1.Research progress on natural active ingredients intervening in the hypoxia-pyroptosis-inflammation cascade in intervertebral disc degeneration through HIF-1α
Hao WANG ; Renchang CHEN ; Wenhao HUANG ; Bingqian ZHOU ; Xiqiu ZHENG ; Jiahao WANG ; Nianhu LI ; Yadong WU
China Pharmacy 2026;37(8):1092-1098
Intervertebral disc degeneration (IVDD) is the core cause of chronic low back pain, which severely impairs patients’ quality of life and imposes a heavy social and medical burden. The hypoxia-pyroptosis-inflammation cascade mediated by hypoxia-inducible factor-1α (HIF-1α) is the core pathological mechanism driving the initiation and progression of IVDD. Natural active ingredients derived from traditional Chinese medicine (TCM) have become a research hotspot in the field of IVDD prevention and treatment due to their advantages of multi-target effects, favorable efficacy, and low toxicity. This paper systematically reviews the mechanism of HIF-1α-mediated hypoxia-pyroptosis-inflammation cascade in degenerative nucleus pulposus tissue and the intervention of related active ingredients. It is found that natural active ingredients such as baicalein, curcumin and resveratrol can intervene in the HIF-1α-mediated pathological cascade through four core links to delay IVDD progression: targeting the HIF-1α oxygen sensing pathway to block the initiation of pyroptosis cascade, inhibiting NOD-like receptor protein 3 inflammasome activation to cut off the cascade amplification of inflammatory signals, intervening in the Gasdermin D-mediated pyroptosis execution stage to protect cell membrane integrity, and regulating extracellular matrix metabolism to reconstruct intervertebral disc homeostasis.
2.Association between obesity and diffuse idiopathic skeletal hyperostosis
Luming KONG ; Diqian ZHAO ; Wenzhe BAI ; Nianhu LI
Chinese Journal of Tissue Engineering Research 2025;29(17):3705-3712
BACKGROUND:Diffuse idiopathic skeletal hyperostosis is a systemic,non-inflammatory disease characterized by calcification and ossification of ligaments,tendons,and their attachments,predominantly affecting men over the age of 50.Studies have shown a higher prevalence of diffuse idiopathic skeletal hyperostosis among obese individuals;however,the causal relationship between the two remains unclear.OBJECTIVE:To investigate the causal relationship between obesity and diffuse idiopathic skeletal hyperostosis using Mendelian randomization analysis.METHODS:The study utilized single nucleotide polymorphisms from the Genome Wide Association Study database as instrumental variables,incorporating data related to obesity and diffuse idiopathic skeletal hyperostosis.A bidirectional two-sample Mendelian randomization analysis was performed to assess the causal relationship between obesity and diffuse idiopathic skeletal hyperostosis,with evaluations for pleiotropy,heterogeneity,and sensitivity.RESULTS AND CONCLUSION:The Mendelian randomization analysis revealed a significant positive causal relationship between obesity and diffuse idiopathic skeletal hyperostosis.The inverse-variance weighted method indicated that"obesity"(odds ratio[OR]=1.111,95%confidence interval[CI]:1.068-1.156,P=1.598×10-7),"obesity due to excess calories"(OR=1.093,95%CI:1.042-1.146,P=0.000),and"obesity,other/unspecified"(OR=1.109,95%CI:1.069-1.152,P=4.908×10-8)were significantly associated with diffuse idiopathic skeletal hyperostosis.Conversely,the reverse Mendelian randomization analysis did not find a causal relationship between diffuse idiopathic skeletal hyperostosis and obesity.The robustness of the Mendelian randomization analysis results was confirmed by pleiotropy,heterogeneity and sensitivity tests,indicating that while obesity significantly increases the risk of diffuse idiopathic skeletal hyperostosis,but diffuse idiopathic skeletal hyperostosis does not pose a risk factor for obesity.
3.Clinical guideline for diagnosis and treatment of nonunion of osteoporotic vertebral fractures (version 2025)
Haipeng SI ; Le LI ; Junjie NIU ; Wencan ZHANG ; Fuxin WEI ; Jinqiu YUAN ; Qiang YANG ; Hongli WANG ; Guangchao WANG ; Shihong CHEN ; Yunzhen CHEN ; Xiaoguang CHENG ; Jianwen DONG ; Shiqing FENG ; Rui GU ; Yong HAI ; Tianyong HOU ; Bo HUANG ; Xiaobing JIANG ; Lei ZANG ; Chunhai LI ; Nianhu LI ; Hua LIN ; Hongjian LIU ; Peng LIU ; Xinyu LIU ; Sheng LU ; Shibao LU ; Chunshan LUO ; Lvy CHAOLIANG ; Lvy WEIJIA ; Xuexiao MA ; Wei MEI ; Chunyang MENG ; Cailiang SHEN ; Chunli SONG ; Ruoxian SONG ; Jiacan SU ; Honglin TENG ; Hui SHENG ; Beiyu WANG ; Bingwu WANG ; Liang WANG ; Xiangyang WANG ; Nan WU ; Guohua XU ; Yayi XIA ; Jin XU ; Youjia XU ; Jianzhong XU ; Cao YANG ; Maowei YANG ; Zibin YANG ; Xiaojian YE ; Hailong YU ; Xijie YU ; Hua YUE ; Zhili ZENG ; Xinli ZHAN ; Hui ZHANG ; Peixun ZHANG ; Wei ZHANG ; Zhenlin ZHANG ; Jianguo ZHANG ; Tengyue ZHU ; Qiang LIU ; Huilin YANG
Chinese Journal of Trauma 2025;41(10):932-945
Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.
4.Association between thyroid function levels and phenotypes associated with sarcopenia
Jiatong LI ; Yue JIN ; Runjia LIU ; Bowen SONG ; Xiaoqian ZHU ; Nianhu LI
Chinese Journal of Tissue Engineering Research 2025;29(6):1312-1320
BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.
5.Biomechanical Mechanism Discussion of Intervertebral Disc Degeneration on Spinal Stability Based on the Theory of"Muscle and Bone Imbalance,Putting Muscle First"
Yadong WU ; Zhiguo ZHANG ; Jing LI ; Xiaoyan QI ; Yuzhou LU ; Nianhu LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(10):2810-2816
The concept of"musculoskeletal imbalance with soft tissue primacy"posits that tendon injury induced by intervertebral disc degeneration constitutes the core pathogenesis of spinal musculoskeletal imbalance.This study systematically elucidates the pathological mechanisms through which tendon injury leads to spinal instability by integrating traditional Chinese medicine(TCM)"musculoskeletal balance"theory with contemporary biomechanical research on disc degeneration.In the process of intervertebral disc degeneration,the change of stress distribution revealed by modern biomechanics is highly consistent with the TCM principle of"tendon impairment affecting bone".Finite element analysis revealing the"stability-instability-restabilization"process further validates the pathological progression from musculoskeletal imbalance to rebalance.This integrated TCM-Western medicine perspective establishes a novel theoretical framework for predicting disease progression and developing personalized therapeutic strategies,particularly in guiding clinical practice of"treating bone disorders through tendon regulation".
6.Biomechanical Mechanism Discussion of Intervertebral Disc Degeneration on Spinal Stability Based on the Theory of"Muscle and Bone Imbalance,Putting Muscle First"
Yadong WU ; Zhiguo ZHANG ; Jing LI ; Xiaoyan QI ; Yuzhou LU ; Nianhu LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(10):2810-2816
The concept of"musculoskeletal imbalance with soft tissue primacy"posits that tendon injury induced by intervertebral disc degeneration constitutes the core pathogenesis of spinal musculoskeletal imbalance.This study systematically elucidates the pathological mechanisms through which tendon injury leads to spinal instability by integrating traditional Chinese medicine(TCM)"musculoskeletal balance"theory with contemporary biomechanical research on disc degeneration.In the process of intervertebral disc degeneration,the change of stress distribution revealed by modern biomechanics is highly consistent with the TCM principle of"tendon impairment affecting bone".Finite element analysis revealing the"stability-instability-restabilization"process further validates the pathological progression from musculoskeletal imbalance to rebalance.This integrated TCM-Western medicine perspective establishes a novel theoretical framework for predicting disease progression and developing personalized therapeutic strategies,particularly in guiding clinical practice of"treating bone disorders through tendon regulation".
7.Association between obesity and diffuse idiopathic skeletal hyperostosis
Luming KONG ; Diqian ZHAO ; Wenzhe BAI ; Nianhu LI
Chinese Journal of Tissue Engineering Research 2025;29(17):3705-3712
BACKGROUND:Diffuse idiopathic skeletal hyperostosis is a systemic,non-inflammatory disease characterized by calcification and ossification of ligaments,tendons,and their attachments,predominantly affecting men over the age of 50.Studies have shown a higher prevalence of diffuse idiopathic skeletal hyperostosis among obese individuals;however,the causal relationship between the two remains unclear.OBJECTIVE:To investigate the causal relationship between obesity and diffuse idiopathic skeletal hyperostosis using Mendelian randomization analysis.METHODS:The study utilized single nucleotide polymorphisms from the Genome Wide Association Study database as instrumental variables,incorporating data related to obesity and diffuse idiopathic skeletal hyperostosis.A bidirectional two-sample Mendelian randomization analysis was performed to assess the causal relationship between obesity and diffuse idiopathic skeletal hyperostosis,with evaluations for pleiotropy,heterogeneity,and sensitivity.RESULTS AND CONCLUSION:The Mendelian randomization analysis revealed a significant positive causal relationship between obesity and diffuse idiopathic skeletal hyperostosis.The inverse-variance weighted method indicated that"obesity"(odds ratio[OR]=1.111,95%confidence interval[CI]:1.068-1.156,P=1.598×10-7),"obesity due to excess calories"(OR=1.093,95%CI:1.042-1.146,P=0.000),and"obesity,other/unspecified"(OR=1.109,95%CI:1.069-1.152,P=4.908×10-8)were significantly associated with diffuse idiopathic skeletal hyperostosis.Conversely,the reverse Mendelian randomization analysis did not find a causal relationship between diffuse idiopathic skeletal hyperostosis and obesity.The robustness of the Mendelian randomization analysis results was confirmed by pleiotropy,heterogeneity and sensitivity tests,indicating that while obesity significantly increases the risk of diffuse idiopathic skeletal hyperostosis,but diffuse idiopathic skeletal hyperostosis does not pose a risk factor for obesity.
8.Clinical guideline for diagnosis and treatment of nonunion of osteoporotic vertebral fractures (version 2025)
Haipeng SI ; Le LI ; Junjie NIU ; Wencan ZHANG ; Fuxin WEI ; Jinqiu YUAN ; Qiang YANG ; Hongli WANG ; Guangchao WANG ; Shihong CHEN ; Yunzhen CHEN ; Xiaoguang CHENG ; Jianwen DONG ; Shiqing FENG ; Rui GU ; Yong HAI ; Tianyong HOU ; Bo HUANG ; Xiaobing JIANG ; Lei ZANG ; Chunhai LI ; Nianhu LI ; Hua LIN ; Hongjian LIU ; Peng LIU ; Xinyu LIU ; Sheng LU ; Shibao LU ; Chunshan LUO ; Lvy CHAOLIANG ; Lvy WEIJIA ; Xuexiao MA ; Wei MEI ; Chunyang MENG ; Cailiang SHEN ; Chunli SONG ; Ruoxian SONG ; Jiacan SU ; Honglin TENG ; Hui SHENG ; Beiyu WANG ; Bingwu WANG ; Liang WANG ; Xiangyang WANG ; Nan WU ; Guohua XU ; Yayi XIA ; Jin XU ; Youjia XU ; Jianzhong XU ; Cao YANG ; Maowei YANG ; Zibin YANG ; Xiaojian YE ; Hailong YU ; Xijie YU ; Hua YUE ; Zhili ZENG ; Xinli ZHAN ; Hui ZHANG ; Peixun ZHANG ; Wei ZHANG ; Zhenlin ZHANG ; Jianguo ZHANG ; Tengyue ZHU ; Qiang LIU ; Huilin YANG
Chinese Journal of Trauma 2025;41(10):932-945
Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.
9.Role of tumor-associated macrophages in osteosarcoma and the implications for targeted therapy
Yue ZELIN ; Wang TIANHUA ; Qu XINTIAN ; Gong HAOQUAN ; Li NIANHU
Chinese Journal of Clinical Oncology 2024;51(24):1285-1290
Osteosarcoma(OS)is a common primary malignant bone tumor occurring predominantly in children and adolescents.The main treatments for OS are surgical resection and chemotherapy.Although overall survival rates have improved,progress has stalled in recent years,particularly in cases of recurrence and metastasis.The tumor microenvironment(TME)is closely related to tumor development,and macrophages are among the most abundant immune cells within the tumor environment.As a new target for tumor immunotherapy,mac-rophages have gained increasing attention due to their significant role in tumor progression.In this review,we explore the role of macro-phages in the OS microenvironment and discuss their clinical significance and involvement in the occurrence and development of OS.Fur-thermore,we summarize the therapeutic strategies targeting macrophages for OS treatment.
10.Percutaneous vertebroplasty combined with radiofrequency ablation for spinal metastases:a meta-analysis of clinical efficacy and safety
Zhongyuan LIU ; Chuanfu WEI ; Nianhu LI
Journal of Interventional Radiology 2024;33(10):1088-1094
Objective To investigate the clinical efficacy and safety of percutaneous vertebroplasty(PVP)combined with radiofrequency ablation(RFA)for spinal metastases.Methods A computerized retrieval of academic papers concerning the case-control studies(CCS)and randomized controlled trials(RCT)of PVP combined with RFA for spinal metastases from the databases of CNKI,Wanfang,Chinese Biomedical Literature Database(CBM),PubMed,Cochrane Library,Web of science and other databases was conducted.A control group(receiving PVP treatment alone)and a test group(receiving PVP combined with RFA treatment)were established.Newcastle-Ottawa scale(NOS)score was used to evaluate case-controlled trial literature,and the Cochrane risk bias assessment tool was used to evaluate the RCT literature.Results A total of 12 articles(10 CCS articles and 2 RCT articles)including 1 051 patients were included in this analysis.Meta-analysis showed that the recurrence rate of spinal metastases(OR=0.17,95%CI=0.08-0.34,P<0.001),incidence of complications(OR=0.29,95%CI=0.21-0.41,P<0.001)and pain visual analog scale(VAS)score(WMD=-1.21,95%CI=-1.64--0.78,P<0.001)in the test group were significantly lower than those in the control group.The Karnofsky functional status(KPS)score(WMD=14.69,95%CI=-12.25-17.14,P<0.001)in the test group was remarkably higher than that in the control group,but the long-term efficacy in the test group(OR=1.55,95%CI=0.90-2.68,P=0.12)was not obviously better than that in the control group.Conclusion For the treatment of spinal metastases,PVP combined with RFA has significant clinical short-term efficacy and safety,although its long-term efficacy is not obvious.Due to the limited quantity and quality of the included literature,larger-scale and higher-quality clinical trial studies need to be done before the above conclusions can be further clarified.

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