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Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop 被引量:21
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作者 Fan Chen Guowei Jiang +8 位作者 Hui Liu Zemin Li Yuxin Pei Hua Wang Hehai Pan Haowen Cui Jun Long Jianru Wang Zhaomin Zheng 《Bone Research》 SCIE CAS CSCD 2020年第2期169-181,共13页
The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin(IL)-1β, and is one of the main causes of intervertebral disc degeneration(IVDD). NLR pyrin domain containing 3(... The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin(IL)-1β, and is one of the main causes of intervertebral disc degeneration(IVDD). NLR pyrin domain containing 3(NLRP3) inflammasome activation is an important source of IL-1β. As an anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. However, its roles in IVDD are still not well understood and require more examination. First, we demonstrated that melatonin delayed the progression of IVDD and relieved IVDD-related low back pain in a rat needle puncture IVDD model;moreover, NLRP3 inflammasome activation(NLRP3, p20, and IL-1β levels) was significantly upregulated in severely degenerated human discs and a rat IVDD model. Subsequently, an IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop was found in nucleus pulposus(NP) cells that were treated with IL-1β. In these cells, expression of NLRP3 and p20 was significantly increased, NF-κB signaling was involved in this regulation, and mitochondrial reactive oxygen species(mt ROS)production increased. Furthermore, we found that melatonin disrupted the IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop in vitro and in vivo. Melatonin treatment decreased NLRP3, p20, and IL-1β levels by inhibiting NF-κB signaling and downregulating mt ROS production. Finally, we showed that melatonin mediated the disruption of the positive feedback loop of IL-1β in vivo. In this study, we showed for the first time that IL-1β promotes its own expression by upregulating NLRP3 inflammasome activation. Furthermore, melatonin disrupts the IL-1β positive feedback loop and may be a potential therapeutic agent for IVDD. 展开更多
关键词 NLRP3 DEGENERATION inflam
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Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID- 19 pandemic
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作者 Thanh N Nguyen Diogo C Haussen +101 位作者 Muhammad M Qureshi Hiroshi Yamagami Toshiyuki Fujinaka Ossama Y Mansour Mohamad Abdalkader Michael Frankel Zhongming Qiu Allan Taylor Pedro Lylyk Omer F Eker Laura Mechtouff Michel Piotin Fabricio Oliveira Lima Francisco Mont'Alverne Wazim Izzath Nobuyuki Sakai Mahmoud Mohammaden Alhamza R Al-Bayati Leonardo Renieri Salvatore Mangiafico David Ozretic Vanessa Chalumeau Saima Ahmad Umair Rashid Syed Irteza Hussain Seby John Emma Griffin John Thornton Jose Antonio Fiorot Rodrigo Rivera Nadia Hammami Anna M Cervantes-Arslanian Hormuzdiyar H Dasenbrock Huynh Le Vu Viet Quy Nguyen Steven Hetts Romain Bourcier Romain Guile Melanie Walker Malveeka Sharma Don Frei Pascal Jabbour Nabeel Herial Fawaz Al-Mufti Atilla Ozcan Ozdemir Ozlem Aykac Dheeraj Gandhi Chandril Chugh Charles Matouk Pascale Lavoie Randall Edgell Andre Beer-Furlan Michael Chen Monika Killer-Oberpfalzer Vitor Mendes Pereira Patrick Nicholson Vikram Huded Nobuyuki Ohara Daisuke Watanabe Dong Hun Shin Pedro SC Magalhaes Raghid Kikano Santiago Ortega-Gutierrez Mudassir Farooqui Amal Abou-Hamden Tatsuo Amano Ryoo Yamamoto Adrienne Weeks Elena A Cora Rotem Sivan-Hoffmann Roberto Crosa Markus Möhlenbruch Simon Nagel Hosam Al-Jehani Sunil A Sheth Victor S Lopez Rivera James E Siegler Achmad Fidaus Sani Ajit S Puri Anna Luisa Kuhn Gianmarco Bernava Paolo Machi Daniel G Abud Octavio M Pontes-Neto Ajay K Wakhloo Barbara Voetsch Eytan Raz Shadi Yaghi Brijesh P Mehta Naoto Kimura Mamoru Murakami Jin Soo Lee Ji Man Hong Robert Fahed Gregory Walker Eiji Hagashi Steve M Cordina Hong Gee Roh Ken Wong Juan F Arenillas Mario Martinez-Galdamez Jord 《Stroke & Vascular Neurology》 SCIE CSCD 2021年第4期542-552,I0026-I0032,共18页
Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ... Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction. 展开更多
关键词 DIAGNOSIS representing SUBARACHNOID
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Robotic solution for orthopedic surgery
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作者 Mingxing Fan Qi Zhang +1 位作者 Yanming Fang Wei Tian 《Chinese Medical Journal》 SCIE CAS CSCD 2023年第12期1387-1389,共3页
In orthopedic surgery,the accuracy of internal fixation is related to the success of the procedure.In the past,orthopedic surgeons usually placed screws freehand according to anatomical landmarks or fluoroscopy images... In orthopedic surgery,the accuracy of internal fixation is related to the success of the procedure.In the past,orthopedic surgeons usually placed screws freehand according to anatomical landmarks or fluoroscopy images.Although there are many surgical techniques for inserting screws freehand,the accuracy of freehand screw placement is not high enough,and the results can be unstable.The accuracy of freehand screw placement reported in the literature varies greatly.Particularly in the spine,with its unique anatomy and important adjacent tissues,inaccurate screw placement may lead to serious complications,such as nerve or vessel injury,cerebrospinal fluid leakage,thoracic or abdominal organ injury,and segment instability.Surgeons must undergo extensive professional training and accumulate in-depth surgical experience to reduce the incidence of inaccurate screw placement. 展开更多
关键词 ANATOMY SURGERY UNSTABLE
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Spinal alignment evolution with age:A prospective gait analysis study 被引量:2
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作者 Sébastien Pesenti Benjamin Blondel +5 位作者 Emilie Peltier Elke Viehweger Vincent Pomero Guillaume Authier Stéphane Fuentes Jean-Luc Jouve 《World Journal of Orthopedics》 2017年第3期256-263,共8页
AIM To describe,using gait analysis,the development of spinal motion in the growing child.METHODS Thirty-six healthy children aged from 3 to 16 years old were included in this study for a gait analysis(9m-walk).Variou... AIM To describe,using gait analysis,the development of spinal motion in the growing child.METHODS Thirty-six healthy children aged from 3 to 16 years old were included in this study for a gait analysis(9m-walk).Various kinematic parameters were recorded and analyzed such as thoracic angle(TA),lumbar angle(LA)and sagittal vertical axis(SVA).The kinetic parameters were the net reaction moments(N.m/kg)at the thoracolumbar and lumbosacral junctions.RESULTS TA and LA curves were not statistically correlated to the age(respectively,P=0.32 and P=0.41).SVA increased significantly with age(P<0.001).Moments in sagittal plane at the lumbosacral junction were statistically correlated to the age(P=0.003),underlining the fact that sagittal mechanical constraints at the lumbosacral junction increase with age.Moments in transversal plane at the thoracolumbar and lumbosacral junctions were statistically correlated to the age(P=0.0002and P=0.0006),revealing that transversal mechanical constraints decrease with age.CONCLUSION The kinetic analysis showed that during growth,a decrease of torsional constraint occurs while an increase of sagittal constraint is observed.These changes in spine biomechanics are related to the crucial role of the trunk for bipedalism acquisition,allowing stabilization despite lower limbs immaturity.With the acquisition of mature gait,the spine will mainly undergo constraints in the sagittal plane. 展开更多
关键词 Sagittal balance Spine biomechanics Gait analysis Thorcic kyphosis Spine growth
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Small bowel entrapment and ureteropelvic junction disruption associated with L3 Chance fracture-dislocation 被引量:2
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作者 Sebastien Pesenti Benjamin Blondel +3 位作者 Alice Faure Emilie Peltier Franck Launay Jean-Luc Jouve 《World Journal of Clinical Cases》 SCIE 2016年第9期264-268,共5页
Paediatric Chance fracture are rare lesions but often associated with abdominal injuries. We herein present the case of a seven years old patient who sustained an entrapment of small bowel and an ureteropelvic disrupt... Paediatric Chance fracture are rare lesions but often associated with abdominal injuries. We herein present the case of a seven years old patient who sustained an entrapment of small bowel and an ureteropelvic disruption associated with a Chance fracture and spine dislocation following a traffic accident. Initial X-rays and computed tomographic(CT) scan showed a Chance fracture with dislocation of L3 vertebra, with an incarceration of a small bowel loop in the spinal canal and a complete section of the left lumbar ureter. Paraplegia was noticed on the initial neurological examination. A posterior L2-L4 osteosynthesis was performed firstly. In a second time she underwent a sus umbilical laparotomy to release the incarcerated jejunum loop in the spinal canal. An end-toend anastomosis was performed on a JJ probe to suture the left injured ureter. One month after the traumatism, she started to complain of severe headaches related to a leakage of cerebrospinalis fluid. Three months after the traumatism there was a clear regression of the leakage. One year after the trauma, an anterior intervertebral fusion was done. At final follow-up, no neurologic recovery was noticed. In case of Chance fracture, all physicians should think about abdominal injuries even if the patient is asymptomatic. Initial abdominal CT scan and magnetic resonance imaging provide in such case crucial info for management of the spine and the associated lesions. 展开更多
关键词 Chance fracture Uretero-pelvic DISRUPTION Small bowel injuries Seatbelt DURAL TEAR
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阿哌沙班vs依诺肝素用于膝关节置换术后血栓预防(ADVANCE-2):随机双盲试验 被引量:1
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作者 Michael Rud Lassen Gary E Raskob +3 位作者 Alexander Gallus Graham Pineo Dalei Chen Philip Hornick 《中华关节外科杂志(电子版)》 CAS 2013年第1期94-102,共9页
背景依诺肝素等低分子肝素是预防大关节置换术后静脉血栓形成的首选。阿哌沙班是一种口服活性的Xa因了抑制剂,在预防大关节置换术后静脉血栓形成方面可能有效,而且相对于依诺肝素来说,出血风险较低、用法也较简便。本研究评估选择性全... 背景依诺肝素等低分子肝素是预防大关节置换术后静脉血栓形成的首选。阿哌沙班是一种口服活性的Xa因了抑制剂,在预防大关节置换术后静脉血栓形成方面可能有效,而且相对于依诺肝素来说,出血风险较低、用法也较简便。本研究评估选择性全膝关节置换术后卜述药物的有效性和安全性。方法 ADVANCE-2为多中心随机双盲Ⅲ期研究,选择性双侧或单侧全膝关节置换术患者通过交互式中心电话系统进行分组,随机接受阿哌沙班2.5mg每天2次口服(1528例)或依诺肝素40mg每天1次皮下注射(1529例)。随机化方案由Bristol-Myers Squibb随机中心生成,按研究中心和单侧或双侧手术分层,区组大小为4。研究者、患者、统计专家、评判者和指导委员会不知道患者分组情况。阿哌沙班于手术伤口闭合后10~12小时使用,依诺肝素于术前12小时使用;两药均持续用药10-14天,按照计划用药结束时行双侧顺行性静脉造影。主要终点是治疗期间无症状和有症状的深静脉血栓形成、非致死性肺栓塞和全因死亡的复合指标。统计学计划要求在检验阿哌沙班的优效性之前达到非劣效;非劣效检验对意向治疗患者进行分析。本研究在ClinicalTrials.gov备案,备案号NCT00452530。结果接受治疗的3057例患者(阿哌沙班组1528例、依诺肝素组1529例)中,1973例符合主要有效性分析的要求。阿哌沙班组976例和依诺肝素组997例中,报告主要终点的患者分别为147例(15%)和243例(24%)[相对危险度0.62(95%可信区间CI为:0.51-0.74),P<0.0001;绝对危险度下降9.3%(5.8~12.7)]。阿哌沙班组1501例和依诺肝素组1508例中,发生大出血或临床相关非大出血的患者分别为53例(4%)和72例(5%)(P=0.09)。解读全膝关节置换术后次日上午使用阿哌沙班2.5mg每天2次,是依诺肝素40mg/天简便而更有效的口服替代措施,且不会增加出血。 展开更多
关键词 全膝关节置换术 随机双盲试验 依诺肝素 血栓预防 术后 深静脉血栓形成 顺行性静脉造影 VS
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Prediction of Driver Gene Matching in Lung Cancer NOG/PDX Models Based on Artificial Intelligence
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作者 Yayi He Haoyue Guo +12 位作者 Li Diao Yu Chen Junjie Zhu Hiran C.Fernando Diego Gonzalez Rivas Hui Qi Chunlei Dai Xuzhen Tang Jun Zhu Jiawei Dai Kan He Dan Chan Yang Yang 《Engineering》 SCIE EI CAS 2022年第8期102-114,共13页
Patient-derived tumor xenografts(PDXs)are a powerful tool for drug discovery and screening in cancer.However,current studies have led to little understanding of genotype mismatches in PDXs,leading to massive economic ... Patient-derived tumor xenografts(PDXs)are a powerful tool for drug discovery and screening in cancer.However,current studies have led to little understanding of genotype mismatches in PDXs,leading to massive economic losses.Here,we established PDX models from 53 lung cancer patients with a genotype matching rate of 79.2%(42/53).Furthermore,17 clinicopathological features were examined and input in stepwise logistic regression(LR)models based on the lowest Akaike information criterion(AIC),least absolute shrinkage and selection operator(LASSO)-LR,support vector machine(SVM)recursive feature elimination(SVM-RFE),extreme gradient boosting(XGBoost),gradient boosting and categorical features(Cat Boost),and the synthetic minority oversampling technique(SMOTE).Finally,the performance of all models was evaluated by the accuracy,area under the receiver operating characteristic curve(AUC),and F1 score in 100 testing groups.Two multivariable LR models revealed that age,number of driver gene mutations,epidermal growth factor receptor(EGFR)gene mutations,type of prior chemotherapy,prior tyrosine kinase inhibitor(TKI)therapy,and the source of the sample were powerful predictors.Moreover,Cat Boost(mean accuracy=0.960;mean AUC=0.939;mean F1 score=0.908)and the eight-feature SVM-RFE(mean accuracy=0.950;mean AUC=0.934;mean F1 score=0.903)showed the best performance among the algorithms.Meanwhile,application of the SMOTE improved the predictive capability of most models,except Cat Boost.Based on the SMOTE,the ensemble classifier of single models achieved the highest accuracy(mean=0.975),AUC(mean=0.949),and F1 score(mean=0.938).In conclusion,we established an optimal predictive model to screen lung cancer patients for non-obese diabetic(NOD)/Shi-scid,interleukin-2 receptor(IL-2R)γ^(null)(NOG)/PDX models and offer a general approach for building predictive models. 展开更多
关键词 Machine learning Patient-derived tumor xenografts NOG mice
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Measurement of forces generated during distraction of growing-rods in early onset scoliosis 被引量:1
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作者 Marco Teli Giuseppe Grava +3 位作者 Victor Solomon Giuseppe Andreoletti Emanuele Grismondi Jay Meswania 《World Journal of Orthopedics》 2012年第2期15-19,共5页
AIM: To measure the forces applied during distraction of growing-rods in early onset scoliosis(EOS), aimed at developing a motorized elongation device.METHODS: A consecutive series of measurements were carried out to ... AIM: To measure the forces applied during distraction of growing-rods in early onset scoliosis(EOS), aimed at developing a motorized elongation device.METHODS: A consecutive series of measurements were carried out to analyze the forces applied by the surgeon during distraction of single growing-rods in 10 patients affected by EOS(mean age 8.3 years; range 6 to 10 years) undergoing the first distraction 6 months following implantation of the rods. For each measurement, output from the transducer of a dedicated pair of distraction calipers was recorded at zero load status and at every 1 mm of distraction, up to a maximum of 12 mm for each of the two connected rods.RESULTS: Twenty measurements were obtained showing a linear increase of the load with increasing distraction, with a mean peak force of 485 N at 12 mm distraction and a single reading over 500 N. We did not observe bone fractures or ligament disruptions during or after rod elongations. There was one case of superficial wound infection in the cohort.CONCLUSION: The safe peak force carrying capacity of a motorized device for distraction of growing-rods is 500 N. 展开更多
关键词 Early onset SCOLIOSIS SPINAL DEFORMITY Growing-rods SPINAL elongation Force measurement
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Postural spinal balance defined by net intersegmental moments: Results of a biomechanical approach and experimental errors measurement
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作者 Benjamin Blondel Elke Viehweger +7 位作者 Bertrand Moal Patrick Tropiano Jean-Luc Jouve Virginie Lafage Raphael Dumas Stéphane Fuentes Gérard Bollini Vincent Pomero 《World Journal of Orthopedics》 2015年第11期983-990,共8页
AIM: To describe initial results and experimental error measurement of a protocol analyzing Human posture through sagittal intersegmental moments. METHODS: Postural analysis has been recently improved by development o... AIM: To describe initial results and experimental error measurement of a protocol analyzing Human posture through sagittal intersegmental moments. METHODS: Postural analysis has been recently improved by development of three-dimensional radiographic imaging systems. However, in various situations such as global sagittal anterior malalignment interpretation of radiographs may not represent the real alignment of the subject. The aim of this study was to present initial results of a 3D biomechanical protocol. This protocol isobtained in a free standing position and characterizes postural balance by measurement of sagittal intersegmental net moments. After elaboration of a specific marker-set, 4 successive recordings were done on two volunteers by three different operators during three sessions in order to evaluate the experimental error measurement. A supplementary acquisition in a "radiographic" posture was also obtained. Once the data acquired, joint center, length, anatomical frame and the center of mass of each body segment was calculated and a mass affected. Sagittal net intersegmental moments were computed in an ascending manner from ground reaction forces at the ankles, knees, hips and the lumbosacral and thoraco-lumbar spinal junctions. Cervicothoracic net intersegmental moment was calculated in a descending manner.RESULTS: Based on average recordings, clinical interpretation of net intersegmental moments(in N.m) showed a dorsal flexion on the ankles(8.6 N.m), a flexion on the knees(7.5 N.m) and an extension on the hips(8.5 N.m). On the spinal junctions, it was flexion moments: 0.34 N.m on the cervico-thoracic; 6.7 N.m on the thoraco-lumbar and 0.65 N.m on the lumbo-sacral. Evaluation of experimental error measurement showed a small inter-trial error(intrinsic variability), with higher inter-session and inter-therapist errors but without important variation between them. For one volunteer the "radiographic" posture was associated to significant changes compared to the free standing position. CONCLUSION: Thes 展开更多
关键词 POSTURE SAGITTAL alignement BIOMECHANICAL evaluation Intersegmental NET MOMENTS
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Volume and fat infiltration of spino-pelvic musculature in adults with spinal deformity
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作者 Bertrand Moal Nicolas Bronsard +4 位作者 José G Raya Jean Marc Vital Frank Schwab Wafa Skalli Virginie Lafage 《World Journal of Orthopedics》 2015年第9期727-737,共11页
AIM: To investigate fat infiltration and volume of spino-pelvic muscles in adults spinal deformity(ASD) with magnetic resonance imaging(MRI) and 3D reconstructions.METHODS: Nineteen female ASD patients(mean age 60 ... AIM: To investigate fat infiltration and volume of spino-pelvic muscles in adults spinal deformity(ASD) with magnetic resonance imaging(MRI) and 3D reconstructions.METHODS: Nineteen female ASD patients(mean age 60 ± 13) were included prospectively and consecutively and had T1-weighted Turbo Spin Echo sequence MRIs with Dixon method from the proximal tibia up to T12 vertebra. The Dixon method permitted to evaluate the proportion of fat inside each muscle(fat-water ratio). In order to investigate the accuracy of the Dixon method for estimating fat vs water, the same MRI acquisition was performed on phantoms of four vials composed of different proportion of fat vs water. With Muscl'X software, 3D reconstructions of 17 muscles or group of muscles were obtained identifying the muscle's contour on a limited number of axial images [Deformation of parametric specific objects(DPSO) Method]. Musclar volume(Vmuscle), infiltrated fat volume(Vfat) and percentage of fat infiltration [Pfat, calculated as follow: Pfat = 100 ×(Vfat/Vmuscle)] were characterized by extensor or flexor function respectively for the spine, hip and knee and theirs relationship with demographic data were investigated. RESULTS: Phantom acquisition demonstrated a non linear relation between Dixon fat-water ratio and the real fat-water ratio. In order to correct the Dixon fatwater ratio, the non linear relation was approximated with a polynomial function of degree three using the phantom acquisition. On average, Pfat was 13.3% ± 5.3%. Muscles from the spinal extensor group had a Pfat significantly greater than the other muscles groups, and the largest variability(Pfat = 31.9% ± 13.8%, P < 0.001). Muscles from the hip extensor group ranked 2nd in terms of Pfat(14% ± 8%), and were significantly greater than those of the knee extensor(P = 0.030). Muscles from the knee extensor group demonstrated the least Pfat(12% ± 8%). They were also the only group with a significant correlation between Vmuscle and Pfat(r =-0.741, P < 0.001), however this correlation 展开更多
关键词 Spino-pelvic MUSCULATURE ADULTS with spinal deformity MUSCULAR degeneration MUSCULAR volume FAT INFILTRATION Dixon method
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