Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mec...Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury. This process may be associated with the Wnt/β-catenin signaling pathway. Our study designed in vitro cell models to simulate myelin regeneration and muscle atrophy. We investigated the effects of SB216763, a glycogen synthase kinase 3 beta inhibitor, on the two major murine cell lines RSC96 and C2C12 derived from Schwann cells and muscle satellite cells. The results showed that SB216763 stimulated the Schwann cell migra- tion and myotube contraction. Quantitative polymerase chain reaction results demonstrated that myelin related genes, myelin associated glycoprotein and cyclin-D1, muscle related gene myogenin and endplate-associated gene nicotinic acetylcholine receptors levels were stimulated by SB216763. Immunocytochemical staining revealed that the expressions of ^-catenin in the RSC96 and C2C12 cytosolic and nuclear compartments were increased in the SB216763-treated cells. These findings confirm that the glycogen synthase kinase 3 beta in- hibitor, SB216763, promoted the myelination and myotube differentiation through the Wnt/β-catenin signaling pathway and contributed to nerve remyelination and reduced denervated muscle atrophy after peripheral nerve injury.展开更多
Repair techniques for short-distance peripheral nerve defects, including adjacent joint flexion to reduce the distance between the nerve stump defects, ＂nerve splint＂ suturing, and nerve sle eve connection, have som...Repair techniques for short-distance peripheral nerve defects, including adjacent joint flexion to reduce the distance between the nerve stump defects, ＂nerve splint＂ suturing, and nerve sle eve connection, have some disadvantages. Therefore, we designed a repair technique involving intraoperative tension-free application of a nerve elongator and obtained good outcomes in the repair of short-distance peripheral nerve defects in a previous animal study. The present study compared the clinical outcomes between the use of this nerve elongator and performance of the conventional method in the repair of short-distance transection injuries in human elbows. The 3-, 6-, and 12-month postoperative follow-up results demonstrated that early neurological function recovery was better in the nerve elongation group than in the conventional group, but no signif- icant difference in long-term neurological function recovery was detected between the two gro ups. In the nerve elongation group, the nerves were sutured without tension, and the duration of postoperative immobilization of the elbow was decreased. Elbow function rehabilitation was significantly better in the nerve elongation group than in the control group. Moreover, there were no security risks. The results of this study confirm that the use of this nerve elongator for repair of short-distance peripheral nerve defects is safe and effective.展开更多
We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role...We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.展开更多
Although autologous nerve transplantation is the gold standard for treating peripheral nerve defects,it has many clinical limitations.As an alternative,various tissue-engineered nerve grafts have been developed to sub...Although autologous nerve transplantation is the gold standard for treating peripheral nerve defects,it has many clinical limitations.As an alternative,various tissue-engineered nerve grafts have been developed to substitute for autologous nerves.In this study,a novel nerve graft composed of chitin scaffolds and a small autologous nerve was used to repair sciatic nerve defects in rats.The novel nerve graft greatly facilitated regeneration of the sciatic nerve and myelin sheath,reduced atrophy of the target muscle,and effectively restored neurological function.When the epineurium of the small autogenous nerve was removed,the degree of nerve regeneration was similar to that which occurs after autogenous nerve transplantation.These findings suggest that our novel nerve graft might eventually be a new option for the construction of tissue-engineered nerve scaffolds.The study was approved by the Research Ethics Committee of Peking University People's Hospital(approval No.2019 PHE27)on October 18,2019.展开更多
Our previous studies have confirmed that during nerve transposition repair to injured peripheral nerves, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively repair dis...Our previous studies have confirmed that during nerve transposition repair to injured peripheral nerves, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively repair distal nerve and target muscle tissue and restore muscle motor function. To observe the effect of nerve regeneration and motor function recovery after several types of nerve transposition for median nerve defect(2 mm), 30 Sprague-Dawley rats were randomly divided into sham operation group, epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group. Three months after nerve repair, the wrist flexion test was used to evaluate the recovery of wrist flexion after regeneration of median nerve in the affected limbs of rats. The number of myelinated nerve fibers, the thickness of myelin sheath, the diameter of axons and the cross-sectional area of axons in the proximal and distal segments of the repaired nerves were measured by osmic acid staining. The ratio of newly produced distal myelinated nerve fibers to the number of proximal myelinated nerve fibers was calculated. Wet weights of the flexor digitorum superficialis muscles were measured. Muscle fiber morphology was detected using hematoxylin-eosin staining. The cross-sectional area of muscle fibers was calculated to assess the recovery of muscles. Results showed that wrist flexion function was restored, and the nerve grew into the distal effector in all three nerve transposition groups and the epineurial neurorrhaphy group. There were differences in the number of myelinated nerve fibers in each group. The magnification of proximal to distal nerves was 1.80, 3.00, 2.50, and 3.12 in epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group, respectively. Nevertheless, axon diameters of new nerve fibers, cross-sectional areas of axons, thicknesses of myelin sheath, wet weights of flexor digitorum superficialis muscle and cross-sectional areas of muscle fibers of all three groups of donor nerves from different anterior horn motor neurons after nerve transposition were similar to those in the epineurial neurorrhaphy group. Our findings indicate that donor nerve translocation from different anterior horn motor neurons can effectively repair the target organs innervated by the median nerve. The corresponding spinal anterior horn motor neurons obtain functional reinnervation and achieve some degree of motor function in the affected limbs.展开更多
During peripheral nerve transposition repair, if the diameter difference between transposed nerves is large or multiple distal nerves must be repaired at the same time, traditional epineurial neurorrhaphy has the prob...During peripheral nerve transposition repair, if the diameter difference between transposed nerves is large or multiple distal nerves must be repaired at the same time, traditional epineurial neurorrhaphy has the problem of high tension at the suture site, which may even lead to the failure of nerve suture. We investigated whether a small gap bio-sleeve suture with different inner diameters at both ends can be used to repair a 2-mm tibial nerve defect by proximal transposition of the common peroneal nerve in rats and compared the results with the repair seen after epineurial neurorrhaphy. Three months after surgery, neurological function, nerve regeneration, and recovery of nerve innervation muscle were assessed using the tibial nerve function index, neuroelectrophysiological testing, muscle biomechanics and wet weight measurement, osmic acid staining, and hematoxylin-eosin staining. There was no obvious inflammatory reaction and neuroma formation in the tibial nerve after repair by the small gap bio-sleeve suture with different inner diameters at both ends. The conduction velocity, muscle strength, wet muscle weight, cross-sectional area of muscle fibers, and the number of new myelinated nerve fibers in the biosleeve suture group were similar to those in the epineurial neurorrhaphy group. Our findings indicate that small gap bio-sleeve suture with different inner diameters at both ends can achieve surgical suture between nerves of different diameters and promote regeneration and functional recovery of injured peripheral nerves.展开更多
Small ubiquitin-like modifiers (SUMOs) have been shown to regulate axonal regeneration, signal transduction, neuronal migration, and myelination, by covalently and reversibly attaching to the protein substrates during...Small ubiquitin-like modifiers (SUMOs) have been shown to regulate axonal regeneration, signal transduction, neuronal migration, and myelination, by covalently and reversibly attaching to the protein substrates during neuronal cell growth, development, and differentiation. It has not been reported whether SUMOs play a role in peripheral nerve injury and regeneration. To investigate any association between SUMOylation and potential neuroprotective effects during peripheral nerve injury and regeneration, C57/BL mice were randomly divided into sham and experimental groups. The sciatic nerve was exposed only in the sham group. The experimental group underwent neurotomy and epineurial neurorrhaphy. Real-time quantitative polymerase chain reaction and western blot assay results revealed different mRNA and protein expression levels of SUMO1, SUMO2, SUM03 and UBC9 in sciatic nerve tissue (containing both 5 mm of proximal and distal stumps at the injury site) at various time points after injury. Compared with the sham group, protein levels of SUM01 and SUMO2/3 increased in both their covalent and free states after sciatic nerve injury in the experimental group, especially in the covalent state. UBC9 protein levels showed similar changes to those of SUMO1 and SUMO2/3 in the covalent states. Immunohistochemical staining demonstrated that SUMO1 and SUMO2/3 immunopositivities were higher in the experimental group than in the sham group. Our results verified that during the repair of sciatic nerve injury, the mRNA and protein expression of SUMO1, SUMO2, SUMO3 and UBC9 in injured nerve tissues changed in varying patterns and there were clear changes in the expression of SUMO-related proteins. These findings reveal that SUMOs possibly play an important role in the repair of peripheral nerve injury. All animal protocols were approved by the Institutional Animal Care and Use Committee of Tianjin Fifth Central Hospital, China (approval No. TJWZXLL2018041) on November & 2018.展开更多
Complex pathological changes occur during the development of spinal cord injury(SCI),and determining the underlying molecular events that occur during SCI is necessary for the development of promising molecular target...Complex pathological changes occur during the development of spinal cord injury(SCI),and determining the underlying molecular events that occur during SCI is necessary for the development of promising molecular targets and therapeutic strategies.This study was designed to explore differentially expressed genes(DEGs)associated with the acute and chronic stages of SCI using bioinformatics analysis.Gene expression profiles(GSE45006,GSE93249,and GSE45550)were downloaded from the Gene Expression Omnibus database.SCI-associated DEGs from rat samples were identified,and Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.In addition,a protein-protein interaction network was constructed.Approximately 66 DEGs were identified in GSE45550 between 3–14 days after SCI,whereas 2418 DEGs were identified in GSE450061–56 days after SCI.Moreover,1263,195,and 75 overlapping DEGs were identified between these two expression profiles,3,7/8,and 14 days after SCI,respectively.Additionally,16 overlapping DEGs were obtained in GSE450061–14 days after SCI,including Pank1,Hn1,Tmem150c,Rgd1309676,Lpl,Mdh1,Nnt,Loc100912219,Large1,Baiap2,Slc24a2,Fundc2,Mrps14,Slc16a7,Obfc1,and Alpk3.Importantly,3882 overlapping DEGs were identified in GSE932491–6 months after SCI,including 3316 protein-coding genes and 567 long non-coding RNA genes.A comparative analysis between GSE93249 and GSE45006 resulted in the enrichment of 1135 overlapping DEGs.The significant functions of these 1135 genes were correlated with the response to the immune effector process,the innate immune response,and cytokine production.Moreover,the biological processes and KEGG pathways of the overlapping DEGs were significantly enriched in immune system-related pathways,osteoclast differentiation,the nuclear factor-κB signaling pathway,and the chemokine signaling pathway.Finally,an analysis of the overlapping DEGs associated with both acute and chronic SCI,assessed using the expression profiles GSE93249 and GSE45006,identified four overlapping DEGs:Slc16a7,Alpk3,Lpl and Nnt.These findings may be useful for revealing the biological processes associated with SCI and the development of targeted intervention strategies.展开更多
Multiple regeneration of axonal buds has been shown to exist during the repair of peripheral nerve injury, which confirms a certain repair potential of the injured peripheral nerve. Therefore, a systematic nerve trans...Multiple regeneration of axonal buds has been shown to exist during the repair of peripheral nerve injury, which confirms a certain repair potential of the injured peripheral nerve. Therefore, a systematic nerve transposition repair technique has been proposed to treat severe peripheral nerve injury. During nerve transposition repair, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively grow into the repaired distal nerve and target muscle tissues, which is conducive to the recovery of motor function. The aim of this study was to explore regeneration and nerve functional recovery after repairing a long-segment peripheral nerve defect by transposition of different donor nerves. A long-segment(2 mm) ulnar nerve defect in Sprague-Dawley rats was repaired by transposition of the musculocutaneous nerve, medial pectoral nerve, muscular branches of the radial nerve and anterior interosseous nerve(pronator quadratus muscle branch). In situ repair of the ulnar nerve was considered as a control. Three months later, wrist flexion function, nerve regeneration and innervation muscle recovery in rats were assessed using neuroelectrophysiological testing, osmic acid staining and hematoxylin-eosin staining, respectively. Our findings indicate that repair of a long-segment ulnar nerve defect with different donor nerve transpositions can reinnervate axonal function of motor neurons in the anterior horn of spinal cord and restore the function of affected limbs to a certain extent.展开更多
Background：This study aimed to evaluate the effects of standard rescue procedure （SRP） in improving severe trauma treatments in China.Methods：This study was conducted in 12 hospitals located in geographically and ...Background：This study aimed to evaluate the effects of standard rescue procedure （SRP） in improving severe trauma treatments in China.Methods：This study was conducted in 12 hospitals located in geographically and industrially different cities in China.A standard procedure on severe trauma rescue was established as a general rule for staff training and patient treatment.A regional network （system） efficiently integrating prehospital rescue,emergency room treatments,and hospital specialist treatments was built under the rule for information sharing and improving severe trauma treatments.Treatment outcomes were compared between before and I year after the implementation of the SRP.Results：The outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12 hospitals before and after the implementation of the SRP.Implementation of the SRP led to efficient cooperation and information sharing of different treatment services.The emergency response time,prehospital transit time,emergency rescue time,consultation call time,and mortality rate of patients were 24.24 ± 4.32 min,45.69 ± 3.89 min,6.38 ± 1.05 min,17.53 ± 0.72 min,and 33.82% ± 3.87% （n =441）,respectively,before the implementation of the standardization and significantly reduced to 10.11 ± 3.21 min,22.39 ± 4.32 min,3.26 ± 0.89 min,3.45 ± 0.45 min,and 20.49% ± 3.11%,separately （n =495,P 〈 0.05） after that.Conclusions：Staff training and SRP can significantly improve the efficiency of severe trauma treatments in China.展开更多
Intertrochanteric fractures have become a severe public health problem in elderly patients.Proximal femoral nail anti-rotation(PFNA)is a commonly used intramedullary fixation device for unstable intertrochanteric frac...Intertrochanteric fractures have become a severe public health problem in elderly patients.Proximal femoral nail anti-rotation(PFNA)is a commonly used intramedullary fixation device for unstable intertrochanteric fractures.Pelvic perforation by cephalic screw is a rare complication.We reported an 84-year-old female who fell at home and sustained an intertrochanteric fracture.The patient underwent surgery with PFNA as the intramedullary fixation device.Routine postoperative examination revealed medial migration of the helical blade that eventually caused pelvic perforation.We performed a cemented total hip arthroplasty as the savage procedure.At the latest follow-up of 12 months after total hip arthroplasty,the patient had no pain or loosening of the prosthesis in the left hip.Pelvic perforation should be considered when choosing PFNA as the intramedullary fixation device,especially in patients with severe osteoporosis wherein the helical blade can be easily inserted during the operation.The lack of devices to avoid oversliding of the helical blade in PFNA is an unreported cause of this complication and should be considered in such cases.展开更多
基金funded by the National Basic Research Program of China(973 Program),No.2014CB542201the National High Technology Research and Development Program of China(863 Program),No.SS2015AA020501the National Natural Science Foundation of China(General Program),No.31571235,31771322,31671248,31571236,31271284,31171150,81171146,31471144,30971526,31100860,31040043,31371210,and 81372044
文摘Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury. This process may be associated with the Wnt/β-catenin signaling pathway. Our study designed in vitro cell models to simulate myelin regeneration and muscle atrophy. We investigated the effects of SB216763, a glycogen synthase kinase 3 beta inhibitor, on the two major murine cell lines RSC96 and C2C12 derived from Schwann cells and muscle satellite cells. The results showed that SB216763 stimulated the Schwann cell migra- tion and myotube contraction. Quantitative polymerase chain reaction results demonstrated that myelin related genes, myelin associated glycoprotein and cyclin-D1, muscle related gene myogenin and endplate-associated gene nicotinic acetylcholine receptors levels were stimulated by SB216763. Immunocytochemical staining revealed that the expressions of ^-catenin in the RSC96 and C2C12 cytosolic and nuclear compartments were increased in the SB216763-treated cells. These findings confirm that the glycogen synthase kinase 3 beta in- hibitor, SB216763, promoted the myelination and myotube differentiation through the Wnt/β-catenin signaling pathway and contributed to nerve remyelination and reduced denervated muscle atrophy after peripheral nerve injury.
基金supported by grants from the National Natural Science Foundation of China,No.31171150,31271284,81171146,30971526,30801169the National Program on Key Basic Research Project of China(973 Program),No.2014CB542206+2 种基金Program for New Star in Science and Technology of Beijing of China,No.A-2008-10Program for New Century Excellent Talents in University of Ministry of Education of China,No.BMU20110270the National Natural Science Foundation of China for Distinguished Youth,No.31100860
文摘Repair techniques for short-distance peripheral nerve defects, including adjacent joint flexion to reduce the distance between the nerve stump defects, ＂nerve splint＂ suturing, and nerve sle eve connection, have some disadvantages. Therefore, we designed a repair technique involving intraoperative tension-free application of a nerve elongator and obtained good outcomes in the repair of short-distance peripheral nerve defects in a previous animal study. The present study compared the clinical outcomes between the use of this nerve elongator and performance of the conventional method in the repair of short-distance transection injuries in human elbows. The 3-, 6-, and 12-month postoperative follow-up results demonstrated that early neurological function recovery was better in the nerve elongation group than in the conventional group, but no signif- icant difference in long-term neurological function recovery was detected between the two gro ups. In the nerve elongation group, the nerves were sutured without tension, and the duration of postoperative immobilization of the elbow was decreased. Elbow function rehabilitation was significantly better in the nerve elongation group than in the control group. Moreover, there were no security risks. The results of this study confirm that the use of this nerve elongator for repair of short-distance peripheral nerve defects is safe and effective.
基金supported by the National Key Research and Development Program of China, No. 2016YFC1101603 (to DYZ)the National Natural Science Foundation of China, Nos. 31640045 (to YHW), 81901251 (to ML)the Natural Science Foundation of Beijing of China, No. 7204323 (to ML)
文摘We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.
基金supported by the National Natural Science Foundation of China,Nos.31571236(to YHK),81971177(to BGJ)Key Laboratory of Trauma and Neural Regeneration(Peking University)of the Ministry of Education of China,No.BMU2020XY005-03(to BGJ)+2 种基金the National Key Research and Development Program of China,No.2016YFC1101604(to DYZ)the Ministry of Education Innovation Program of China,No.IRT_16R01(to BGJ)China Postdoctoral Science Foundation-Funded Project,No.2019M664007(to ZYL)。
文摘Although autologous nerve transplantation is the gold standard for treating peripheral nerve defects,it has many clinical limitations.As an alternative,various tissue-engineered nerve grafts have been developed to substitute for autologous nerves.In this study,a novel nerve graft composed of chitin scaffolds and a small autologous nerve was used to repair sciatic nerve defects in rats.The novel nerve graft greatly facilitated regeneration of the sciatic nerve and myelin sheath,reduced atrophy of the target muscle,and effectively restored neurological function.When the epineurium of the small autogenous nerve was removed,the degree of nerve regeneration was similar to that which occurs after autogenous nerve transplantation.These findings suggest that our novel nerve graft might eventually be a new option for the construction of tissue-engineered nerve scaffolds.The study was approved by the Research Ethics Committee of Peking University People's Hospital(approval No.2019 PHE27)on October 18,2019.
基金funded by the National Natural Science Foundation of China,No.31571236,31571235(to YHK,PXZ)National Key Research and Development Program of China,No.2016YFC1101604(to DYZ)+3 种基金National Key Basic Research Program of China(973 Program),No.2014CB542200(to BGJ)Ministry of Education Innovation Program of China,No.IRT_16R01(to BGJ)Beijing Science and Technology New Star Cross Program of China,No.2018019(to PXZ)Peking University People’s Hospital Research and Development Funds,No.RDH2017-01(to HLX)
文摘Our previous studies have confirmed that during nerve transposition repair to injured peripheral nerves, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively repair distal nerve and target muscle tissue and restore muscle motor function. To observe the effect of nerve regeneration and motor function recovery after several types of nerve transposition for median nerve defect(2 mm), 30 Sprague-Dawley rats were randomly divided into sham operation group, epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group. Three months after nerve repair, the wrist flexion test was used to evaluate the recovery of wrist flexion after regeneration of median nerve in the affected limbs of rats. The number of myelinated nerve fibers, the thickness of myelin sheath, the diameter of axons and the cross-sectional area of axons in the proximal and distal segments of the repaired nerves were measured by osmic acid staining. The ratio of newly produced distal myelinated nerve fibers to the number of proximal myelinated nerve fibers was calculated. Wet weights of the flexor digitorum superficialis muscles were measured. Muscle fiber morphology was detected using hematoxylin-eosin staining. The cross-sectional area of muscle fibers was calculated to assess the recovery of muscles. Results showed that wrist flexion function was restored, and the nerve grew into the distal effector in all three nerve transposition groups and the epineurial neurorrhaphy group. There were differences in the number of myelinated nerve fibers in each group. The magnification of proximal to distal nerves was 1.80, 3.00, 2.50, and 3.12 in epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group, respectively. Nevertheless, axon diameters of new nerve fibers, cross-sectional areas of axons, thicknesses of myelin sheath, wet weights of flexor digitorum superficialis muscle and cross-sectional areas of muscle fibers of all three groups of donor nerves from different anterior horn motor neurons after nerve transposition were similar to those in the epineurial neurorrhaphy group. Our findings indicate that donor nerve translocation from different anterior horn motor neurons can effectively repair the target organs innervated by the median nerve. The corresponding spinal anterior horn motor neurons obtain functional reinnervation and achieve some degree of motor function in the affected limbs.
基金funded by the National Natural Science Foundation of China,No.31571236,31571235(to YHK and PXZ)National Key Research and Development Program of China,No.2016YFC1101604(to DYZ)+2 种基金National Key Basic Research Program of China(973 Program),No.2014CB542200(to BGJ)Ministry of Education Innovation Program of China,No.IRT_16R01(to BGJ)Beijing Science and Technology New Star Cross Program of China,No.2018019(to PXZ)
文摘During peripheral nerve transposition repair, if the diameter difference between transposed nerves is large or multiple distal nerves must be repaired at the same time, traditional epineurial neurorrhaphy has the problem of high tension at the suture site, which may even lead to the failure of nerve suture. We investigated whether a small gap bio-sleeve suture with different inner diameters at both ends can be used to repair a 2-mm tibial nerve defect by proximal transposition of the common peroneal nerve in rats and compared the results with the repair seen after epineurial neurorrhaphy. Three months after surgery, neurological function, nerve regeneration, and recovery of nerve innervation muscle were assessed using the tibial nerve function index, neuroelectrophysiological testing, muscle biomechanics and wet weight measurement, osmic acid staining, and hematoxylin-eosin staining. There was no obvious inflammatory reaction and neuroma formation in the tibial nerve after repair by the small gap bio-sleeve suture with different inner diameters at both ends. The conduction velocity, muscle strength, wet muscle weight, cross-sectional area of muscle fibers, and the number of new myelinated nerve fibers in the biosleeve suture group were similar to those in the epineurial neurorrhaphy group. Our findings indicate that small gap bio-sleeve suture with different inner diameters at both ends can achieve surgical suture between nerves of different diameters and promote regeneration and functional recovery of injured peripheral nerves.
基金supported by the National Natural Science Foundation of China(General Program),No.316781246(to DYZ)the Science and Technology Fund of Health Planning Commission of Binhai New Area of Tianjin of China,No.2011BHKY008,2012BWKZ002(to KY)the National Key Research and Development Program of China,No.2016YFC1101600(to DYZ)
文摘Small ubiquitin-like modifiers (SUMOs) have been shown to regulate axonal regeneration, signal transduction, neuronal migration, and myelination, by covalently and reversibly attaching to the protein substrates during neuronal cell growth, development, and differentiation. It has not been reported whether SUMOs play a role in peripheral nerve injury and regeneration. To investigate any association between SUMOylation and potential neuroprotective effects during peripheral nerve injury and regeneration, C57/BL mice were randomly divided into sham and experimental groups. The sciatic nerve was exposed only in the sham group. The experimental group underwent neurotomy and epineurial neurorrhaphy. Real-time quantitative polymerase chain reaction and western blot assay results revealed different mRNA and protein expression levels of SUMO1, SUMO2, SUM03 and UBC9 in sciatic nerve tissue (containing both 5 mm of proximal and distal stumps at the injury site) at various time points after injury. Compared with the sham group, protein levels of SUM01 and SUMO2/3 increased in both their covalent and free states after sciatic nerve injury in the experimental group, especially in the covalent state. UBC9 protein levels showed similar changes to those of SUMO1 and SUMO2/3 in the covalent states. Immunohistochemical staining demonstrated that SUMO1 and SUMO2/3 immunopositivities were higher in the experimental group than in the sham group. Our results verified that during the repair of sciatic nerve injury, the mRNA and protein expression of SUMO1, SUMO2, SUMO3 and UBC9 in injured nerve tissues changed in varying patterns and there were clear changes in the expression of SUMO-related proteins. These findings reveal that SUMOs possibly play an important role in the repair of peripheral nerve injury. All animal protocols were approved by the Institutional Animal Care and Use Committee of Tianjin Fifth Central Hospital, China (approval No. TJWZXLL2018041) on November & 2018.
基金This study was supported by the National Natural Science Foundation of China,No.31571236(to YHK)Science and Technology Planning Project of Beijing of China,No D161100002816001+1 种基金the National Key Research and Development Program of China,No.2016YFC1101604(to DYZ)the Ministry of Education Innovation Program of China,No.IRT_16R01.
文摘Complex pathological changes occur during the development of spinal cord injury(SCI),and determining the underlying molecular events that occur during SCI is necessary for the development of promising molecular targets and therapeutic strategies.This study was designed to explore differentially expressed genes(DEGs)associated with the acute and chronic stages of SCI using bioinformatics analysis.Gene expression profiles(GSE45006,GSE93249,and GSE45550)were downloaded from the Gene Expression Omnibus database.SCI-associated DEGs from rat samples were identified,and Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.In addition,a protein-protein interaction network was constructed.Approximately 66 DEGs were identified in GSE45550 between 3–14 days after SCI,whereas 2418 DEGs were identified in GSE450061–56 days after SCI.Moreover,1263,195,and 75 overlapping DEGs were identified between these two expression profiles,3,7/8,and 14 days after SCI,respectively.Additionally,16 overlapping DEGs were obtained in GSE450061–14 days after SCI,including Pank1,Hn1,Tmem150c,Rgd1309676,Lpl,Mdh1,Nnt,Loc100912219,Large1,Baiap2,Slc24a2,Fundc2,Mrps14,Slc16a7,Obfc1,and Alpk3.Importantly,3882 overlapping DEGs were identified in GSE932491–6 months after SCI,including 3316 protein-coding genes and 567 long non-coding RNA genes.A comparative analysis between GSE93249 and GSE45006 resulted in the enrichment of 1135 overlapping DEGs.The significant functions of these 1135 genes were correlated with the response to the immune effector process,the innate immune response,and cytokine production.Moreover,the biological processes and KEGG pathways of the overlapping DEGs were significantly enriched in immune system-related pathways,osteoclast differentiation,the nuclear factor-κB signaling pathway,and the chemokine signaling pathway.Finally,an analysis of the overlapping DEGs associated with both acute and chronic SCI,assessed using the expression profiles GSE93249 and GSE45006,identified four overlapping DEGs:Slc16a7,Alpk3,Lpl and Nnt.These findings may be useful for revealing the biological processes associated with SCI and the development of targeted intervention strategies.
基金funded by the National Natural Science Foundation of China,No.31571236,31571235(to YHK,PXZ)National Key Research and Development Program of China,No.2016YFC1101604(to DYZ)+2 种基金National Key Basic Research Program of China(973 Program),No.2014CB542200(to BGJ)Ministry of Education Innovation Program of China,No.IRT_16R01(to BGJ)Beijing Science and Technology New Star Cross Program of China,No.2018019(to PXZ)
文摘Multiple regeneration of axonal buds has been shown to exist during the repair of peripheral nerve injury, which confirms a certain repair potential of the injured peripheral nerve. Therefore, a systematic nerve transposition repair technique has been proposed to treat severe peripheral nerve injury. During nerve transposition repair, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively grow into the repaired distal nerve and target muscle tissues, which is conducive to the recovery of motor function. The aim of this study was to explore regeneration and nerve functional recovery after repairing a long-segment peripheral nerve defect by transposition of different donor nerves. A long-segment(2 mm) ulnar nerve defect in Sprague-Dawley rats was repaired by transposition of the musculocutaneous nerve, medial pectoral nerve, muscular branches of the radial nerve and anterior interosseous nerve(pronator quadratus muscle branch). In situ repair of the ulnar nerve was considered as a control. Three months later, wrist flexion function, nerve regeneration and innervation muscle recovery in rats were assessed using neuroelectrophysiological testing, osmic acid staining and hematoxylin-eosin staining, respectively. Our findings indicate that repair of a long-segment ulnar nerve defect with different donor nerve transpositions can reinnervate axonal function of motor neurons in the anterior horn of spinal cord and restore the function of affected limbs to a certain extent.
文摘Background：This study aimed to evaluate the effects of standard rescue procedure （SRP） in improving severe trauma treatments in China.Methods：This study was conducted in 12 hospitals located in geographically and industrially different cities in China.A standard procedure on severe trauma rescue was established as a general rule for staff training and patient treatment.A regional network （system） efficiently integrating prehospital rescue,emergency room treatments,and hospital specialist treatments was built under the rule for information sharing and improving severe trauma treatments.Treatment outcomes were compared between before and I year after the implementation of the SRP.Results：The outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12 hospitals before and after the implementation of the SRP.Implementation of the SRP led to efficient cooperation and information sharing of different treatment services.The emergency response time,prehospital transit time,emergency rescue time,consultation call time,and mortality rate of patients were 24.24 ± 4.32 min,45.69 ± 3.89 min,6.38 ± 1.05 min,17.53 ± 0.72 min,and 33.82% ± 3.87% （n =441）,respectively,before the implementation of the standardization and significantly reduced to 10.11 ± 3.21 min,22.39 ± 4.32 min,3.26 ± 0.89 min,3.45 ± 0.45 min,and 20.49% ± 3.11%,separately （n =495,P 〈 0.05） after that.Conclusions：Staff training and SRP can significantly improve the efficiency of severe trauma treatments in China.
基金National Key R&D Program of China,2018YFF0301103,The funding body will support the publication fees without affecting the diagnosis and treatment of the patient and the writing of the manuscript.
文摘Intertrochanteric fractures have become a severe public health problem in elderly patients.Proximal femoral nail anti-rotation(PFNA)is a commonly used intramedullary fixation device for unstable intertrochanteric fractures.Pelvic perforation by cephalic screw is a rare complication.We reported an 84-year-old female who fell at home and sustained an intertrochanteric fracture.The patient underwent surgery with PFNA as the intramedullary fixation device.Routine postoperative examination revealed medial migration of the helical blade that eventually caused pelvic perforation.We performed a cemented total hip arthroplasty as the savage procedure.At the latest follow-up of 12 months after total hip arthroplasty,the patient had no pain or loosening of the prosthesis in the left hip.Pelvic perforation should be considered when choosing PFNA as the intramedullary fixation device,especially in patients with severe osteoporosis wherein the helical blade can be easily inserted during the operation.The lack of devices to avoid oversliding of the helical blade in PFNA is an unreported cause of this complication and should be considered in such cases.
