Intervertebral disc degeneration(IVDD),a disease associated with ageing,is characterised by a notable increase in senescent nucleus pulposus cells(NPCs)as IVDD progresses.However,the specific mechanisms that regulate ...Intervertebral disc degeneration(IVDD),a disease associated with ageing,is characterised by a notable increase in senescent nucleus pulposus cells(NPCs)as IVDD progresses.However,the specific mechanisms that regulate the senescence of NPCs remain unknown.In this study,we observed impaired autophagy in IVDD-NPCs,which contributed to the upregulation of NPCs senescence and the senescence-associated secretory phenotype(SASP).The dysregulated SASP disrupted NPCs viability and initiated extracellular matrix degradation.Conversely,the restoration of autophagy reversed the senescence phenotype by inhibiting GATA binding protein 4(GATA4).Moreover,we made the novel observation that a cross-talk between histone H3 lysine 4 trimethylation(H3K4me3)modification and N6-methyladenosine(m6A)-methylated modification regulates autophagy in IVDD-NPCs.Mechanistically,lysine methyltransferase 2A(KMT2A)promoted the expression of methyltransferase-like 3(METTL3)through H3K4me3 modification,whereas METTL3-mediated m6A modification reduced the expression of autophagy-associated 4a(ATG4a)by attenuating its RNA stability,leading to autophagy damage in NPCs.Silencing KMT2A and METTL3 enhanced autophagic flux and suppressed SASP expression in IVDD-NPCs.Therefore,targeting the H3K4me3-regulated METTL3/ATG4a/GATA4 axis may represent a promising new therapeutic strategy for IVDD.展开更多
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
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
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
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: These initial results confirm the technical feasibility of the protocol. The low intrinsic error and the small differences between inter-session and intertherapist errors seem to traduce postural variability over time, more than a failure of the protocol. Characterization of sagittal intersegmental net moments can have clinical applications such as evaluation of an unfused segment after a spinal arthrodesis.展开更多
基金supported by the National Natural Science Foundation of China (82272555,82272522,82422044,82101647)Zhejiang Provincial Natural Science Foundation of China (LGF21H060010,LR22H060001,LY23H060011)+1 种基金Wenzhou Major Scientific and Technological Innovation Project (ZY2022010)Zhejiang Provincial Medical Technology Foundation of China (2022PY071)。
文摘Intervertebral disc degeneration(IVDD),a disease associated with ageing,is characterised by a notable increase in senescent nucleus pulposus cells(NPCs)as IVDD progresses.However,the specific mechanisms that regulate the senescence of NPCs remain unknown.In this study,we observed impaired autophagy in IVDD-NPCs,which contributed to the upregulation of NPCs senescence and the senescence-associated secretory phenotype(SASP).The dysregulated SASP disrupted NPCs viability and initiated extracellular matrix degradation.Conversely,the restoration of autophagy reversed the senescence phenotype by inhibiting GATA binding protein 4(GATA4).Moreover,we made the novel observation that a cross-talk between histone H3 lysine 4 trimethylation(H3K4me3)modification and N6-methyladenosine(m6A)-methylated modification regulates autophagy in IVDD-NPCs.Mechanistically,lysine methyltransferase 2A(KMT2A)promoted the expression of methyltransferase-like 3(METTL3)through H3K4me3 modification,whereas METTL3-mediated m6A modification reduced the expression of autophagy-associated 4a(ATG4a)by attenuating its RNA stability,leading to autophagy damage in NPCs.Silencing KMT2A and METTL3 enhanced autophagic flux and suppressed SASP expression in IVDD-NPCs.Therefore,targeting the H3K4me3-regulated METTL3/ATG4a/GATA4 axis may represent a promising new therapeutic strategy for IVDD.
文摘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.
文摘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.
文摘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.
基金Supported by The Association pour le Développement des Recherches biologiques et Médicales and the French Society of Orthopaedics and trauma surgery(Blondel B)
文摘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: These initial results confirm the technical feasibility of the protocol. The low intrinsic error and the small differences between inter-session and intertherapist errors seem to traduce postural variability over time, more than a failure of the protocol. Characterization of sagittal intersegmental net moments can have clinical applications such as evaluation of an unfused segment after a spinal arthrodesis.
