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Digital intelligent hepatobiliary surgery has evolved over decades.It has experienced an evolution course from digital virtual human technology to the establishment of a quality-controlled and homogeneous three-dimensional visualization system for precision diagnosis and treatment of diseases, from three-dimensional visualization to the clinical transformation of digital intelligent technology and changes in the diagnosis and treatment model, from empirical diagnosis of diseases to the application of deep learning for the intelligent diagnosis and treatment of diseases, from empirical surgery to real-time multi-modal image guidance during surgery, and from the morphological diagnosis of tumors to accurate diagnosis from molecular imaging.During the whole process, only through continuous innovation in research, theory and technology can the "life" of digital intelligent surgery be endowed with new vitality.In the future, the definition of tumor boundary from the molecular and cellular levels and the early diagnosis and treatment of liver tumor through the functional visualization of key molecules will have significant clinical value for changing the prognosis of liver cancer.In addition, in order to realize intelligent navigation for hepatectomy and break through the technical bottleneck, it is of great clinical significance to develop an intelligent robot real-time navigation hepatectomy system with automatic navigation technology, machine learning intelligent planning technology and multimodal image fusion technology.This provides unprecedented opportunities and challenges for the development of digital intelligent hepatobiliary surgery.
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Digital intelligent diagnostic and treatment technology is a novel technology which is based by combining modern medicine with digitalized and intelligent high-tech to form a multidisciplinary and multi-knowledge domain. This technology plays an important role in areas including precision diagnosis, preoperative planning and surgical navigation. Its core technologies are: (1) quality control research on high-quality CT imaging data acquisition; (2) quality control and homogenization research on three-dimensional (3D) reconstruction; (3) high-quality 3D printed physical models; (4) virtual reality 3D simulation platform; (5) molecular fluorescence imaging to define tumor boundaries; (6) non-rigid registration multi-mode image fusion surgical navigation system; (7) image feature extraction and prediction model establishment. The workflow of this system includes: First, CT data acquisition and 3D visualization of hepatobiliary and pancreatic diseases; followed by individualized vascular assessment, liver volume calculation and surgical planning using the 3D model; then virtual simulation surgery, 3D printing, virtual reality technology and molecular fluorescence imaging accordance to the required specific conditions. Preoperative radiomics are used to predict the risk of complications and long-term follow-up results. Intraoperative multi-modal fusion image navigation and its consistency are evaluated with the findings in actual surgery and preoperative planning. This technology, hopefully, will bring in novel strategies and approaches in the diagnosis and treatment of hepatobiliary and pancreatic diseases.
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Objective Comparison of the levator ani muscles in three-dimensional (3D) MRI-based models in women with and without pelvic organ prolapse at rest to analyze the morphological characteristics of levator ani muscles in women with POP. Methods Twenty-five women with POP and 22 women with normal pelvic support were selected from Nanfang Hospital of Southern Medical University. Axial, sagittal, and coronal T2-weighted pelvic magnetic resonance scans were obtained with the women in the supine position.The 3D models were reconstructed from the source images. Morphological changes was compared within the two groups of levator ani muscles, and the 3D models were measured to determine the levator ani muscle volume (LVOL), levator plate angle (LPA), levator hiatus width (LH-W) and length (LH-L), distance between symphysis and levator sling muscle (LSG). Results There were no puborectalis avulsions in control, in POP, 3 cases of avulsions just in left, 3 cases of avulsions just in right, 7 cases in bilateral. The shape of iliococcygeus were all dome-shaped in control, 11 cases were U-shaped and 14 cases were dome-shaped in POP. The shape of levator hiatus were 7 cases of U-shape, 12 cases of V-shape, 3 cases of irregular in control; 5 cases of U-shape, 4 cases of V-shape, 16 cases of irregular in POP. POP versus control: LH-L: (68.0 ± 8.9) versus (61.6 ± 7.2) mm (P0.05). Conclusions It is possible to assess the morphologic changes of levator ani by using 3D MRI models objectively, our 3D data demonstrate larger in LVOL, LPA, LH-W, LH-L, LSG, and the changes in shape. It is helpful to diagnose and assess the specific situation of patients POP in clinic.
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The development of science and technology not only promotes the development of the society,but also has a great influence on the progress of medicine.The three dimensional (3D) printing technology together with other digital production modes will promote the realization of the third industrial revolution.New 3D equipments and concepts brought a huge leap of surgery,and pancreatic surgery is also benefited from this.The author has committed himself to the scientific research of 3D pancreatic surgery for decades,and applying 3D visualization technology of the diagnosis and treatment of pancreatic cancer,3D visualization of peri-pancreatic vessels,resectability evaluation of the pancreatic cancer and prevention of pancreatic fistula.This article presents a new idea on the development of pancreatic surgery and introduces not only the progress in the diagnosis and treatment of pancreatic diseases in the era of digital medicine,but also the relative advantages brough about by the new equipments (such as da Vinci robotic surgical system,3D laparoscope).
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Objective To explore the correlation between the incidence of abdominal and pelvic artery distortion and age using dig-ital three-dimensional reconstruction,in order to assess risk in uterine artery embolization surgical approach.Methods Collecting the CTA datasets of 475 patients,group A aged 11-27 (n=40),group B aged 28-44(n=218),group C aged 45-61(n=197), group D aged 62-78(n=20).The 3D model of pelvic arteries was reconstructed by mimics software,and the arterial distortion was recorded by rotating and observing the 3D model,which was further classified into three categories.One was the distortion of the aorta only,the second was the distortion of iliac artery,and the third being distortion of both sturctures.the number of cases appeared arterial distortion in every age group was calculated and the ratio of the total cases to each age group was counted.Results There were 128(26.9%)cases appeared arterial distortion,the last 347(73.1%)were not found distortion in any artery.Of the 128 cases,the occurrence rates of arterial distortion in each age group were 2.5%、11.9%、44.7%、65% for group A,B,C and D respec-tively.Pearson linear correlation analysis showed that the incidence of arterial distortion positively correlated with age (r=0.404,help of three-dimensional reconstruction.The occurrence rate of artery distortion is increased with age and the iliac artery distortion occurrence is higher than that of the aorta artery.
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Digital medical technology pioneered the three dimensional (3D) era of the surgery.The 3D reconstruction and visualization technology made a breakthrough of the bottleneck of clinical diagnosis and therapy of the biliary surgery,and are widely used for the treatment of biliary disease such as hepatolithiasis and hilar cholangiocarcinoma,and achieved digital anatomy,procedural diagnosis and visualized surgery,just as provide a 3D Ⅹ-ray vision to surgeons.With the development of the digital medical technology and the wide application of 3D laparoscopy and robotic system,biliary tract surgery access to a 3D era.
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In the cross-cutting areas of information science and life science,a subdiscipline—digital medicine is established.As a new subdiscipline,several problems need to be resolved for the development of digital medicine. Paying attention to actual benefits and fulfilling the need in clinical practice are the demand for digital nedicine,and they are also the spirit of translational medicine. Deeply rooted in clinical practice and oriated by the requirement of clinicians are helpful for a healthier development of digital medicine research.
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<p><b>OBJECTIVE</b>To assess the value of abdominal three-dimensional medical image visualization system (MI-3DVS) in assisting complicated hepatectomy.</p><p><b>METHODS</b>Twenty-four patients undergoing complicated hepatectomy for hepatic carcinoma or hepatic focal nodular hyperplasia were enrolled in this study. Three-dimensional models of the organs, vessels and tumors were reconstructed with MI-3DVS, and virtual operations were carried out to assess the feasibility of hepatectomy. The diameter of the liver tumors, intraoperative blood loss and transfusion, complications, in-hospital mortality rate, and one-year survival rate were analyzed in these cases.</p><p><b>RESULTS</b>The operations were safely completed in all the cases without perioperative deaths. The mean diameter of liver tumor was 9.8∓4.3 cm, and the median volumes of intraoperative blood loss and transfusion were 800 ml and 600 ml, respectively, with a blood transfusion rate of 91.7% (22/24). The incidence of complications was 29.2% (7/24), and the one-year survival rate was 37.5%.</p><p><b>CONCLUSION</b>Three-dimensional techniques such as volumetric analysis and risk evaluation of residual liver blood supply and drainage can increase the accuracy of surgical planning and improve the safety of complicated hepatectomy.</p>
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Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular , General Surgery , Hepatectomy , Methods , Imaging, Three-Dimensional , Liver Neoplasms , General Surgery , Treatment OutcomeABSTRACT
ObjectiveTo observe the shape, size, position and vessels of greater omentum. To explore the design of greater omentum and clarify its clinical significance. MethodsThree fresh and 12 formalin-fixed cadaveres were dissected. All of them had no damage nor injury. 1. Macro-micro-dissection: The shape, size and position of greater omentum were observed. The vessels of the greater omentum were studied.2.Lead oxide-gelatin injection technique and three-dimensional reconstruction.Results The length of greater omentum was(24.7±6.9)cm,the width was(28.3+2.8)cm. It could be divided into 3 types: thin type,middle type and thick type, the occurrence rate was 33.3％, 46.7％ and 20.0％ respectively. The blood supply of greater omentum mainly came from the gastroepiploic arch composed of the left gastroepiploic artery and the right gastroepiploic artery.There were 4 main arteries of the greater omentum: ①The right epiploic artery: The external diameter at origination was (1.0±0.4)mm. ② The middle epiploic artery: The external diameter at origination was(0.7 + 0.3)mm. ③The left epiploic artery:The external diameter at origination was (1.2±0.4)mm.④ The accessary epiploic artery:The external diameter at origination was (0.5 ± 0.1)mm.ConclusionAccording to the characteristic of the anterior arch and posterior arch,the position of the middle epiploic artery divarication and the method of spread,the greater omentum is divided into 5 types.It should be according to the characteristic, when the greater omentum is designed and clipped.
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ObjectiveTo explore clinical application of selecting flap by using of digital technique in treatment of hemifacial atrophy.MethodsSeven patients with hemifacial atrophy were selected,preoperative CT angiography was performed,deformity and flap three-dimensional reconstruction and design bone and soft tissues using Mimics 14.3 software, latissimus muscular flap or femur anterolateral flap were selected,according to tilt donor area and recipient area blood vessel diameter. Defect model were printed using rapid prototyping. ResultsHemifacial atrophy had a good postoperative shape,and the flaps survived in all the 7 cases.Follow-up 3 years,the flaps look well and the patients get expecting results. ConclusionsThe digital technique was a relatively useful tool that can assist surgeons with reconstruction of the flap,and accurate marking of the extent of the flap to be harvested.Therefore avoiding intraoperative injuries to the blood vessels to better survival of the flaps.
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Objective To investigate the guiding significance of medical image three-dimensional visualization system (MI-3DVS) in precise hepatectomy. Methods The clinical data of 45 patients with hepatic neoplasms who were admitted to the Zhujiang Hospital from June 2008 to September 2010 were prospectively analyzed. The preoperative image data of the liver were three-dimensionally reconstructed by MI-3DVS. According to the distribution of the intrahepatic portal veins and hepatic veins, the liver was divided into different sections,and then tumors can be located within these hepatic segments. The volume percentage of residual liver and volume of liver resected were detected. Evaluation of surgical resectability and surgery simulation were done before operation. Results According to the distribution of the intrahepatic portal veins and hepatic veins, all patients were divided into seven types: 21 patients were with normal type which was the same as Couinaud type, six with nondivided type, 11 with non-divided right liver type, four with non-divided left liver type, one with right hepatic vein type, one with double middle hepatic vein type and one with right posterior vein type. Thirty-nine patients received open hepatectomy, and the volume percentage of the residual liver was 74% ± 17%. Postoperative pathological examination confirmed that all the 39 patients were with hepatocellular carcinoma. Six patients received transcatheter arterial chemoembolization. No severe complications such as acute hepatic failure, bleeding, bile leakage were detected. All patients were followed up for six months, and they survived with or without tumor. Conclusion MI-3DVS has guiding significance in preoperative assessment and perioperative guidance for precise hepatectomy.
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Objective To study the medical image three dimensional visualization system(MI-3DVS)in the diagnosis and treatment of hepatolithiasis.Methods The data of 64-slice spiral computed tomography of 54 patients with hepatolithiasis who were admitted to the Zhujiang Hospital of the Southern Medical University from August 2008 to August 2010 were collected.The liver and bile duct were three dimensionally(3D)constructed.Preoperative diagnosis and pathological classification were made according to the results of the 3D model of liver and bile duct.The optimal surgical procedure was determined by simulating operations based on the 3D model.The compliance of simulated operation and actual operation was observed,and residual stones were detected by cholangiography.Results Of the 54 patients,11 were with type Ⅰ,5 with type Ⅱ(including 2 patients with type Ⅱ a and 3 with Ⅱ b),38 with type E.There were 23 patients with intrahepatic bile duct stricture and 27 with atrophy-hypertrophy syndrome complex.The anatomy of intra-and extrahepatic bile duct,dilation and stricture of the bile duct,site,size and number of the bile duct stones were clearly displayed in the MI-3DVS.The compliance rate of simulated surgery and actual surgery was 94%(51/54).There was no residual stones in 51 patients who received elective surgery and the rate of residual stone of the 54 patients was 6%(3/54).Conclusion Acurate preoperative diagnosis and intraoperative precise operation can be achieved and the rate of residual stone can be reduced by using the MI-3DVS.
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BACKGROUND: Our team has built finite element dynamic bone models of different parts, but how to ensure the model’s precision and effectiveness, there still needs further study.OBJECTIVE: To provide accurate biomechanics model of Digital Human. METHODS: The CT data of Virtual Chinese Human --the male No.1 (VCH-M1) were imported into the MIMICS13.1 software authorized by the Materialise Company, and then the outcome document was entered into the ABAQUS6.7 software to perform finite element analysis. The result was observed and then the effectiveness of the models was tested. RESULTS AND CONCLUSION: The “.lis” document was chosen in the finite element analysis software ABAQUS6.7. Three dimension models of cervicalt were acquired. The model has 10 465 panel points and 52 752 units. It is verified that this model is effective. Results confirmed that the biomechanics model of Digital Human can be calculated for meeting the revolutionary requirement of the future digital medical science.
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Objective To observe the resection of the scapholunate interosseous ligament (SLIL)and its subregions on the three-dimensional(3-D)movement of the scaphoid and lunate so as to discuss the role of SLIL in the 3D flexion-extension motion of the scaphoid and lunate.Methods Twelve upper extremities(six left extremities and six right extremities)from adult cadaver were used in this study and divided into five groups:normal group,proximal subregion resection group,proximal subregion plus dorsal subregion resection group,proximal subregion plus palmar subregion resection group and whole SLIL resection group.The 3-D laser scan and reconstruction technique were used for meusure ment of the 3-D flexion-extension motion of the scaphoid and lunate.Results In the normal group,the scaphoid and lunate flexed and the radial deviated at the same direction during wrist flexion-extension motion.At the same time,there was minimal scaphoid and lunate pronation-supination during wrist flexionextension.After resection of the proximal and palmar(or dorsal)subregions of the SLIL,some different movements were found compared with the normal specimen.Whole SLIL resection resulted in increase of the flexion motion of the scaphoid but decrease of the palmar flexion of the lunate.Conclusions 3-D laser scanning and image reconstruction techniques can accurately measure the 3D motion of the scaphoid and lunate.Partial or whole resection of SLIL may exert significant effect on the flexion-extension motion of the scaphoid and lunate.However,the proximal subregion of SLIL has no prominent effect on the motion of the scaphoid and lunate.
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OBJECTIVE@#To evaluate the feasibility of surface tractotomy of trigeminal nerve sensory root (STS) for the treatment of trigeminal neuralgia (TN).@*METHOD@#Seven patients with TN were operated on using the STS. The six patients were followed up for 4.8-9.8 years. The trigeminal nerve root (TNR) obtained from 30 cadavers were performed microanatomical research using paraffin embedding and hematoxylin-eosin staining technique.@*RESULT@#Clinically, the patients' symptoms, such as face ache, disappeared after the surface nerve fiber bundles of trigeminal nerve sensory root (TNSR) were cut off. Only one patient died of brainstem bleeding on postoperative day 18. Histological examination: The common type of sensory root fibers were arranged parallel for 3-6 mm at its exit of brainstem, and then the glial myelin transformed to Schwann cells. The axon bifurcated from outer layer to middle region, and gradually formed the tiny nerve fiber bundles in the surface layer and the giant nerve fiber bundles in the center of the root.@*CONCLUSION@#TN can be radical cured by STS without lesioning of nerve functions. Therefore,this new approach is an effective, advanced surgical technique for TN treatment.
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Aged , Female , Humans , Male , Middle Aged , Denervation , Methods , Trigeminal Nerve , General Surgery , Trigeminal Neuralgia , General SurgeryABSTRACT
@#ObjectiveTo evaluate the relationship between the level of thoracic complete spinal cord injury(SCI) and ambulatory function wearing Reciprocating Gait Orthosis(RGO) through three dimentional gait analysis, and to explore the quantitative indicators of reconstructing walking capacity of thoracic complete SCI patients.Methods10 patients with thoracic complete spinal cord injury of lesion level from T4 to T12 who had experienced RGO gait training for at least 3 months. Three dimentional gait analysis system of Vicon Nexus 1.2 was used to test and examine the gait speed, cadence, stride length, pelvic angle of rotation, hip range of motion(ROM), crutch force, angular velocity of hip flexion and extension phases, etc. Pearson's product moment correlation coefficient and Spearman rank correlation coefficient were used to examine the relationship between the level of spinal cord injury and the kinematic and kinetic values.ResultsThe mean cadence and stride length were (37.4±2.15) steps/min and (91.6±9.09) cm. The mean hip ROM, angular velocity of hip flexion and extension phases were (42.57 °±5.43 °), (20.88 °±2.18 °)/s and (124.75 °±9.31 °)/s respectively. The gait speed, stride length, peak crutch force, hip ROM, mean crutch force and angular velocity of hip extension phase all had significant pertinence with the level of spinal cord injury.ConclusionThe limitation of hip ROM and excessive load of upper limbs mainly result in ambulatory disorder in higher thoracic complete SCI patients who should be undertaken some rehabilitation training to reduce excessive physiological load in order to improve their ambulatory capacity.
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Objective To explore the accuracy and practical significance of the 3-dimensional (3D) reconstruction of the liver and the abdominal blood vessels based on the data of 64-slice spiral computerized tomography (64S-SCT). Methods The 2D images of the liver and the abdominal blood vessels were collected after TLC-scanning with 64S-SCT. The 3D images of the liver, hepatic internal duct system and the abdominal blood vessels were reconstructed by the medical image processing system. The volume of the 3D reconstructed liver was compared with that of the actual liver measured by the 64S-SCT, and the portal vein of the reconstructed liver model was compared with that reconstructed by the Mxview workstation based on the 64S-SCT data. Results The 3D models of the liver, hepatic internal duct system and abdominal blood vessels were vivid, and could be revolved and observed at any direction. The spatial relationship among main intrahepatic ducts was clearly displayed. The actual liver volume and the condition of the intrahepatic ducts were accurately demonstrated. The reconstructed liver, the branches of the hepatic artery and portal vein, and the abdominal blood vessels were simultaneously displayed by adjusting the transparency of the liver model. The portal vein of the reconstructed liver model completely matched that reconstructed by the Mxview workstation based on the 64S-SCT data. Conclusions The 3D models of the liver, hepatic internal duct system and abdominal blood vessels reflect the human anatomy structure, and provide reliable virtual organs and vessel system for virtual liver surgery.
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@#Objective To build a method of mandible 3D model to measure and analysis, then to finish the operation simulation, providing anatomic data to avoiding the complicafious of mandible osteotomy. Methods Using CT data to reconstruct 3D model of mandible with blood vessel and bone, then using Simpleware to measure and analysis, and using Freeform system and an incision method of Boolean to simulation mandible osteotomy safely. Re, tits It was possible to use CT data to rebuild 3D model for 3D measure and analysis for operation simulation. The inferior alveolar artery and never were the main tiasues which went through the madibhilar. The length of mandibular foramen to anterior minus was (19.13±0.66) ram,and the ones to posterior ramus was (18.96± 0.64)mm. The angle of the mandible was (109.70±4.67)°. The rages of the remus for safe operation was (12.62±0.28)mm, and the safe rages about angle of the body and bottom of the mandible was (22.30±4.67)°. There were obvious differences from children to the aged in the mandible physiological and anatomic study. We can use Freeform system to simulate the operation on 3D model. Conclusion It is a new method to build 3D model and use Freefonn system to simulate operation and a new path to communion with patients for a good operation.
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This experiment was designed to observe the morphologic changes of aortic endothelial cells in diabetic rats and to investigate the influence of hyperglycemia. Diabetic rats were used and their aortic endothelial cells were observed under atomic force microscope, then these pictures were 3D reconstructed. The results showed that numerous microvilli and round window-hollow-like structures and insect- bitten-like caveloae were scattered on the surface of the vascular endothelia, and a few ball-like granules were adhering to the endothelial cells. In diabetic rats, microvilli decreased and the cells looked as if they were weather-beaten rocks. The adhering ball-like granules in the diabetic group were significantly more than those in the control group. They were most numerous at 12 weeks. The insect-bitten-like caveloae began deepening at 7 weeks, and their diameters markedly increased at 12 weeks, but they decreased in number. After 3D figures were reconstructed, the surface of cells manifested smoothness. However, in diabetic rats, the morphology of their endothelial cells was characterized by roughness and small surface projections. The quantitative results showed that the average roughness increased gradually as the experiment time prolonged. These indicate that excess sugar in the blood may destroy the endothelial structure, make the cells rougher, and hence cause the protein granules to adhere onto the endothelial cells. At the same time, the deepening and enlargement of the insect-bitten-like caveloae may indicate the increasing endocytosis.
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Animals , Male , Rats , Aorta , Pathology , Diabetes Mellitus, Experimental , Pathology , Endothelial Cells , Pathology , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Microscopy, Atomic Force , Random Allocation , Rats, Sprague-DawleyABSTRACT
BACKGROUND: A lot of important organs are worthless for clinical application because they are hard to store for a long time. In addition, tissues or organs which are dealt with cryopreservation also attack ischemia/reperfusion injury with the recovery of blood flow; especially, skeletal muscle is the most involved tissue.OBJECTIVE: To observe the protective influence of edaravone on cellular membrane and mitochondria of replanted rat extremities following ischemia/reperfusion injury due to cryopreservation and rewarming.DESIGN: Randomized contrast animal study.SETTING: Basic Medical College of Southern Medical University; Department of Hand and Foot Surgery, Shandong Provincial Hospital.MATERIALS: The experiment was carried out in the Cryopreservation Laboratory, Shandong Provincial Hospital from April to November 2006. A total of 36 healthy adult male Wistar rats were provided by Experimental Animal Center of Medical College of Shandong University. All rats were randomly divided into control group, cryopreservation group and edaravone group with 12 in each group.METHODS: Femoral artery and vein of rats in control group were exposured, but extremities were not blocked. Rats in other two groups were used to establish ischemia/reperfusion injury models of replanted extremities. Before cryopreservation, their right hindlimbs were cut off and maintained in liquid nitrogen container for 1 month. After the operation mentioned above, the broken limbs were rewarmed, perfused with routine eluant and replanted. Four hours later, blood supply of extremities was recirculated and the samples were selected. Eluant in edaravone group contained 0.5 mg/kg edaravone. Samples of skeletal muscle were selected at the same time point to establish cellular membrane and extract mitochondria. Furthermore, fluorescence polarization of cellular membrane (reflecting liquidity in cellular membrane lipid area), malondialdehyde (MDA) content of mitochondria, superoxide dismutase (SOD) activity and respiratory controlling rate were measured; meanwhile, mitochondrial ultrastructure of skeletal muscle was observed under transmission electron microscope.MAIN OUTCOME MEASURES:①Fluorescence polarization of cellular membrane, MDA content of mitochondria, SOD activity and respiratory controlling rate of skeletal muscle; ②mitochondrial ultrastructure of skeletal muscle.RESULTS: All 36 rats were involved in the final analysis without any loss. ①SOD activity and respiratory controlling rate of mitochondria in skeletal muscle: The values of these two items were higher in edaravone group that those in cryopreservation group (P＜0.05).②Fluorescence polarization of cellular membrane and MDA content of mitochondria in skeletal muscle: The values of these two items were lower in edaravone group than those in cryopreservation group (P＜0.05). ③Mitochondrial ultrastructure of skeletal muscle: Injured degree of skeletal muscle was milder in edaravone group than that in cryopreservation group.CONCLUSION: Edaravone can relieve ischemia/reperfusion injury of skeletal muscle and protect cellular membrane and mitochondria of skeletal muscle. Its mechanism may be related to directly inhibiting hydroxy free radicals, increasing SOD activity of skeletal muscle, reducing generation of MDA and promoting normal oxidative phosphorylation.