1.Triangular Wave tACS Improves Working Memory Performance by Enhancing Brain Activity in the Early Stage of Encoding.
Jianxu ZHANG ; Jian OUYANG ; Tiantian LIU ; Xinyue WANG ; Binbin GAO ; Jinyan ZHANG ; Manli LUO ; Anshun KANG ; Zilong YAN ; Li WANG ; Guangying PEI ; Shintaro FUNAHASHI ; Jinglong WU ; Jian ZHANG ; Tianyi YAN
Neuroscience Bulletin 2025;41(7):1213-1228
Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.
Humans
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Memory, Short-Term/physiology*
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Male
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Female
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Young Adult
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Transcranial Direct Current Stimulation/methods*
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Brain/physiology*
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Adult
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Electroencephalography
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Single-Blind Method
2.Comparative analysis of efficacy and safety of different regimens in the treatment of AIDS-related Burkitt lymphoma:a single-center retrospective study
Qinglian WANG ; Ying TENG ; Wenying QIAO ; Jinglong CHEN ; Xiaoyan DING
Journal of Capital Medical University 2025;46(3):427-435
Objective To evaluate the efficacy and safety of the dose-adjusted etoposide,doxorubicin and cyclophosphamide with vincristine,prednisone and rituximab without radiotherapy(DA-EPOCH-R)regimen versus the modified cyclophosphamide,vincristine,doxorubicin,high-dose methotrexate(CODOX-M/IVAC-R)regimen in the treatment of patients with acquired immune deficiency syndrome(AIDS)-related Burkitt lymphoma(BL).Methods This single-center retrospective cohort study included 41 patients diagnosed with AIDS-related BL at Beijing Ditan Hospital,Capital Medical University,from December 2010 to June 2022.Among them,26 patients received the DA-EPOCH-R regimen(observation group),and 15 patients received the modified CODOX-M/IVAC-R regimen(control group).Clinical characteristics,laboratory findings,toxicities,and treatment outcomes were analyzed.Prognostic risk factors were assessed using a multivariate Cox proportional hazards model.Results Of the 41 enrolled patients,97.6%were male,with a median age of 43 years.The baseline median CD4+cell count was below 200 cells/μL in 41.5%of patients.After a median follow-up of 17 months,the complete response(CR)rate was significantly higher in the observation group compared to the control group(57.7%vs 33.3%).The median overall survival(OS)was also significantly prolonged in the observation group(18.0 months)versus the control group(6.7 months,95%CI:5.0-16.6)(P<0.001).Treatment-related mortality was notably lower in the observation group(0%vs.26.7%,P<0.01).Conclusion Compared to the modified CODOX-M/IVAC-R regimen,the DA-EPOCH-R regimen demonstrates superior survival benefits and enhanced safety in the treatment of AIDS-related BL,suggesting it as the preferred chemotherapy option for this patient population.
3.Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture-dislocation in adults (version 2025)
Qingde WANG ; Tongwei CHU ; Jian DONG ; Liangjie DU ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Yong HAI ; Da HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Fang LI ; Feng LI ; Li LI ; Weishi LI ; Fangcai LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Xuhua LU ; Keya MAO ; Xuexiao MA ; Yong QIU ; Limin RONG ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Bing WANG ; Linfeng WANG ; Yu WANG ; Qinghe WANG ; Jigong WU ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Yong YANG ; Qiang YANG ; Cao YANG ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Zezhang ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Yan ZENG ; Dingjun HAO ; Baorong HE ; Wei MEI
Chinese Journal of Trauma 2025;41(3):243-252
Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.
4.Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures (version 2025)
Yong YANG ; Xiaoguang ZHOU ; Qixin CHEN ; Jian CHEN ; Jian DONG ; Liangjie DU ; Shunwu FAN ; Jin FAN ; Zhong FANG ; Haoyu FENG ; Shiqing FENG ; Haishan GUAN ; Aiguo GAO ; Yanzheng GAO ; Yong HAI ; Da HE ; Dengwei HE ; Haiyi HE ; Dianming JIANG ; Xuewen KANG ; Bin LIN ; Baoge LIU ; Changqing LI ; Fang LI ; Li LI ; Fangcai LI ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Xinyu LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Xuhua LU ; Fei LUO ; Yuhai MA ; Keya MAO ; Xuexiao MA ; Bin MENG ; Xu NING ; Limin RONG ; Hongxun SANG ; Jun SHU ; Tiansheng SUN ; Dasheng TIAN ; Zheng WANG ; Bing WANG ; Linfeng WANG ; Qingde WANG ; Qinghe WANG ; Lan WEI ; Jigong WU ; Baoshan XU ; Youjia XU ; Guoyong YIN ; Jinglong YAN ; Feng YAN ; Cao YANG ; Huilin YANG ; Qiang YANG ; Bin ZHAO ; Jie ZHAO ; Yue ZHU ; Jianguo ZHANG ; Wenzhi ZHANG ; Zhongmin ZHANG ; Zhaomin ZHENG ; Yan ZENG ; Baorong HE ; Wei MEI
Chinese Journal of Trauma 2025;41(7):613-626
Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.
5.Comparative analysis of efficacy and safety of different regimens in the treatment of AIDS-related Burkitt lymphoma:a single-center retrospective study
Qinglian WANG ; Ying TENG ; Wenying QIAO ; Jinglong CHEN ; Xiaoyan DING
Journal of Capital Medical University 2025;46(3):427-435
Objective To evaluate the efficacy and safety of the dose-adjusted etoposide,doxorubicin and cyclophosphamide with vincristine,prednisone and rituximab without radiotherapy(DA-EPOCH-R)regimen versus the modified cyclophosphamide,vincristine,doxorubicin,high-dose methotrexate(CODOX-M/IVAC-R)regimen in the treatment of patients with acquired immune deficiency syndrome(AIDS)-related Burkitt lymphoma(BL).Methods This single-center retrospective cohort study included 41 patients diagnosed with AIDS-related BL at Beijing Ditan Hospital,Capital Medical University,from December 2010 to June 2022.Among them,26 patients received the DA-EPOCH-R regimen(observation group),and 15 patients received the modified CODOX-M/IVAC-R regimen(control group).Clinical characteristics,laboratory findings,toxicities,and treatment outcomes were analyzed.Prognostic risk factors were assessed using a multivariate Cox proportional hazards model.Results Of the 41 enrolled patients,97.6%were male,with a median age of 43 years.The baseline median CD4+cell count was below 200 cells/μL in 41.5%of patients.After a median follow-up of 17 months,the complete response(CR)rate was significantly higher in the observation group compared to the control group(57.7%vs 33.3%).The median overall survival(OS)was also significantly prolonged in the observation group(18.0 months)versus the control group(6.7 months,95%CI:5.0-16.6)(P<0.001).Treatment-related mortality was notably lower in the observation group(0%vs.26.7%,P<0.01).Conclusion Compared to the modified CODOX-M/IVAC-R regimen,the DA-EPOCH-R regimen demonstrates superior survival benefits and enhanced safety in the treatment of AIDS-related BL,suggesting it as the preferred chemotherapy option for this patient population.
6.Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture-dislocation in adults (version 2025)
Qingde WANG ; Tongwei CHU ; Jian DONG ; Liangjie DU ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Yong HAI ; Da HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Fang LI ; Feng LI ; Li LI ; Weishi LI ; Fangcai LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Xuhua LU ; Keya MAO ; Xuexiao MA ; Yong QIU ; Limin RONG ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Bing WANG ; Linfeng WANG ; Yu WANG ; Qinghe WANG ; Jigong WU ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Yong YANG ; Qiang YANG ; Cao YANG ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Zezhang ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Yan ZENG ; Dingjun HAO ; Baorong HE ; Wei MEI
Chinese Journal of Trauma 2025;41(3):243-252
Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.
7.Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures (version 2025)
Yong YANG ; Xiaoguang ZHOU ; Qixin CHEN ; Jian CHEN ; Jian DONG ; Liangjie DU ; Shunwu FAN ; Jin FAN ; Zhong FANG ; Haoyu FENG ; Shiqing FENG ; Haishan GUAN ; Aiguo GAO ; Yanzheng GAO ; Yong HAI ; Da HE ; Dengwei HE ; Haiyi HE ; Dianming JIANG ; Xuewen KANG ; Bin LIN ; Baoge LIU ; Changqing LI ; Fang LI ; Li LI ; Fangcai LI ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Xinyu LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Xuhua LU ; Fei LUO ; Yuhai MA ; Keya MAO ; Xuexiao MA ; Bin MENG ; Xu NING ; Limin RONG ; Hongxun SANG ; Jun SHU ; Tiansheng SUN ; Dasheng TIAN ; Zheng WANG ; Bing WANG ; Linfeng WANG ; Qingde WANG ; Qinghe WANG ; Lan WEI ; Jigong WU ; Baoshan XU ; Youjia XU ; Guoyong YIN ; Jinglong YAN ; Feng YAN ; Cao YANG ; Huilin YANG ; Qiang YANG ; Bin ZHAO ; Jie ZHAO ; Yue ZHU ; Jianguo ZHANG ; Wenzhi ZHANG ; Zhongmin ZHANG ; Zhaomin ZHENG ; Yan ZENG ; Baorong HE ; Wei MEI
Chinese Journal of Trauma 2025;41(7):613-626
Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.
8.Changes and clinical prognostic significance of serum eNAMPT and sPD-L1 in patients with sepsis secondary to severe pancreatitis
Naixi JI ; Yunyun CUI ; Shangzhen LI ; Xiankui WANG ; Jinglong LIU
International Journal of Laboratory Medicine 2024;45(22):2737-2742
Objective To investigate the expression and clinical significance of extracellular nicotinamide phosphate ribose transferase(eNAMPT)and soluble programmed death ligand 1(sPD-L1)in serum of pa-tients with sepsis secondary to severe pancreatitis(SAP).Methods A total of 92 SAP patients admitted to the hospital from February 2019 to February 2022 were selected as(SAP grou),and divided into a sepsis group(42 cases)and a non-sepsis group(50 cases).Moreover,50 patients with mild to moderate pancreatitis who were diagnosed and treated at the same time were selected as the disease control group,and 50 healthy in-dividuals who underwent the physical examination in the hospital during the same pariod were selected as the healthy control group.Enzyme linked immunosorbent assay was used to detect serum levels of eNAMPT and sPD-L1.Pearson correlation analysis was used for correlation analysis.Multivariate Logistic regression analy-sis was used to analyze factors affecting the occurrence of secondary sepsis in SAP.The predictive value of ser-um eNAMPT,sPD-L1 and their combination in the secondary sepsis of SAP was conducted by receiver operat-ing characteristic(ROC)curve.Results The serum levels of eNAMPT and sPD-L1 in the SAP group were higher than those in the disease control group and the healthy control group,and the differences were statisti-cally significant(P<0.05).The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score,Sequential Organ Failure Assessment(SOFA)score,white blood cell count,C-reactive protein,pancreatic nec-rosis,systemic inflammatory response syndrome,multiple organ failure,serum eNAMPT and sPD-L1 in the sepsis group were higher than those in the non-sepsis group,and the differences were statistically significant(P<0.05).There was a positive correlation between serum eNAMPT,sPD-L1 and APACHE Ⅱ score,SOFA score in sepsis SAP patients(P<0.05).Serum eNAMPT and sPD-L1 were independent risk factors for sec-ondary sepsis in SAP patients.The area under the curve(AUC)of the combination of serum eNAMPT and sPD-L1 for predicting secondary sepsis in SAP patients was 0.916(95%CI:0.868-0.947),which was signif-icantly larger than 0.846(95%CI:0.791-0.879)and 0.830(95%CI:0.774-0.861)of the single indicator detections,and the differences were statistically significant(Z=4.129,4.885,P<0.001).Conclusion The serum eNAMPT and sPD-L1 levels in patients with sepsis secondary to SAP are elevated,which are related to the severity of the disease.The combination of serum eNAMPT and sPD-L1 has high predictive value for sec-ondary sepsis in SAP.
9.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
10.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

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