1.Mechanism by which vascular endothelial growth factor A targets regulation of angiogenesis in the treatment of steroid-induced osteonecrosis of the femoral head
Zhengye WANG ; Wanlin LIU ; Zhenqun ZHAO
Chinese Journal of Tissue Engineering Research 2026;30(3):671-679
BACKGROUND:Steroid-induced osteonecrosis of the femoral head(SANFH)is a severe orthopedic disease characterized by interruption of the blood supply to the femoral head and necrosis of subchondral bone,leading to joint dysfunction.Long-term use of glucocorticoids is the main cause of SANFH,and its pathogenesis involves multiple factors,including intravascular coagulation and osteocyte apoptosis.Vascular endothelial growth factor A(VEGF-A),as a key angiogenic factor,has potential value in the treatment of SANFH.OBJECTIVE:To summarize the mechanisms of action of VEGF-A in SANFH,including its progress in promoting angiogenesis,anti-apoptosis,and lipid metabolism regulation,and to discuss the prospects for clinical application of VEGF-A targeted therapy.METHODS:Literature related to VEGF-A targeted regulation of angiogenesis in the treatment of SANFH was identified through searches of PubMed,Web of Science,CNKI,and WanFang databases from database inception to November 2024.After quality assessment,71 articles were selected,data were extracted by independent researchers,and disagreements were resolved through group discussions.RESULTS AND CONCLUSION:(1)VEGF-A binds to its receptors VEGFR-1 and VEGFR-2,activating downstream signaling pathways that promote the proliferation,migration,and angiogenesis of endothelial cells.Therefore,it can promote the formation of collateral circulation and improve blood supply to the area of bone necrosis.(2)Reduced expression of VEGF-A may lead to a decrease in the number of blood vessels within bone tissue,exacerbating the ischemic state of the femoral head.Furthermore,VEGF-A has anti-apoptotic effects and reduce apoptosis in osteocytes and bone marrow cells,thus protecting bone tissue.(3)The role of VEGF-A in regulating lipid metabolism and inflammatory responses,as well as promoting the osteogenic differentiation of bone marrow mesenchymal stem cells,provides a new perspective for the treatment of SANFH.(4)The development of VEGF-A protein delivery systems,such as lipid nanoparticles and exosome-based delivery systems,offers new possibilities for the clinical application of VEGF-A.(5)The research progress of VEGF-A in SANFH treatment has laid a solid foundation for the development of new treatment strategies and has opened up new avenues for future research directions and clinical applications.(6)With further clarification of the mechanisms of action of VEGF-A and continuous advancements in delivery technologies,more effective treatments will be provided for SANFH patients,improving their prognosis.
2.Advance in the mechanisms underlying miRNAs in steroid-induced osteonecrosis of the femoral head
Zhengye WANG ; Wanlin LIU ; Zhenqun ZHAO
Chinese Journal of Tissue Engineering Research 2026;30(5):1207-1214
BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is complex,involving vascular endothelial injury,osteocyte apoptosis,inflammatory responses,and bone metabolism disorders.MicroRNAs(miRNAs),as key regulators of gene expression,play an important role in steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To comprehensively analyze the regulatory role of miRNAs in steroid-induced osteonecrosis of the femoral head and to evaluate their potential as biomarkers and therapeutic tools.METHODS:Relevant literature was retrieved from PubMed,Web of Science,CNKI,and WanFang databases using specific keywords,and articles were selected based on the inclusion and exclusion criteria.By reading titles,abstracts,or full texts,articles with poor relevance or repetitive content were excluded,and 76 articles were finally included for analysis.RESULTS AND CONCLUSION:miRNAs regulate gene expression by binding to the 3'untranslated region of target mRNAs,affecting cell differentiation,proliferation,apoptosis,and stress responses.Specific miRNAs such as miR-33-5p,miR-99a,miR-106b-5p,miR-155,miR-146a,and miR-21 play a central regulatory role in vascular injury,inflammatory responses,osteocyte differentiation,and apoptosis in steroid-induced osteonecrosis of the femoral head.Additionally,the expression patterns of miRNAs are closely related to the pathogenesis of steroid-induced osteonecrosis of the femoral head,showing potential as biomarkers.Although miRNAs shows great potential as biomarkers in therapeutic strategies,the current limitation of sample size and lack of multi-population validation restrict the universality and reliability of the results.Moreover,the efficacy and safety of miRNA therapeutic strategies(including off-target effects and delivery issues)remain major challenges in realizing clinical applications.
3.Mechanism by which vascular endothelial growth factor A targets regulation of angiogenesis in the treatment of steroid-induced osteonecrosis of the femoral head
Zhengye WANG ; Wanlin LIU ; Zhenqun ZHAO
Chinese Journal of Tissue Engineering Research 2026;30(3):671-679
BACKGROUND:Steroid-induced osteonecrosis of the femoral head(SANFH)is a severe orthopedic disease characterized by interruption of the blood supply to the femoral head and necrosis of subchondral bone,leading to joint dysfunction.Long-term use of glucocorticoids is the main cause of SANFH,and its pathogenesis involves multiple factors,including intravascular coagulation and osteocyte apoptosis.Vascular endothelial growth factor A(VEGF-A),as a key angiogenic factor,has potential value in the treatment of SANFH.OBJECTIVE:To summarize the mechanisms of action of VEGF-A in SANFH,including its progress in promoting angiogenesis,anti-apoptosis,and lipid metabolism regulation,and to discuss the prospects for clinical application of VEGF-A targeted therapy.METHODS:Literature related to VEGF-A targeted regulation of angiogenesis in the treatment of SANFH was identified through searches of PubMed,Web of Science,CNKI,and WanFang databases from database inception to November 2024.After quality assessment,71 articles were selected,data were extracted by independent researchers,and disagreements were resolved through group discussions.RESULTS AND CONCLUSION:(1)VEGF-A binds to its receptors VEGFR-1 and VEGFR-2,activating downstream signaling pathways that promote the proliferation,migration,and angiogenesis of endothelial cells.Therefore,it can promote the formation of collateral circulation and improve blood supply to the area of bone necrosis.(2)Reduced expression of VEGF-A may lead to a decrease in the number of blood vessels within bone tissue,exacerbating the ischemic state of the femoral head.Furthermore,VEGF-A has anti-apoptotic effects and reduce apoptosis in osteocytes and bone marrow cells,thus protecting bone tissue.(3)The role of VEGF-A in regulating lipid metabolism and inflammatory responses,as well as promoting the osteogenic differentiation of bone marrow mesenchymal stem cells,provides a new perspective for the treatment of SANFH.(4)The development of VEGF-A protein delivery systems,such as lipid nanoparticles and exosome-based delivery systems,offers new possibilities for the clinical application of VEGF-A.(5)The research progress of VEGF-A in SANFH treatment has laid a solid foundation for the development of new treatment strategies and has opened up new avenues for future research directions and clinical applications.(6)With further clarification of the mechanisms of action of VEGF-A and continuous advancements in delivery technologies,more effective treatments will be provided for SANFH patients,improving their prognosis.
4.Advance in the mechanisms underlying miRNAs in steroid-induced osteonecrosis of the femoral head
Zhengye WANG ; Wanlin LIU ; Zhenqun ZHAO
Chinese Journal of Tissue Engineering Research 2026;30(5):1207-1214
BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is complex,involving vascular endothelial injury,osteocyte apoptosis,inflammatory responses,and bone metabolism disorders.MicroRNAs(miRNAs),as key regulators of gene expression,play an important role in steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To comprehensively analyze the regulatory role of miRNAs in steroid-induced osteonecrosis of the femoral head and to evaluate their potential as biomarkers and therapeutic tools.METHODS:Relevant literature was retrieved from PubMed,Web of Science,CNKI,and WanFang databases using specific keywords,and articles were selected based on the inclusion and exclusion criteria.By reading titles,abstracts,or full texts,articles with poor relevance or repetitive content were excluded,and 76 articles were finally included for analysis.RESULTS AND CONCLUSION:miRNAs regulate gene expression by binding to the 3'untranslated region of target mRNAs,affecting cell differentiation,proliferation,apoptosis,and stress responses.Specific miRNAs such as miR-33-5p,miR-99a,miR-106b-5p,miR-155,miR-146a,and miR-21 play a central regulatory role in vascular injury,inflammatory responses,osteocyte differentiation,and apoptosis in steroid-induced osteonecrosis of the femoral head.Additionally,the expression patterns of miRNAs are closely related to the pathogenesis of steroid-induced osteonecrosis of the femoral head,showing potential as biomarkers.Although miRNAs shows great potential as biomarkers in therapeutic strategies,the current limitation of sample size and lack of multi-population validation restrict the universality and reliability of the results.Moreover,the efficacy and safety of miRNA therapeutic strategies(including off-target effects and delivery issues)remain major challenges in realizing clinical applications.
5.Application of NeoVI-RADS scoring in patients with bladder cancer undergoing neoadjuvant therapy
Lingkai CAI ; Xiao YANG ; Zhengye TAN ; Rongjie BAI ; Chenghao WANG ; Chang CHEN ; Qikai WU ; Hao YU ; Chenjiang WU ; Qiang LYU ; Qiang CAO
Chinese Journal of Surgery 2025;63(12):1111-1117
Objective:To evaluate the utility of neoadjuvant vesical imaging-reporting and data system (NeoVI-RADS) in predicting tumor residuals and diagnosing muscle-invasive bladder cancer (MIBC) in patients undergoing neoadjuvant therapy, as well as its application in prognostic stratification.Methods:A retrospective case series analysis was conducted on the clinical data of 91 patients with bladder cancer who received neoadjuvant therapy at the Department of Urology, First Affiliated Hospital of Nanjing Medical University from July 2014 to June 2024. There were 84 male cases and 7 female cases, with an age of (66±9) years (range:45 to 85 years). The clinical staging of the patients was ≥T2 based on imaging. All of them underwent three or more cycles of neoadjuvant therapy, and had post-treatment multiparametric MRI (mp-MRI) evaluation. Based on the results of mp-MRI, the NeoVI-RADS was established and employed to assess tumor residuals and muscle invasion. The receiver operating characteristic curve was plotted, and the area under the curve (AUC) was calculated. Kaplan-Meier survival curves based on overall survival (OS) and cancer-specific survival (CSS) were plotted, and the Log-rank test was used for survival analysis comparison between groups.Results:In the neoadjuvant treatment cohort, the AUC for predicting tumor residuals post-neoadjuvant therapy using NeoVI-RADS was 0.900, with an accuracy of 93.4%, sensitivity of 95.8%, and a specificity of 85.0%. The NeoVI-RADS demonstrated strong diagnostic performance for MIBC, achieving an AUC of 0.900. At a NeoVI-RADS score cutoff of 4, the accuracy was 84.5%, with a sensitivity of 87.5% and a specificity of 72.9%. Additionally, compared to patients with NeoVI-RADS scores of 0 (5-year OS and CSS rates both 100%) or scores of 1 to 3 (5-year OS and CSS rates both 90.9%), patients with scores of 4 to 5 had significantly worse OS (5-year rate 63.0%) and CSS (5-year rate 66.3%) (all P<0.05). There was no statistically significant difference in OS or CSS between patients with NeoVI-RADS scores of 0 and those with scores of 1 to 3 (all P>0.05). Conclusion:NeoVI-RADS demonstrates significant diagnostic and prognostic value in the context of neoadjuvant treatment for bladder cancer, effectively assessing tumor residuals and muscle invasion, thereby enhancing patient management and facilitating personalized treatment approaches.
6.Schroth therapy for adolescent idiopathic scoliosis: a meta-analysis
Yang CHEN ; Jie WANG ; Yuanpeng ZHU ; Zhengye ZHAO ; Jianguo ZHANG ; Nan WU
Chinese Journal of Orthopaedics 2025;45(7):429-435
Objective:To analyze the clinical efficacy of the Schroth therapy in the treatment of adolescent idiopathic scoliosis.Methods:Relevant clinical studies on Schroth therapy for adolescent idiopathic scoliosis were retrieved from CNKI, Wanfang Data, SinoMed, Chinese Medical Journal Full-text Database, PubMed, Embase, Cochrane Library, and Web of Science. The search time was from the establishment of the database to November 2024. Two authors independently conducted the literature search and imported all potentially eligible studies into EndNote X9 to determine whether the studies met the inclusion criteria. If there was any disagreement, the two parties would discuss and solve it or add a third author for judgment. The scoliosis Cobb angle and the Scoliosis Research Society question-naires-22 (SRS-22) or SRS-23 were extracted from the scoliosis after treatment. The Schroth therapy was compared with other conservative treatment methods (functional exercise or no intervention). The modified Jadad scale was used to evaluate the quality of the included randomized controlled trials. When the heterogeneity between groups was small, the fixed-effect model was used for analysis, and when the heterogeneity between groups was large, the random-effect model was used for analysis. Sensitivity analysis was used to evaluate the stability of the meta-analysis results.Results:A total of 189 patients from 8 literatures were included in the meta-analysis, including 2 Chinese literatures and 6 English literatures, all of which were randomized controlled trials, with a modified Jadad score of 4-6 points. The results of meta-analysis showed that the Cobb angle of Schroth therapy in the treatment of adolescent idiopathic scoliosis was smaller than that of functional exercise or no intervention [ WMD=-3.63, 95% CI (-4.76, -2.51), P<0.001]. SRS-22 or SRS-23 was superior to functional exercise or no intervention [ WMD=0.23, 95% CI(0.14, 0.32), P<0.001], and the difference was statistically significant. The results of subgroup analysis showed that the Cobb angle of Schroth treatment was smaller than that of other conservative treatment methods such as functional exercise [ WMD=-3.48, 95% CI(-4.76, -2.20), P<0.001]. Conclusion:Compared with other conservative treatment methods and no intervention, Schroth therapy can effectively improve the Cobb angle and quality of life in the treatment of adolescent idiopathic scoliosis.
7.Schroth therapy for adolescent idiopathic scoliosis: a meta-analysis
Yang CHEN ; Jie WANG ; Yuanpeng ZHU ; Zhengye ZHAO ; Jianguo ZHANG ; Nan WU
Chinese Journal of Orthopaedics 2025;45(7):429-435
Objective:To analyze the clinical efficacy of the Schroth therapy in the treatment of adolescent idiopathic scoliosis.Methods:Relevant clinical studies on Schroth therapy for adolescent idiopathic scoliosis were retrieved from CNKI, Wanfang Data, SinoMed, Chinese Medical Journal Full-text Database, PubMed, Embase, Cochrane Library, and Web of Science. The search time was from the establishment of the database to November 2024. Two authors independently conducted the literature search and imported all potentially eligible studies into EndNote X9 to determine whether the studies met the inclusion criteria. If there was any disagreement, the two parties would discuss and solve it or add a third author for judgment. The scoliosis Cobb angle and the Scoliosis Research Society question-naires-22 (SRS-22) or SRS-23 were extracted from the scoliosis after treatment. The Schroth therapy was compared with other conservative treatment methods (functional exercise or no intervention). The modified Jadad scale was used to evaluate the quality of the included randomized controlled trials. When the heterogeneity between groups was small, the fixed-effect model was used for analysis, and when the heterogeneity between groups was large, the random-effect model was used for analysis. Sensitivity analysis was used to evaluate the stability of the meta-analysis results.Results:A total of 189 patients from 8 literatures were included in the meta-analysis, including 2 Chinese literatures and 6 English literatures, all of which were randomized controlled trials, with a modified Jadad score of 4-6 points. The results of meta-analysis showed that the Cobb angle of Schroth therapy in the treatment of adolescent idiopathic scoliosis was smaller than that of functional exercise or no intervention [ WMD=-3.63, 95% CI (-4.76, -2.51), P<0.001]. SRS-22 or SRS-23 was superior to functional exercise or no intervention [ WMD=0.23, 95% CI(0.14, 0.32), P<0.001], and the difference was statistically significant. The results of subgroup analysis showed that the Cobb angle of Schroth treatment was smaller than that of other conservative treatment methods such as functional exercise [ WMD=-3.48, 95% CI(-4.76, -2.20), P<0.001]. Conclusion:Compared with other conservative treatment methods and no intervention, Schroth therapy can effectively improve the Cobb angle and quality of life in the treatment of adolescent idiopathic scoliosis.
8.Application of NeoVI-RADS scoring in patients with bladder cancer undergoing neoadjuvant therapy
Lingkai CAI ; Xiao YANG ; Zhengye TAN ; Rongjie BAI ; Chenghao WANG ; Chang CHEN ; Qikai WU ; Hao YU ; Chenjiang WU ; Qiang LYU ; Qiang CAO
Chinese Journal of Surgery 2025;63(12):1111-1117
Objective:To evaluate the utility of neoadjuvant vesical imaging-reporting and data system (NeoVI-RADS) in predicting tumor residuals and diagnosing muscle-invasive bladder cancer (MIBC) in patients undergoing neoadjuvant therapy, as well as its application in prognostic stratification.Methods:A retrospective case series analysis was conducted on the clinical data of 91 patients with bladder cancer who received neoadjuvant therapy at the Department of Urology, First Affiliated Hospital of Nanjing Medical University from July 2014 to June 2024. There were 84 male cases and 7 female cases, with an age of (66±9) years (range:45 to 85 years). The clinical staging of the patients was ≥T2 based on imaging. All of them underwent three or more cycles of neoadjuvant therapy, and had post-treatment multiparametric MRI (mp-MRI) evaluation. Based on the results of mp-MRI, the NeoVI-RADS was established and employed to assess tumor residuals and muscle invasion. The receiver operating characteristic curve was plotted, and the area under the curve (AUC) was calculated. Kaplan-Meier survival curves based on overall survival (OS) and cancer-specific survival (CSS) were plotted, and the Log-rank test was used for survival analysis comparison between groups.Results:In the neoadjuvant treatment cohort, the AUC for predicting tumor residuals post-neoadjuvant therapy using NeoVI-RADS was 0.900, with an accuracy of 93.4%, sensitivity of 95.8%, and a specificity of 85.0%. The NeoVI-RADS demonstrated strong diagnostic performance for MIBC, achieving an AUC of 0.900. At a NeoVI-RADS score cutoff of 4, the accuracy was 84.5%, with a sensitivity of 87.5% and a specificity of 72.9%. Additionally, compared to patients with NeoVI-RADS scores of 0 (5-year OS and CSS rates both 100%) or scores of 1 to 3 (5-year OS and CSS rates both 90.9%), patients with scores of 4 to 5 had significantly worse OS (5-year rate 63.0%) and CSS (5-year rate 66.3%) (all P<0.05). There was no statistically significant difference in OS or CSS between patients with NeoVI-RADS scores of 0 and those with scores of 1 to 3 (all P>0.05). Conclusion:NeoVI-RADS demonstrates significant diagnostic and prognostic value in the context of neoadjuvant treatment for bladder cancer, effectively assessing tumor residuals and muscle invasion, thereby enhancing patient management and facilitating personalized treatment approaches.
9.Application of Optimized Latex Perfusion Technique in the Establishment of Craniofacial Venous Model in Mice
Chengji WANG ; Jue WANG ; Haijie WANG ; Weisheng LU ; Yan SHI ; Zhengye GU ; Mingqiu WAN ; Ruling SHEN
Laboratory Animal and Comparative Medicine 2023;43(5):574-578
ObjectiveOptimize the latex perfusion technique and apply it to the construction of a murine craniofacial venous vascular model.Methods A total of nine 8-week-old male C57BL/6 mice weighing (25.0±1.3) g were randomly divided into three groups: 60% latex physiological saline group, 60% latex heparin group, and 30% latex heparin group. After completion of the perfusion, the specimens were immersed in 4 °C formalin fixative for 24 h, followed by dissection, observation, and measurement of the extracranial blood vessel diameters. Results After 200 μL latex perfusion solution was injected into the external jugular vein, the supraorbital vein, infraorbital vein, temporal vein, retrofacial vein, masseter vein and external jugular vein were perfused in each group.After comparing the perfusion degree of the distal branches of blood vessels, sublingual vein and tip venule, it was found that the 30% latex heparin group had the best perfusion effect, followed by the 60% latex heparin group, and the 60% latex saline group had the worst perfusion effect.ConclusionThe optimized latex perfusion technique can effectively infuse the veins in the head and face of mice, and this technique can provide a good reference for the study of the direction and morphology of facial veins in mice.
10.Comparative Analysis of Three-Link Model in Deep Squatting
Zhengye PAN ; Hong WANG ; Shijie LIN ; Weitao ZHENG
Journal of Medical Biomechanics 2020;35(6):E658-E664
Objective To discuss rationality of the three-link model used in analysis on interactive dynamics of deep squatting, and clarify the source of differences in calculation of joint torque by three-link model and Visual 3D. Methods Eight subjects were selected to obtain kinematic data of the squat motion through Vicon. The second Lagrangian equation was used to establish the three-link dynamic equation. The joint torque was calculated based on the Mathematica programming. The results were compared with the calculation results of lower limb chain segment model by Visual 3D, and the similarity between the two results was evaluated by the coefficient of complex correlation (CMC). Results The CMC of hip joint and knee joint from 8 subjects was larger than 0.85, and the CMC of ankle joint was between 0.50-0.85. The joint torque calculated by three-link dynamic equation and Visual 3D was highly similar in hip joint and knee joint, and there was only a moderate similarity in ankle joint. Conclusions The three-link model can be used in further analysis on interactive dynamics of deep squatting, but the influence of interactive moment caused by ground reaction force (external moment) on ankle torque should be considered.

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