Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In...Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In this study, we performed double-target neural circuit-magnetic stimulation on the left motor cortex and bilateral L5 nerve root for 3 successive weeks in a rat model of incomplete spinal cord injury caused by compression at T10. Results showed that in the injured spinal cord, the expression of the astrocyte marker glial fibrillary acidic protein and inflammatory factors interleukin 1β, interleukin-6, and tumor necrosis factor-α had decreased, whereas that of neuronal survival marker microtubule-associated protein 2 and synaptic plasticity markers postsynaptic densification protein 95 and synaptophysin protein had increased. Additionally, neural signaling of the descending corticospinal tract was markedly improved and rat locomotor function recovered significantly. These findings suggest that double-target neural circuit-magnetic stimulation improves rat motor function by attenuating astrocyte activation, thus providing a theoretical basis for application of double-target neural circuit-magnetic stimulation in the clinical treatment of spinal cord injury.展开更多
Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctua...Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctuation(ALFF)metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control co rtical impact(CCI)rat model simulating traumatic brain injury.At 3 days after control co rtical impact model establishment,we found that the mean ALFF(mALFF)signals were decreased in the left motor cortex,somatosensory co rtex,insula cortex and the right motor co rtex,and were increased in the right corpus callosum.After 3 weeks of an 8-hour daily mClMT treatment,the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively.The mALFF signal valu es of left corpus callosum,left somatosensory cortex,right medial prefro ntal cortex,right motor co rtex,left postero dorsal hippocampus,left motor cortex,right corpus callosum,and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group.Finally,we identified brain regions with significantly decreased mALFF valu es at 3 days postoperatively.Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions.Our findings suggest that functional co rtical plasticity changes after brain injury,and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric co rtical remodeling.mALFF values correlate with behavio ral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.展开更多
Objective:Serum albumin(ALB)can transport nutrients to circulating and local immune cells by passing through blood vessels and has attracted attention as a prognostic predictor of non-small cell lung cancer(NSCLC)beca...Objective:Serum albumin(ALB)can transport nutrients to circulating and local immune cells by passing through blood vessels and has attracted attention as a prognostic predictor of non-small cell lung cancer(NSCLC)because it reflects the host immunity from peripheral blood(PBL)to the tumor microenvironment. Methods:Clinical data regarding the PBL and tumor tissues were obtained at The First Hospital of Jilin University between February 2009 and March 2017.We detected indices of glucose and lipid metabolism,classified and counted PBL lymphocytes using flow cy-tometry,determined the tumor-infiltrating lymphocytes by quantitative immunofluorescence,and analyzed the T-cell receptor(TCR)rep-ertoire by high-throughput sequencing of the TCR β-chain.The correlations between ALB and metabolic immune indices were analyzed by t tests and Pearson chi-square test. Results:A total of 211 enrolled NSCLC patients were divided into a relatively high-ALB group(>41.75 g/L,n = 56)and a low-ALB group(≤41.75 g/L,n = 155);patients with high ALB had lower Treg cells(P<0.05)and more CD8+ cytotoxic T cells in the PBL(P<0.01)and a higher proportion of stromal CD8+ tumor-infiltrating lymphocytes(P = 0.047)than patients with low ALB.High ALB was also significantly related to more diversity in the TCR repertoire(P = 0.0021,r2 = 0.5481).Moreover,ALB was identified as an in-dependent prognostic factor based on a multivariate Cox regression analysis(P = 0.032;hazard ratio(HR)= 1.804;95%confidence interval(CI)= 1.035-3.146).The median overall survival in patients with low ALB vs high ALB was 28.2 vs 42.2 months(P=0.0142),respectively.Among patients with nonmetastatic NSCLC(stage Ⅰ-Ⅲ),there was a higher incidence of distant metastasis in the low-ALB group than that in the high-ALB group(41.3%and 22.2%,P=0.043).A low ALB also had a strong association with a higher risk for disease progression(P<0.001)and death(P<0.01;HR = 0.555;95%CI= 0.312-0.988). Conclusions:Albumin could affect the host immunity,and high ALB predicted a reduced risk of distant metastasis and improved the prognosis in NSCLC patients.展开更多
Spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural dysfunction.Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord ...Spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural dysfunction.Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury,which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies.Besides the involvement of endogenous stem cells in neurogenesis and neural repair,exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases.However,to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury,appropriate interventional measures(e.g.,neuromodulation)should be adopted.Neuromodulation techniques,such as noninvasive magnetic stimulation and electrical stimulation,have been safely applied in many neuropsychiatric diseases.There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system;namely,by exciting,inhibiting,or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury.Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth,encourages the formation of new synaptic connections to promote neural plasticity,and improves motor function recovery in patients with spinal cord injury.With the development of biomaterial technology and biomechanical engineering,several emerging treatments have been developed,such as robots,brain-computer interfaces,and nanomaterials.These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury.However,large-scale clinical trials need to be conducted to validate their efficacy.This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence,to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.展开更多
Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb.Ho...Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb.However,the molecular mechanism underlying its efficacy remains unclear.In this study,a middle cerebral artery occlusion(MCAO)rat model was produced by the suture method.Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days,starting from the 7^th day after middle cerebral artery occlusion.Day 1 of treatment lasted for 10 minutes at 2r/min,day 2 for 20 minutes at 2 r/min,and from day 3 onward for 20 minutes at 4 r/min.CatWalk gait analysis,adhesive removal test,and Y-maze test were used to investigate motor function,sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21^st day after MCAO.On the 21^st day after MCAO,the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay.The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography.The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats,but had no effect on cognitive function.The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3(Gria3)in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1 A,Avprla in the middle cerebral artery-occluded rats.In the ipsilateral hippocampus,only Adra2 a was downregulated,and there was no significant change in Gria3.Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3,which is an a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor,within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region.The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged.Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion,but had no effect on Synapsin I levels.Besides,we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus.This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats,and suggests that these positive effects occur via the upregulation of the postsynaptic membrane a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression.This study was approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.展开更多
More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments.Therefore,new rehabilitation technologies are urgently needed as auxiliary treatments...More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments.Therefore,new rehabilitation technologies are urgently needed as auxiliary treatments for motor rehabilitation.Based on routine rehabilitation treatments,a new intelligent rehabilitation platform has been developed for accurate evaluation of function and rehabilitation training.The emerging intelligent rehabilitation techniques can promote the development of motor function rehabilitation in terms of informatization,standardization,and intelligence.Traditional assessment methods are mostly subjective,depending on the experience and expertise of clinicians,and lack standardization and precision.It is therefore difficult to track functional changes during the rehabilitation process.Emerging intelligent rehabilitation techniques provide objective and accurate functional assessment for stroke patients that can promote improvement of clinical guidance for treatment.Artificial intelligence and neural networks play a critical role in intelligent rehabilitation.Multiple novel techniques,such as braincomputer interfaces,virtual reality,neural circuit-magnetic stimulation,and robot-assisted therapy,have been widely used in the clinic.This review summarizes the emerging intelligent rehabilitation techniques for the evaluation and treatment of motor dysfunction caused by nervous system diseases.展开更多
Paired associative stimulation has been used in stroke patients as an innovative recovery treatment.However,the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological fun...Paired associative stimulation has been used in stroke patients as an innovative recovery treatment.However,the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear.In this study,rats were randomly divided into middle cerebral occlusion model(MCAO)and paired associated magnetic stimulation(PAMS)groups.The MCAO rat model was produced by middle cerebral artery embolization.The PAMS group received PAMS on days 3 to 20 post MCAO.The MCAO group received sham stimulation,three times every week.Within 18 days after ischemia,rats were subjected to behavioral experiments—the foot-fault test,the balance beam walking test,and the ladder walking test.Balance ability was improved on days 15 and 17,and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group.Western blot assay showed that the expression levels of brain derived neurotrophic factor,glutamate receptor 2/3,postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21.Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere,but decreased in the contralateral hemisphere on day 20.By finite element simulation,the electric field distribution showed a higher intensity,of approximately 0.4 A/m^2,in the ischemic cortex compared with the contralateral cortex in the template.Together,our findings show that PAMS upregulates neuroplasticity-related proteins,increases regional brain activity,and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model.The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.展开更多
Encouraging results have been reported for the use of transcranial magnetic stimulationbased nerve stimulation in studies of the mechanisms of neurological regulation,nerve injury repair,and nerve localization.However...Encouraging results have been reported for the use of transcranial magnetic stimulationbased nerve stimulation in studies of the mechanisms of neurological regulation,nerve injury repair,and nerve localization.However,to date,there are only a few reviews on the use of transcranial magnetic stimulation for diabetic neuropathy.Patients with diabetic neuropathy vary in disease progression and show neuropathy in the early stage of the disease with mild symptoms,making it difficult to screen and identify.In the later stage of the disease,irreversible neurological damage occurs,resulting in treatment difficulties.In this review,we summarize the current state of diabetic neuropathy research and the prospects for the application of transcranial magnetic stimulation in diabetic neuropathy.We review significant studies on the beneficial effects of transcranial magnetic stimulation in diabetic neuropathy treatment,based on the outcomes of its use to treat neurodegeneration,pain,blood flow change,autonomic nervous disorders,vascular endothelial injury,and depression.Collectively,the studies suggest that transcranial magnetic stimulation can produce excitatory/inhibitory stimulation of the cerebral cortex or local areas,promote the remodeling of the nervous system,and that it has good application prospects for the localization of the injury,neuroprotection,and the promotion of nerve regeneration.Therefore,transcranial magnetic stimulation is useful for the screening and early treatment of diabetic neuropathy.transcranial magnetic stimulation can also alleviate pain symptoms by changing the cortical threshold and inhibiting the conduction of sensory information in the thalamo-spinal pathway,and therefore it has therapeutic potential for the treatment of pain and pain-related depressive symptoms in patients with diabetic neuropathy.Additionally,based on the effect of transcranial magnetic stimulation on local blood flow and its ability to change heart rate and urine protein content,transcranial magnetic stimulation has potential in the treatment of autonomic nerve dysfunction and vascular injury in diabetic neuropathy.Furthermore,oxidative stress and the inflammatory response are involved in the process of diabetic neuropathy,and transcranial magnetic stimulation can reduce oxidative damage.The pathological mechanisms of diabetic neuropathy should be further studied in combination with transcranial magnetic stimulation technology.展开更多
Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patien...Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral(right only)cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots,five times a week.Bilateral resting motor evoked potential amplitude was increased,central motor conduction time on the side receiving cortical stimulation was significantly decreased,and lower extremity motor score,Berg balance score,spinal cord independence measure-III score,and 10 m-walking speed were all increased after treatment.Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment.These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.展开更多
Classic paired associative stimulation can improve synaptic plasticity,as demonstrated by animal expe riments and human clinical trials in spinal cord injury patients.Paired associative magnetic stimulation(dual-targe...Classic paired associative stimulation can improve synaptic plasticity,as demonstrated by animal expe riments and human clinical trials in spinal cord injury patients.Paired associative magnetic stimulation(dual-target peripheral and central magnetic stimulation)has been shown to promote neurologic recove ry after stroke.However,it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury.We hypothesize that the curre nt caused by central and peripheral magnetic stimulation will conve rge at the synapse,which will promote synapse function and improve the motor function of the relevant muscles.Therefore,this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials,motor and sensory function of the lower limbs,functional health and activities of daily living,and depression in patients with spinal co rd injury.We will recruit 110 thora cic spinal trauma patients treated in the Department of Spinal Cord Injury,China Rehabilitation Hospital and randomly assign them to expe rimental and control groups in a 1:1 ratio.The trial group(n=55)will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment.The control group(n=55)will be treated with sham stimulation and co nventional rehabilitation treatment.Outcomes will be measured at four time points:baseline and 4,12,and 24 wee ks after the start of inte rvention(active or sham paired associative magnetic stimulation).The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up.Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function sco re,motor evoked potentials,sensory evoked potentials,modified Ashwo rth scale score,Maslach Burnout Invento ry score,and Hamilton Depression Scale score over time.Motor evoked potential latency reflects corticospinal tract transmission time,while amplitude reflects recruitment ability;both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency.Adve rse events will be recorded.Findings from this trial will help to indicate whether paired associative magnetic stimulation(1)promotes recove ry of lower limb sensory and motor function,reduces spasticity,and improves quality of life;(2)promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity;and(3)improves rehabilitation outcome in patients with spinal cord injury.Recruitment for this trial began in April 2021 and is currently ongoing.It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University,China(approval No.YZ2020-018)on May 18,2020.The study protocol was registered in the Chinese Clinical Trial Registry(registration number:ChiCTR2100044794)on March 27,2021(protocol version 1.0).This trial will be completed in April 2022.展开更多
Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits tha...Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits that enable motor function.Our group previously designed a novel magnetic stimulation protocol,targeting the motor cortex and the spinal nerve roots,that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury.Here,we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury.Rats underwent surgery to clamp the spinal cord at T10;three days later,the rats were treated with repetitive magnetic stimulation(5 Hz,25 pulses/train,20 pulse trains)targeting the nerve roots at the L5-L6 vertebrae.The treatment was repeated five times a week over a period of three weeks.We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord.In addition,the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex.Overall,the results suggest that nerve root magnetic stimulation may be an effective,noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.展开更多
The mouse model of multiple cerebral infarctions,established by injecting fluorescent microspheres into the common carotid artery,is a recent development in animal models of cerebral ischemia.To investigate its effect...The mouse model of multiple cerebral infarctions,established by injecting fluorescent microspheres into the common carotid artery,is a recent development in animal models of cerebral ischemia.To investigate its effectiveness,mouse models of cerebral infarction were created by injecting fluorescent microspheres,45–53μm in diameter,into the common carotid artery.Six hours after modeling,fluorescent microspheres were observed directly through a fluorescence stereomicroscope,both on the brain surface and in brain sections.Changes in blood vessels,neurons and glial cells associated with microinfarcts were examined using fluorescence histochemistry and immunohistochemistry.The microspheres were distributed mainly in the cerebral cortex,striatum and hippocampus ipsilateral to the side of injection.Microinfarcts were found in the brain regions where the fluorescent microspheres were present.Here the lodged microspheres induced vascular and neuronal injury and the activation of astroglia and microglia.These histopathological changes indicate that this animal model of multiple cerebral infarctions effectively simulates the changes of various cell types observed in multifocal microinfarcts.This model is an effective,additional tool to study the pathogenesis of ischemic stroke and could be used to evaluate therapeutic interventions.This study was approved by the Animal Ethics Committee of the Institute of Acupuncture and Moxibustion,China Academy of Chinese Medical Sciences(approval No.D2021-03-16-1)on March 16,2021.展开更多
Neural tract tracing is used to study neural pathways and evaluate neuronal regeneration following nerve injuries.However,it is not always clear which tracer should be used to yield optimal results.In this study,we ex...Neural tract tracing is used to study neural pathways and evaluate neuronal regeneration following nerve injuries.However,it is not always clear which tracer should be used to yield optimal results.In this study,we examined the use of Alexa Fluor 488-conjugated cholera toxin subunit B(AF488-CTB).This was injected into the gastrocnemius muscle of rats,and it was found that motor,sensory,and sympathetic neurons were labeled in the spinal ventral horn,dorsal root ganglia,and sympathetic chain,respectively.Similar results were obtained when we injected AF594-CTB into the tibialis anterior muscle.The morphology and number of neurons were evaluated at different time points following the AF488-CTB injection.It was found that labeled motor and sensory neurons could be observed 12 hours post-injection.The intensity was found to increase over time,and the morphology appeared clear and complete 3-7 days post-injection,with clearly distinguishable motor neuron axons and dendrites.However,14 days after the injection,the quality of the images decreased and the neurons appeared blurred and incomplete.Nissl and immunohistochemical staining showed that the AF488-CTB-labeled neurons retained normal neurochemical and morphological features,and the surrounding microglia were also found to be unaltered.Overall,these results imply that the cholera toxin subunit B,whether unconjugated or conjugated with Alexa Fluor,is effective for retrograde tracing in muscular tissues and that it would also be suitable for evaluating the regeneration or degeneration of injured nerves.展开更多
Objective:The aim of this study is to assess the neural interconnection between the acupoint"Chéngshān(承山BL57)"and sciatic nerve from the peripheral nervous system(PNS)to the central nervous system(C...Objective:The aim of this study is to assess the neural interconnection between the acupoint"Chéngshān(承山BL57)"and sciatic nerve from the peripheral nervous system(PNS)to the central nervous system(CNS).Methods:SD rats were systematically examined from the hip to the hind limb along the route of sciatic nerve with regional anatomical technique,and further traced from the BL57 and the trunk of sciatic nerve by the neural tracing technique with cholera toxin subunit B(CTB)and CTB conjugated Alexa Fluor 488 and 594(CTB-AF488/594).Results:After regional anatomy,it was found that the sciatic nerve ran down from the hip to the hind limb and sequentially sent out the tibial and sural branches respectively to the deep and superficial layers of BL57.The CTB labeling associated with both BL57 and sciatic nerve distributed in the same spinal segments and definite regions,including the sensory neurons in lumber 3(L3)-lumber 6(L6)dorsal root ganglia(DRGs),transganglionic axons mainly in the L3-L6 spinal dorsal horn,Clarke’s nucleus,and gracile nucleus,as well as motor neurons mainly in the L3-L6 spinal ventral horn.However,the amount of neural labeling was significantly less in the cases of BL57 than that of sciatic nerve.Conclusions:These results indicate that there is distinct sensory and motor interconnection between the BL57 and the sciatic nerve,which may potentially serve for the active role of the BL57 playing in meliorating the disorders of sciatic nerve.展开更多
Objective:The innervations in Yinlingquan(阴陵泉SP9)and Yanglingquan(阳陵泉GB34)were investigated to explore the neuroanatomical interconnection of the complementary acupoints in the rat hindlimb.Methods:A dual neural...Objective:The innervations in Yinlingquan(阴陵泉SP9)and Yanglingquan(阳陵泉GB34)were investigated to explore the neuroanatomical interconnection of the complementary acupoints in the rat hindlimb.Methods:A dual neural tracing technique was used,six male Sprague-Dawley rats were included in experiment.Under anesthesia with isoflurane,cholera toxin subunit B conjugated with Alexa Fluor 488 and 594(CTB-AF488/594)were separately injected into SP9 and GB34 in the same rat.Three days later,the neural labeling was examined in the dorsal root ganglion(DRG),spinal cord,and sympathetic chain at lumbar(L)spinal segments under a laser scanning confocal microscope.Results:All neural labeling were present on the ipsilateral side of tracer injection,including sensory,motor and sympathetic postganglionic neurons.The sensory neurons associated with SP9 and GB34 were distributed in the DRG from L2 to L6 and concentrated in L3-L4 and L4-L5 respectively,while most of the double labeled sensory neurons were presented in L4.On the other hand,the labeled motor neurons for SP9 and GB34 were observed in the dorsolateral part of spinal ventral horn at L2-L4 and L3-L5 respectively,and some of them were double labeled at L4.In addition,the sympathetic postganglionic neurons related to SP9 and GB34 were found in the lumbar sympathetic chain respectively.Conclusion:The similarities of the sensory,motor,and sympathetic innervation of SP9 and GB34 in the rat provide the neuroanatomical evidence to understand the synergetic effect that arise from the stimulation at the complementary acupoints.展开更多
Using scanning, transmission electron microscopy and aberration-corrected scanning transmission electron microscopy, we have studied the interactions between dislocations and twins in impact deformed polysynthetic twi...Using scanning, transmission electron microscopy and aberration-corrected scanning transmission electron microscopy, we have studied the interactions between dislocations and twins in impact deformed polysynthetic twinned TiAl crystal. The 1/3 < 111] and 1/6 < 211] step dislocations on coherent twin boundaries reveal the interactions of glissile 1/2 < 101> dislocations with the coherent twin boundaries.An abnormal stacking fault was found adjacent to the coherent twin boundary. It has the same stacking sequence but different atom species in the [110] direction with an additional displacement of 1/4[110]in two neighboring {111} layers, and is likely induced by the slip of a 1/12[112](i.e. 1/4[110] + 1/6[211])dislocation.展开更多
A quantitative phase field method of multi-component diffusion-controlled phase transformations coupled with the Kim–Kim–Suzuki model was applied to study the effect of initial particle size distribution(PSD) in 3D ...A quantitative phase field method of multi-component diffusion-controlled phase transformations coupled with the Kim–Kim–Suzuki model was applied to study the effect of initial particle size distribution(PSD) in 3D and space distribution in 2D on dissolution of α particles in Ti–6Al–4V alloy below β transus temperature in real time and length scale. The thermodynamic and mobility data were obtained from Thermo-Calc and DICTRA softwares, respectively. The results show that the volume fractions of α particles decay with time as: f =f_(eq)+ (f_0-f_(eq))exp(-Kt^n) for four cases of PSD. The sequence of dissolution kinetics from fast to slow is: uniform PSD, normal PSD, lognormal PSD and bimodal PSD. The space distribution is found to be a major factor affecting the dissolution kinetics and the microstructures. When the distance of the particles is less than critical value, the dissolution rates reduce with the decrease in distance. The Al and V concentration fields around the particles appear more obvious soft impingement.展开更多
The microstructural evolution and tensile properties of Ti-3Al-8V-6Cr-4Mo-xZr(x = 0,2,4 and 6) titanium alloys were investigated.The precipitated phases and tensile fracture morphologies were observed using scanning e...The microstructural evolution and tensile properties of Ti-3Al-8V-6Cr-4Mo-xZr(x = 0,2,4 and 6) titanium alloys were investigated.The precipitated phases and tensile fracture morphologies were observed using scanning electron microscopy and transmission electron microscopy.Experimental results show that the presence of trace impurity Si and the addition of Zr induce the formation of(TiZr)_6Si_3 silicides.The quantity of silicides increases with Zr content increasing.The dispersed silicides refined the grain size of β Zr-containing alloys,and the grain size decreases significantly with Zr content increasing.Accompanying these microstructural changes,the strength of the alloys is enhanced gradually with the increase of Zr content,which is attributed to the combination of precipitation strengthening and grain refinement.展开更多
基金supported by the National Natural Science Foundation of China,Nos. 81772453 and 81974358 (both to DSX)Shanghai Municipal Key Clinical Specialty Program,No. shslczdzk02701 (to QX)。
文摘Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In this study, we performed double-target neural circuit-magnetic stimulation on the left motor cortex and bilateral L5 nerve root for 3 successive weeks in a rat model of incomplete spinal cord injury caused by compression at T10. Results showed that in the injured spinal cord, the expression of the astrocyte marker glial fibrillary acidic protein and inflammatory factors interleukin 1β, interleukin-6, and tumor necrosis factor-α had decreased, whereas that of neuronal survival marker microtubule-associated protein 2 and synaptic plasticity markers postsynaptic densification protein 95 and synaptophysin protein had increased. Additionally, neural signaling of the descending corticospinal tract was markedly improved and rat locomotor function recovered significantly. These findings suggest that double-target neural circuit-magnetic stimulation improves rat motor function by attenuating astrocyte activation, thus providing a theoretical basis for application of double-target neural circuit-magnetic stimulation in the clinical treatment of spinal cord injury.
基金supported by the National Key R&D Program of China,Nos.2020YFC2004202(to DSX),2018 YFC2001600(to XYH)the National Natural Science Foundation of China,Nos.81974358(to DSX),81802249(to XYH)and 82172554(to XYH)。
文摘Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctuation(ALFF)metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control co rtical impact(CCI)rat model simulating traumatic brain injury.At 3 days after control co rtical impact model establishment,we found that the mean ALFF(mALFF)signals were decreased in the left motor cortex,somatosensory co rtex,insula cortex and the right motor co rtex,and were increased in the right corpus callosum.After 3 weeks of an 8-hour daily mClMT treatment,the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively.The mALFF signal valu es of left corpus callosum,left somatosensory cortex,right medial prefro ntal cortex,right motor co rtex,left postero dorsal hippocampus,left motor cortex,right corpus callosum,and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group.Finally,we identified brain regions with significantly decreased mALFF valu es at 3 days postoperatively.Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions.Our findings suggest that functional co rtical plasticity changes after brain injury,and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric co rtical remodeling.mALFF values correlate with behavio ral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.
基金supported by Research on Chronic Noncommunicable Diseases Prevention and Control of National Ministry of Science and Technology(No.2016YFC1303804)National Natural Science Foundation of China grant(No.81672275,No.81874052,No.3A214DJ63428)to J-WC+1 种基金the Youth Fund of the National Natural Science Foundation of China(No.81802487)the Youth Development Foundation of The First Hospital of jilin University(No.JDYY92018028)to L-YL.
文摘Objective:Serum albumin(ALB)can transport nutrients to circulating and local immune cells by passing through blood vessels and has attracted attention as a prognostic predictor of non-small cell lung cancer(NSCLC)because it reflects the host immunity from peripheral blood(PBL)to the tumor microenvironment. Methods:Clinical data regarding the PBL and tumor tissues were obtained at The First Hospital of Jilin University between February 2009 and March 2017.We detected indices of glucose and lipid metabolism,classified and counted PBL lymphocytes using flow cy-tometry,determined the tumor-infiltrating lymphocytes by quantitative immunofluorescence,and analyzed the T-cell receptor(TCR)rep-ertoire by high-throughput sequencing of the TCR β-chain.The correlations between ALB and metabolic immune indices were analyzed by t tests and Pearson chi-square test. Results:A total of 211 enrolled NSCLC patients were divided into a relatively high-ALB group(>41.75 g/L,n = 56)and a low-ALB group(≤41.75 g/L,n = 155);patients with high ALB had lower Treg cells(P<0.05)and more CD8+ cytotoxic T cells in the PBL(P<0.01)and a higher proportion of stromal CD8+ tumor-infiltrating lymphocytes(P = 0.047)than patients with low ALB.High ALB was also significantly related to more diversity in the TCR repertoire(P = 0.0021,r2 = 0.5481).Moreover,ALB was identified as an in-dependent prognostic factor based on a multivariate Cox regression analysis(P = 0.032;hazard ratio(HR)= 1.804;95%confidence interval(CI)= 1.035-3.146).The median overall survival in patients with low ALB vs high ALB was 28.2 vs 42.2 months(P=0.0142),respectively.Among patients with nonmetastatic NSCLC(stage Ⅰ-Ⅲ),there was a higher incidence of distant metastasis in the low-ALB group than that in the high-ALB group(41.3%and 22.2%,P=0.043).A low ALB also had a strong association with a higher risk for disease progression(P<0.001)and death(P<0.01;HR = 0.555;95%CI= 0.312-0.988). Conclusions:Albumin could affect the host immunity,and high ALB predicted a reduced risk of distant metastasis and improved the prognosis in NSCLC patients.
基金supported by the Major International(Regional)Joint Research Project of the National Natural Science Foundation of China,No.81820108013(to LMC)the General Research Project of the National Natural Science Foundation of China,No.81772453(to DSX)the National Key Research and Development Program of China,No.2016YFA0100800(to LMC)
文摘Spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural dysfunction.Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury,which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies.Besides the involvement of endogenous stem cells in neurogenesis and neural repair,exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases.However,to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury,appropriate interventional measures(e.g.,neuromodulation)should be adopted.Neuromodulation techniques,such as noninvasive magnetic stimulation and electrical stimulation,have been safely applied in many neuropsychiatric diseases.There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system;namely,by exciting,inhibiting,or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury.Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth,encourages the formation of new synaptic connections to promote neural plasticity,and improves motor function recovery in patients with spinal cord injury.With the development of biomaterial technology and biomechanical engineering,several emerging treatments have been developed,such as robots,brain-computer interfaces,and nanomaterials.These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury.However,large-scale clinical trials need to be conducted to validate their efficacy.This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence,to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.
基金supported by the National Natural Science Foundation of China,No.81871841(to YLB) and No.81772453(to DSX)
文摘Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb.However,the molecular mechanism underlying its efficacy remains unclear.In this study,a middle cerebral artery occlusion(MCAO)rat model was produced by the suture method.Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days,starting from the 7^th day after middle cerebral artery occlusion.Day 1 of treatment lasted for 10 minutes at 2r/min,day 2 for 20 minutes at 2 r/min,and from day 3 onward for 20 minutes at 4 r/min.CatWalk gait analysis,adhesive removal test,and Y-maze test were used to investigate motor function,sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21^st day after MCAO.On the 21^st day after MCAO,the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay.The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography.The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats,but had no effect on cognitive function.The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3(Gria3)in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1 A,Avprla in the middle cerebral artery-occluded rats.In the ipsilateral hippocampus,only Adra2 a was downregulated,and there was no significant change in Gria3.Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3,which is an a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor,within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region.The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged.Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion,but had no effect on Synapsin I levels.Besides,we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus.This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats,and suggests that these positive effects occur via the upregulation of the postsynaptic membrane a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression.This study was approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.
基金the National Key Research and Development Project of China,No.2020YFC2004200(to ZYL)the National Natural Science Foundation of China,Nos.61761166007(to ZYL),81772453(to DSX),81974358(to DSX),31771071(to ZYL)Fundamental Research Funds for Central Public Welfare Research Institutes,No.118009001000160001(to ZYL)。
文摘More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments.Therefore,new rehabilitation technologies are urgently needed as auxiliary treatments for motor rehabilitation.Based on routine rehabilitation treatments,a new intelligent rehabilitation platform has been developed for accurate evaluation of function and rehabilitation training.The emerging intelligent rehabilitation techniques can promote the development of motor function rehabilitation in terms of informatization,standardization,and intelligence.Traditional assessment methods are mostly subjective,depending on the experience and expertise of clinicians,and lack standardization and precision.It is therefore difficult to track functional changes during the rehabilitation process.Emerging intelligent rehabilitation techniques provide objective and accurate functional assessment for stroke patients that can promote improvement of clinical guidance for treatment.Artificial intelligence and neural networks play a critical role in intelligent rehabilitation.Multiple novel techniques,such as braincomputer interfaces,virtual reality,neural circuit-magnetic stimulation,and robot-assisted therapy,have been widely used in the clinic.This review summarizes the emerging intelligent rehabilitation techniques for the evaluation and treatment of motor dysfunction caused by nervous system diseases.
基金supported by the National Natural Science Foundation of China,Nos.81974358,81772453(to DSX)。
文摘Paired associative stimulation has been used in stroke patients as an innovative recovery treatment.However,the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear.In this study,rats were randomly divided into middle cerebral occlusion model(MCAO)and paired associated magnetic stimulation(PAMS)groups.The MCAO rat model was produced by middle cerebral artery embolization.The PAMS group received PAMS on days 3 to 20 post MCAO.The MCAO group received sham stimulation,three times every week.Within 18 days after ischemia,rats were subjected to behavioral experiments—the foot-fault test,the balance beam walking test,and the ladder walking test.Balance ability was improved on days 15 and 17,and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group.Western blot assay showed that the expression levels of brain derived neurotrophic factor,glutamate receptor 2/3,postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21.Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere,but decreased in the contralateral hemisphere on day 20.By finite element simulation,the electric field distribution showed a higher intensity,of approximately 0.4 A/m^2,in the ischemic cortex compared with the contralateral cortex in the template.Together,our findings show that PAMS upregulates neuroplasticity-related proteins,increases regional brain activity,and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model.The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.
基金This work was financially supported by the Science and Technology Project of Nantong City of China,No.JC2018060(to XX).
文摘Encouraging results have been reported for the use of transcranial magnetic stimulationbased nerve stimulation in studies of the mechanisms of neurological regulation,nerve injury repair,and nerve localization.However,to date,there are only a few reviews on the use of transcranial magnetic stimulation for diabetic neuropathy.Patients with diabetic neuropathy vary in disease progression and show neuropathy in the early stage of the disease with mild symptoms,making it difficult to screen and identify.In the later stage of the disease,irreversible neurological damage occurs,resulting in treatment difficulties.In this review,we summarize the current state of diabetic neuropathy research and the prospects for the application of transcranial magnetic stimulation in diabetic neuropathy.We review significant studies on the beneficial effects of transcranial magnetic stimulation in diabetic neuropathy treatment,based on the outcomes of its use to treat neurodegeneration,pain,blood flow change,autonomic nervous disorders,vascular endothelial injury,and depression.Collectively,the studies suggest that transcranial magnetic stimulation can produce excitatory/inhibitory stimulation of the cerebral cortex or local areas,promote the remodeling of the nervous system,and that it has good application prospects for the localization of the injury,neuroprotection,and the promotion of nerve regeneration.Therefore,transcranial magnetic stimulation is useful for the screening and early treatment of diabetic neuropathy.transcranial magnetic stimulation can also alleviate pain symptoms by changing the cortical threshold and inhibiting the conduction of sensory information in the thalamo-spinal pathway,and therefore it has therapeutic potential for the treatment of pain and pain-related depressive symptoms in patients with diabetic neuropathy.Additionally,based on the effect of transcranial magnetic stimulation on local blood flow and its ability to change heart rate and urine protein content,transcranial magnetic stimulation has potential in the treatment of autonomic nerve dysfunction and vascular injury in diabetic neuropathy.Furthermore,oxidative stress and the inflammatory response are involved in the process of diabetic neuropathy,and transcranial magnetic stimulation can reduce oxidative damage.The pathological mechanisms of diabetic neuropathy should be further studied in combination with transcranial magnetic stimulation technology.
基金supported by National Key R&D Program of China,No.2020YFC2004202the National Natural Science Foundation of China,Nos.81974358 and 81772453(all to DSX).
文摘Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral(right only)cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots,five times a week.Bilateral resting motor evoked potential amplitude was increased,central motor conduction time on the side receiving cortical stimulation was significantly decreased,and lower extremity motor score,Berg balance score,spinal cord independence measure-III score,and 10 m-walking speed were all increased after treatment.Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment.These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.
基金the National Key Research and Development Program of China,No.2020YFC2004202(to DSX)the National Natural Science Foundation of China(General Program),Nos.81772453,81974358(to DSX)Scientific Research Project of Yangzhi Rehabilitation Hospital Affliated to Tongji University,No.KYPY202006(to TTS)。
文摘Classic paired associative stimulation can improve synaptic plasticity,as demonstrated by animal expe riments and human clinical trials in spinal cord injury patients.Paired associative magnetic stimulation(dual-target peripheral and central magnetic stimulation)has been shown to promote neurologic recove ry after stroke.However,it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury.We hypothesize that the curre nt caused by central and peripheral magnetic stimulation will conve rge at the synapse,which will promote synapse function and improve the motor function of the relevant muscles.Therefore,this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials,motor and sensory function of the lower limbs,functional health and activities of daily living,and depression in patients with spinal co rd injury.We will recruit 110 thora cic spinal trauma patients treated in the Department of Spinal Cord Injury,China Rehabilitation Hospital and randomly assign them to expe rimental and control groups in a 1:1 ratio.The trial group(n=55)will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment.The control group(n=55)will be treated with sham stimulation and co nventional rehabilitation treatment.Outcomes will be measured at four time points:baseline and 4,12,and 24 wee ks after the start of inte rvention(active or sham paired associative magnetic stimulation).The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up.Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function sco re,motor evoked potentials,sensory evoked potentials,modified Ashwo rth scale score,Maslach Burnout Invento ry score,and Hamilton Depression Scale score over time.Motor evoked potential latency reflects corticospinal tract transmission time,while amplitude reflects recruitment ability;both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency.Adve rse events will be recorded.Findings from this trial will help to indicate whether paired associative magnetic stimulation(1)promotes recove ry of lower limb sensory and motor function,reduces spasticity,and improves quality of life;(2)promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity;and(3)improves rehabilitation outcome in patients with spinal cord injury.Recruitment for this trial began in April 2021 and is currently ongoing.It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University,China(approval No.YZ2020-018)on May 18,2020.The study protocol was registered in the Chinese Clinical Trial Registry(registration number:ChiCTR2100044794)on March 27,2021(protocol version 1.0).This trial will be completed in April 2022.
基金supported by the National Natural Science Foundation of China(General Program),Nos.81772453,81974358(both to DSX).
文摘Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits that enable motor function.Our group previously designed a novel magnetic stimulation protocol,targeting the motor cortex and the spinal nerve roots,that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury.Here,we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury.Rats underwent surgery to clamp the spinal cord at T10;three days later,the rats were treated with repetitive magnetic stimulation(5 Hz,25 pulses/train,20 pulse trains)targeting the nerve roots at the L5-L6 vertebrae.The treatment was repeated five times a week over a period of three weeks.We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord.In addition,the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex.Overall,the results suggest that nerve root magnetic stimulation may be an effective,noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.
基金supported by the Project of National Key R&D Program of China,No.2019YFC1709103(to WZB)the National Natural Science Foundation of China,Nos.81774211(to WZB),81873040(to MJY),81774432(to JJC),81801561(to DSX),82004492(to JW)。
文摘The mouse model of multiple cerebral infarctions,established by injecting fluorescent microspheres into the common carotid artery,is a recent development in animal models of cerebral ischemia.To investigate its effectiveness,mouse models of cerebral infarction were created by injecting fluorescent microspheres,45–53μm in diameter,into the common carotid artery.Six hours after modeling,fluorescent microspheres were observed directly through a fluorescence stereomicroscope,both on the brain surface and in brain sections.Changes in blood vessels,neurons and glial cells associated with microinfarcts were examined using fluorescence histochemistry and immunohistochemistry.The microspheres were distributed mainly in the cerebral cortex,striatum and hippocampus ipsilateral to the side of injection.Microinfarcts were found in the brain regions where the fluorescent microspheres were present.Here the lodged microspheres induced vascular and neuronal injury and the activation of astroglia and microglia.These histopathological changes indicate that this animal model of multiple cerebral infarctions effectively simulates the changes of various cell types observed in multifocal microinfarcts.This model is an effective,additional tool to study the pathogenesis of ischemic stroke and could be used to evaluate therapeutic interventions.This study was approved by the Animal Ethics Committee of the Institute of Acupuncture and Moxibustion,China Academy of Chinese Medical Sciences(approval No.D2021-03-16-1)on March 16,2021.
基金supported by the CACMS Innovation Fund,No.CI2021A03407(to WZB)the Project of National Key R&D Program of China,No.2019YFC1709103(to WZB)+1 种基金the National Natural Science Foundation of China,Nos.81774432(to JJC),81774211(to WZB),82004492(to JW),81801561(to DSX)the Fundamental Research Funds for the Central Public Welfare Research Institutes of China,Nos.ZZ13-YQ-068(to JJC),ZZ14-YQ-032(to JW),ZZ14-YQ-034(to DSX).
文摘Neural tract tracing is used to study neural pathways and evaluate neuronal regeneration following nerve injuries.However,it is not always clear which tracer should be used to yield optimal results.In this study,we examined the use of Alexa Fluor 488-conjugated cholera toxin subunit B(AF488-CTB).This was injected into the gastrocnemius muscle of rats,and it was found that motor,sensory,and sympathetic neurons were labeled in the spinal ventral horn,dorsal root ganglia,and sympathetic chain,respectively.Similar results were obtained when we injected AF594-CTB into the tibialis anterior muscle.The morphology and number of neurons were evaluated at different time points following the AF488-CTB injection.It was found that labeled motor and sensory neurons could be observed 12 hours post-injection.The intensity was found to increase over time,and the morphology appeared clear and complete 3-7 days post-injection,with clearly distinguishable motor neuron axons and dendrites.However,14 days after the injection,the quality of the images decreased and the neurons appeared blurred and incomplete.Nissl and immunohistochemical staining showed that the AF488-CTB-labeled neurons retained normal neurochemical and morphological features,and the surrounding microglia were also found to be unaltered.Overall,these results imply that the cholera toxin subunit B,whether unconjugated or conjugated with Alexa Fluor,is effective for retrograde tracing in muscular tissues and that it would also be suitable for evaluating the regeneration or degeneration of injured nerves.
基金the project of National Key R&D Program of China:2019YFC1709103National Natural Science Foundation of China:81774211,81774432,81801561:82004492the Fundamental Research Funds for the Central Public Welfare Research Institutes:ZZ13-YQ-068,ZZ201914001,ZZ202017006,ZZ202017015。
文摘Objective:The aim of this study is to assess the neural interconnection between the acupoint"Chéngshān(承山BL57)"and sciatic nerve from the peripheral nervous system(PNS)to the central nervous system(CNS).Methods:SD rats were systematically examined from the hip to the hind limb along the route of sciatic nerve with regional anatomical technique,and further traced from the BL57 and the trunk of sciatic nerve by the neural tracing technique with cholera toxin subunit B(CTB)and CTB conjugated Alexa Fluor 488 and 594(CTB-AF488/594).Results:After regional anatomy,it was found that the sciatic nerve ran down from the hip to the hind limb and sequentially sent out the tibial and sural branches respectively to the deep and superficial layers of BL57.The CTB labeling associated with both BL57 and sciatic nerve distributed in the same spinal segments and definite regions,including the sensory neurons in lumber 3(L3)-lumber 6(L6)dorsal root ganglia(DRGs),transganglionic axons mainly in the L3-L6 spinal dorsal horn,Clarke’s nucleus,and gracile nucleus,as well as motor neurons mainly in the L3-L6 spinal ventral horn.However,the amount of neural labeling was significantly less in the cases of BL57 than that of sciatic nerve.Conclusions:These results indicate that there is distinct sensory and motor interconnection between the BL57 and the sciatic nerve,which may potentially serve for the active role of the BL57 playing in meliorating the disorders of sciatic nerve.
基金Supported by National Natural Science Foundation of China Project:81774211,81774432,81801561
文摘Objective:The innervations in Yinlingquan(阴陵泉SP9)and Yanglingquan(阳陵泉GB34)were investigated to explore the neuroanatomical interconnection of the complementary acupoints in the rat hindlimb.Methods:A dual neural tracing technique was used,six male Sprague-Dawley rats were included in experiment.Under anesthesia with isoflurane,cholera toxin subunit B conjugated with Alexa Fluor 488 and 594(CTB-AF488/594)were separately injected into SP9 and GB34 in the same rat.Three days later,the neural labeling was examined in the dorsal root ganglion(DRG),spinal cord,and sympathetic chain at lumbar(L)spinal segments under a laser scanning confocal microscope.Results:All neural labeling were present on the ipsilateral side of tracer injection,including sensory,motor and sympathetic postganglionic neurons.The sensory neurons associated with SP9 and GB34 were distributed in the DRG from L2 to L6 and concentrated in L3-L4 and L4-L5 respectively,while most of the double labeled sensory neurons were presented in L4.On the other hand,the labeled motor neurons for SP9 and GB34 were observed in the dorsolateral part of spinal ventral horn at L2-L4 and L3-L5 respectively,and some of them were double labeled at L4.In addition,the sympathetic postganglionic neurons related to SP9 and GB34 were found in the lumbar sympathetic chain respectively.Conclusion:The similarities of the sensory,motor,and sympathetic innervation of SP9 and GB34 in the rat provide the neuroanatomical evidence to understand the synergetic effect that arise from the stimulation at the complementary acupoints.
基金Foundation of China (Grant Nos. 51390473 and 51771203)the Key Research Program of Frontier Sciences, Chinese Academy of Sciences+1 种基金the National Key Research and Development Plan (Grant No. 2016YFB0701304)the Fundamental Research Fund for the Central Universities (Grant No. N140108001)
文摘Using scanning, transmission electron microscopy and aberration-corrected scanning transmission electron microscopy, we have studied the interactions between dislocations and twins in impact deformed polysynthetic twinned TiAl crystal. The 1/3 < 111] and 1/6 < 211] step dislocations on coherent twin boundaries reveal the interactions of glissile 1/2 < 101> dislocations with the coherent twin boundaries.An abnormal stacking fault was found adjacent to the coherent twin boundary. It has the same stacking sequence but different atom species in the [110] direction with an additional displacement of 1/4[110]in two neighboring {111} layers, and is likely induced by the slip of a 1/12[112](i.e. 1/4[110] + 1/6[211])dislocation.
基金support from the National Natural Science Foundation of China (Nos. 51601078 and 51201147)the National Key R&D Program of China (Grant No. 2016YFB0701302)+1 种基金the Informalization Construction Program of Chinese Academy of Science (INFO-115-B01)Shenyang Supercomputer Centers for the computational resource of Chinese Academy of Science
文摘A quantitative phase field method of multi-component diffusion-controlled phase transformations coupled with the Kim–Kim–Suzuki model was applied to study the effect of initial particle size distribution(PSD) in 3D and space distribution in 2D on dissolution of α particles in Ti–6Al–4V alloy below β transus temperature in real time and length scale. The thermodynamic and mobility data were obtained from Thermo-Calc and DICTRA softwares, respectively. The results show that the volume fractions of α particles decay with time as: f =f_(eq)+ (f_0-f_(eq))exp(-Kt^n) for four cases of PSD. The sequence of dissolution kinetics from fast to slow is: uniform PSD, normal PSD, lognormal PSD and bimodal PSD. The space distribution is found to be a major factor affecting the dissolution kinetics and the microstructures. When the distance of the particles is less than critical value, the dissolution rates reduce with the decrease in distance. The Al and V concentration fields around the particles appear more obvious soft impingement.
文摘The microstructural evolution and tensile properties of Ti-3Al-8V-6Cr-4Mo-xZr(x = 0,2,4 and 6) titanium alloys were investigated.The precipitated phases and tensile fracture morphologies were observed using scanning electron microscopy and transmission electron microscopy.Experimental results show that the presence of trace impurity Si and the addition of Zr induce the formation of(TiZr)_6Si_3 silicides.The quantity of silicides increases with Zr content increasing.The dispersed silicides refined the grain size of β Zr-containing alloys,and the grain size decreases significantly with Zr content increasing.Accompanying these microstructural changes,the strength of the alloys is enhanced gradually with the increase of Zr content,which is attributed to the combination of precipitation strengthening and grain refinement.
