The orbitofrontal cortex(OFC)is involved in diverse brain functions via its extensive projections to multiple target regions.There is a growing understanding of the overall outputs of the OFC at the population level,b...The orbitofrontal cortex(OFC)is involved in diverse brain functions via its extensive projections to multiple target regions.There is a growing understanding of the overall outputs of the OFC at the population level,but reports of the projection patterns of individual OFC neurons across different cortical layers remain rare.Here,by combining neuronal sparse and bright labeling with a whole-brain florescence imaging system(fMOST),we obtained an uninterrupted three-dimensional whole-brain dataset and achieved the full morphological reconstruction of 25 OFC pyramidal neurons.We compared the wholebrain projection targets of these individual OFC neurons in different cortical layers as well as in the same cortical layer.We found cortical layer-dependent projections characterized by divergent patterns for information delivery.Our study not only provides a structural basis for understanding the principles of laminar organizations in the OFC,but also provides clues for future functional and behavioral studies on OFC pyramidal neurons.展开更多
Cerebral blood perfusion and cerebrovascular lesions are important factors that can affect the therapeutic efficacy of thrombolysis.At present,the majority of studies focus on assessing the accuracy of lesion location...Cerebral blood perfusion and cerebrovascular lesions are important factors that can affect the therapeutic efficacy of thrombolysis.At present,the majority of studies focus on assessing the accuracy of lesion location using imaging methods before treatment,with less attention to predictions of outcomes after thrombolysis.Thus,in the present study,we assessed the efficacy of combined computed tomography（CT） perfusion and CT angiography in predicting clinical outcomes after thrombolysis in ischemic stroke patients.The study included 52 patients who received both CT perfusion and CT angiography.Patients were grouped based on the following criteria to compare clinical outcomes：（1） thrombolytic and non-thrombolytic patients,（2） thrombolytic patients with CT angiography showing the presence or absence of a vascular stenosis,（3） thrombolytic patients with CT perfusion showing the presence or absence of hemodynamic mismatch,and（4） different CT angiography and CT perfusion results.Short-term outcome was assessed by the 24-hour National Institution of Health Stroke Scale score change.Long-term outcome was assessed by the 3-month modified Rankin Scale score.Of 52 ischemic stroke patients,29 were treated with thrombolysis and exhibited improved short-term outcomes compared with those without thrombolysis treatment（23 patients）.Patients with both vascular stenosis and blood flow mismatch（13 patients） exhibited the best short-term outcome,while there was no correlation of long-term outcome with CT angiography or CT perfusion findings.These data suggest that combined CT perfusion and CT angiography are useful for predicting short-term outcome,but not long-term outcome,after thrombolysis.展开更多
Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheime...Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.展开更多
Background：For patients with a brain metastasis （BM）,systemic therapy is usually administered after the completion of radiotherapy,especially in cases of multiple BMs.However,the role of systemic therapy in patient...Background：For patients with a brain metastasis （BM）,systemic therapy is usually administered after the completion of radiotherapy,especially in cases of multiple BMs.However,the role of systemic therapy in patients with a limited number of BMs is not clear.Therefore,we conducted a retrospective study to explore this question.Methods：Consecutive patients with a pathologically confirmed malignancy and 1-3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in China.Results：A total of 250 patients were enrolled;of them,135 received radiotherapy alone and 115 received radiotherapy plus systemic therapy.In patients receiving whole-brain radiation therapy （WBRT） as radiotherapy,28 received WBRT alone and 35 patients received WBRT plus systemic therapy.Of the patients treated with stereotactic radiosurgery （SRS）,107 received SRS alone and 80 received SRS plus systemic therapy.Multivariate analysis revealed that systemic therapy significantly reduced the risk of mortality compared with radiotherapy alone （hazard ratio [HR] =0.294,95% confidence interval [CI] =0.158-0.548）.Further,when the analysis was conducted in subgroups ofWBRT （HR =0.230,95% CI =0.081-0.653） or SRS （HR=0.305,95% CI=0.127-0.731）,systemic therapy still showed the ability to reduce the risk of mortality in patients with BMs.Conclusion：Systemic therapy after either SRS or WBRT radiotherapy may significantly reduce the risk of mortality of patients with 1-3 BMs.展开更多
Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimul...Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson’s disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity(up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity(Unified Parkinson’s Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy,and warrant future experimental investigation to validate its clinical utility.展开更多
Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely u...Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal ch展开更多
Background：The role ofpostradiation systemic therapy in non-small cell lung cancer （NSCLC） patients with brain metastasis （BM） was controversial.Thus,we explored the role of Radiation Therapy Oncology Group recur...Background：The role ofpostradiation systemic therapy in non-small cell lung cancer （NSCLC） patients with brain metastasis （BM） was controversial.Thus,we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis （RTOG-RPA） and graded prognostic assessment （GPA） in identifying population who may benefit from postradiation systemic therapy.Methods：The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively.Cox regression was used for multivariate analysis.Survival of patients with or without postradiation systemic therapy was compared in subgroups stratified according to RTOG-RPA or GPA.Results：Of 216 included patients,67.1% received stereotactic radiosurgery （SRS）,24.1% received whole-brain radiation therapy （WBRT）,and 8.8% received both.After radiotherapy,systemic therapy was administered in 58.3% of patients.Multivariate analysis found that postradiation systemic therapy （yes vs.no） （hazard ratio [HR] =0.36 l,95% confidence interval [CI] =0.202-0.648,P =0.001）,radiation technique （SRS vs.WBRT） （HR =0.462,95% CI =0.238-0.849,P =0.022）,extracranial metastasis （yes vs.no） （HR =3.970,95% CI =1.757-8.970,P =0.001）,and Kamofsky performance status （〈70 vs.≥70） （HR =5.338,95% CI =2.829-10.072,P 〈 0.001） were independent factors for survival.Further analysis found that subsequent tyrosine kinase inhibitor （TKI） therapy could significantly reduce the risk of mortality of patients in RTOG-RPA Class IⅡ （HR =0.411,95% CI =0.183-）.923,P =0.031） or with a GPA score of 1.5-2.5 （HR =0.420,95% CI =0.182-0.968,P =0.042）.However,none of the subgroups stratified according to RTOG-RPA or GPA benefited from the additional conventional chemotherapy.Conclusion：RTOG-RPA and GPA may be useful to identify beneficial populations in NSCLC patients with BM ifTKIs were chosen as postradiation systemic therapy.展开更多
In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients....In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.展开更多
Astudy published in Science on February 2 revealed the spatial connectivity patterns of over 10,000 mouse hippocampal neurons at the mesoscopic level.The study was conducted by teams from the Center for Excellence in ...Astudy published in Science on February 2 revealed the spatial connectivity patterns of over 10,000 mouse hippocampal neurons at the mesoscopic level.The study was conducted by teams from the Center for Excellence in Brain Science and Intelligence Technology(CEBSIT),the Institute of Neuroscience(ION)of the Chinese Academy of Sciences(CAS).展开更多
As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and mani...As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and manipulation.Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular,cellular,structural,and functional levels,including the anatomy,functional neural network,and interaction among different brain regions,thus facilitating the discovery of brain development and evolution.In addition to studying the neuro-electrophysiological features of brain cortex development,human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease,especially in mimicking malformations of cortical development,thus revealing pathological mechanism and identifying effective drugs.In this review,we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype,underlying mechanisms and rescue strategies.展开更多
The zona incerta(ZI)is involved in various functions and may serve as an integrative node of the circuits for global behavioral modulation.However,the long-range connectivity of different sectors in the mouse ZI has n...The zona incerta(ZI)is involved in various functions and may serve as an integrative node of the circuits for global behavioral modulation.However,the long-range connectivity of different sectors in the mouse ZI has not been comprehensively mapped.Here,we obtained whole-brain images of the input and output connections via fluorescence micro-optical sectioning tomography and viral tracing.The principal regions in the input-output circuits of ZI GABAergic neurons were topologically organized.The 3D distribution of cortical inputs showed rostro-caudal correspondence with different ZI sectors,while the projection fibers from ZI sectors were longitudinally organized in the superior colliculus.Clustering results show that the medial and lateral ZI are two different major functional compartments,and they can be further divided into more subdomains based on projection and input connectivity.This study provides a comprehensive anatomical foundation for understanding how the ZI is involved in integrating different information,conveying motivational states,and modulating global behaviors.展开更多
Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration.However,morphological assessments of retinorecipient regions are...Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration.However,morphological assessments of retinorecipient regions are limited by the opacity of brain tissue.In this study,we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury.Specifically,we performed light-sheet imaging of whole brain tissue after a clearing process.We found that pseudorabies virus 724(PRV724)mostly infected retinal ganglion cells,and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains.Unexpectedly,PRV724-traced neurons were more widely distributed compared with data from previous studies.We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus,intergeniculate leaflet,ventral lateral geniculate nucleus,central amygdala,basolateral amygdala,Edinger-Westphal nucleus,and oculomotor nucleus,but not the superior vestibular nucleus,red nucleus,locus coeruleus,gigantocellular reticular nucleus,or facial nerve nucleus.Our findings demonstrate that the tissue clearing technique,combined with retrograde trans-synaptic viral tracing,can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury.Thus,our approach may be useful for future estimations of optic nerve injury and regeneration.展开更多
基金the National Natural Science Foundation of China(61827825,31770924,31470056,and 31600692)the Science Fund for Creative Research Group of China(61721092)the Director Fund of Wuhan National Laboratory for Optoelectronics。
文摘The orbitofrontal cortex(OFC)is involved in diverse brain functions via its extensive projections to multiple target regions.There is a growing understanding of the overall outputs of the OFC at the population level,but reports of the projection patterns of individual OFC neurons across different cortical layers remain rare.Here,by combining neuronal sparse and bright labeling with a whole-brain florescence imaging system(fMOST),we obtained an uninterrupted three-dimensional whole-brain dataset and achieved the full morphological reconstruction of 25 OFC pyramidal neurons.We compared the wholebrain projection targets of these individual OFC neurons in different cortical layers as well as in the same cortical layer.We found cortical layer-dependent projections characterized by divergent patterns for information delivery.Our study not only provides a structural basis for understanding the principles of laminar organizations in the OFC,but also provides clues for future functional and behavioral studies on OFC pyramidal neurons.
基金supported by the Science and Technical Committee of Shanghai Municipality of China,No.16QA1400900the Outstanding Youth Grant from Shanghai Municipal Commission of Health and Family Planning of China,No.XYQ2013107+1 种基金the China Postdoctoral Science Foundation,No.2016M592595the National Key Research and Development Program of China,No.2016YFA0203700
文摘Cerebral blood perfusion and cerebrovascular lesions are important factors that can affect the therapeutic efficacy of thrombolysis.At present,the majority of studies focus on assessing the accuracy of lesion location using imaging methods before treatment,with less attention to predictions of outcomes after thrombolysis.Thus,in the present study,we assessed the efficacy of combined computed tomography（CT） perfusion and CT angiography in predicting clinical outcomes after thrombolysis in ischemic stroke patients.The study included 52 patients who received both CT perfusion and CT angiography.Patients were grouped based on the following criteria to compare clinical outcomes：（1） thrombolytic and non-thrombolytic patients,（2） thrombolytic patients with CT angiography showing the presence or absence of a vascular stenosis,（3） thrombolytic patients with CT perfusion showing the presence or absence of hemodynamic mismatch,and（4） different CT angiography and CT perfusion results.Short-term outcome was assessed by the 24-hour National Institution of Health Stroke Scale score change.Long-term outcome was assessed by the 3-month modified Rankin Scale score.Of 52 ischemic stroke patients,29 were treated with thrombolysis and exhibited improved short-term outcomes compared with those without thrombolysis treatment（23 patients）.Patients with both vascular stenosis and blood flow mismatch（13 patients） exhibited the best short-term outcome,while there was no correlation of long-term outcome with CT angiography or CT perfusion findings.These data suggest that combined CT perfusion and CT angiography are useful for predicting short-term outcome,but not long-term outcome,after thrombolysis.
基金supported by the National Natural Science Foundation of China,Nos.82171194 and 81974155(both to JL)the Shanghai Municipal Science and Technology Commission Medical Guide Project,No.16411969200(to WZ)Shanghai Municipal Science and Technology Commission Biomedical Science and Technology Project,No.22S31902600(to JL)。
文摘Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.
文摘Background：For patients with a brain metastasis （BM）,systemic therapy is usually administered after the completion of radiotherapy,especially in cases of multiple BMs.However,the role of systemic therapy in patients with a limited number of BMs is not clear.Therefore,we conducted a retrospective study to explore this question.Methods：Consecutive patients with a pathologically confirmed malignancy and 1-3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in China.Results：A total of 250 patients were enrolled;of them,135 received radiotherapy alone and 115 received radiotherapy plus systemic therapy.In patients receiving whole-brain radiation therapy （WBRT） as radiotherapy,28 received WBRT alone and 35 patients received WBRT plus systemic therapy.Of the patients treated with stereotactic radiosurgery （SRS）,107 received SRS alone and 80 received SRS plus systemic therapy.Multivariate analysis revealed that systemic therapy significantly reduced the risk of mortality compared with radiotherapy alone （hazard ratio [HR] =0.294,95% confidence interval [CI] =0.158-0.548）.Further,when the analysis was conducted in subgroups ofWBRT （HR =0.230,95% CI =0.081-0.653） or SRS （HR=0.305,95% CI=0.127-0.731）,systemic therapy still showed the ability to reduce the risk of mortality in patients with BMs.Conclusion：Systemic therapy after either SRS or WBRT radiotherapy may significantly reduce the risk of mortality of patients with 1-3 BMs.
基金supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02050006)the National Natural Science Foundation of China (81571300, 81527901, 31771174, 81271518 and 81471387)+4 种基金the National Key R&D Program of China (2017YFC1310400)the Natural Science Foundation and Major Basic Research Program of Shanghai (16JC1420100)the support from Shanghai JiaoTong University School of Medicine Institute of Neuroscience Research Center for Brain Disordersthe Shanghai JiaoTong University K.C. Wong Medical Fellowship Fundfunded by the Michael J. Fox Foundation for Parkinson’s Research
文摘Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson’s disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity(up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity(Unified Parkinson’s Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy,and warrant future experimental investigation to validate its clinical utility.
基金supported by the National Natural Science Foundation of China,Nos.81671671(to JL),61971451(to JL),U22A2034(to XK),62177047(to XK)the National Defense Science and Technology Collaborative Innovation Major Project of Central South University,No.2021gfcx05(to JL)+6 种基金Clinical Research Cen terfor Medical Imaging of Hunan Province,No.2020SK4001(to JL)Key Emergency Project of Pneumonia Epidemic of Novel Coronavirus Infection of Hu nan Province,No.2020SK3006(to JL)Innovative Special Construction Foundation of Hunan Province,No.2019SK2131(to JL)the Science and Technology lnnovation Program of Hunan Province,Nos.2021RC4016(to JL),2021SK53503(to ML)Scientific Research Program of Hunan Commission of Health,No.202209044797(to JL)Central South University Research Program of Advanced Interdisciplinary Studies,No.2023Q YJC020(to XK)the Natural Science Foundation of Hunan Province,No.2022JJ30814(to ML)。
文摘Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal ch
文摘Background：The role ofpostradiation systemic therapy in non-small cell lung cancer （NSCLC） patients with brain metastasis （BM） was controversial.Thus,we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis （RTOG-RPA） and graded prognostic assessment （GPA） in identifying population who may benefit from postradiation systemic therapy.Methods：The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively.Cox regression was used for multivariate analysis.Survival of patients with or without postradiation systemic therapy was compared in subgroups stratified according to RTOG-RPA or GPA.Results：Of 216 included patients,67.1% received stereotactic radiosurgery （SRS）,24.1% received whole-brain radiation therapy （WBRT）,and 8.8% received both.After radiotherapy,systemic therapy was administered in 58.3% of patients.Multivariate analysis found that postradiation systemic therapy （yes vs.no） （hazard ratio [HR] =0.36 l,95% confidence interval [CI] =0.202-0.648,P =0.001）,radiation technique （SRS vs.WBRT） （HR =0.462,95% CI =0.238-0.849,P =0.022）,extracranial metastasis （yes vs.no） （HR =3.970,95% CI =1.757-8.970,P =0.001）,and Kamofsky performance status （〈70 vs.≥70） （HR =5.338,95% CI =2.829-10.072,P 〈 0.001） were independent factors for survival.Further analysis found that subsequent tyrosine kinase inhibitor （TKI） therapy could significantly reduce the risk of mortality of patients in RTOG-RPA Class IⅡ （HR =0.411,95% CI =0.183-）.923,P =0.031） or with a GPA score of 1.5-2.5 （HR =0.420,95% CI =0.182-0.968,P =0.042）.However,none of the subgroups stratified according to RTOG-RPA or GPA benefited from the additional conventional chemotherapy.Conclusion：RTOG-RPA and GPA may be useful to identify beneficial populations in NSCLC patients with BM ifTKIs were chosen as postradiation systemic therapy.
文摘In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.
文摘Astudy published in Science on February 2 revealed the spatial connectivity patterns of over 10,000 mouse hippocampal neurons at the mesoscopic level.The study was conducted by teams from the Center for Excellence in Brain Science and Intelligence Technology(CEBSIT),the Institute of Neuroscience(ION)of the Chinese Academy of Sciences(CAS).
基金supported by the National Natural Science Foundation of China(Major Project),No.82030110(to CYM)the National Natural Science Foundation(Youth Program),No.82003754(to SNW)+1 种基金Medical Innovation Major Project,No.16CXZ009(to CYM)Shanghai Science and Technology Commission Projects,Nos.20YF1458400(to SNW)and 21140901000(to CYM)。
文摘As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and manipulation.Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular,cellular,structural,and functional levels,including the anatomy,functional neural network,and interaction among different brain regions,thus facilitating the discovery of brain development and evolution.In addition to studying the neuro-electrophysiological features of brain cortex development,human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease,especially in mimicking malformations of cortical development,thus revealing pathological mechanism and identifying effective drugs.In this review,we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype,underlying mechanisms and rescue strategies.
基金National Natural ScienceFoundation of China(61890953 and 31871088)the Chinese Academy of Medical Sciences Innovation Fund forMedical Sciences(2019-12M-5-014)the Director Fund of Wuhan National Laboratory for Optoelectronics.
文摘The zona incerta(ZI)is involved in various functions and may serve as an integrative node of the circuits for global behavioral modulation.However,the long-range connectivity of different sectors in the mouse ZI has not been comprehensively mapped.Here,we obtained whole-brain images of the input and output connections via fluorescence micro-optical sectioning tomography and viral tracing.The principal regions in the input-output circuits of ZI GABAergic neurons were topologically organized.The 3D distribution of cortical inputs showed rostro-caudal correspondence with different ZI sectors,while the projection fibers from ZI sectors were longitudinally organized in the superior colliculus.Clustering results show that the medial and lateral ZI are two different major functional compartments,and they can be further divided into more subdomains based on projection and input connectivity.This study provides a comprehensive anatomical foundation for understanding how the ZI is involved in integrating different information,conveying motivational states,and modulating global behaviors.
基金supported by the National Natural Science Foundation of China,No.81870655(to MBY)。
文摘Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration.However,morphological assessments of retinorecipient regions are limited by the opacity of brain tissue.In this study,we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury.Specifically,we performed light-sheet imaging of whole brain tissue after a clearing process.We found that pseudorabies virus 724(PRV724)mostly infected retinal ganglion cells,and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains.Unexpectedly,PRV724-traced neurons were more widely distributed compared with data from previous studies.We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus,intergeniculate leaflet,ventral lateral geniculate nucleus,central amygdala,basolateral amygdala,Edinger-Westphal nucleus,and oculomotor nucleus,but not the superior vestibular nucleus,red nucleus,locus coeruleus,gigantocellular reticular nucleus,or facial nerve nucleus.Our findings demonstrate that the tissue clearing technique,combined with retrograde trans-synaptic viral tracing,can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury.Thus,our approach may be useful for future estimations of optic nerve injury and regeneration.
