1.Decompression mechanism of symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous
Chunlin ZHANG ; Zhaohua HOU ; Xu YAN ; Yan JIANG ; Su FU ; Yongming NING ; Dongzhe LI ; Chao DONG ; Xiaokang LIU ; Yongkui WANG ; Zhengming CAO ; Tengyue YANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1810-1819
BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.
2.Diterpenoids and lignans from fossil Chinese medicinal succinum and their activity against renal fibrosis.
Yefei CHEN ; Yunfei WANG ; Yunyun LIU ; Yongming YAN ; Yongxian CHENG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):888-896
Five previously undescribed diterpenoids, named succipenoids D‒H (1‒5), along with four undescribed lignans, named succignans A‒D (6‒9), were isolated from the dichloromethane extract of Chinese medicinal succinum. Compounds 1‒5 were characterized as nor-abietane diterpenoids, while compounds 6‒9 were identified as lignans polymerized from two groups of phenylpropanoid units. The structures of these novel compounds, including their absolute configurations, were determined through spectroscopic and computational methods. Biological assessments of renal fibrosis demonstrated that compounds 6 and 7 effectively reduce the expression of proteins associated with renal fibrosis, including α-smooth muscle actin (α-SMA), collagen I, and fibronectin in transforming growth factor-β1 (TGF-β1) induced normal rat kidney proximal tubular epithelial cells (NRK-52e).
Animals
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Rats
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Lignans/isolation & purification*
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Diterpenes/isolation & purification*
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Fibrosis/drug therapy*
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Drugs, Chinese Herbal/pharmacology*
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Molecular Structure
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Cell Line
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Kidney Diseases/pathology*
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Transforming Growth Factor beta1/genetics*
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Kidney/metabolism*
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Actins/genetics*
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Fibronectins/genetics*
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Collagen Type I/genetics*
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Epithelial Cells/metabolism*
3.Application of A Tiered Progressive Training Model in the Standardized Residency Training on Laboratory Medicine
Guiyu SONG ; Zhenrong LIU ; Yongming ZHANG ; Liyuan ZHANG ; Wenqi TAI ; Yan JIAO ; Wei CUI
Journal of Modern Laboratory Medicine 2024;39(2):181-183,191
Objective To cultivate the ability of laboratory resident physicians in multiple aspects and enhance their post-competence for laboratory medicine.Methods The residents recruited into the Cancer Hospital of China Academy of Medical Sciences Laboratory Base were divided into junior residents and senior residents.According to the different training contents and objectives,the exploration of the hierarchically progressive training model was carried out,which mainly included three aspects:training plan,process training and process assessment.Results After the implementation of the hierarchical progressive training model,the average theoretical score and the average score in the skill operation examination of the residents increased to over 90 and 95,respectively.Meanwhile,the comprehensive clinical ability was also improved.Breakthroughs of teaching,scientific research and honor were achieved from"nothing"before the implementation to"something"after the implementation,and it actively promoted the improvement of the post-competency of the residents in laboratory medicine.Conclusion The application of the hierarchically progressive training mode in standardized training of residents in laboratory medicine could play a good role in promoting the training of post-competence for residents.
4.Clinical efficacy of UBE-LIF versus posterior lesion removal bone graft fusion fixation in the treatment of lumbar brucelli spondylitis
Bei LIU ; Yongming LIU ; Jiandong ZHAO ; Yinjun YANG ; Yiqi LI ; Fayan WEN ; Yan LI ; Zhenjun LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(1):160-166,封3
Objective To compare the safety and clinical efficacy of lesion removal combined with percutaneous pedicle screw fixation with classical posterior lesion removal in the treatment of lumbar brucelli spondylitis(LBS)by unilateral biportal endoscopic technique with transforaminal lumbar interbody fusion(UBE-LIF)technique.Methods The clinical data of 32 patients with LBS admitted by the Department of Spine and Orthopedics of Gansu Provincial Hospital of Traditional Chinese Medicine from January 2020 to January 2022 were retrospectively analyzed,and the clinical data of the 32 LBS patients were divided into 15 cases in the UBE-LIF group and 17 cases in the posterior group.The general data,surgery-related indexes,and postoperative pathological HE staining of the two groups were recorded and analyzed.The patients'clinical recovery was assessed according to their erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP),low back pain visual analogue score(VAS),Japanese Orthopaedic Association(JOA)score,and Oswestry Dysfunction Index(ODI)preoperative,1 week after surgery,1,3,6 months and 1 year after surgery.Lumbar lordosis angle(LL)and intervertebral space height(DH)were measured by imaging before surgery and at the last follow-up,and intervertebral bone graft fusion was assessed using Suk grading criteria.Results Both groups successfully completed the operation and no serious postoperative complications occurred.There were no significant differences in gender,age,surgical segment,operation time,preoperative ESR and CRP,preoperative VAS,JOA score and ODI index,preoperative LL and DH(P>0.05).The intraoperative blood loss,postoperative drainage,postoperative getting out of bed,and postoperative hospital stay in UBE-LIF group were significantly lower than those in the posterior group(P<0.001).Pathological examination of diseased tissues was performed during surgery,all of which was consistent with brucellosis changes.Patients in both groups were followed up for 12-18 months,with an average of 14.8 months.The VAS,JOA score,and ODI index at all postoperative time points in the two groups were significantly improved compared with the preoperative period(P<0.05).The difference between the two groups was significantly greater than that in the postoperative group:VAS score was lower in UBE-LIF group than in the posterior group(P<0.01),CRP in both groups was higher than that in the preoperative group,and the elevation level was significantly lower in UBE-LIF group than in the posterior group(P<0.001).There was no significant difference in ESR between the two groups compared with that before surgery(P>0.05).There were no significant differences in VAS,JOA score,ODI index,CRP or ESR between the remaining time points after surgery(P>0.05).At the last follow-up,imaging examination showed that the overall fusion rate of intervertebral bone graft in UBE-LIF group was 93.3%and 94.1%in the posterior group,without significant difference(x2=0.246,P=0.884).LL and DH were significantly improved in both groups compared with preoperative ones(P<0.01),and the two groups did not significantly differ before and after surgery(P>0.05).Conclusion Both surgical treatments for LBS are safe effect.Compared with posterior lesion removal bone graft fusion internal fixation,UBE-LIF technology combined with percutaneous pedicle screw internal fixation has the advantages of clear intraoperative vision,less blood loss,faster early postoperative recovery,and shorter postoperative hospital stay,and thus is a feasible surgical method for the minimally invasive treatment of LBS.
5.Therapeutic effects of Isaria felina combined with cyclophosphamide in hepatoma H22 tumor-bearing mice
Xiaowei SHI ; Jingjing CHEN ; Guoyan YU ; Yiyin ZHANG ; Lixia CHEN ; Lili ZHAO ; Yongming YANG ; Jing WANG ; Lei YAN ; Xihua YANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(3):362-368
Objective To investigate the therapeutic effects of Isaria felina derived from Cordyceps sinensis combined with cyclophosphamide(CTX)in hepatoma H22 tumor-bearing mice.Methods An H22 tumor-bearing mouse model was established and mice were divided randomly into a normal control group(NC group,distilled water),model control group(MC group,distilled water),positive control group(CTX group,25 mg/kg),Isaria felina group(IF group,400 mg/kg),and combined administration group(IF+CTX group,IF 400 mg/kg+CTX 25 mg/kg),with 5 mice in each group.Distilled water and IF were administered by gavage,and CTX was administered by intraperitoneal injection.The administration cycle was 10 days.At the end of the experiment,the mean tumor volume and weight,tumor inhibition rate,q value,and immune organ index were calculated,and routine blood indexes and cytokine levels were determined.Histopathological changes in tumor tissues were observed by HE staining.Results The tumor volume and mass were significantly lower in mice in each treatment group compared with those in mice in the MC group(P<0.05).The tumor inhibition rates in the CTX,IF,and IF+CTX groups were 49.3%,34.2%,and 72.8%,respectively,and the q value was 1.09.The numbers of white blood cells,Lymph,and platelets were significantly higher in the IF+CTX group than in the CTX group(P<0.05).The spleen index was significantly higher in the MC group compared with that in the NC group,and significantly lower in the IF+CTX group compared with that in the MC group(P<0.05).Serum interferon-γ levels were significantly lower in the MC group than in the NC group,and were significantly higher in the IF and IF+CTX groups compared with those in the MC and CTX groups(P<0.05).Pathologically,tumor cells in the MC group grew well and were numerous and closely arranged,while cells in the CTX,IF,and IF+CTX groups were arranged loosely,with focal necrosis and nuclear pyknosis of necrotic cells in many places.Conclusions The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice,which can alleviate immunosuppression and have an immunomodulatory function.
6.Analysis of clinical changes and magnetic resonance imaging features of 37 patients with temporomandibular joint disc condylar complex with anterior disc displacement without reduction
Sen YAN ; Yongming QIAO ; Liangwei DUAN
West China Journal of Stomatology 2024;42(1):82-88
Objective This study aims to investigate clinical outcomes,imaging changes,and age differences with re-gard to temporomandibular joint disc condylar complex with anterior disc displacement without reduction(ADDWoR).Methods A total of 37 patients(45 lateral joints)with ADDWoR who were admitted to The First Affiliated Hospital of Zheng Zhou University from January 2016 to June 2023 were selected.The patients were composed of 4 males and 33 females and had an average age of 23.5 years.The average course of the disease was 14.4 months.Clinical and magnetic resonance imaging(MRI)data were collected at the end of initial diagnosis and follow-up,and the length and thickness of the articular disc,the angle of the disc con-dyle,and the height of the condyle were measured.The statistical significance of the changes was assessed using SPSS 25.0 software package.Results At the end of follow-up,disc displacement in three patients(three lateral joints)was healed.Approximately 48.4%of the patients felt that limi-tation of mandibular movement was not alleviated;58.3%of patients reported that pain during mouth opening was not re-duced;54.5%reported pain while chewing;33.3%of the patients showed facial deviation,and only one showed remis-sion.The mean disk-condyle angle increased from 61.63° to 67.81°.The average length of articular disc shortened from 8.20 mm to 7.27 mm,and the height of the condyle significantly decreased from 23.17 mm to 22.76 mm(P<0.05).The absorption ratio of the condyle increased,and no significant differences in the changes of joint soft and hard tissues be-tween the adolescent and adult groups(P>0.05).Conclusion In different age groups of patients with ADDWoR,clini-cal symptoms cannot be completely relieved.The disc is anteriorly displaced and shortens,condylar height decreases,and secondary facial asymmetry and mandibular retraction occur.
7.Survey of the cognition of interventional radiology and employment intention in the students majoring in imaging technology in medical school
Yongming ZHANG ; Hanfeng YANG ; Jiayu SUN ; Yan FU ; Jingui LI ; Yuxi LIU ; Ruosu WANG ; Xiao LI
Journal of Interventional Radiology 2024;33(8):910-914
Objective To discuss the cognition of interventional radiology(IR)and employment intention in the students majoring in imaging technology in medical school.Methods From June 7 to July 31 of 2023,a voluntary and anonymous online questionnaire survey concerning the cognition of IR and employment intention was conducted in the students majoring in medical imaging technology in Sichuan University,North Sichuan Medical College,Harbin Medical University,Hebei Medical University,Changzhi Medical College and Sichuan Vocational College of Health and Rehabilitation.The data obtained from the survey were analyzed by descriptive analysis and chi-square test using SPSS 24.0 statistical software.Results A total of 126 valid questionnaires were received.Eighty-seven students(69.05%),94 students(74.61%)and 81(64.28%)students had no knowledge or just had a little bit knowledge about the medical position and current status of IR in the fields of cardiovascular diseases,neurological diseases,and tumor diagnosis and treatment respectively.The IR course was obligatory course for the medical imaging technology specialty in all the schools participating in this survey,and 112 students(91.8%)stated that the school curriculum is the main way to acquire knowledge of IR,and the internet platforms,television science popularization and academic conferences were the other ways to acquire knowledge of IR.Four students(3.17%),17 students(13.49%),57 students(45.24%),39 students(30.95%)and 9 students(7.14%)participating in this survey expressed that they had no intention,no willingness,neutral attitude,high willingness and high intention respectively to engage in IR work in future.The difference in the degree of willingness to engage in IR specialty in future between students of different gender as well as between students with different schooling level was not statistically significant,and the exposure to radiation,work-related high stress,and long working time were the main influencing factors for students to consider IR as their professional career.Conclusion At present,both the cognition of IR and the employment intention are not high in the students majoring in imaging technology in medical school.Therefore,it is very important to improve their cognition of IR and willingness to engage in IR profession.
8.Associations of serum low-density lipoprotein cholesterol with hematoma enlargement, early neurological deterioration, and outcome in patients with acute spontaneous intracerebral hemorrhage
Ting LAN ; Xiwa HAO ; Lin LYU ; Cuiqin ZHANG ; Hongmei QIAO ; Bobo ZHANG ; Yongming CHEN ; Qidi BO ; Meiyou YAN ; Hui LYU ; Jingfen ZHANG
International Journal of Cerebrovascular Diseases 2024;32(7):506-511
Objective:To investigate associations of serum low-density lipoprotein cholesterol (LDL-C) with hematoma enlargement, early neurological deterioration (END), and outcome in patients with acute spontaneous intracerebral hemorrhage (ICH).Methods:"A multi-center registration study for spontaneous intracerebral hemorrhage in Inner Mongolia" (registration number: ChiCTR2000029494) database was used to include patients with ICH who completed their first head CT scan within 6 hours after onset, underwent blood lipid examination, CT follow-up within 24 hours of onset, and accurately measured hematoma volume using 3D Slicer software between June 2020 and September 2022. HE was defined as hematoma volume increasing >33% or >6 ml at 24 hours, or ventricular hematoma volume increasing ≥1 ml compared to the baseline. END was defined as an increase of ≥4 in the National Institutes of Health Stroke Scale (NIHSS) score from the baseline or death within 24 hours after onset. The follow-up was conducted at 3 months after onset, and the modified Rankin Scale score >2 was defined as poor outcome. Multivariate logistic analysis was used to determine the independent correlation between LDL-C and HE, END, and outcome. Results:A total of 338 patients with ICH were enrolled, including 206 males (60.9%). LDL-C was 2.39±1.22 mmol/L. Eighty-eight patients (26.0%) developed HE, 67 (19.8%) developed END, and 162 (47.9%) had poor outcome at 3 months. Multivariate logistic analysis showed that after adjusting for confounding factors, there was a significant independent negative correlation between LDL-C and HE (odds ratio 0.312, 95% confidence interval 0.208-0.467; P<0.001) and END (odds ratio 0.408, 95% confidence interval 0.275-0.606; P<0.001), but not with the outcome at 3 months. Conclusion:Lower LDL-C is associated with HE and END in patients with ICH, but not with the outcome.
9.Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus disease 2019 (version 2023)
Zeli ZHANG ; Shoujia SUN ; Yijun BAO ; Li BIE ; Yunxing CAO ; Yangong CHAO ; Juxiang CHEN ; Wenhua FANG ; Guang FENG ; Lei FENG ; Junfeng FENG ; Liang GAO ; Bingsha HAN ; Ping HAN ; Chenggong HU ; Jin HU ; Rong HU ; Wei HE ; Lijun HOU ; Xianjian HUANG ; Jiyao JIANG ; Rongcai JIANG ; Lihong LI ; Xiaopeng LI ; Jinfang LIU ; Jie LIU ; Shengqing LYU ; Binghui QIU ; Xizhou SUN ; Xiaochuan SUN ; Hengli TIAN ; Ye TIAN ; Ke WANG ; Ning WANG ; Xinjun WANG ; Donghai WANG ; Yuhai WANG ; Jianjun WANG ; Xingong WANG ; Junji WEI ; Feng XU ; Min XU ; Can YAN ; Wei YAN ; Xiaofeng YANG ; Chaohua YANG ; Rui ZHANG ; Yongming ZHANG ; Di ZHAO ; Jianxin ZHU ; Guoyi GAO ; Qibing HUANG
Chinese Journal of Trauma 2023;39(3):193-203
The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.
10.Clinical guideline for diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture (version 2023)
Jianan ZHANG ; Bohua CHEN ; Tongwei CHU ; Yirui CHEN ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Yong HAI ; Lijun HE ; Yuan HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Dechun LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Wei MEI ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Honghui SUN ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Yongming XI ; Hong XIA ; Jinglong YAN ; Liang YAN ; Wen YUAN ; Gang ZHAO ; Jie ZHAO ; Jianguo ZHANG ; Xiaozhong ZHOU ; Yue ZHU ; Yingze ZHANG ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2023;39(3):204-213
Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

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