Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-li...Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.展开更多
BACKGROUND Patients with Parkinson's disease(PD)exhibit symptoms such as antecollis(AC)and camptocormia(CC).The pathology of these two conditions is unclear.Additionally,standard treatment methods have not been es...BACKGROUND Patients with Parkinson's disease(PD)exhibit symptoms such as antecollis(AC)and camptocormia(CC).The pathology of these two conditions is unclear.Additionally,standard treatment methods have not been established.The article reports the case of a 65-year-old female patient with AC and CC who was treated with central and peripheral interventions to alleviate symptoms.CASE SUMMARY We present the case of a 65-year-old female PD patient with AC and CC.The course of the disease was 5 years.She was treated with rehabilitation strategies such as sensory tricks and trunk strength training.During the inpatient period,we compared and analyzed the patient's gait,rehabilitation assessment scale score,and angles of her abnormal trunk posture in the first week,the third week,and the fifth week.The patient's stride length increased,indicating that the patient's walking ability was improved.The Unified Parkinson's Disease Scale Part Three score and CC severity score decreased.Furthermore,the score of the other scale increased.In addition,the patient showed significant improvements in AC,upper CC,and lower CC angles.CONCLUSION This case study suggested that sensory tricks and trunk strength training are beneficial and safe for patients with AC and CC.展开更多
The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development.However,its function in retina regeneration remains elusive.Here we report that Sox11 b,a zebrafish Sox11 ...The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development.However,its function in retina regeneration remains elusive.Here we report that Sox11 b,a zebrafish Sox11 homolog,regulates the migration and fate determination of Müller glia-derived progenitors(MGPCs)in an adult zebrafish model of mechanical retinal injury.Following a stab injury,the expression of Sox11 b was induced in proliferating MGPCs in the retina.Sox11 b knockdown did not affect MGPC formation at 4 days post-injury,although the nuclear morphology and subsequent radial migration of MGPCs were alte red.At 7 days post-injury,Sox11 b knockdown res ulted in an increased proportion of MGPCs in the inner retina and a decreased propo rtion of MGPCs in the outer nuclear layer,compared with controls.Furthermore,Sox11 b knockdown led to reduced photoreceptor regeneration,while it increased the numbe rs of newborn amacrines and retinal ganglion cells.Finally,quantitative polymerase chain reaction analysis revealed that Sox11 b regulated the expression of Notch signaling components in the retina,and Notch inhibition partially recapitulated the Sox11 b knockdown phenotype,indicating that Notch signaling functions downstream of Sox11 b.Our findings imply that Sox11 b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish,which may have critical im plications for future explorations of retinal repair in mammals.展开更多
Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that ...Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.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
Schizophrenia(SCZ)is a devastating and complicated mental disorder accompanied by variable positive and negative symptoms and cognitive deficits.Although many genetic risk factors have been identified,SCZ is also cons...Schizophrenia(SCZ)is a devastating and complicated mental disorder accompanied by variable positive and negative symptoms and cognitive deficits.Although many genetic risk factors have been identified,SCZ is also considered as a neurodevelopmental disorder.Elucidation of the pathogenesis and the development of treatment is challenging because complex interactions occur between these genetic risk factors and environment in essential neurodevelopmental processes.Adult neural stem cells share a lot of similarities with embryonic neural stem cells and provide a promising model for studying neuronal development in adulthood.These adult neural stem cells also play an important role in cognitive functions including temporal and spatial memory encoding and context discrimination,which have been shown to be closely linked with many psychiatric disorders,such as SCZ.Here in this review,we focus on the SCZ risk genes and the key components in related signaling pathways in adult hippocampal neural stem cells and summarize their roles in adult neurogenesis and animal behaviors.We hope that this would be helpful for the understanding of the contribution of dysregulated adult neural stem cells in the pathogenesis of SCZ and for the identification of potential therapeutic targets,which could facilitate the development of novel medication and treatment.展开更多
The discovery of G-protein coupled receptor(GPCR)accessory proteins has fundamentally redefined the pharmacological concept of GPCR signaling,demonstrating a more complex molecular basis for receptor specificity on th...The discovery of G-protein coupled receptor(GPCR)accessory proteins has fundamentally redefined the pharmacological concept of GPCR signaling,demonstrating a more complex molecular basis for receptor specificity on the plasma membrane and impressionable downstream intracellular cascades.GPCR accessory proteins not only contribute to the proper folding and trafficking of receptors but also exhibit selectable receptor preferences.展开更多
To the Editor:Currently known syndromes of acute post-infectious or inflammatory demyelination include acute disseminated encephalomyelitis,encephalitis,transverse myelitis(TM),and Guillain–Barrésyndrome(GBS).De...To the Editor:Currently known syndromes of acute post-infectious or inflammatory demyelination include acute disseminated encephalomyelitis,encephalitis,transverse myelitis(TM),and Guillain–Barrésyndrome(GBS).Demyelination is frequently limited to the central or peripheral nervous systems.The coexistence of myelitis and demyelinating peripheral neuropathy has only been reported in a few children[1,2]and young adults.[3]Also,concomitant TM and GBS in elderly immunocompetent patients has been rarely described.展开更多
Melanocortins,including a-melanocyte stimulating hormone(a-MSH),b-MSH,g-MSH,and adrenocorticotropin(ACTH),are ancient peptides highly conserved in vertebrates and exhibit diverse well-established functions,including d...Melanocortins,including a-melanocyte stimulating hormone(a-MSH),b-MSH,g-MSH,and adrenocorticotropin(ACTH),are ancient peptides highly conserved in vertebrates and exhibit diverse well-established functions,including dermal pigmentation,adrenal steroidogenesis and cell proliferation,energy homeostasis,and inflammation.1 Melanocortins exert their diverse functions through five melanocortin receptors(MCRs),MC1R-MC5R,numbered based on the sequence of their cloning.展开更多
The locking plate and percutaneous crossing metallic screws and crossing absorbable screws have been used clinically to treat intra-articular calcaneal fractures, but little is known about the biomechanical difference...The locking plate and percutaneous crossing metallic screws and crossing absorbable screws have been used clinically to treat intra-articular calcaneal fractures, but little is known about the biomechanical differences between them. This study compared the biomechanical stability of calcaneal fractures fixed using a locking plate and crossing screws. Three-dimensional finite-element models of intact and fractured calcanei were developed based on the CT images of a cadaveric sample. Surgeries were simulated on models of Sanders type III calcaneal fractures to produce accurate postoperative models fixed by the three implants. A vertical force was applied to the superior surface of the subtalar joint to simulate the stance phase of a walking gait. This model was validated by an in vitro experiment using the same calcaneal sample. The intact calcaneus showed greater stiffness than the fixation models. Of the three fixations, the locking plate produced the greatest stiffness and the highest von Mises stress peak. The micromotion of the fracture fixated with the locking plate was similar to that of the fracture fixated with the metallic screws but smaller than that fixated with the absorbable screws. Fixation with both plate and crossing screws can be used to treat intra-articular calcaneal fractures. In general, fixation with crossing metallic screws is preferable because it provides sufficient stability with less stress shielding.展开更多
Physical activity has been known as an essential element to promote human health for centuries.Thus,exercise intervention is encouraged to battle against sedentary lifestyle.Recent rapid advances in molecular biotechn...Physical activity has been known as an essential element to promote human health for centuries.Thus,exercise intervention is encouraged to battle against sedentary lifestyle.Recent rapid advances in molecular biotechnology have demonstrated that both endurance and resistance exercise training,two traditional types of exercise,trigger a series of physiological responses,unraveling the mechanisms of exercise regulating on the human body.Therefore,exercise has been expected as a candidate approach of alleviating a wide range of diseases,such as metabolic diseases,neurodegenerative disorders,tumors,and cardiovascular diseases.In particular,the capacity of exercise to promote tissue regeneration has attracted the attention of many researchers in recent decades.Since most adult human organs have a weak regenerative capacity,it is currently a key challenge in regenerative medicine to improve the efficiency of tissue regeneration.As research progresses,exercise-induced tissue regeneration seems to provide a novel approach for fighting against injury or senescence,establishing strong theoretical basis for more and more“exercise mimetics.”These drugs are acting as the pharmaceutical alternatives of those individuals who cannot experience the benefits of exercise.Here,we comprehensively provide a description of the benefits of exercise on tissue regeneration in diverse organs,mainly focusing on musculoskeletal system,cardiovascular system,and nervous system.We also discuss the underlying molecular mechanisms associated with the regenerative effects of exercise and emerging therapeutic exercise mimetics for regeneration,as well as the associated opportunities and challenges.We aim to describe an integrated perspective on the current advances of distinct physiological mechanisms associated with exercise-induced tissue regeneration on various organs and facilitate the development of drugs that mimics the benefits of exercise.展开更多
As a markerless motion capture system(MLS),the Microsoft Kinect sensor may be a low-cost and portable option for measuring shoulder joint angles.However,the system's concurrent validity to capture shoulder functio...As a markerless motion capture system(MLS),the Microsoft Kinect sensor may be a low-cost and portable option for measuring shoulder joint angles.However,the system's concurrent validity to capture shoulder functional movement is unclear.The purpose of this study was to investigate the concurrent validity of MLS for capturing shoulder kinematics during functional movement by comparing the MLS measures to those of the marker-based motion capture system(MBS).Twenty-five healthy participants were included in this study.Using the Microsoft Kinect sensor as the MLS and Vicon as the MBS,six shoulder functional movements were measured in all three anatomical planes concurrently.The six movements included flexion to max,maximum extension,abduction to 90°,internal rotation at 90°abduction,external rotation at 0°abduction,and maximum horizontal adduction.The shoulder joint kinematics was measured with both systems.The MLS showed a good to excellent correlation(r>0.75)with MBS for abduction to 90°,maximum external rotation at 0°abduction and maximum internal rotation at 90°abduction.The results for maximum extension(r=0.727)and maximum horizontal adduction(r=0.619)showed a moderate to good correlation.For maximum flexion,a poor correlation was observed(r=0.479).The validity of the MLS to measure shoulder kinematics would be acceptable.The system demonstrates potential as a measurement tool of joint motions for a function assessment and rehabilitation purpose.展开更多
Mechanical signal capture without physical contact has emerged as a highly promising research field and attracted tremendous attention due to its prosperous applications in household medical care,lifestyle monitoring ...Mechanical signal capture without physical contact has emerged as a highly promising research field and attracted tremendous attention due to its prosperous applications in household medical care,lifestyle monitoring and remote operation,offering users high level of safety,convenience and comfort.Moreover,noncontact sensing is ideal to maximize the immersive user experience in the human–machine interaction(HMI),eliminating interference to human activities and mechanical fatigue to the sensor,simultaneously.Herein,we report a self-powered flexible sensor integrated with irradiation cross-linked polypropylene(IXPP)piezoelectret film for noncontact sensing,featuring multi-functions to detect mechanical signals transmitted through solid,liquid and gaseous media and would facilitate their versatile practical applications.The folded-structure configuration of the sensor facilitates the improvement of the noncontact sensing sensitivity.For solid media,such as the rectangular wooden stick used in this study,the sensor can detect mechanical stimulus exerted at a distance of 100 cm.A system detection sensitivity up to 57 pC/kPa with a low detection limit of 0.6 kPa is achieved at a noncontact distance of 10 cm.Even when partly or completely immersed in water,the sensor effectively traces movement signals of human bodies underwater,demonstrating great advantages for non-inductive aquatic fitness training monitoring.Furthermore,due to the low acoustic impedance of piezoelectret film,speech recognition through gaseous medium is also achieved.We further introduce application demonstrations of the developed film sensors to monitor exercise postures and physiological signals without direct contact between human body and the sensor,displaying great potential to be incorporated into future smart electronics.This study commendably expands the application scope of piezoelectret materials,which will have profound implications for exploring novel intelligent human–machine interactions.展开更多
基金supported by the National Key R&D Program of China,No.2019YFA0110300(to ZG)the National Natural Science Foundation of China,Nos.81773302(to YF),32070862(to ZG).
文摘Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.
文摘BACKGROUND Patients with Parkinson's disease(PD)exhibit symptoms such as antecollis(AC)and camptocormia(CC).The pathology of these two conditions is unclear.Additionally,standard treatment methods have not been established.The article reports the case of a 65-year-old female patient with AC and CC who was treated with central and peripheral interventions to alleviate symptoms.CASE SUMMARY We present the case of a 65-year-old female PD patient with AC and CC.The course of the disease was 5 years.She was treated with rehabilitation strategies such as sensory tricks and trunk strength training.During the inpatient period,we compared and analyzed the patient's gait,rehabilitation assessment scale score,and angles of her abnormal trunk posture in the first week,the third week,and the fifth week.The patient's stride length increased,indicating that the patient's walking ability was improved.The Unified Parkinson's Disease Scale Part Three score and CC severity score decreased.Furthermore,the score of the other scale increased.In addition,the patient showed significant improvements in AC,upper CC,and lower CC angles.CONCLUSION This case study suggested that sensory tricks and trunk strength training are beneficial and safe for patients with AC and CC.
基金supported by the National Key Research and Development Project of China,Nos.2017YFA0104100(to JL),2017YFA0701304(to HX)National Natural Science Foundation of China Nos.81970820(to HX),31930068(to JL)。
文摘The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development.However,its function in retina regeneration remains elusive.Here we report that Sox11 b,a zebrafish Sox11 homolog,regulates the migration and fate determination of Müller glia-derived progenitors(MGPCs)in an adult zebrafish model of mechanical retinal injury.Following a stab injury,the expression of Sox11 b was induced in proliferating MGPCs in the retina.Sox11 b knockdown did not affect MGPC formation at 4 days post-injury,although the nuclear morphology and subsequent radial migration of MGPCs were alte red.At 7 days post-injury,Sox11 b knockdown res ulted in an increased proportion of MGPCs in the inner retina and a decreased propo rtion of MGPCs in the outer nuclear layer,compared with controls.Furthermore,Sox11 b knockdown led to reduced photoreceptor regeneration,while it increased the numbe rs of newborn amacrines and retinal ganglion cells.Finally,quantitative polymerase chain reaction analysis revealed that Sox11 b regulated the expression of Notch signaling components in the retina,and Notch inhibition partially recapitulated the Sox11 b knockdown phenotype,indicating that Notch signaling functions downstream of Sox11 b.Our findings imply that Sox11 b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish,which may have critical im plications for future explorations of retinal repair in mammals.
基金National Key R&D Program of China,Nos.2019YFA0110300 (to LZ),2021YFA1201400 (to LZ)Natural Science Foundation of Shanghai,No.21ZR1468600 (to LZ)Open Fund of the Key Laboratory of Cellular Physiology (Shanxi Medical University),Ministry of Education,No.KLMEC/SXMU-201910 (to XJ)。
文摘Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.
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.
文摘Schizophrenia(SCZ)is a devastating and complicated mental disorder accompanied by variable positive and negative symptoms and cognitive deficits.Although many genetic risk factors have been identified,SCZ is also considered as a neurodevelopmental disorder.Elucidation of the pathogenesis and the development of treatment is challenging because complex interactions occur between these genetic risk factors and environment in essential neurodevelopmental processes.Adult neural stem cells share a lot of similarities with embryonic neural stem cells and provide a promising model for studying neuronal development in adulthood.These adult neural stem cells also play an important role in cognitive functions including temporal and spatial memory encoding and context discrimination,which have been shown to be closely linked with many psychiatric disorders,such as SCZ.Here in this review,we focus on the SCZ risk genes and the key components in related signaling pathways in adult hippocampal neural stem cells and summarize their roles in adult neurogenesis and animal behaviors.We hope that this would be helpful for the understanding of the contribution of dysregulated adult neural stem cells in the pathogenesis of SCZ and for the identification of potential therapeutic targets,which could facilitate the development of novel medication and treatment.
基金supported by the National Natural Science Foundation of China(Grant No.32271165)Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by the Science and Technology Commission of Shanghai Municipality(Grant No.22MC1940300)+2 种基金the Innovative Research Team of High-level Local Universities in Shanghai(Grant No.SHSMU-ZDCX20210400)the Key Laboratory Program of the Education Commission of Shanghai Municipality(No.ZDSYS14005)China Postdoctoral Science Foundation(Grant No.2022M722127).
文摘The discovery of G-protein coupled receptor(GPCR)accessory proteins has fundamentally redefined the pharmacological concept of GPCR signaling,demonstrating a more complex molecular basis for receptor specificity on the plasma membrane and impressionable downstream intracellular cascades.GPCR accessory proteins not only contribute to the proper folding and trafficking of receptors but also exhibit selectable receptor preferences.
基金This study was supported by a grant from the Shanghai Municipal Science and Technology Major Project(No.2021SHZDZX0100)and the Fundamental Research Funds for the Central Universities.
文摘To the Editor:Currently known syndromes of acute post-infectious or inflammatory demyelination include acute disseminated encephalomyelitis,encephalitis,transverse myelitis(TM),and Guillain–Barrésyndrome(GBS).Demyelination is frequently limited to the central or peripheral nervous systems.The coexistence of myelitis and demyelinating peripheral neuropathy has only been reported in a few children[1,2]and young adults.[3]Also,concomitant TM and GBS in elderly immunocompetent patients has been rarely described.
基金supported by the National Natural Science Foundation of China(grant no.32271165 to Chao Zhang).
文摘Melanocortins,including a-melanocyte stimulating hormone(a-MSH),b-MSH,g-MSH,and adrenocorticotropin(ACTH),are ancient peptides highly conserved in vertebrates and exhibit diverse well-established functions,including dermal pigmentation,adrenal steroidogenesis and cell proliferation,energy homeostasis,and inflammation.1 Melanocortins exert their diverse functions through five melanocortin receptors(MCRs),MC1R-MC5R,numbered based on the sequence of their cloning.
基金supported by the Shanghai Municipal Commission of Health and Family Planning(20144Y0250,20134Y207)the National Natural Science Foundation of China(11302154,11272273)The Hong Kong Research Grant Council GRF(PolyU152216/14E,PolyU5326/11E)
文摘The locking plate and percutaneous crossing metallic screws and crossing absorbable screws have been used clinically to treat intra-articular calcaneal fractures, but little is known about the biomechanical differences between them. This study compared the biomechanical stability of calcaneal fractures fixed using a locking plate and crossing screws. Three-dimensional finite-element models of intact and fractured calcanei were developed based on the CT images of a cadaveric sample. Surgeries were simulated on models of Sanders type III calcaneal fractures to produce accurate postoperative models fixed by the three implants. A vertical force was applied to the superior surface of the subtalar joint to simulate the stance phase of a walking gait. This model was validated by an in vitro experiment using the same calcaneal sample. The intact calcaneus showed greater stiffness than the fixation models. Of the three fixations, the locking plate produced the greatest stiffness and the highest von Mises stress peak. The micromotion of the fracture fixated with the locking plate was similar to that of the fracture fixated with the metallic screws but smaller than that fixated with the absorbable screws. Fixation with both plate and crossing screws can be used to treat intra-articular calcaneal fractures. In general, fixation with crossing metallic screws is preferable because it provides sufficient stability with less stress shielding.
基金National Natural Science Foundation of China(92068101,31871498)Project from Shanghai Municipal Health Commission(2022XD050)+3 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(828313)Project from National Research Center for Translational Medicine at Shanghai(TMSK-2021–106)Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(2019CXJQ01)Innovative Research Team of High-level Local Universities in Shanghai.
文摘Physical activity has been known as an essential element to promote human health for centuries.Thus,exercise intervention is encouraged to battle against sedentary lifestyle.Recent rapid advances in molecular biotechnology have demonstrated that both endurance and resistance exercise training,two traditional types of exercise,trigger a series of physiological responses,unraveling the mechanisms of exercise regulating on the human body.Therefore,exercise has been expected as a candidate approach of alleviating a wide range of diseases,such as metabolic diseases,neurodegenerative disorders,tumors,and cardiovascular diseases.In particular,the capacity of exercise to promote tissue regeneration has attracted the attention of many researchers in recent decades.Since most adult human organs have a weak regenerative capacity,it is currently a key challenge in regenerative medicine to improve the efficiency of tissue regeneration.As research progresses,exercise-induced tissue regeneration seems to provide a novel approach for fighting against injury or senescence,establishing strong theoretical basis for more and more“exercise mimetics.”These drugs are acting as the pharmaceutical alternatives of those individuals who cannot experience the benefits of exercise.Here,we comprehensively provide a description of the benefits of exercise on tissue regeneration in diverse organs,mainly focusing on musculoskeletal system,cardiovascular system,and nervous system.We also discuss the underlying molecular mechanisms associated with the regenerative effects of exercise and emerging therapeutic exercise mimetics for regeneration,as well as the associated opportunities and challenges.We aim to describe an integrated perspective on the current advances of distinct physiological mechanisms associated with exercise-induced tissue regeneration on various organs and facilitate the development of drugs that mimics the benefits of exercise.
基金The present study was funded by the National Key Research&Development Program of China(2021YFE0204500)Shanghai Disabled Persons’Federation(K2018031)the Shanghai Traditional Chinese Medicine Inheritance and Technological Innovation Project(ZYKC2019032).
文摘As a markerless motion capture system(MLS),the Microsoft Kinect sensor may be a low-cost and portable option for measuring shoulder joint angles.However,the system's concurrent validity to capture shoulder functional movement is unclear.The purpose of this study was to investigate the concurrent validity of MLS for capturing shoulder kinematics during functional movement by comparing the MLS measures to those of the marker-based motion capture system(MBS).Twenty-five healthy participants were included in this study.Using the Microsoft Kinect sensor as the MLS and Vicon as the MBS,six shoulder functional movements were measured in all three anatomical planes concurrently.The six movements included flexion to max,maximum extension,abduction to 90°,internal rotation at 90°abduction,external rotation at 0°abduction,and maximum horizontal adduction.The shoulder joint kinematics was measured with both systems.The MLS showed a good to excellent correlation(r>0.75)with MBS for abduction to 90°,maximum external rotation at 0°abduction and maximum internal rotation at 90°abduction.The results for maximum extension(r=0.727)and maximum horizontal adduction(r=0.619)showed a moderate to good correlation.For maximum flexion,a poor correlation was observed(r=0.479).The validity of the MLS to measure shoulder kinematics would be acceptable.The system demonstrates potential as a measurement tool of joint motions for a function assessment and rehabilitation purpose.
基金supported by the National Natural Science Foundation of China(NSFC,Nos.62201392,12174061 and 12374451).
文摘Mechanical signal capture without physical contact has emerged as a highly promising research field and attracted tremendous attention due to its prosperous applications in household medical care,lifestyle monitoring and remote operation,offering users high level of safety,convenience and comfort.Moreover,noncontact sensing is ideal to maximize the immersive user experience in the human–machine interaction(HMI),eliminating interference to human activities and mechanical fatigue to the sensor,simultaneously.Herein,we report a self-powered flexible sensor integrated with irradiation cross-linked polypropylene(IXPP)piezoelectret film for noncontact sensing,featuring multi-functions to detect mechanical signals transmitted through solid,liquid and gaseous media and would facilitate their versatile practical applications.The folded-structure configuration of the sensor facilitates the improvement of the noncontact sensing sensitivity.For solid media,such as the rectangular wooden stick used in this study,the sensor can detect mechanical stimulus exerted at a distance of 100 cm.A system detection sensitivity up to 57 pC/kPa with a low detection limit of 0.6 kPa is achieved at a noncontact distance of 10 cm.Even when partly or completely immersed in water,the sensor effectively traces movement signals of human bodies underwater,demonstrating great advantages for non-inductive aquatic fitness training monitoring.Furthermore,due to the low acoustic impedance of piezoelectret film,speech recognition through gaseous medium is also achieved.We further introduce application demonstrations of the developed film sensors to monitor exercise postures and physiological signals without direct contact between human body and the sensor,displaying great potential to be incorporated into future smart electronics.This study commendably expands the application scope of piezoelectret materials,which will have profound implications for exploring novel intelligent human–machine interactions.
