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Inhibiting endogenous tissue plasminogen activator enhanced neuronal apoptosis and axonal injury after traumatic brain injury 预览
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作者 Jun-Jie Zhao Zun-Wei Liu +4 位作者 Bo Wang Ting-Qin Huang Dan Guo Yong-Lin Zhao Jin-Ning Song 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期667-675,共9页
Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumat... Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumatic brain injury was established by weight-drop method.The tissue plasminogen activator inhibitor neuroserpin(5μL,0.25 mg/mL)was injected into the lateral ventricle.Neurological function was assessed by neurological severity score.Neuronal and axonal injuries were assessed by hematoxylin-eosin staining and Bielschowsky silver staining.Protein level of endogenous tissue plasminogen activator was analyzed by western blot assay.Apoptotic marker cleaved caspase-3,neuronal marker neurofilament light chain,astrocyte marker glial fibrillary acidic protein and microglial marker Iba-1 were analyzed by immunohistochemical staining.Apoptotic cell types were detected by immunofluorescence double labeling.Apoptotic cells in the damaged cortex were detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling staining.Degenerating neurons in the damaged cortex were detected by Fluoro-Jade B staining.Expression of tissue plasminogen activator was increased at 6 hours,and peaked at 3 days after traumatic brain injury.Neuronal apoptosis and axonal injury were detected after traumatic brain injury.Moreover,neuroserpin enhanced neuronal apoptosis,neuronal injury and axonal injury,and activated microglia and astrocytes.Neuroserpin further deteriorated neurobehavioral function in rats with traumatic brain injury.Our findings confirm that inhibition of endogenous tissue plasminogen activator aggravates neuronal apoptosis and axonal injury after traumatic brain injury,and activates microglia and astrocytes.This study was approved by the Biomedical Ethics Committee of Animal Experiments of Shaanxi Province of China in June 2015. 展开更多
关键词 apoptosis ASTROCYTES AXONAL INJURY inflammation microglia nerve REGENERATION neural REGENERATION neuronal INJURY neurons NEUROSERPIN tissue PLASMINOGEN activator traumatic brain INJURY
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Changes in neurological and pathological outcomes in a modified rat spinal cord injury model with closed canal 预览
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作者 Xin Sun Xing-Zhen Liu +4 位作者 Jia Wang Hai-Rong Tao Tong Zhu Wen-Jie Jin Kang-Ping Shen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期697-704,共8页
Most animal spinal cord injury models involve a laminectomy,such as the weight drop model or the transection model.However,in clinical practice,many patients undergo spinal cord injury while maintaining a relatively c... Most animal spinal cord injury models involve a laminectomy,such as the weight drop model or the transection model.However,in clinical practice,many patients undergo spinal cord injury while maintaining a relatively complete spinal canal.Thus,open spinal cord injury models often do not simulate real injuries,and few previous studies have investigated whether having a closed spinal canal after a primary spinal cord injury may influence secondary processes.Therefore,we aimed to assess the differences in neurological dysfunction and pathological changes between rat spinal cord injury models with closed and open spinal canals.Sprague-Dawley rats were randomly divided into three groups.In the sham group,the tunnel was expanded only,without inserting a screw into the spinal canal.In the spinal cord injury with open canal group,a screw was inserted into the spinal canal to cause spinal cord injury for 5 minutes,and then the screw was pulled out,leaving a hole in the vertebral plate.In the spinal cord injury with closed canal group,after inserting a screw into the spinal canal for 5 minutes,the screw was pulled out by approximately 1.5 mm and the flat end of the screw remained in the hole in the vertebral plate so that the spinal canal remained closed;this group was the modified model,which used a screw both to compress the spinal cord and to seal the spinal canal.At 7 days post-operation,the Basso-Beattie-Bresnahan scale was used to measure changes in neurological outcomes.Hematoxylin-eosin staining was used to assess histopathology.To evaluate the degree of local secondary hypoxia,immunohistochemical staining and western blot assays were applied to detect the expression of hypoxia-inducible factor 1α(HIF-1α)and vascular endothelial growth factor(VEGF).Compared with the spinal cord injury with open canal group,in the closed canal group the Basso-Beattie-Bresnahan scores were lower,cell morphology was more irregular,the percentage of morphologically normal neurons was lower,the percentages of HIF-1α-and VEGF-immunorea 展开更多
关键词 Basso-Beattie-Bresnahan scores CLOSED SPINAL CANAL HIF-1α hypoxia MODEL nerve regeneration open SPINAL CANAL rat secondary INJURY SPINAL cord INJURY VEGF
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A pulmonary source of infection in patients with sepsis-associated acute kidney injury leads to a worse outcome and poor recovery of kidney function 预览
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作者 Yi-wen Fan Shao-wei Jiang +4 位作者 Jia-meng Chen Hui-qi Wang Dan Liu Shu-ming Pan Cheng-jin Gao 《世界急诊医学杂志(英文)》 CAS CSCD 2020年第1期18-26,共9页
BACKGROUND:Hospital mortality rates are higher among patients with sepsis-associated acute kidney injury(SA-AKI)than among patients with sepsis.However,the pathogenesis underlying SA-AKI remains unclear.We hypothesize... BACKGROUND:Hospital mortality rates are higher among patients with sepsis-associated acute kidney injury(SA-AKI)than among patients with sepsis.However,the pathogenesis underlying SA-AKI remains unclear.We hypothesized that the source of infection affects development of SA-AKI.We aim to explore the relationship between the anatomical source of infection and outcome in patients with SA-AKI.METHODS:Between January 2013 and January 2018,113 patients with SA-AKI admitted to our Emergency Center were identifi ed and divided into two groups:those with pulmonary infections and those with other sources of infection.For each patient,we collected data from admission until either discharge or death.We also recorded the clinical outcome after 90 days for the discharged patients.RESULTS:The most common source of infection was the lung(52/113 cases,46%),followed by gastrointestinal(GI)(25/113 cases,22.1%)and urinary(22/113,19.5%)sources.Our analysis showed that patients with SA-AKI had a significantly worse outcome(30/52 cases,P<0.001)and poorer kidney recovery(P=0.015)with pulmonary sources of infection than those infected by another source.Data also showed that patients not infected by a pulmonary source more likely experienced shock(28/61 cases,P=0.037).CONCLUSION:This study demonstrated that the source of infection infl uenced the outcome of SA-AKI patients in an independent manner.Lung injury may influence renal function in an asyet undetermined manner as the recovery of kidney function was poorer in SA-AKI patients with a pulmonary source of infection. 展开更多
关键词 SEPSIS Infection source Acute kidney injury Lung injury Renal function
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Unfolded protein response in myelin disorders 预览
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作者 Wensheng Lin Sarrabeth Stone 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期636-645,共10页
Activation of the unfolded protein response in response to endoplasmic reticulum stress preserves cell viability and function under stressful conditions.Nevertheless,persistent,unresolvable activation of the unfolded ... Activation of the unfolded protein response in response to endoplasmic reticulum stress preserves cell viability and function under stressful conditions.Nevertheless,persistent,unresolvable activation of the unfolded protein response can trigger apoptosis to eliminate stressed cells.Recent studies show that the unfolded protein response plays an important role in the pathogenesis of various disorders of myelin,including multiples sclerosis,Charcot-Marie-Tooth disease,Pelizaeus-Merzbacher disease,vanishing white matter disease,spinal cord injury,tuberous sclerosis complex,and hypoxia-induced perinatal white matter injury.In this review we summarize the current literature on the unfolded protein response and the evidence for its role in the pathogenesis of myelin disorders. 展开更多
关键词 AXON ER multiples SCLEROSIS MYELIN OLIGODENDROCYTE Schwann cell spinal cord injury UPR
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Inflammation-related gene expression profiles of salivary extracellular vesicles in patients with head trauma 预览
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作者 Yan Cheng Mandy Pereira +10 位作者 Neha P.Raukar John L.Reagan Mathew Quesenberry Laura Goldberg Theodor Borgovan W Curt LaFrance Jr Mark Dooner Maria Deregibus Giovanni Camussi Bharat Ramratnam Peter Quesenberry 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期676-681,共6页
At present,there is no reliable biomarker for the diagnosis of traumatic brain injury(TBI).Studies have shown that extracellular vesicles released by damaged cells into biological fluids can be used as potential bioma... At present,there is no reliable biomarker for the diagnosis of traumatic brain injury(TBI).Studies have shown that extracellular vesicles released by damaged cells into biological fluids can be used as potential biomarkers for diagnosis of TBI and evaluation of TBI severity.We hypothesize that the genetic profile of salivary extracellular vesicles in patients with head trauma differs from that in uninjured subjects.Findings from this hypothesis would help investigate the severity of TBI.This study included 19 subjects,consisting of seven healthy controls who denied history of head trauma,six patients diagnosed with concussion injury from an outpatient concussion clinic,and six patients with TBI who received treatment in the emergency department within 24 hours after injury.Real-time PCR analysis of salivary extracellular vesicles in participants was performed using TaqMan Human Inflammation array.Gene expression analysis revealed nine upregulated genes in emergency department patients(LOX5,ANXA3,CASP1,IL2RG,ITGAM,ITGB2,LTA4H,MAPK14,and TNFRSF1A)and 13 upregulated genes in concussion clinic patients compared with healthy participants(ADRB1,ADRB2,BDKRB1,HRH1,HRH2,LTB4R2,LTB4R,PTAFR,CYSLTR1,CES1,KLK1,MC2R,and PTGER3).Each patient group had a unique profile.Comparison between groups showed that 15 inflammation-related genes had significant expression change.Our results indicate that inflammation biomarkers can be used for diagnosis of TBI and evaluation of disease severity.This study was approved by the Institutional Review Board on December 18,2015(approval No.0078-12)and on June 9,2016(approval No.4093-16). 展开更多
关键词 chronic TRAUMATIC encephalopathy emergency department extracellular vesicles INFLAMMATION OUTPATIENT CONCUSSION clinic real-time PCR analysis SALIVA TRAUMATIC brain injury
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Remnant neuromuscular junctions in denervated muscles contribute to functional recovery in delayed peripheral nerve repair 预览
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作者 Leyang Li Hiroyuki Yokoyama +5 位作者 Hidetoshi Kaburagi Takashi Hirai Kunikazu Tsuji Mitsuhiro Enomoto Yoshiaki Wakabayashi Atsushi Okawa 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期731-738,共8页
Schwann cell proliferation in peripheral nerve injury(PNI)enhances axonal regeneration compared to central nerve injury.However,even in PNI,long-term nerve damage without repair induces degeneration of neuromuscular j... Schwann cell proliferation in peripheral nerve injury(PNI)enhances axonal regeneration compared to central nerve injury.However,even in PNI,long-term nerve damage without repair induces degeneration of neuromuscular junctions(NMJs),and muscle atrophy results in irreversible dysfunction.The peripheral regeneration of motor axons depends on the duration of skeletal muscle denervation.To overcome this difficulty in nerve regeneration,detailed mechanisms should be determined for not only Schwann cells but also NMJ degeneration after PNI and regeneration after nerve repair.Here,we examined motor axon denervation in the tibialis anterior muscle after peroneal nerve transection in thy1-YFP mice and regeneration with nerve reconstruction using allografts.The number of NMJs in the tibialis anterior muscle was maintained up to 4 weeks and then decreased at 6 weeks after injury.In contrast,the number of Schwann cells showed a stepwise decline and then reached a plateau at 6 weeks after injury.For regeneration,we reconstructed the degenerated nerve with an allograft at 4 and 6 weeks after injury,and evaluated functional and histological outcomes for 10 to 12 weeks after grafting.A higher number of pretzel-shaped NMJs in the tibialis anterior muscle and better functional recovery were observed in mice with a 4-week delay in surgery than in those with a 6-week delay.Nerve repair within 4 weeks after PNI is necessary for successful recovery in mice.Prevention of synaptic acetylcholine receptor degeneration may play a key role in peripheral nerve regeneration.All animal experiments were approved by the Institutional Animal Care and Use Committee of Tokyo Medical and Dental University on 5 July 2017,30 March 2018,and 15 May 2019(A2017-311C,A2018-297A,and A2019-248A),respectively. 展开更多
关键词 AXON NERVE ALLOGRAFT NERVE regeneration NEURODEGENERATION NEUROMUSCULAR junction peripheral NERVE injury Schwann cell skeletal muscle
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Effects of miR-219/miR-338 on microglia and astrocyte behaviors and astrocyte-oligodendrocyte precursor cell interactions 预览
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作者 Lan Huong Nguyen William Ong +3 位作者 Kai Wang Mingfeng Wang Dean Nizetic Sing Yian Chew 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期739-747,共9页
MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which ... MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which may enhance axonal remyelination after nerve injuries in the central nervous system(CNS).As such,the delivery of miR-219/miR-338 to the CNS to promote oligodendrocyte precursor cell differentiation,maturation and myelination could be a promising approach for nerve repair.However,nerve injuries in the CNS also involve other cell types,such as microglia and astrocytes.Herein,we investigated the effects of miR-219/miR-338 treatment on microglia and astrocytes in vitro and in vivo.We found that miR-219/miR-338 diminished microglial expression of pro-inflammatory cytokines and suppressed astrocyte activation.In addition,we showed that miR-219/miR-338 enhanced oligodendrocyte precursor cell differentiation and maturation in a scratch assay paradigm that re-created a nerve injury condition in vitro.Collectively,our results suggest miR-219/miR-338 as a promising treatment for axonal remyelination in the CNS following nerve injuries.All experimental procedures were approved by the Institutional Animal Care and Use Committee(IACUC),Nanyang Technological University(approval No.A0309 and A0333)on April 27,2016 and October 8,2016. 展开更多
关键词 central nervous system electrospinning gene SILENCING GLIA hydrogel MYELINATION nanofibers oligodendroglial POLYCAPROLACTONE spinal cord injury
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Effects of neural stem cell transplantation on the motor function of rats with contusion spinal cord injuries:a meta-analysis 预览
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作者 Kai Qian Tuo-Ye Xu +7 位作者 Xi Wang Tao Ma Kai-Xin Zhang Kun Yang Teng-Da Qian Jing Shi Li-Xin Li Zheng Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期748-758,共11页
Objective:To judge the efficacies of neural stem cell(NSC)transplantation on functional recovery following contusion spinal cord injuries(SCIs).Data sources:Studies in which NSCs were transplanted into a clinically re... Objective:To judge the efficacies of neural stem cell(NSC)transplantation on functional recovery following contusion spinal cord injuries(SCIs).Data sources:Studies in which NSCs were transplanted into a clinically relevant,standardized rat model of contusion SCI were identified by searching the PubMed,Embase and Cochrane databases,and the extracted data were analyzed by Stata 14.0.Data selection:Inclusion criteria were that NSCs were used in in vivo animal studies to treat contusion SCIs and that behavioral assessment of locomotor functional recovery was performed using the Basso,Beattie,and Bresnahan lo-comotor rating scale.Exclusion criteria included a follow-up of less than 4 weeks and the lack of control groups.Outcome measures:The restoration of motor function was assessed by the Basso,Beattie,and Bresnahan locomotor rating scale.Results:We identified 1756 non-duplicated papers by searching the aforementioned electronic databases,and 30 full-text articles met the inclusion criteria.A total of 37 studies reported in the 30 articles were included in the meta-analysis.The meta-analysis results showed that transplanted NSCs could improve the motor function recovery of rats following contusion SCIs,to a moderate extent(pooled standardized mean difference(SMD)=0.73;95%confidence interval(CI):0.47–1.00;P<0.001).NSCs obtained from different donor species(rat:SMD=0.74;95%CI:0.36–1.13;human:SMD=0.78;95%CI:0.31–1.25),at different donor ages(fetal:SMD=0.67;95%CI:0.43–0.92;adult:SMD=0.86;95%CI:0.50–1.22)and from different origins(brain-derived:SMD=0.59;95%CI:0.27–0.91;spinal cord-derived:SMD=0.51;95%CI:0.22–0.79)had similar efficacies on improved functional recovery;however,adult induced pluripotent stem cell-derived NSCs showed no significant efficacies.Furthermore,the use of higher doses of transplanted NSCs or the administration of immunosuppressive agents did not promote better locomotor function recovery(SMD=0.45;95%CI:0.21–0.70).However,shorter periods between the contusion induction and the NSC tr 展开更多
关键词 Basso Beattie and Bresnahan locomotor rating scale CELL TRANSPLANTATION META-ANALYSIS motor functional recovery NEURAL regeneration NEURAL stem CELL NEURAL stem CELL TRANSPLANTATION rat model SPINAL CONTUSION SPINAL cord injury
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Therapeutic effect of regulating autophagy in spinal cord injury: a network meta-analysis of direct and indirect comparisons 预览
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作者 Duo Zhang Di Zhu +4 位作者 Fang Wang Ji-Chao Zhu Xu Zhai Yuan Yuan Chen-Xi Li 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第6期1120-1132,共13页
Objective:An increasing number of studies indicate that autophagy plays an important role in the pathogenesis of spinal cord injury,and that regulating autophagy can enhance recovery from spinal cord injury.However,th... Objective:An increasing number of studies indicate that autophagy plays an important role in the pathogenesis of spinal cord injury,and that regulating autophagy can enhance recovery from spinal cord injury.However,the effect of regulating autophagy and whether autophagy is detrimental or beneficial after spinal cord injury remain unclear.Therefore,in this study we evaluated the effects of autophagy regulation on spinal cord injury in rats by direct and indirect comparison,in an effort to provide a basis for further research.Data source:Relevant literature published from inception to February 1,2018 were included by searching Wanfang,CNKI,Web of Science,MEDLINE(OvidSP),PubMed and Google Scholar in English and Chinese.The keywords included"autophagy","spinal cord injury",and"rat".Data selection:The literature included in vivo experimental studies on autophagy regulation in the treatment of spinal cord injury(including intervention pre-and post-spinal cord injury).Meta-analyses were conducted at different time points to compare the therapeutic effects of promoting or inhibiting autophagy,and subgroup analyses were also conducted.Outcome measure:Basso,Beattie,and Bresnahan scores.Results:Of the 622 studies,33 studies of median quality were included in the analyses.Basso,Beattie,and Bresnahan scores were higher at 1 day(MD=1.80,95%CI:0.81-2.79,P=0.0004),3 days(MD=0.92,95%CI:0.72-1.13,P<0.00001),1 week(MD=2.39,95%CI:1.85-2.92,P<0.00001),2 weeks(MD=3.26,95%CI:2.40-4.13,P<0.00001),3 weeks(MD=3.13,95%CI:2.51-3.75,P<0.00001)and 4 weeks(MD=3.18,95%CI:2.43-3.92,P<0.00001)after spinal cord injury with upregulation of autophagy compared with the control group(drug solvent control,such as saline group).Basso,Beattie,and Bresnahan scores were higher at 1 day(MD=6.48,95%CI:5.83-7.13,P<0.00001),2 weeks(MD=2.43,95%CI:0.79-4.07,P=0.004),3 weeks(MD=2.96,95%CI:0.09-5.84,P=0.04)and 4 weeks(MD=4.41,95%CI:1.08-7.75,P=0.01)after spinal cord injury with downregulation of autophagy compared with the control group.Indirect comparison of upr 展开更多
关键词 AUTOPHAGY Basso Beattie and Bresnahan scores indirect comparison META-ANALYSIS nerve regeneration neural regeneration neurological function rat models REGULATION spinal cord injury strategy analysis
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Neurological recovery and antioxidant effects of resveratrol in rats with spinal cord injury:a meta-analysis 预览
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作者 Bao-Ping Xu Min Yao +4 位作者 Zhen-Jun Li Zi-Rui Tian Jie Ye Yong-Jun Wang Xue-Jun Cui 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第3期482-490,共9页
Objective:To critically assess the neurological recovery and antioxidant effects of resveratrol in rat models of spinal cord injury.Data sources:Using“spinal cord injury”,“resveratrol”and“animal experiment”as th... Objective:To critically assess the neurological recovery and antioxidant effects of resveratrol in rat models of spinal cord injury.Data sources:Using“spinal cord injury”,“resveratrol”and“animal experiment”as the main search terms,all studies on the treatment of spinal cord injury in rats by resveratrol were searched for in PubMed,EMBASE,MEDLINE,Web of Science,Science Direct,China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases by computer.The search was conducted from their inception date to April 2017.No language restriction was used in the literature search.Data selection:The methodological quality of each study was assessed by the initial Stroke Therapy Academic Industry Roundtable recommendations.Two reviewers independently selected studies according to the title,abstract and full text.The risk of bias in the included studies was also evaluated.Meta-analyses were performed with Review Manager 5.3 software.Outcome measures:Neurological function was assessed by the Basso,Beattie,and Bresnahan scale score,inclined plane score and Gale’s motor function score.Molecular-biological analysis of antioxidative effects was conducted to determine superoxide dismutase levels,malondialdehyde levels,nitric oxide synthase activity,nitric oxide levels,xanthine oxidase and glutathione levels in spinal cord tissues.Results:The methodological quality of the 12 included studies was poor.The results of meta-analysis showed that compared with the control group,resveratrol significantly increased the Basso,Beattie,and Bresnahan scale scores after spinal cord injury(n=300,mean difference(MD)=3.85,95%confidence interval(CI)[2.10,5.59],P<0.0001).Compared with the control group,superoxide dismutase levels were significantly elevated(n=138,standardized mean difference(SMD)=5.22,95%CI[2.98,7.45],P<0.00001),but malondialdehyde levels were significantly diminished(n=84,SMD=–3.64,95%CI[–5.84,–1.43],P=0.001)in the spinal cord of the resveratrol treatment group.Conclusions:Resveratrol promoted neurologi 展开更多
关键词 ANTIOXIDATION META-ANALYSIS NEUROLOGICAL recovery PHARMACOTHERAPY RATS RESVERATROL spinal cord injury systematic review
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Three-dimensional bioprinting collagen/silk fibroin scaffold combined with neural stem cells promotes nerve regeneration after spinal cord injury 预览
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作者 Ji-Peng Jiang Xiao-Yin Liu +9 位作者 Fei Zhao Xiang Zhu Xiao-Yin Li Xue-Gang Niu Zi-Tong Yao Chen Dai Hui-You Xu Ke Ma Xu-Yi Chen Sai Zhang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期959-968,共10页
Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods... Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration.This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord.This scaffold allows cell growth in vitro and in vivo.To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury.Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed),spinal cord injury (transection injury of T10 spinal cord without any transplantation),3D-CF (3D scaffold was transplanted into the local injured cavity),and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity.Neuroelectrophysiology,imaging,hematoxylin-eosin staining,argentaffin staining,immunofluorescence staining,and western blot assay were performed.Apart from the sham group,neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups.Moreover,latency of the 3D-CF + NSCs group was significantly reduced,while the amplitude was significantly increased in motor evoked potential tests.The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group.Moreover,regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups.These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord.This study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No.2017-0007.2). 展开更多
关键词 3D BIOPRINTING COLLAGEN diffusion tensor IMAGING functional recovery magnetic resonance IMAGING nerve REGENERATION NEURAL REGENERATION NEURAL stem cell SCAFFOLD silk fibroin spinal cord injury
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Peripheral nerve injury induced changes in the spinal cord and strategies to counteract/enhance the changes to promote nerve regeneration 预览
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作者 Yan Liu Huan Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期189-198,共10页
Peripheral nerve injury leads to morphological, molecular and gene expression changes in the spinal cord and dorsal root ganglia, some of which have positive impact on the survival of neurons and nerve regeneration, w... Peripheral nerve injury leads to morphological, molecular and gene expression changes in the spinal cord and dorsal root ganglia, some of which have positive impact on the survival of neurons and nerve regeneration, while the effect of others is the opposite. It is crucial to take prompt measures to capitalize on the positive effects of these reactions and counteract the negative impact after peripheral nerve injury at the level of spinal cord, especially for peripheral nerve injuries that are severe, located close to the cell body, involve long distance for axons to regrow and happen in immature individuals. Early nerve repair, exogenous supply of neurotrophic factors and Schwann cells can sustain the regeneration inductive environment and enhance the positive changes in neurons. Administration of neurotrophic factors, acetyl-L-carnitine, N-acetyl-cysteine, and N-methyl-D-aspartate receptor antagonist MK-801 can help counteract axotomy-induced neuronal loss and promote regeneration, which are all time-dependent. Sustaining and reactivation of Schwann cells after denervation provides another effective strategy. FK506 can be used to accelerate axonal regeneration of neurons, especially after chronic axotomy. Exploring the axotomy-induced changes after peripheral nerve injury and applying protective and promotional measures in the spinal cord which help to retain a positive functional status for neuron cell bodies will inevitably benefit regeneration of the peripheral nerve and improve functional outcomes. 展开更多
关键词 AXOTOMY DORSAL root GANGLION neural regeneration NEUROTROPHIC factors outcomes peripheral nerve injury repair spinal CORD
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Protein microarray analysis of cytokine expression changes in distal stumps after sciatic nerve transection 预览
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作者 Xiao-Qing Cheng Xue-Zhen Liang +9 位作者 Shuai Wei Xiao Ding Gong-Hai Han Ping Liu Xun Sun Qi Quan He Tang Qing Zhao Ai-Jia Shang Jiang Peng 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第3期503-511,共9页
A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors... A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors for regenerative success.Therefore,it is important to investigate the key molecules and regulators affecting nerve regeneration after peripheral nerve injury.However,the identities of specific cytokines at various time points after sciatic nerve injury have not been determined.The study was performed by transecting the sciatic nerve to establish a model of peripheral nerve injury and to analyze,by protein microarray,the expression of different cytokines in the distal nerve after injury.Results showed a large number of cytokines were up-regulated at different time points post injury and several cytokines,e.g.,ciliary neurotrophic factor,were downregulated.The construction of a protein-protein interaction network was used to screen how the proteins interacted with differentially expressed cytokines.Kyoto Encyclopedia of Genes and Genomes pathway and Gene ontology analyses indicated that the differentially expressed cytokines were significantly associated with chemokine signaling pathways,Janus kinase/signal transducers and activators of transcription,phosphoinositide 3-kinase/protein kinase B,and notch signaling pathway.The cytokines involved in inflammation,immune response and cell chemotaxis were up-regulated initially and the cytokines involved in neuronal apoptotic processes,cell-cell adhesion,and cell proliferation were up-regulated at 28 days after injury.Western blot analysis showed that the expression and changes of hepatocyte growth factor,glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were consistent with the results of protein microarray analysis.The results provide a comprehensive understanding of changes in cytokine expression and changes in these cytokines and classical signaling pathways and biological functions during Wallerian degeneration,as well as a bas 展开更多
关键词 cytokines DISTAL stump gene ontology KYOTO ENCYCLOPEDIA of Genes and Genomes pathway peripheral nerve injury protein microarray PROTEIN-PROTEIN interaction network Wallerian degeneration
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Protective effect of rhodioloside and bone marrow mesenchymal stem cells infected with HIF-1-expressing adenovirus on acute spinal cord injury 预览
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作者 Xiao-Qin Ha Bo Yang +3 位作者 Huai-Jing Hou Xiao-Ling Cai Wan-Yuan Xiong Xu-Pan Wei 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期690-696,共7页
Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells o... Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury,a rat model of spinal cord injury was established using the Infinite Horizons method.After establishing the model,the rats were randomly divided into five groups.Rats in the control group were intragastrically injected with phosphate buffered saline(PBS)(5μL).PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm.Rats in the rhodioloside group were intragastrically injected with rhodioloside(5 g/kg)and intramuscularly injected with PBS.Rats in the mesenchymal stem cell(MSC)group were intramuscularly injected with PBS and intramuscularly with MSCs(8×10^6/mL in a 50-μL cell suspension).Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs.Rats in the rhodioloside+Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside.One week after treatment,exercise recovery was evaluated with a modified combined behavioral score scale.Hematoxylin-eosin staining and Pischingert’s methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue.Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord.Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord.The results showed that:(1)compared with the other groups,the rhodioloside+Ad-HIF-MSC group exhibited the highest combined behavioral score(P<0.05),the most recovered tissue,and the greatest number of neurons,as indicated by Pischingert’s methylene blue staining.(2)Compared with the PBS group,HIF-1 pro 展开更多
关键词 acute spinal cord injury ADENOVIRUS ADENOVIRUS gene IX bone MARROW mesenchymal stem cells combined behavioral score scale HIF-1α NERVE regeneration NERVE repair RHODIOLA rosea SRY
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Adult neurogenesis from reprogrammed astrocytes 预览
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作者 Brian B.Griffiths Anvee Bhutani Creed MStary 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第6期973-979,共7页
The details of adult neurogenesis,including environmental triggers,region specificity,and species homology remain an area of intense investigation.Slowing or halting age-related cognitive dysfunction,or restoring neur... The details of adult neurogenesis,including environmental triggers,region specificity,and species homology remain an area of intense investigation.Slowing or halting age-related cognitive dysfunction,or restoring neurons lost to disease or injury represent just a fraction of potential therapeutic applications.New neurons can derive from stem cells,pluripotent neural progenitor cells,or non-neuronal glial cells,such as astrocytes.Astrocytes must be epigenetically"reprogrammed"to become neurons,which can occur both naturally in vivo,and via artificial exogenous treatments.While neural progenitor cells are localized to a few neurogenic zones in the adult brain,astrocytes populate almost every brain structure.In this review,we will summarize recent research into neurogenesis that arises from conversion of post-mitotic astrocytes,detail the genetic and epigenetic pathways that regulate this process,and discuss the possible clinical relevance in supplementing stem-cell neurogenic therapies. 展开更多
关键词 ASTROCYTE brain DEDIFFERENTIATION development disease GLIA INJURY NEUROGENESIS
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Heterogeneity in the regenerative abilities of central nervous system axons within species:why do some neurons regenerate better than others? 预览
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作者 William Rodemer Jianli Hu +1 位作者 Michael E.Selzer Michael I.Shifman 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第6期996-1005,共10页
Some neurons,especially in mammalian peripheral nervous system or in lower vertebrate or in vertebrate central nervous system(CNS)regenerate after axotomy,while most mammalian CNS neurons fail to regenerate.There is a... Some neurons,especially in mammalian peripheral nervous system or in lower vertebrate or in vertebrate central nervous system(CNS)regenerate after axotomy,while most mammalian CNS neurons fail to regenerate.There is an emerging consensus that neurons have different intrinsic regenerative capabilities,which theoretically could be manipulated therapeutically to improve regeneration.Population-based comparisons between"good regenerating"and"bad regenerating"neurons in the CNS and peripheral nervous system of most vertebrates yield results that are inconclusive or difficult to interpret.At least in part,this reflects the great diversity of cells in the mammalian CNS.Using mammalian nervous system imposes several methodical limitations.First,the small sizes and large numbers of neurons in the CNS make it very difficult to distinguish regenerating neurons from non-regenerating ones.Second,the lack of identifiable neurons makes it impossible to correlate biochemical changes in a neuron with axonal damage of the same neuron,and therefore,to dissect the molecular mechanisms of regeneration on the level of single neurons.This review will survey the reported responses to axon injury and the determinants of axon regeneration,emphasizing non-mammalian model organisms,which are often under-utilized,but in which the data are especially easy to interpret. 展开更多
关键词 axonal regeneration identifiable neurons intrinsic factors LAMPREY Mauthner cell Müller cell neuronal death non-mammalian model organisms spinal cord injury zebrafish
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Adipose-derived stem cells modified by BDNF gene rescue erectile dysfunction after cavernous nerve injury 预览
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作者 Mei Yang Jiang-Yang Sun +2 位作者 Cheng-Cheng Ying Yong Wang Yong-Lian Guo 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期120-127,共8页
Cavernous nerve injury is the main cause of erectile dysfunction following radical prostatectomy.The recovery of erectile function following radical prostatectomy remains challenging.Our previous studies found that in... Cavernous nerve injury is the main cause of erectile dysfunction following radical prostatectomy.The recovery of erectile function following radical prostatectomy remains challenging.Our previous studies found that injecting adipose-derived stem cells(ADSCs)into the cavernosa could repair the damaged cavernous nerves,but the erectile function of the treated rats could not be restored to a normal level.We evaluated the efficacy of ADSCs infected with a lentiviral vector encoding rat brain-derived neurotrophic factor(lenti-rBDNF)in a rat model of cavernous nerve injury.The rats were equally and randomly divided into four groups.In the control group,bilateral cavernous nerves were isolated but not injured.In the bilateral cavernous nerve injury group,bilateral cavernous nerves were isolated and injured with a hemostat clamp for 2 minutes.In the ADSCGFP and ADSCrBDNF groups,after injury with a hemostat clamp for 2 minutes,rats were injected with ADSCs infected with lenti-GFP(1×106 in 20μL)and lenti-rBDNF(1×106 in 20μL),respectively.Erectile function was assessed 4 weeks after injury by measuring intracavernosal pressures.Then,penile tissues were collected for histological detection and western blot assay.Results demonstrated that compared with the bilateral cavernous nerve injury group,erectile function was significantly recovered in the ADSCGFP and ADSCrBDNF groups,and to a greater degree in the ADSCrBDNF group.Neuronal nitric oxide synthase content in the dorsal nerves and the ratio of smooth muscle/collagen were significantly higher in the ADSCrBDNF and ADSCGFP groups than in the bilateral cavernous nerve injury group.Neuronal nitric oxide synthase expression was obviously higher in the ADSCrBDNF group than in the ADSCGFP group.These findings confirm that intracavernous injection with ADSCs infected with lenti-rBDNF can effectively improve erectile dysfunction caused by cavernous nerve injury.This study was approved by the Medical Animal Care and Welfare Committee of Wuhan University,China(approval No.2017-163 展开更多
关键词 adipose-derived stem cells BRAIN-DERIVED NEUROTROPHIC factor CAVERNOUS nerve injury erectile dysfunction infection intracavernous injection LENTIVIRAL vector neuronal nitric oxide SYNTHASE radical prostatectomy
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Transdermal delivery of 4-aminopyridine accelerates motor functional recovery and improves nerve morphology following sciatic nerve crush injury in mice 预览
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作者 Andrew RClark Chia George Hsu +2 位作者 M A Hassan Talukder Mark Noble John CElfar 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期136-144,共9页
Oral 4-aminopyridine(4-AP)is clinically used for symptomatic relief in multiple sclerosis and we recently demonstrated that systemic 4-AP had previously unknown clinically-relevant effects after traumatic peripheral n... Oral 4-aminopyridine(4-AP)is clinically used for symptomatic relief in multiple sclerosis and we recently demonstrated that systemic 4-AP had previously unknown clinically-relevant effects after traumatic peripheral nerve injury including the promotion of re-myelination,improvement of nerve conductivity,and acceleration of functional recovery.We hypothesized that,instead of oral or injection administration,transdermal 4-AP(TD-4-AP)could also improve functional recovery after traumatic peripheral nerve injury.Mice with surgical traumatic peripheral nerve injury received TD-4AP or vehicle alone and were examined for skin permeability,pharmacokinetics,functional,electrophysiological,and nerve morphological properties.4-AP showed linear pharmacokinetics and the maximum plasma 4-AP concentrations were proportional to TD-4-AP dose.While a single dose of TD-4-AP administration demonstrated rapid transient improvement in motor function,chronic TD-4-AP treatment significantly improved motor function and nerve conduction and these effects were associated with fewer degenerating axons and thicker myelin sheaths than those from vehicle controls.These findings provide direct evidence for the potential transdermal applicability of 4-AP and demonstrate that 4-AP delivered through the skin can enhance in-vivo functional recovery and nerve conduction while decreasing axonal degeneration.The animal experiments were approved by the University Committee on Animal Research(UCAR)at the University of Rochester(UCAR-2009-019)on March 31,2017. 展开更多
关键词 4-AMINOPYRIDINE electron MICROSCOPY functional recovery NERVE conduction velocity PERIPHERAL NERVE injury PHARMACOKINETICS TRANSDERMAL administration
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Effect of the combination of high-frequency repetitive magnetic stimulation and neurotropin on injured sciatic nerve regeneration in rats 预览
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作者 Jie Chen Xian-Ju Zhou Rong-Bin Sun 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期145-151,共7页
Repetitive magnetic stimulation is effective for treating posttraumatic neuropathies following spinal or axonal injury.Neurotropin is a potential treatment for nerve injuries like demyelinating diseases.This study sou... Repetitive magnetic stimulation is effective for treating posttraumatic neuropathies following spinal or axonal injury.Neurotropin is a potential treatment for nerve injuries like demyelinating diseases.This study sought to observe the effects of high-frequency repetitive magnetic stimulation,neurotropin and their combined use in the treatment of peripheral nerve injury in 32 adult male Sprague-Dawley rats.To create a sciatic nerve injury model,a 10 mm-nerve segment of the left sciatic nerve was cut and rotated through 180°and each end restored continuously with interrupted sutures.The rats were randomly divided into four groups.The control group received only a reversed autograft in the left sciatic nerve with no treatment.In the high-frequency repetitive magnetic stimulation group,peripheral high-frequency repetitive magnetic stimulation treatment(20 Hz,20 min/d)was delivered for 10 consecutive days after auto-grafting.In the neurotropin group,neurotropin therapy(0.96 NU/kg per day)was administrated for 10 consecutive days after surgery.In the combined group,the combination of peripheral high-frequency repetitive magnetic stimulation(20 Hz,20 min/d)and neurotropin(0.96 NU/kg per day)was given for 10 consecutive days after the operation.The Basso-Beattie-Bresnahan locomotor rating scale was used to assess the behavioral recovery of the injured nerve.The sciatic functional index was used to evaluate the recovery of motor functions.Toluidine blue staining was performed to determine the number of myelinated fibers in the distal and proximal grafts.Immunohistochemistry staining was used to detect the length of axons marked by neurofilament 200.Our results reveal that the Basso-Beattie-Bresnahan locomotor rating scale scores,sciatic functional index,the number of myelinated fibers in distal and proximal grafts were higher and axon lengths were longer in the high-frequency repetitive magnetic stimulation,neurotropin and combined groups compared with the control group.These measures were not significantly different am 展开更多
关键词 AXON myelinated NERVE fibers NERVE REGENERATION neurological rehabilitation NEUROTROPIN peripheral NERVE injury REPETITIVE magnetic stimulation SCIATIC NERVE trauma
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Claudin-15 overexpression inhibits proliferation and promotes apoptosis of Schwann cells in vitro 预览
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作者 Jian-Nan Li Zhan Zhang +2 位作者 Guang-Zhi Wu Deng-Bing Yao Shu-Sen Cui 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期169-177,共9页
Our previous experiments have discovered that Claudin-15 was up-regulated in Schwann cells of the distal nerve stumps of rat models of sciatic nerve injury.However,how Claudin-15 affects Schwann cell function is still... Our previous experiments have discovered that Claudin-15 was up-regulated in Schwann cells of the distal nerve stumps of rat models of sciatic nerve injury.However,how Claudin-15 affects Schwann cell function is still unknown.This study aimed to identify the effects of Claudin-15 on proliferation and apoptosis of Schwann cells cultured in vitro and explore the underlying mechanisms.Primary Schwann cells were obtained from rats.Claudin-15 in Schwann cells was knocked down using siRNA(siRNA-1 group)compared with the negative control siRNA transfection group(negative control group).Claudin-15 in Schwann cells was overexpressed using pGV230-Claudin-15 plasmid(pGV230-Claudin-15 group).The pGV230 transfection group(pGV230 group)acted as the control of the pGV230-Claudin-15 group.Cell proliferation was analyzed with EdU assay.Cell apoptosis was analyzed with flow cytometric analysis.Cell migration was analyzed with Transwell inserts.The mRNA and protein expressions were analyzed with quantitative polymerase chain reaction assay and western blot assay.The results showed that compared with the negative control group,cell proliferation rate was up-regulated;p-AKT/AKT ratio,apoptotic rate,p-c-Jun/c-Jun ratio,mRNA expression of protein kinase C alpha,Bcl-2 and Bax were down-regulated;and mRNA expression of neurotrophins basic fibroblast growth factor and neurotrophin-3 were increased in the siRNA-1 group.No significant difference was found in cell migration between the negative control and siRNA-1 groups.Compared with the pGV230 group,the cell proliferation rate was down-regulated;apoptotic rate,p-c-Jun/c-Jun ratio and c-Fos protein expression increased;mRNA expression of protein kinase C alpha and Bax decreased;and mRNA expressions of neurotrophins basic fibroblast growth factor and neurotrophin-3 were up-regulated in the pGV230-Claudin-15 group.The above results demonstrated that overexpression of Claudin-15 inhibited Schwann cell proliferation and promoted Schwann cell apoptosis in vitro.Silencing of Claudin-15 had the re 展开更多
关键词 apoptosis Bax cell PROLIFERATION c-Jun Claudin-15 NERVE regeneration peripheral NERVE injury protein kinase C alpha Schwann cells Wallerian DEGENERATION
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