1.Expression of S100A4 in synovium of patients with rheumatoid arthritis and its effect on angiogenesis of fibroblast-like synoviocytes by secreting VEGF
Dingsheng ZHA ; Hao WU ; Hongsheng LIN ; Ping YAO ; Zhengang ZHA ; Chunhong JIA ; Chao SHENG
Chinese Journal of Pathophysiology 2017;33(6):1119-1124
AIM:To study the expression level of S100 calcium-binding protein A4 (S100A4) in synovial tissue of the knee joint in rheumatoid arthritis (RA) patients and normal persons, and the effect of S100A4 on the angiogenesis induced by rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs).METHODS:The synovial tissue was taken from the knee joint of the RA patients (RA group) and the normal persons (control group).The protein expression of S100A4 and vascular endothelial growth factor (VEGF) in the synovial tissue of the 2 groups was observed by immunohistochemistry.RAFLSs were isolated from synovial tissue of patients with active RA.ELISA was used to detect the effect of S100A4 on the secretion of VEGF by RAFLSs.The effect of S100A4 on the angiogenesis of HUVECs cultured with conditioned medium from RAFLSs was also detected.RESULTS:The protein of S100A4 and VEGF was highly expressed in the synovial tissues of RA group (P<0.05).rhS100A4 significantly stimulated the secretion of VEGF in RAFLSs in a time-and dose-dependent manner (P<0.05).Cultured with conditioned medium from RAFLSs, rhS100A4 significantly promoted HUVECs to form tube-like structures in vitro.CONCLUSION:S100A4 protein is highly expressed in synovial tissue of the knee joint in RA patients, and S100A4 stimulates synovial angiogenesis by promoting RAFLSs to generate VEGF, indicating that S100A4 may be used as a potential target for the treatment of RA.
2.Mechanism of recombinant human S100 calcium binding protein A4 inducing vascular endothelial growth factors in rheumatoid arthritis fibroblast-like synoviocytes
Dingsheng ZHA ; Wuyan XU ; Hao WU ; Hongsheng LIN ; Zhengang ZHA ; Hua YANG ; Yuhao YANG ; Jie REN
Chinese Journal of Orthopaedic Trauma 2018;20(5):430-438
Objective To investigate the mechanism of inducing production of vascular endothelial growth factors (VEGF) by recombinant human S100 calcium binding protein A4 (rhS100A4) in rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs).Methods Synovial tissue was sampled from the patients with rheumatoid arthritis (RA) undergoing knee arthroplasty for in vitro culture of RAFLSs.CCK-8 assay was conducted to detect the effect of rhS100A4 and the effect of its interaction with Rapamycin (Rap),an inhibitor of mammalian rapamycin target 1 (mTORC1) signaling pathway,on the proliferation of RAFLSs.The effects of rhS100A4 and its interaction with Rap on the expression of VEGF in RAFLSs were detected by immunofluorescence.After rhS100A4 and its cooperation with Rap stimulated the conditioned medium (CM)produced by RAFLSs,the effect of CM on formation of lumen in human unbilical vein endothelial cells (HUVECs) in vitro was observed to detect the angiogenic ability of rhS100A4.Western blot was used to detect the effect of rhS100A4 on the phosphorylation of downstream ribosomal protein S6 (S6) in the mTORC1 signaling pathway in RAFLSs and to analyze the effects of rhS100A4 and Rap on phosphorylation of S6 protein and expression of VEGF protein in RAFLSs.Results rhS100A4 promoted cell proliferation and expression of VEGF protein in RAFLSs,and the CM formed by rhS100A4 promoted HUVECs to form blood vessels in vitro.Rap inhibited the above biological effects of rhS100A4,rhS100A4 activated the downstream protein S6 in the mTORC1 signaling pathway in RAFLSs cells to increase their phosphorylation levels.The effects of rhS100A4 on the phosphorylation of S6 protein and on the expression of VEGF protein in RAFLSs were inhibited by Rap.Conclusion rhS10OA4 promotes production of VEGF in RAFLSs by activating the mTORC 1 signaling pathway.
3.Clinical efficacy and safety of unilateral biportal endoscopy versus microendoscopic discectomy in treatment of lumbar spinal stenosis: a Meta-analysis
Shaojie HE ; Dingsheng ZHA ; Jiawen HUANG ; Zhenyu ZHAO ; Sheng TANG ; Xiaofeng LAI ; Hao WU
Chinese Journal of Orthopaedic Trauma 2022;24(7):634-639
Objective:To compare the efficacy and safety of unilateral biportal endoscopy (UBE) and microendoscopic discectomy (MED) in the treatment of lumbar spinal stenosis by Meta-analysis.Methods:PubMed, Web of Science, CNKI and Wanfang Data were searched from their establishment to January 2021 for all the studies on UBE and MED in the treatment of lumbar spinal stenosis. The data extracted were authors, year of publication, study design, subject characteristics, sample size, surgical protocol, age, sex ratio, duration of surgery, length of hospital stay, complications, visual analogue scale (VAS), and Oswestry Disability Index (ODI). The Meta-analysis was conducted with software Revman 5.3 to analyze the operation time, hospital stay, complication rate, waist and lower extremity VAS scores and ODI scores at preoperation, early postoperation and the last follow-up. The quality of the case-control studies included was evaluated using the Newcastle Ottawa Scale (NOS) while the methodological quality and risk of bias of the randomized controlled studies (RCT) included were evaluated using the Cochrane Bias Risk Assessment Tool.Results:Finally, 7 studies were included, 6 in English and one in Chinese. There were 2 RCTs and 5 case-control studies. There were 251 patients in the UBE group and 224 patients in the MED group. Compared with the MED group, the UBE group had a significantly shorter hospital stay ( MD=-2.28, 95% CI: -3.42 to -1.14, P<0.001), and a significantly lower VAS score for early postoperative low back pain ( MD=-0.80, 95% CI:-1.44 to -0.16, P=0.01). There were no significant differences between the 2 groups in operation time, complication rate, waist VAS scores at preoperation or the last follow-up, lower extremity VAS or ODI scores at preoperation, early postoperation or the last follow-up, or dural dilatation area ( P>0.05). Conclusions:In the treatment of lumbar spinal stenosis, compared with MED, UBE is superior in early relief of low back pain and hospital stay after operation, but shows no significant difference in long-term efficacy or safety.
4.Risk factors for prognosis of traumatic spinal cord injury
Shaojie HE ; Zhenyu ZHAO ; Xincheng YU ; Weikuan LI ; Chang KONG ; Hangzhan MA ; Dingsheng ZHA
Chinese Journal of Orthopaedic Trauma 2024;26(7):590-596
Objective:To analyze the risk factors for 6-month prognosis of traumatic spinal cord injury (TSCI).Methods:A retrospective analysis was conducted of the 133 patients with TSCI who had been admitted to Department of Orthopaedics, The First Hospital Affiliated to Jinan University from January 2017 to August 2021. The patients with TSCI were categorized into an improved group ( n=82) and a non-improved group ( n=51) according to the improvements in the American Spinal Injury Association (ASIA) grading between admission and 6 months after injury. To identify the risk factors that might affect the prognosis of TSCI patients at 6 months after injury, univariate and logistic regression analyses were conducted of indicators such as gender, age, length of MRI spinal cord signal change, maximum canal compromise (MCC), maximum spinal cord compression (MSCC), brain and spinal cord injury center(BASIC)score, neutrophil-to-lymphocyte ratio (NLR) within 3 days after injury, ASIA grading within 3 days after injury, mean arterial pressure (MAP) at 3 days after operation, and presence of complications. Results:The univariate analysis showed significant differences between the improved and non-improved groups in length of MRI spinal cord signal change, MCC, MSCC, BASIC, NLR within 3 days after injury, ASIA grading within 3 days after injury, MAP at 3 days after operation, and presence of complications (all P<0.05). The logistic regression analysis showed that NLR ( OR=0.463, 95% CI: 0.287 to 0.748, P=0.002) and ASIA grading ( OR=11.684, 95% CI: 1.684 to 81.086, P=0.013) within 3 days after injury, as well as MAP at 3 days after operation ( OR=2.224, 95% CI: 1.306 to 3.787, P=0.003), were risk factors affecting the 6-month prognosis in TSCI patients. Conclusion:The NLR and ASIA grading within 3 days after injury, and MAP at 3 days after operation are risk factors that may affect the prognosis of TSCI patients at 6 months after injury.