
    Luo Yicai, Li Hao
    2021, 25 (14):  2166-2171.  doi: 10.3969/j.issn.2095-4344.3144
    Abstract ( 268 )   PDF(mobile) (817KB) ( 15 )   Save
    BACKGROUND: Under high glucose conditions, inflammatory responses in the defect site of alveolar bone are intensified, resulting in delayed bone healing. Previous studies have shown that enhanced aryl hydrocarbon receptor (AhR) expression can inhibit inflammatory responses and promote tissue healing.
    OBJECTIVE: To study the effect and mechanism of enhanced AhR expression on inflammatory response and healing of alveolar bone defects in diabetic rats.
    METHODS: Ten of 40 Sprague-Dawley rats were randomly selected as normal controls. Diabetic models were established in the other 30 rats, and randomly divided into AhR enhancement, negative control, and blank control groups, with 10 rats in each group. Bone defects were made by surgery in both sides of maxillae of each diabetic rat. After surgery, AteloGene gel with AhR lentiviruses was injected into the defect sites of rats in the AhR enhancement group. AteloGene gel with control lentiviruses was injected into the defect sites of rats in the negative control group. Rats in blank control group and normal control group received no injection. Twenty-eight days after defects were made, all rats were sacrificed, and left maxillary bone tissues were collected to detect bone healing using hematoxylin-eosin staining. Tissues from right maxillary bone defect sites were detached, and qRT-PCR was used to detect the gene expression of AhR and Notch signaling pathway members and inflammatory factors and alkaline phosphatase. Animal experiment was approved by the Animal Experimental Ethics Committee of Guangxi Medical University. 
    RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that the Lane-Sandhu scores of bone tissue regeneration in the AhR enhancement group were higher than those of negative control and blank control groups (P < 0.05); and the levels of inflammatory cell infiltration were lower than those of negative control and blank control groups (P < 0.05). qRT-PCR results showed that the levels of tumor necrosis factor α, interleukin-6, Notch1, Jagged1 levels, and Jagged2 in the AhR enhancement group were lower than those in the negative control and blank control groups (P < 0.05), and the levels of interleukin-10 and alkaline phosphatase were higher than those in the negative control and blank control groups (P < 0.05). These findings suggest that under high glucose conditions, enhanced AhR expression could reduce inflammatory response in alveolar bone defect sites of diabetic rats and promote the healing of bone defects, which may be associated with the inhibition of Notch signaling activation.

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    Relationship between root resorption and intrusive force during maxillary molar intrusion in Beagle dogs
    Liu Hong, Wan Zhe, Zhang Zhen, Zhang Qin
    2021, 25 (14):  2172-2176.  doi: 10.3969/j.issn.2095-4344.3143
    Abstract ( 323 )   PDF (899KB) ( 35 )   Save
    BACKGROUND: Root resorption is a common complication in the process of tooth intrusion. The choice of intrusion force and the development of root resorption are issues that clinicians are more confused and concerned about.
    OBJECTIVE: To investigate the effect of different force values on root absorption during molar intrusion in Beagle dogs. 
    METHODS: In this study, the Beagle dog was used as the research object to establish the animal model of experimental root resorption. Through morphology, hematoxylin-eosin staining, immunohistochemistry and western blot, the root surface absorption and the expression of osteoprotegerin (OPG)/receptor activator for nuclear factor kappa B ligand (RANKL) in periodontal tissue were observed. 
    RESULTS AND CONCLUSION: Hematoxylin-eosin staining results showed that root absorption was limited to alveolar bone and cementum at a intrusive force of 150-200 g. In the 250 g group, dentin absorption also occurred around the root tip. Immunohistochemical results showed similar RANKL/OPG ratios in the control group and the 150 g group, and the RANKL/OPG ratio in the 200 g group and the 250 g group presented an increasing trend. Pairwise comparison between the two groups showed statistically significant differences except for the control group and the 150 g group as well as the control group and the 200 g group (P < 0.05). Western blot results showed that RANKL/OPG ratio showed an increasing trend during 3-14 days, and after 14 days, the ratio went down. Pairwise comparison between groups showed that there were statistically significant differences among all the groups except for the 3 days and 7 days groups (P < 0.05). To conclude, with the increase of the additive force, the degree of root absorption will be aggravated. Excessive intrusive force will result in irreversible root absorption. A 150 g force is the recommended intrusive force for molar intrusion. RANKL/OPG ratio can be used as a biological indicator for the early diagnosis of root absorption.

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    Yaotu Granule deals with the proliferation and apoptosis of nucleus pulposus cells via regulating the expression of microRNA-221
    He Shenghua, Fu Yuanfei, Lan Zhiming, Sun Zhitao, Lai Juyi, Feng Hualong, Guo Zibin, Li Gai
    2021, 25 (14):  2177-2182.  doi: 10.3969/j.issn.2095-4344.3123
    Abstract ( 192 )   PDF (992KB) ( 19 )   Save
    BACKGROUND: MicroRNA is involved in intervertebral disc degeneration, and Yaotu Granule can significantly delay the progress of intervertebral disc degeneration.
    OBJECTIVE: To investigate the effect of Yaotu Granule in the proliferation and apoptosis of nucleus pulposus cells by regulating the expression of microRNA-221 (miR-221). 
    METHODS: MiR-221 mimics and inhibitors were transfected into rat nucleus pulposus cells to establish miR-221 overexpression and inhibition models. Tumor necrosis factor-α was used to induce nucleus pulposus cell degeneration model. The degenerated nucleus pulposus cells were treated with 100 and 200 mg/L Yaotu Granule freeze-dried powder (low and high dose groups). In the miR-221 mimics + Yaotu Granule group, miR-221 mimic and 200 mg/L Yaotu Granule freeze-dried powder were added. Cell counting kit-8 and TUNEL assay were used to detect the cell proliferation and apoptosis, RT-qPCR was used to detect mRNA expression of miR-221, and western blot was used to detect the expression of Bax and Bcl-2. 
    RESULTS AND CONCLUSION: MiR-221 mimics reduced cell prolifecation at 24, 48, 72 hours (P < 0.05) and promoted cell apoptosis at 48 hours (P < 0.05); miR-221 inhibitors had the opposite results (P < 0.05). Compared with the normal group, tumor necrosis factor-α inhibited cell proliferation, increased cell apoptosis, and upregulated miR-221 expression (all P < 0.05). Compared with the model group, low- and high-dose Yaotu Granules increased cell proliferation, reduced cell apoptosis, and downregulated miR-221 expression (all P < 0.05). Compared with the mimics group, cell proliferation improved, apoptosis rate decreased, the protein expression of Bax reduced, and the Bcl-2 protein expression up-regulated in the miR-221 mimics + Yaotu Granule group (all P < 0.05). To conclude, miR-221 has an effect on the proliferation and apoptosis of nucleus pulposus cells, and Yaotu Granule can delay the progression of intervertebral disc degeneration by downregulating the expression of miR-221.  

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    Immune infiltration mechanism of differential expression genes in rheumatoid arthritis and potential therapeutic prediction of Chinese herbs
    Shen Fu, Kuang Gaoyan, Yang Zhuo, Wen Meng, Zhu Kaimin, Yu Guizhi, Xu Wuji, Deng Bo
    2021, 25 (14):  2183-2191.  doi: 10.3969/j.issn.2095-4344.3797
    Abstract ( 313 )   PDF (4692KB) ( 41 )   Save
    BACKGROUND: The pathogenesis of rheumatoid arthritis is not completely clear. Immune imbalance is an important link in the pathogenesis of rheumatoid arthritis, and research on the related regulatory mechanism of immune infiltration in rheumatoid arthritis is less reported. 
    OBJECTIVE: to analyze the pathway enrichment and immune infiltration of rheumatoid arthritis gene probe chip data by using GEO gene chip database, and to predict the biological process of immune regulation in rheumatoid arthritis, thereby providing a theoretical basis for understanding the immune mechanism of rheumatoid arthritis and the intervention of traditional Chinese medicine in immune regulation.
    METHODS: The GEO gene chip database was searched for synovial tissue-related gene probes of rheumatoid arthritis, and the normal synovial tissue was used as control. Protein-protein interaction network of different genes was analyzed using STRING database, to screen out core target genes. The gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) gene pathway enrichment analysis of differential genes related to rheumatoid arthritis was performed using R language and related installation package program. The content and proportion of 22 kinds of immune cells in rheumatoid arthritis group and control group were analyzed by CIBERSORT deconvolution method. Significantly enriched immune-related biological processes and core target genes were predicted using the COREMINE database.
    RESULTS AND CONCLUSION: Rheumatoid arthritis-associated protein networks interacted with core target genes involving CDC20, GNB3, QSOX1 and 12 genes associated with chemokines. GO enrichment analysis showed that up-regulated genes were more closely related to immune inflammation. KEGG enrichment analysis showed that immune regulation of rheumatoid arthritis was closely related to chemokine signaling pathway, interleukin-17 related pathway and nuclear factor-κB pathway. Analysis of the infiltration matrix of immune cells showed that the proportion of plasma cells, memory B cells and M0 macrophages in rheumatoid arthritis group increased significantly, while the number of M2 macrophages and resting mast cells was significantly reduced in the synovial tissues of rheumatoid arthritis. Correlation analysis between immune cells indicated that the unactivated natural killer cells of rheumatoid arthritis were positively correlated with neutrophils, and the activated CD4 memory T cells were strongly negatively correlated with activated natural killer cells. Through COREMINE prediction, mulberry leaf, fish brain stone and yam were found to be most closely related to the immune pathways and core target genes associated with rheumatoid arthritis. The mechanism may be related to interference with leukocyte and T cell migration by acting on the target genes, CCR5, CXCL10, CXCR3, and CXCL13. Overall, M2 macrophages and resting mast cells are closely related to rheumatoid arthritis. Rheumatoid arthritis-related differential genes are involved in immune-related biological processes, including neutrophil activation, leukocyte chemotaxis and T cell migration, as well as correlated with chemokine signaling pathways, interleukin-17-related pathway, and nuclear factor-κB-related pathway. Mulberry leaves, fish-brain stones, and yam may be the potential molecular drug sources.
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    Relationship between joint function and circadian rhythm in a rat model of knee osteoarthritis  undergoing acupuncture and moxibustion at acupoints selected based on liver theory
    Zhou Xiaohong, Li Bocun, Li Jia, Peng Rui
    2021, 25 (14):  2192-2198.  doi: 10.3969/j.issn.2095-4344.3121
    Abstract ( 192 )   PDF (1112KB) ( 19 )   Save
    BACKGROUND: The pathogenesis of knee osteoarthritis is complex. In recent years, studies have found that circadian rhythm is closely related to knee osteoarthritis, and the liver is related to circadian rhythm to some extent. However, there are rare reports on the influence of acupuncture and moxibustion on the circadian rhythm from the liver theory. 
    OBJECTIVE: To explore the relationship between circadian rhythm and joint function of  the articular cartilage when treating osteoarthritis with acupuncture at acupoints associated with the liver. 
    METHODS: Forty 3-month-old male SPF Sprague-Dawley rats were randomly divided into normal group, model group, conventional acupuncture group and acupuncture at acupoints associated with the liver group, with 10 rats in each group. In the latter three groups, the osteoarthritis model was constructed in the right knee joint of rats by surgical modeling. Zusanli+Neixiyan+Waixiyan were selected in the conventional acupuncture group, Yanglinquan+Ganshu+Taichong were selected in the group of acupuncture at acupoint associated with the liver. Open field test, plantar pain threshold test and range of motion of the right knee joint were performed and detected since the 1st  week from modeling. After treatment, the pathological structure of cartilage tissues was observed by hematoxylin-eosin staining. RT-PCR and immunofluorescence were used to detect the expression of Bmal1 and Clock gene and protein in cartilage tissues. 
    RESULTS AND CONCLUSION: Compared with the normal group, in the model group, the average speed and total movement distance were significantly reduced, the rest time was significantly prolonged (P < 0.05), the plantar pain threshold was significantly reduced (P < 0.05), the range of motion of the knee joint was reduced (P < 0.05), the histological score was significantly increased (P < 0.05), and the mRNA and protein expressions of Bmal1 and Clock were significantly reduced (P < 0.01). Compared with the model group, all indexes were improved in the conventional acupuncture group and in the group of acupuncture at acupoints associated with the liver (P < 0.05), and a better improvement of each index was in the group of acupuncture at acupoints associated with the liver (P < 0.05). Therefore, it is possible to repair cartilage tissue, relieve osteoarthritic pain and restore joint function by influencing circadian rhythm in chondrocytes. 
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    Correlation between inflammatory factors in synovial cells and microRNA-145/mitogen-activated protein kinase 4 molecular axis
    Zhu Lixuan, Cui Yue, Luo Jing
    2021, 25 (14):  2199-2204.  doi: 10.3969/j.issn.2095-4344.3145
    Abstract ( 247 )   PDF (868KB) ( 17 )   Save
    BACKGROUND: Inflammatory cytokines have been shown to be abnormally expressed in chondrocytes and double-knuckle cells. Targeting inflammatory pathways may be an effective strategy for the treatment of osteoarthritis, but few reports focus on inflammatory responses in synovial cells.
    OBJECTIVE: To investigate the effect of 99Tc-MDP on synovial cells-produced inflammatory factors through microRNA-145 (miR-145)/mitogen-activated protein kinase 4 (MKK4) molecular axis. 
    METHODS: Osteoarthritis fibroblast-like synovial cells (HFLS-RA cells) were treated with 99Tc-MDP of  different mass concentrations for 48 hours. The expression levels of miR-145 and inflammatory factors, caspase 1, interleukin (IL)-1, IL-18 and tumor necrosis factor-α (TNF-α) in HFLS-RA cells were measured by qRT-PCR, and the survival rate of HFLS-RA cells was measured by cell counting kit-8. After determining the optimal mass concentration for 99Tc-MDP intervention, HFLS-RA cells were divided into four groups: blank control group (without any treatment), 99Tc-MDP group (13 μg/L 99Tc-MDP treated HFLS-RA cells for 48 hours), 99Tc-MDP+miR-145 inhibitor group (13 μg/L 99Tc-MDP treated HFLS-RA cells followed by transfection with miR-145 inhibitor), 99Tc-MDP+miR-145 inhibitor+sh-MKK4 group (13 μg/L 99Tc-MDP treated HFLS-RA cells followed by transfection with miR-145 inhibitor+sh-MKK4). The expression levels of miR-145 and the inflammatory factors, caspase 1, IL-1, IL-18 and TNF-α, in HFLS-RA cells were measured by qRT-PCR, and the survival rate of HFLS-RA cell was measured by cell counting kit-8.
    RESULTS AND CONCLUSION: 99Tc-MDP significantly inhibited the expression of caspase 1, IL-1, IL-18 and TNF-α as well as the cell survival rate of hFLS-RA cells. The 50% inhibiting concentration of 99Tc-MDP was 13 μg/L. 99Tc-MDP significantly upregulated the expression of miR-145, and downregulated the expression of MKK4 expression in HFLS-RA cells (P < 0.01). MiR-145 targeted MKK4, and overexpression of miR-145 could significantly inhibit the expression of MKK4. Compared with the 99Tc-MDP group, the 99Tc-MDP+miR-145 inhibitor group significantly inhibited the expression of miR-145 in HFLS-RA cells (P < 0.05) and promoted the expression of inflammatory factors in the cells (P < 0.05) and cell proliferation (P < 0.05). Compared with the 99Tc-MDP+miR-145 inhibitor+sh-MKK4 group, the 99Tc-MDP+miR-145 inhibitor group could significantly promote HFLS-RA cell proliferation (P < 0.05) and increase the expression of inflammatory factors in the cells (P < 0.05). To conclude, 99Tc-MDP relieves osteoarthritis by inhibiting HFLS-RA cell-produced inflammatory factors via the downregulation of MKK4 by miR-145.

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    Electroacupuncture intervention on the expression of synaptic plasticity-related proteins in the hippocampi of mice with radiation-induced brain injury
    Wang Donghui, Wu Xin, Sun Ningning, Zhang Han, Gao Jianfeng
    2021, 25 (14):  2205-2210.  doi: 10.3969/j.issn.2095-4344.3511
    Abstract ( 224 )   PDF (1231KB) ( 26 )   Save
    BACKGROUND: Radiation-induced brain injury, as one of the serious complications after radiotherapy, seriously endangers people's health and damages learning and memory functions. However, there are relatively few reports on the prevention and treatment of brain damage caused by electroacupuncture intervention.
    OBJECTIVE: To explore the effect of electroacupuncture intervention on the expression of synaptic plasticity related proteins in mice with radiation-induced brain injury. 
    METHODS:  C57BL/6J mice, 30 days old. were randomly divided into blank group, model group and electroacupuncture group. Except for the blank group, the other groups were given 8 Gy radiation dose to construct a radiation-induced brain injury model. The electroacupuncture group was given acupuncture at “Baihui” (GV 20), “Fengfu” (GV 16) and bilateral “Shenshu” (BL 23) for 21 days for intervention, and mice were intraperitoneally injected with BrdU. After electroacupuncture, Morris water maze test and T maze test were used to detect the learning and memory abilities of mice. Immunohistochemical method was used to detect the expression of BrdU in the hippocampus. Western blot assay was used to detect Notch1 and Hes1 related to Notch signaling pathway in the hippocampus, and synaptic plasticity-related proteins synaptophysin (SYN), postsynaptic density protein-95 (PSD-95) and brain-derived neurotrophic factor (BDNF) expression. 
    RESULTS AND CONCLUSION: Electroacupuncture intervention significantly improved learning and memory impairment in mice with radiation-induced brain injury. The positive expression of BrdU in the model group was significantly lower than that in the blank group (P < 0.01), and the positive expression of BrdU in the electroacupuncture group was significantly increased (P < 0.01). The expression levels of Notch1, Hes1, PSD- 95, SYN and BDNF were lower in the model group than that of the blank group (P < 0.01, P < 0.01, P < 0.01, P < 0.05, P < 0.01). Compared with the model group, the expression levels of Notch1, PSD-95, SYN and BDNF increased in the electroacupuncture group (P < 0.01, P < 0.01, P < 0.05, P < 0.01), and the expression level of Hes1 decreased significantly (P < 0.05). Therefore, the mechanism by which electroacupuncture improves the learning and memory function of mice with radiation-induced brain injury may be related to the Notch signaling pathway and the increased expression of synaptic plasticity protein regulated by electroacupuncture.
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    Effects of post-exercise gastrocnemius needling on Achilles tendon degeneration in obese rats
    Liu Yunyi, Wang Bo, Wang Lin
    2021, 25 (14):  2211-2218.  doi: 10.3969/j.issn.2095-4344.3146
    Abstract ( 198 )   PDF (1148KB) ( 24 )   Save
    BACKGROUND: Post-exercise gastrocnemius tension increase is the main cause of degeneration, and overweight people are more susceptible. The gastrocnemius needling treatment has been considered as an effective way to reduce post-exercise muscle tension. 
    OBJECTIVE: To study the effect of post-exercise gastrocnemius needling treatment on the risk of Achilles tendon degeneration by observing the changes in the expression of mechanical growth factors and tissue proteins after needling.
    METHODS: Thirty-two 12-week-old male Sprague-Dawley rats were fed with high fat diet for 4 weeks to establish obese rats with a body weight of (500.27±29.11) g. All rat models were randomly divided into blank control group, exercise group, needling group and post-exercise needling group. Eccentric running at -16° was performed, and the exercise intensity was set at 60% of the maximum oxygen uptake (15.6 m/min) for 60 minutes. The exercise was performed 6 days per week for 4 continuous weeks. Needling treatment was performed in the needling group and the post-exercise needling group at the end of each exercise. The needle position was in the middle of the gastrocnemius muscle, and the needling time was 5 minutes. Achilles tendon and gastrocnemius of rats were harvested followed by histological analysis in the 5th week. Hematoxylin-eosin staining was used to observe the structural changes of Achilles tendon; immunofluorescence staining was used to detect the expression of collagen and related cytokines in the Achilles tendon; western blot assay was used to detect transforming growth factor β1 expression in the gastrocnemius. The study protocol was approved by the Experimental Animal Ethics Committee of Beijing Sport University.
    RESULTS AND CONCLUSION: The collagen fibers of the Achilles tendon were disordered in the exercise and post-exercise needling groups. The expression of transforming growth factor β1 in the gastrocnemius was significantly higher in the exercise group than the other three groups (P < 0.05), and was significantly higher in the post-exercise needling group than the blank control and needling groups (P < 0.05). The expression of type I collagen in the Achilles tendon was significantly lower in the exercise group than in the other three groups (P < 0.05). The expression of type III collagen was significantly higher in the exercise group than in the other three groups (P < 0.05), and significantly higher in the post-exercise needling group than the needling and blank control groups (P < 0.05). The expression of matrix metalloproteinase 1 in the Achilles tendon was significantly lower in the exercise group than the other three groups (P < 0.05), whereas the expression of matrix metalloproteinase 13 in the Achilles tendon was significantly higher in the exercise group than the other three groups (P < 0.05). The expression of transforming growth factor β1 in the Achilles tendon was significantly higher in the exercise group than the other three groups (P < 0.05), and was significantly higher in the post-exercise needling group than the needling and control groups (P < 0.05). There was no significant difference in insulin-like growth factor 1 expression among the four groups. To conclude, post-exercise gastrocnemius needling can reduce the risk of Achilles tendon degeneration in obese rats.

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    Effect of Bushen Jianpi Huoxue Recipe on transforming growth factor beta/bone morphogenetic protein 2 signaling pathway in the muscle and skeleton of ovariectomized rats
    Liu Zhijun, Liu Shaojin, Wei Hewei, Wan Lei, Huang Hongxing, Qiao Rongqin
    2021, 25 (14):  2219-2223.  doi: 10.3969/j.issn.2095-4344.3137
    Abstract ( 210 )   PDF (788KB) ( 20 )   Save
    BACKGROUND: Bushen Jianpi Huoxue Recipe is an empirical prescription for treating osteoporosis in the Third Affiliated Hospital of Guangzhou University of Chinese Medicine. Studies have confirmed that the transforming growth factor β (TGF-β)/bone morphogenetic protein 2 (BMP-2) signaling pathway can regulate bone formation, which is an important pathway for the differentiation and synthesis of osteoblasts. 
    OBJECTIVE: To investigate the effect of Bushen Jianpi Huoxue Recipe on TGF-β/BMP-2 signaling pathway in the muscle and skeleton of ovariectomized rats. 
    METHODS: Seventy-two SPF female Sprague-Dawley rats aged 6 months were randomly divided into sham operation group (n=24) and model group (n=48). In the model group, ovariectomized models were made in rats. Twelve rats from each group were randomly selected 3 months after operation for testing bone density. The remaining 36 rats in the model group were randomly divided into model group, Bushen Jianpi Huoxue Recipe group (BSJPHX group, dose 2.979 g/kg), and alendronate sodium D3 tablets (II) group (ALN group, dose 1.02 mg/kg). The sham operation group and the model group were given an equal volume of normal saline. After 12 weeks, rats in each group were sacrificed under anesthesia. The bone density of lumbar vertebrae and femur were detected by dual-energy X-ray method. Real-time quantitative polymerase chain reaction (real-time PCR) and western blot were used to detect TGF-β and BMP-2 mRNA and protein in rat muscle and bone, respectively. The experiment was approved by the Ethics Committee of Guangzhou University of Chinese Medicine, with an approval No. S2016046. 
    RESULTS AND CONCLUSION: After 3 months of modeling, the bone mineral density of the model group was significantly lower than that of the sham operation group (P < 0.05). After 3 months of drug intervention, compared with the model group, bone mineral density was significantly increased in the BSJPHX group and ALN group, and TGF-β and BMP-2 mRNA and protein expression levels were significantly increased (P < 0.05). To conclude, Bushen Jianpi Huoxue Recipe regulates the transduction of TGF-β/BMP-2 signaling pathway by increasing the expression of TGF-β and BMP-2 at mRNA and protein levels, and then plays a preventive role in postmenopausal osteoporosis.
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    Huangqi Guizhi Wuwu Decoction in the treatment of osteoarthritis: analysis based on network pharmacology and molecular docking technology
    Han Jie, Zhang Xiaoyun, Chen Rilan, Zhang Chi, Liao Zilong, Chen Yueping, Chen Feng, Liao Jianzhao
    2021, 25 (14):  2224-2230.  doi: 10.3969/j.issn.2095-4344.3129
    Abstract ( 280 )   PDF (1583KB) ( 66 )   Save
    BACKGROUND: Studies have shown that Huangqi Guizhi Wuwu Decoction can reduce cartilage damage, promote cartilage repair, and delay the disease development by inhibiting angiogenesis, but its mechanism of action is not yet clear.
    OBJECTIVE: To investigate the molecular mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of osteoarthritis based on network pharmacology and molecular docking technology. 
    METHODS: The active ingredients of Huangqi Guizhi Wuwu Decoction were screened by TCMSP database and corresponding targets were collected. The potential targets for treating osteoarthritis were obtained by OMIM, GeneCards, and TTD databases, and the intersected targets of Huangqi Guizhi Wuwu Decoction for treating osteoarthritis were obtained. The STRING database was used to construct the single drug-active ingredient-acting target network, followed by protein-protein interaction network analysis using Cytoscape software. David database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking of active ingredients and key targets was finally performed using PyMOL software. 
    RESULTS AND CONCLUSION: Sixty-three compounds of Huangqi Guizhi Wuwu Decoction and 217 related targets were screened, and 130 targets were obtained after the intersection, mainly involving AGE−RAGE signaling pathway, MAPK signaling pathway, nuclear factor-κB signaling pathway, tumor necrosis factor signaling pathway, and interleukin-17 signaling pathway. Treatment of osteoarthritis might be achieved by the response to lipopolysaccharide, molecules of bacterial origin, nutrient level, and oxidative stress. ESR1, PRKDC, HSPA8, EP300 and HSP90AA1 were the hub targets in the protein-protein interaction network. A total of five key active ingredients were docked with five key targets. To conclude, Huangqi Guizhi Wuwu Decoction plays a role in the treatment of osteoarthritis through multi-component, multi-target and multi-channel regulations.

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    Anaerobic threshold intensity of adults aged 20 to 29: a speculation based on a 20-meter shuttle run test
    Jia Xiao, Xue Xiaojing, Kong Zhenxing, Yu Jingjing, Sun Tingting, Zhang Yimin
    2021, 25 (14):  2231-2235.  doi: 10.3969/j.issn.2095-4344.3102
    Abstract ( 238 )   PDF (733KB) ( 21 )   Save
    BACKGROUND: The selection of appropriate exercise intensity is the key to develop personalized and accurate guidance scheme. The anaerobic threshold intensity is the best intensity to develop aerobic endurance. The measurement of the commonly used anaerobic threshold needs to be carried out in a laboratory environment. There are certain limitations, including complicated steps, high cost, and professional personnel required for calculation and analysis.
    OBJECTIVE: To explore the feasibility of speculating the anaerobic threshold intensity by combining the results of 20-meter shuttle run test and the indicators of sex, age, height, body mass and exercise conditions, and to establish a regression equation to speculate the anaerobic threshold intensity of adults aged 20-29 years. 
    METHODS: In total, 126 participants were enrolled, aged 20 to 29 years, including 61 males and 65 females. Information on sex, age, height, body mass and exercise conditions was collected and recorded. Then Graded Exercise Test was conducted using a cycle ergometer, to collect gas metabolism indicators and calculate the ventilatory threshold (VT). A 20-meter shuttle test was conducted at a later date. According to the correlation analysis results of all indicators, the regression equation was established using the method of stepwise regression, with the VT as dependent variable, the results of 20-meter shuttle run test and other relevant indicators as independent variables. 
    RESULTS AND CONCLUSION: The laps of 20-meter shuttle run test was moderately correlated with the absolute value of VT (r=0.684, P < 0.01). The regression equation of speculating anaerobic threshold intensity in adults aged 20 to 29 is: VT (L/min) =-0.201+0.008 * laps+0.01 * weight + 0.096 * exercise condition (R=0.828, R2=0.686, SEE=0.210). To conclude, it is feasible using the 20-meter shuttle run test to speculate the anaerobic threshold intensity of adults aged 20 to 29, which can be used to guide the public to exercise scientifically, safely and effectively.
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    Influence of conversion from cyclosporine to tacrolimus on glucose metabolism and cardiovascular risk profiles in stable kidney transplant patients
    Wang Xiaobo, Wang Changan, Han Jianle, Yang Qingyan, Yang Shuaiping, Yang Junwei
    2021, 25 (14):  2236-2240.  doi: 10.3969/j.issn.2095-4344.3124
    Abstract ( 277 )   PDF (704KB) ( 64 )   Save
    BACKGROUND: The pros and cons of conversion from cyclosporine to tacrolimus are unclear in stable kidney transplant patients. It is generally believed that cyclosporine increases cardiovascular risks, while tacrolimus has a negative effect on glucose metabolism.
    OBJECTIVE: To discuss the effects of conversion from cyclosporine to tacrolimus on glucose metabolism and cardiovascular risk in stable kidney transplant patients.
    METHODS: Sixty-nine renal transplant recipients who met the inclusion criteria were randomly divided into a conversion group (n=36, cyclosporine was converted to tacrolimus) and a control group (n=33, cyclosporine was given continuously). Blood glucose, blood lipid, blood pressure, renal function, cardiovascular risk factors, body mass and combination medication were monitored at enrollment, 3 months and 6 months. The study was approved by the Ethics Committee of the 7th People’s Hospital of Zhengzhou.
    RESULTS AND CONCLUSION: After 6 months of conversion, fasting blood glucose level increased from (5.6±1.0) to (6.0±1.2) mmol/L (P=0.007); the glycosylated hemoglobin level increased from (5.7±0.8)% to (6.0±1.2)% (P=0.016). Among cardiovascular risk factors, fibrinogen level decreased from (3.16±0.7) to (2.89±0.7) g/L (P=0.015); high-density lipoprotein cholesterol level decreased from (1.76±0.5) to (1.65±0.4) mmol/L (P=0.012); body mass index decreased from (24.3±3.6) to (23.7±3.4) kg/m2 (P=0.037). There were no significant changes in the other factors, including creatinine, urinary protein-creatinine ratio, blood pressure and blood lipid (P > 0.05). These findings indicate that switching immunosuppressant therapy from cyclosporine to tacrolimus significantly increases blood glucose level in stable kidney transplant patients, with no evident advantage in reducing cardiovascular risk.

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    Ultraviolet resistance-associated gene (Uvrag) deficiency promotes cellular senescence in the heart
    Lai Shuaiwei, Zhang Shasha, Liu Xiaoyun, Haniya Mazhar, Amber Naz, He Lin, Zhu Hongxin
    2021, 25 (14):  2241-2246.  doi: 10.3969/j.issn.2095-4344.3126
    Abstract ( 220 )   PDF (1138KB) ( 27 )   Save
    BACKGROUND: Previously we have shown that ultraviolet resistance-associated gene (Uvrag) deficient mice develop age-related cardiomyopathy. However, whether cellular senescence contributes to the pathogenesis remains unknown.
    OBJECTIVE: To determine cellular senescence in Uvrag-deficient hearts. 
    METHODS: Wild-type and Uvrag-deficient male mice at 3 and 8 months of age were utilized. Real-time RT-PCR was used to detect the changes in the mRNA expression of senescence-associated secretory phenotype-related factors in mouse heart tissue, and myocardial histological observation was performed using hematoxylin-eosin staining, Sirius scarlet staining, and aging-related β-galactosidase staining. Transmission electron microscopy was used to observe the ultrastructure changes of mouse cardiomyocytes. Western blot was used to detect the expression of p53 protein in mouse heart tissue. An approval was obtained from the Experimental Animal Ethics Committee of Shanghai Jiaotong University.
    RESULTS AND CONCLUSION: Hematoxylin-eosin staining and Sirius red staining showed that cross-sectional area of individual cardiomyocytes was enlarged and cardiac fibrosis was enhanced in the Uvrag-deficient mice. In addition, cardiomyocytes in the Uvrag-deficient mice exhibited abnormal mitochondrial morphology, disordered arrangement, and swollen sarcoplasmic reticulum as revealed by transmission electron microscopy. Senescence-associated ß-galactosidase staining suggested that Uvrag deficiency significantly increased senescent cells in the hearts from Uvrag-deficient mice. Furthermore, real-time RT-PCR demonstrated a marked increase in the expression of the senescence-associated secretory phenotype genes in Uvrag-deficient hearts. Finally, western blot showed that the expression of p53, a key regulator of cellular senescence, was upregulated in Uvrag-deficient hearts. To conclude, Uvrag deficiency promotes cellular senescence in the mouse heart. Uvrag is a potential target for delaying senescence of the heart and anti-aging-related heart disease.
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    Kinesiology taping combined with manual lymph drainage reduces postoperative lymphedema related to breast cancer
    Cai Hongmei, Wang Wei, Wang Wenjuan, Zhou Xiaohong
    2021, 25 (14):  2247-2251.  doi: 10.3969/j.issn.2095-4344.3127
    Abstract ( 340 )   PDF (693KB) ( 65 )   Save
    BACKGROUND: Kinesiology taping promotes the lymph circulation, and has certain effect in patients with lymphedema after breast cancer surgery. Manual lymph drainage is a technique of sequential massage of the lymph nodes to promote the free flow of retained lymph fluid, thereby reducing swelling. 
    OBJECTIVE: To observe and analyze the clinical effects of kinesiology taping combined with manual lymph drainage in patients with lymphedema of the upper limbs after breast cancer surgery. 
    METHODS: Seventy patients with breast cancer related lymphedema of the upper limbs were randomly divided into two groups. The control group was treated with routine therapy, and the combined group was treated with kinesiology taping and manual lymph drainage based on routine therapy for 4 weeks. Degree of lymphedema, lymph flow, Disability of Shoulder and Hand Scale, and World Health Organization Quality of Life Scale (WHOQOL-BREF) were used to analyze the differences in each group before and after treatment as well as between the two groups after 4 weeks of treatment. The study protocol was implemented in line with the relevant ethical requirements of the First Affiliated Hospital of Jinzhou Medical University (approval No. 201712), and all patients were informed of the study procedures and signed an informed consent.
    RESULTS AND CONCLUSION: After 4 weeks of treatment, the degree of lymphedema, lymph flow, and the scores on the Disability of Shoulder and Hand and WHOQOL-BREF in the two groups were significantly improved (P < 0.05), and all the parameters were better in the combined group than the control group (P < 0.05). To conclude,  the combination of kinesiology taping and manual lymph drainage has a positive clinical effect on breast cancer related lymphedema. 
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    Potential of Nel-like molecule 1 to treat osteoarthritis by promoting cartilage formation and             anti-inflammatory effects 
    Tang Xiaokai, Li Weiming
    2021, 25 (14):  2252-2258.  doi: 10.3969/j.issn.2095-4344.3796
    Abstract ( 216 )   PDF (724KB) ( 22 )   Save
    BACKGROUND: Osteoarthritis is a complex total joint disease. The main affected joint is the knee joint, followed by the hand and hip joints. Treatments for osteoarthritis mainly focus on the relief of pain symptoms. Unfortunately, no drugs can stop the progression of the disease until now. Recently, an osteogenic protein with the characteristics of promoting cartilage formation, anti-inflammatory, anti-fat, and vascularization. Nel-like molecule 1 (Nell-1) has attracted researchers’ attentions. Because of its dual functional properties of promoting cartilage production and anti-inflammation, Nell-1 is expected to become a drug for improving the condition of osteoarthritis.
    OBJECTIVE: To review the pathogenesis of osteoarthritis, ability of Nell-1 to promote chondrogenesis and its molecular cascade signals, anti-inflammatory effects of Nell-1 and its molecular mechanism, Nell-1’s deficiencies in the treatment of osteoarthritis and the latest clinical application of Nell-1, thereby providing new ideas for the treatment of osteoarthritis.
    METHODS: CNKI and PubMed were retrieved for articles tightly related to Nell-1 and osteoarthritis with an impact factor > 3 using the keywords of “Nell-1 AND Osteoarthritis,” and “Osteoarthritis” in Chinese and English, respectively. The time range for literature retrieval was from January 1995 to March 2020. Finally, 88 articles were included for review.
    RESULTS AND CONCLUSION: With the aging of population and increasing of obesity, osteoarthritis is more common than it was a few decades ago, thus leading to a heavier family and socioeconomic burden. Traditional analgesic methods cannot be used as curative treatments because they cannot reduce inflammation and cartilage damage. It is helpful for a clinical orthopedist to develop a more effective treatment protocol by fully understanding the pathogenesis, disease progression and outcome of osteoarthritis, and initiating multidisciplinary discussions involving biological technology, pharmacology, and molecular biology related to genetic engineering and tissue construction. The ultimate goal of an effective treatment protocol is to relieve the suffering of osteoarthritis patients and to reduce the financial burden of individuals and the society. Although the emerging role of Nell-1 in the pathogenesis of osteoarthritis is still in its infancy, there are still some limitations, including a lack of the best route of administration, incomplete understanding of relevant molecular mechanisms, and no optimal animal models. However, Nell-1 has a great potential in the treatment of osteoarthritis as a result of its dual effects of anti-inflammation and promoting cartilage production. Future research should reveal detailed potential mechanisms, and optimize the dosage, regimen, and method of Nell-1 administration, with an attempt to translate Nell-1’s therapeutic potential for osteoarthritis into clinical practice.
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    Classification of intertrochanteric fractures with medial wall destruction in elderly patients and recovery of bony support and continuity of the cortical bone
    Xu Xiaopei, Lü Xin
    2021, 25 (14):  2259-2265.  doi: 10.3969/j.issn.2095-4344.3112
    Abstract ( 218 )   PDF (751KB) ( 24 )   Save
    BACKGROUND:  Intertrochanteric fracture with medial wall injury is a common type of intertrochanteric fracture. Since the medial parietal cortex is responsible for the major mechanical conduction of the proximal femur, the classification and treatment of such injuries have been updated in clinical practice.
    OBJECTIVE: Through the analysis of the fracture classification, injury mechanism and mechanics of intertrochanteric fracture with medial wall injury, to summarize the different internal fixation treatment methods, thereby providing help for the treatment of this kind of fracture.
    METHODS: CNKI, WanFang, PubMed and Web of Science database were searched using “intertrochanteric fracture, femoral intertrochanteric fracture, medial wall, fracture fixation” in Chinese and English, respectively. According to the inclusion and exclusion criteria, eligible literatures were included for final analysis and review.
    RESULTS AND CONCLUSION: The medial parietal cortex of the intertrochanter bears the main pressure conduction of the proximal femur, and the calcar femorale is particularly important. The common fracture types include Evans type, Jensen type, AO/ATO type, Kyle type and Muller ME type, which are of guiding significance for fractures with medial wall injury. For the treatment of intertrochanteric fractures with medial wall injury in the elderly, there is no unified view on which internal fixation method is used. The best choice of internal fixation needs to be made according to the stability of the medial wall and the basic condition of elderly patients. However, for elderly patients with unstable medial wall injury, we should first restore the continuity of the cortex and bony support to the medial wall.

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    Mechanisms of inflammatory cytokines and related signaling pathways in osteoarthritis
    Wang Guoxiang, Zhang Xiaoyun
    2021, 25 (14):  2266-2273.  doi: 10.3969/j.issn.2095-4344.3113
    Abstract ( 279 )   PDF (1147KB) ( 21 )   Save
    BACKGROUND:  Most studies have shown that MAPK, nuclear factor κB, and Wnt signaling pathways are the major signaling pathways associated with osteoarthritis.
    OBJECTIVE: To review the related literature at home and abroad, and to summarize the mechanism of inflammatory cytokines and related signaling pathways in osteoarthritis, in order to further understand the pathogenesis of osteoarthritis.
    METHODS: CNKI, WanFang, VIP, MEDLINE, and PubMed databases were searched for relevant articles addressing inflammatory cytokines and related signaling pathways in osteoarthritis using the keywords of “osteoarthritis, inflammatory cytokine, signal path, pathogenesis, interleukin, BMP, treatment ” in Chinese and English, respectively. After reading the titles and abstracts, 55 articles were included according to the inclusion and exclusion criteria.
    RESULTS AND CONCLUSION: Up to now, the mechanism of osteoarthritis is not clear. Previous studies have shown that inflammation and inflammatory cytokines play an important role in the occurrence and development of osteoarthritis. Strengthening the research on inflammatory cytokines may improve the therapeutic potential of osteoarthritis. Among these cytokines, interleukin-1β is considered to be the main inducer of osteoarthritis, which plays a key role in cartilage degradation and bone regeneration. Therefore, inhibiting the expression of interleukin-1β and inflammatory mediators induced by interleukin-1β may provide a promising method for the treatment of osteoarthritis. The development of osteoarthritis may involve the correlation and interaction between many cytokines and different signaling pathways, but the relationship between inflammatory cytokines and signaling pathways has not yet been clearly clarified, and the mechanism of changes between their molecules is still unclear. A full understanding of these signaling pathways will help us to find a more reliable treatment for osteoarthritis.

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    Mechanism of Runx2 gene in fracture healing
    Wu Yukun, Han Jie, Wen Shuaibo
    2021, 25 (14):  2274-2279.  doi: 10.3969/j.issn.2095-4344.3111
    Abstract ( 335 )   PDF (695KB) ( 24 )   Save
    BACKGROUND: Regeneration of periosteal osteoblasts is essential for fracture healing. Runx2 is crucial for bone cell development and even for bone formation.
    OBJECTIVE: To review relevant domestic and foreign literatures, summarize the relationship between Runx2 gene and fracture healing, and understand the mechanism and prospect of Runx2 gene in fracture healing.
    METHODS: CNKI, WanFang, VIP, and PubMed databases were retrieved with the keywords of “runx2, fracture healing, osteoblasts, chondrocytes, osteoclasts” in Chinese and English, respectively. Literature reports related to the mechanism of Runx2 gene in fracture healing were included. According to the selection criteria, the literature was screened, and the repetitive research and the long-standing literature were excluded. A total of 52 articles were included for review and analysis.
    RESULTS AND CONCLUSION: Runx2 plays important roles in regulation of skeletal development-related genes. Runx2 regulates the processes of bone resorption, formation and remodeling by regulating osteoblasts, chondrocytes, osteoclasts and other bone cells. It also can maintain the formation and differentiation of osteoblasts by interaction with Wnt, bone morphogenetic protein/transforming growth factor β signaling pathways, parathyroid hormone and fibroblast growth factor molecules. Runx2 has been confirmed by a number of animal experiments that it can effectively regulate the transcription and related factors of osteocyte differentiation and proliferation. However, the mechanism of Runx2 in cytokines and signal pathways still remains unclear.

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    Exercise-induced muscle damage: mechanism, quantitative MRI evaluation and treatment advances
    Lyu Xiaohong, Gao Yue, Liu Qiang, Pan Shinong
    2021, 25 (14):  2280-2286.  doi: 10.3969/j.issn.2095-4344.3122
    Abstract ( 286 )   PDF (761KB) ( 40 )   Save
    BACKGROUND: Exercise-induced muscle damage is a common phenomenon in both general population and professional sports training, of which the light can affect daily life and the heavy can restrict the development of sports skills.
    OBJECTIVE: To review the changes of quantitative MRI, advances in treatment and unsolved problems based on the core mechanism of exercise-induced muscle damage.
    METHODS: The first author searched PubMed, Web of Science, Embase, CNKI and WanFang databases to retrieve relevant articles published from 1900 to 2020 with the search terms of “exercise-induced muscle damage, delayed onset muscle soreness, eccentric exercise, eccentric contractions, skeletal muscle” in English and Chinese, respectively. Finally, 70 relevant literatures were included for review.
    RESULTS AND CONCLUSION: The international mainstream views on the mechanism of exercise-induced muscle damage tend to be the theory of mechanical injury, metabolic disorder and inflammation. MRI plays an increasingly important role in the field of sports injury. Different sequences and measurement parameters can quantify muscle damage in terms of the level of restricted diffusion of water molecules, anisotropy, the degree of inflammation, and the ability of energy metabolism. Based on the main mechanism of muscle damage, treatments for muscle damage mainly include exercise, medication, and rehabilitation, all of which have made some achievements. Future research on the threshold value of MRI parameters quantifying whether the damage is reversible or not as well as more targeted prevention and treatment means is warranted.
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    Gait training for spinal cord injury based on radar plotting: an overview of systematic reviews
    Wu Cunshu, Zhan Xiaoxuan, Zhao Siyi, Huang Fan, Zhang Yue, Qiu Mingwang, Xia Jingxian, Lu Xiaobo
    2021, 25 (14):  2287-2296.  doi: 10.3969/j.issn.2095-4344.3132
    Abstract ( 234 )   PDF (1241KB) ( 27 )   Save
    OBJECTIVE: Whether a systematic review/meta-analysis is of high quality is the premise for the reliability of clinical evidence. However, there is still no quality evaluation of systematic review/meta-analysis regarding the walking training after spinal cord injury at home and abroad. This paper aims to evaluate the systematic reviews/meta-analysis regarding the effect of different gait training methods on walking function of patients with spinal cord injury by radar plotting, so as to provide intuitive basis for clinical research. 
    METHODS: Nine Chinese or English databases were searched by computer for collecting systematical reviews/meta-analysis regarding gait training for spinal cord injury. The retrieval time was from inception to October 2019. Literature quality was analyzed from six dimensions: publication year, design type, AMSTAR-2 methodological quality score, PRISMA publication quality score, homogeneity and publication bias risk, and the rank average score was then calculated. For the evidence level of outcome indicators, GRADE tool was used to evaluate the included systematic reviews/meta-analysis. Excel 2016 was used to draw and optimize radar plot for further analysis. 
    RESULTS: A total of 20 eligible literatures were included. Radar plots showed that the average scores on the year of publication, design type, AMSTAR-2 methodological quality score, PRISMA publication quality score, homogeneity, and publication bias risk were 11.50, 14.25, 10.90, 10.95, 14.85, and 14.95, respectively. The average rank score of all the included literatures was 12.90. The GRADE tool evaluation indicated that 17 outcome indicators were of low quality, 40 of medium quality, and only 2 of high quality. The main problems are the low quality of methodology and research report, such as the project failed to register in the international pre-registration database and explain the study protocol, did not explain the comprehensive and systematic retrieval strategy, did not report the included research content in detail, did not carry out heterogeneity test or did not explain the results.
    CONCLUSION: The quality of systematic reviews/meta-analysis literature regarding gait training of spinal cord injury is not high, and the quality of methodology and research report should be strengthened to further improve the quality of literature. The research and analysis should be conducted in strict accordance with the standards proposed by AMSTAR-2 and PRISMA. Most of the systematic reviews/meta-analyses included show that gait training can improve walking function of patients with spinal cord injury. Among them, orthosis therapy with higher literature quality and higher level of evidence is more effective for patients with spinal cord injury, and orthosis therapy can be used as much as possible in clinical practice. Radar plot is an intuitive, scientific and effective graphical evaluation method, which is worthy of popularization and application in rehabilitation medicine in the future.

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