BACKGROUND Sepsis is a life-threatening condition defined by organ dysfunction,triggered by a dysregulated host response to infection.there is limited published literature combining cognitive impairment with topologic...BACKGROUND Sepsis is a life-threatening condition defined by organ dysfunction,triggered by a dysregulated host response to infection.there is limited published literature combining cognitive impairment with topological property alterations in brain networks in sepsis survivors.Therefore,we employed graph theory and Granger causality analysis(GCA)methods to analyze resting-state functional magnetic resonance imaging(rs-fMRI)data,aiming to explore the topological alterations in the brain networks of intensive care unit(ICU)sepsis survivors.Using correlation analysis,the interplay between topological property alterations and cognitive impairment was also investigated.AIM To explore the topological alterations of the brain networks of sepsis survivors and their correlation with cognitive impairment.METHODS Sixteen sepsis survivors and nineteen healthy controls from the community were recruited.Within one month after discharge,neurocognitive tests were administered to assess cognitive performance.Rs-fMRI was acquired and the topological properties of brain networks were measured based on graph theory approaches.GCA was conducted to quantify effective connectivity(EC)between brain regions showing positive topological alterations and other regions in the brain.The correlations between topological properties and cognitive were analyzed.RESULTS Sepsis survivors exhibited significant cognitive impairment.At the global level,sepsis survivors showed lower normalized clustering coefficient(γ)and small-worldness(σ)than healthy controls.At the local level,degree centrality(DC)and nodal efficiency(NE)decreased in the right orbital part of inferior frontal gyrus(ORBinf.R),NE decreased in the left temporal pole of superior temporal gyrus(TPOsup.L)whereas DC and NE increased in the right cerebellum Crus 2(CRBLCrus2.R).Regarding directional connection alterations,EC from left cerebellum 6(CRBL6.L)to ORBinf.R and EC from TPOsup.L to right cerebellum 1(CRBLCrus1.R)decreased,whereas EC from right lingual gyrus(LING.R)to TPOsup.L increased.The implementation of correlation analysis revealed a negative correlation between DC in CRBLCrus2.R and both Mini-mental state examination(r=-0.572,P=0.041)and Montreal cognitive assessment(MoCA)scores(r=-0.629,P=0.021)at the local level.In the CRBLCrus2.R cohort,a negative correlation was identified between NE and MoCA scores,with a statistically significant result of r=-0.633 and P=0.020.CONCLUSION Frontal,temporal and cerebellar topological property alterations are possibly associated with cognitive impairment of ICU sepsis survivors and may serve as biomarkers for early diagnosis.展开更多
AIM: To evaluate the short and long-term effects of the complex cell therapy of 202 cases of spinal cord injury(SCI).METHODS: The main arm included 202 cases of SCI and the control arm included 20 SCI cases. For the t...AIM: To evaluate the short and long-term effects of the complex cell therapy of 202 cases of spinal cord injury(SCI).METHODS: The main arm included 202 cases of SCI and the control arm included 20 SCI cases. For the therapy the hematopoietic stem cells(HSCs) and progenitor cells(PCs) were mobilized to peripheral blood by 8 subcutaneous injections of granulocyte colonystimulating factor(G-CSF) for 4 d and are harvested at day 5. The cells were administered to the main arm intrathecally every 3 mo for a long term(3-5 years) according to the internal research protocol international medical institute of tissue engineering. Magnetic resonance imaging of the site of injury and urodyna-mic tests were performed every 6 mo. Motor evoked potentials(MEP), somatosensory evoked potentials(SSEP) were evaluated every 3 mo. The patients were evaluated with american spianl injury association(ASIA) index, functional independence measure index, the Medical Research Council Scale, the International Standards for Neurological Classification of Spinal Cord Injury(ISCSCI-92) and specifically developed scales. The function of bladder was evaluated by a specifically developed clinical scale. The long-term clinical outcomes were assessed for the SCI patients who received no less than 20 intrathecal transplantations of HSCs and hematopoietic precursors(HPs).RESULTS: The restoration of neurologic deficit after HSCs and HPs transplantations was proved stable and evident in 57.4% of the cases. In 42.6% cases no neurologic improvement has been observed. In 50% of the cases the motor restoration began after the first transplantation, which is confirmed in average by 9.9 points improvement in neurologic impairment as compared to the baseline(P < 0.05). Repair of the urinary system was observed in 47.7% of the cases. The sensitivity improved from baseline 124.3 points to 138.4 after the first and to 153.5 points after the second transplantations of HSCs and HPs(P < 0.05, between the stages of research). The evaluation with ASIA index demonstrated regress of neurologic symptoms in 23 cases. Motor progress was also assessed with the ISCISCI-92 motor and sensory scores, and the data coincided with those received with the specifically developed scale. The number of the patients with the signs of locomotive repair was 56.9%. No life threatening complications or adverse effects have been observed.CONCLUSION: The method is safe, effective and considerably improves the life quality of SCI patients. The therapy is approved for clinical use as the treatment of choice.展开更多
Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment fo...Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment for ICAD is a crucial issue;data from recent trials indicate that aggressive medical management and life style modifications are better than endovascular treatments for prevention of recurrent stroke in high-risk patients with ICAD. Endovascular treatment is still an option for subgroup of patients who are not responded to optimal medical therapy.展开更多
Oral microbiota is the second largest microbial colony in the body and forms a complex ecological community that influences oral and brain health.Impaired homeostasis of the oral microbiota can lead to pathological ch...Oral microbiota is the second largest microbial colony in the body and forms a complex ecological community that influences oral and brain health.Impaired homeostasis of the oral microbiota can lead to pathological changes,resulting in central nervous system(CNS)diseases.However,the mechanisms and clinical value of how the oral microbiome influences the brain remain unclear.This review summarizes recent clinical findings on the role of the oral microbiota in CNS diseases and proposes potential approaches to understand the way the oral microbiota and brain communicate.We propose three underlying patterns involving neuroinflammation,neuroendocrine regulation,and CNS signaling between oral microbiota and CNS diseases.We also summarize the clinical characteristics and potential utilization of the oral microbiota in ischemic stroke,Alzheimer's and Parkinson's disease,intracranial aneurysms,and mental disorders.Although the current findings are preliminary and clinical evidence is incomplete,oral microbiota is a potential biomarker for the clinical diagnosis and treatment of CNS diseases.展开更多
background The outcome of acute ischaemic stroke due to tandem vertebrobasilar artery occlusion was poor.Endovascular revascularisation may be a positive approach for acute basilar artery occlusion combined with verte...background The outcome of acute ischaemic stroke due to tandem vertebrobasilar artery occlusion was poor.Endovascular revascularisation may be a positive approach for acute basilar artery occlusion combined with vertebral ostium stenosis or occlusion.We reported seven patients with acute vertebrobasilar tandem occlusion by using angioplasty or stenting for proximal lesion and thrombectomy for distal occlusion.Materials and methods Consecutive patients with acute tandem vertebrobasilar artery occlusion at two centres were included in this study.We retrospectively analysed the clinical,technical and functional outcomes of the patients.results From March 2016 to March 2017,seven patients were included.The mean age and National Institute of Health Stroke Scale score at admission was 57 years and 22,respectively.A reverse approach was used in five patients.The Thrombolysis in Cerebral Infarction score 2b-3 was acquired in all patients.There were no procedural complications.The modified Rankin Scale score was 1-2 for three patients and 4 for one patient at 3 months.Three patients died at 3 months of follow-up.Conclusions Endovascular revascularisation may be feasible for acute tandem vertebrobasilar artery occlusion,and more researches are needed.展开更多
Background and purpose It remains controversial if endovascular treatment(EVT)can improve the outcome of patients with acute basilar artery occlusion(BAO).This study aims to compare the functional outcomes between EVT...Background and purpose It remains controversial if endovascular treatment(EVT)can improve the outcome of patients with acute basilar artery occlusion(BAO).This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis(IVT)first in patients who had acute ischaemic stroke(AIS)due to BAO.Methods Patients who had AIS with BAO who underwent EVT within 24 hours of onset were enrolled in this multicentre cohort study,and the efficacy and safety were compared between IVT+EVT and direct EVT.The primary outcome was 90-day functional independence.All outcomes were assessed with adjusted OR(aOR)from the multivariable logistic regression.In addition,a meta-analysis was performed on all recently published pivotal studies on functional independence after EVT in patients with BAO.Results Of 310 enrolled patients with BAO,241(78%)were treated with direct EVT and 69(22%)with IVT+EVT.Direct EVT was associated with a worse functional outcome(aOR,0.46(95%CI 0.24 to 0.85),p=0.01).IVT+EVT was associated with a lower percentage of patients who needed≥3 passes of stent retriever(10.14%vs 20.75%).The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence(r=0.14(95%CI 0.05 to 0.24),p<0.01).Conclusions This study showed that compared with direct EVT,EVT with IVT first was associated with better functional outcomes in patients with BAO treated within 24 hours of onset.The meta-analysis demonstrated similar favourable efficacy of IVT first followed by EVT in patients with BAO.展开更多
Background and purpose We investigated the baseline demographics of patients with severe unilateral atherosclerotic stenosis of the middle cerebral artery(MCA)using multimodal MRI and evaluated the haemodynamic impair...Background and purpose We investigated the baseline demographics of patients with severe unilateral atherosclerotic stenosis of the middle cerebral artery(MCA)using multimodal MRI and evaluated the haemodynamic impairments and plaque characteristics of patients who had a recurrent stroke.Materials and methods We retrospectively recruited consecutive patients with severe unilateral atherosclerotic MCA stenosis who underwent arterial spin labelling(ASL)with postlabelling delay(PLD)of 1.5 and 2.5 s,and vessel wall MRI.For each PLD,cerebral blood flow(CBF)maps were generated.Hypoperfusion volume ratio(HVR)from 2 PLD CBF was calculated.An HVR value≥50%was considered as severe HVR.Plaque areas,plaque burden,plaque length and remodelling index were measured.Plaque enhancement at maximal lumen narrowing site were graded.Baseline clinical and imaging characteristics were compared between patients with(event+)and without(event?)1 year ischaemic events.Results Forty-three patients(47.23±12.15 years;28 men)were enrolled in this study.Seven patients had an HVR≥50%.During the 1-year follow-up,7 patients had experienced a recurrent stroke.HVR were significantly higher in the event+than event?(53.17%±29.82%vs 16.9%±15.57%,p=0.0002),whereas no significant difference was detected in plaque areas,plaque burden,remodelling index,plaque length and plaque enhancement grade.The multivariable analysis revealed that a severe HVR was significantly associated with a recurrent stroke(Odds ratio=12.93,95%confidence interval 1.57 to 106.24,p=0.017)after adjusted by hypertension and smoking.Conclusion HVR obtained from two PLD ASL may be a useful imaging predictor of recurrent stroke.展开更多
Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors an...Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical pathway.Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling pathways.This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes.Dys-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic lethality.The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments.However,both stimulatory and inhibitory treatments come with potential risks that need to be addressed.This review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt signaling.It thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+pathway.Further description involved each of its components and their involvement in other cellular processes.Finally,this review explained the various other pathways and processes that crosstalk with Wnt signaling.展开更多
Background and purpose Endovascular treatment could improve functional outcomes and reduce mortality in patients with intracranial large artery occlusion. This registry aims to evaluate the endovascular treatment deli...Background and purpose Endovascular treatment could improve functional outcomes and reduce mortality in patients with intracranial large artery occlusion. This registry aims to evaluate the endovascular treatment delivery and to improve endovascular treatment algorithm in clinical practice for patients with stroke in China. Methods and analysis This multicentric, nationwide, prospective registry plans to include 20 stroke centres and recruit 900 consecutive AIS patients with large- artery occlusion under endovascular treatment. This registry will enrol acute large vessel occlusion patients suitable for endovascular treatment and the inclusion and exclusion criteria. In this study, 90 days functional independence (modified Rankin Scale score ≤2) is the primary efficacy endpoint. The procedural efficacy endpoint of this registry is target artery recanalisation defined by modified Thrombolysis in Cerebral Infarction score 2b or 3 after endovascular therapy. Symptomatic intracranial haemorrhage with 24±3 hours after the procedure is the primary safety endpoint of this registry. Ethics and dissemination Beijing Tiantan Hospital’s Ethics committee and all other participating centres approved the protocol and data collection of Acute Ischaemic Stroke Cooperation Group of Endovascular Treatment registry. Each participant or representative had a written informed consent.展开更多
background and purpose A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis(ICAS)combined with poor collaterals in China showe...background and purpose A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis(ICAS)combined with poor collaterals in China showed that the short-term safety and efficacy of stenting was acceptable.However,it remained uncertain whether the low event rate could be of a long term.We reported the 1-year outcome of this registry study to evaluate the long-term efficacy of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Methods Patients with symptomatic ICAS caused by 70%-99% stenosis located at the intracranial internal carotid,middle cerebral,intracranial vertebral or basilar arteries combined with poor collaterals were enrolled.Balloon-mounted stent or balloon plus self-expanding stent were selected based on the ease of vascular access and lesion morphology determined by the operators.The primary outcome was the rate of 30-day stroke,transient ischaemic attack and death,and 12-month ischaemic stroke within the same vascular territory,haemorrhagic stroke and vascular death after stenting.results From September 2013 to January 2015,300 patients(ages 58.3±9.78 years)were recruited.Among them,159 patients were treated with balloon-mounted stent and 141 with balloon plus self-expanding stent.During the 1-year follow-up,25 patients had a primary end point event.The probability of primary outcome at 1 year was 8.1%(95% CI 5.3% to 11.7%).In 76 patients with digital subtraction angiography follow-up,27.6%(21/76)had re-stenosis≥50% and 18.4%(14/76)had re-stenosis≥70%.No baseline characteristic was associated with the primary outcome.Conclusion The event rate remains low over 1 year of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Further randomised trial of comparing individually tailored stenting with best medical therapy is needed.展开更多
With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogene...With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.展开更多
Background and purpose:5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke(AIS)due to large vessel occlusion of the anterior circulation.This study aims to evaluate the safety a...Background and purpose:5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke(AIS)due to large vessel occlusion of the anterior circulation.This study aims to evaluate the safety and efficacy of Solitaire thrombectomy in patients with moderate-to-severe stroke in the Chinese population,which has a high prevalence of intracranial atherosclerosis.Methods and analysis:This multicentre prospective control study will involve 17 stroke centres in China,and plans to recruit 150 patients in the intervention group,and 150 patients in the medical group,in which patients meet enrolment criteria but refuse intervention.Patients with AIS due to large vessel occlusion indicated for treatment with Solitaire stent retriever within 12 hours of symptom onset,and who meet the inclusion and exclusion criteria,will be enrolled in this study.The primary efficacy endpoint is functional independence as defined by a modified Rankin Scale(mRS)score≤2 at 90 days or by functional improvement as defined by mRS,using shift analysis.The procedural efficacy endpoint is arterial recanalisation of the occluded target vessel measured by a modified Thrombolysis in Cerebral Infarction(mTICI)score equal or superior to 2b right following the use of the study device.The primary safety endpoint is symptomatic intracranial haemorrhage(sICH)within 24±3 hours postprocedure.Ethics and dissemination:The protocol was approved by the Ethics Committee at the coordinating centre and by the local Institutional Review Board of each participating centre.Trial registration number:NCT02350283.展开更多
Adult neurogenesis occurs in two specialized regions of the mammalian brain,the subventricular zone(SVZ)and the subgranular zone(SGZ)of the dentate gyrus(DG).^(1)Adult hippocampal neural stem cells(NSCs),referred to a...Adult neurogenesis occurs in two specialized regions of the mammalian brain,the subventricular zone(SVZ)and the subgranular zone(SGZ)of the dentate gyrus(DG).^(1)Adult hippocampal neural stem cells(NSCs),referred to as Type 1 cells represented by radial glia-like cells(RGLs),generate Type 2 cells that are divided into Type 2a and Type 2 b subpopulations,the latter of which give rise to Type 3 cells(neuroblasts).展开更多
Objectives: Significant advances in neurosciences will result from research focused on the non‐contact treatment of the nervous tissue(NT).The objective of the article is to describe a novel non‐contact method of re...Objectives: Significant advances in neurosciences will result from research focused on the non‐contact treatment of the nervous tissue(NT).The objective of the article is to describe a novel non‐contact method of restoration of damaged NT of the human brain and spinal cord that was termed multi‐wave neuro‐bioengineering. Methods: The method includes a purposeful complex program of different therapeutic ionizing and non‐ionizing electromagnetic radiation effects on the damaged NT,which is approved for clinical practice. Exposure of the human brain to a stepwise algorithmized combination of different ionizing and non‐ionizing radiations and simultaneous application of various types of electromagnetic radiation at the specific site of restoration considerably reduce the adverse effects of all types of radiation on NT.Results: The technology for non‐contact restoration of the injured tissue of brain or spinal cord was appiled in 30 cases of neurological disorders using the stereotaxic system, structural resonance therapy, radiotherapy and focused ultrasound. The applied methods are approved for humans and theor programmed combination opens new perspective for the treatment of brain and spinal cord disorders. Conclusions: The approach provides quick restoration of the disordered function of damaged brain tissue and establishes a new paradigm of radio non‐contact neurorestoration of the brain and spinal cord.展开更多
Cerebral venous sinus thrombosis(CVST)is a type of stroke associated with COVID-19 vaccine-induced immune thrombotic thrombocytopenia.The precise etiology of CVST often remains elusive due to the highly heterogeneous ...Cerebral venous sinus thrombosis(CVST)is a type of stroke associated with COVID-19 vaccine-induced immune thrombotic thrombocytopenia.The precise etiology of CVST often remains elusive due to the highly heterogeneous nature of its governing mechanisms,specifically,Virchow’s triad that involves altered blood flow,endothelial dysfunction,and hypercoagulability,which varies substantially amongst individuals.Existing diagnostic and monitoring approaches lack the capability to reflect the combination of these patient-specific thrombotic determinants.In response to this challenge,we introduce a Vein-Chip platform that recapitulates the CVST vascular anatomy from magnetic resonance venography and the associated hemodynamic flow profile using the“Chinese Movable Type-like”soft stereolithography technique.The resultant full-lumen personalized Vein-Chips,functionalized with endothelial cells,enable in-vitro thrombosis assays that can elucidate distinct thrombogenic scenarios between normal vascular conditions and those of endothelial dysfunction.The former displayed minimal platelet aggregation and negligible fibrin deposition,while the latter presented significant fibrin extrusion from platelet aggregations.The low-cost movable typing technique further enhances the potential for commercialization and broader utilization of personalized Vein-Chips in surgical labs and at-home monitoring.Future research and development in this direction will pave the way for improved management and prevention of CVST,ultimately benefiting both patients and healthcare systems.展开更多
The retrospective study summarizes 28 years of cell therapy for neurotrauma of different origin. The four experimental groups were the groups of neurotrama that included traumatic disease of the spinal cord, traumatic...The retrospective study summarizes 28 years of cell therapy for neurotrauma of different origin. The four experimental groups were the groups of neurotrama that included traumatic disease of the spinal cord, traumatic disease of the brain and chronic vegetative post‐traumatic state. The first group received transplantations of the fetal cells of neural tissue. The second group received the tissue engineering surgery with the transplantation of the fetal cells of neural tissue. The third group were the cases of the bioengineering pasty of the damaged brain tissue;and fourth were the cases of neurotrauma that were treated with the transplantation of the hematopoietic stem cells (HSCs) and hematopoietic precursor cells (HPCs). The long‐term follow up proved the cell therapy with HSCs and HPCs to be the safest and most effective.展开更多
Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ...Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction.展开更多
基金Supported by National Natural Science Foundation of China,No.82372182,No.82172131,and No.U23A20421Training Project of the Leading Expert Team:"Jiyang Medical Elites",No.RC2023-004.
文摘BACKGROUND Sepsis is a life-threatening condition defined by organ dysfunction,triggered by a dysregulated host response to infection.there is limited published literature combining cognitive impairment with topological property alterations in brain networks in sepsis survivors.Therefore,we employed graph theory and Granger causality analysis(GCA)methods to analyze resting-state functional magnetic resonance imaging(rs-fMRI)data,aiming to explore the topological alterations in the brain networks of intensive care unit(ICU)sepsis survivors.Using correlation analysis,the interplay between topological property alterations and cognitive impairment was also investigated.AIM To explore the topological alterations of the brain networks of sepsis survivors and their correlation with cognitive impairment.METHODS Sixteen sepsis survivors and nineteen healthy controls from the community were recruited.Within one month after discharge,neurocognitive tests were administered to assess cognitive performance.Rs-fMRI was acquired and the topological properties of brain networks were measured based on graph theory approaches.GCA was conducted to quantify effective connectivity(EC)between brain regions showing positive topological alterations and other regions in the brain.The correlations between topological properties and cognitive were analyzed.RESULTS Sepsis survivors exhibited significant cognitive impairment.At the global level,sepsis survivors showed lower normalized clustering coefficient(γ)and small-worldness(σ)than healthy controls.At the local level,degree centrality(DC)and nodal efficiency(NE)decreased in the right orbital part of inferior frontal gyrus(ORBinf.R),NE decreased in the left temporal pole of superior temporal gyrus(TPOsup.L)whereas DC and NE increased in the right cerebellum Crus 2(CRBLCrus2.R).Regarding directional connection alterations,EC from left cerebellum 6(CRBL6.L)to ORBinf.R and EC from TPOsup.L to right cerebellum 1(CRBLCrus1.R)decreased,whereas EC from right lingual gyrus(LING.R)to TPOsup.L increased.The implementation of correlation analysis revealed a negative correlation between DC in CRBLCrus2.R and both Mini-mental state examination(r=-0.572,P=0.041)and Montreal cognitive assessment(MoCA)scores(r=-0.629,P=0.021)at the local level.In the CRBLCrus2.R cohort,a negative correlation was identified between NE and MoCA scores,with a statistically significant result of r=-0.633 and P=0.020.CONCLUSION Frontal,temporal and cerebellar topological property alterations are possibly associated with cognitive impairment of ICU sepsis survivors and may serve as biomarkers for early diagnosis.
文摘AIM: To evaluate the short and long-term effects of the complex cell therapy of 202 cases of spinal cord injury(SCI).METHODS: The main arm included 202 cases of SCI and the control arm included 20 SCI cases. For the therapy the hematopoietic stem cells(HSCs) and progenitor cells(PCs) were mobilized to peripheral blood by 8 subcutaneous injections of granulocyte colonystimulating factor(G-CSF) for 4 d and are harvested at day 5. The cells were administered to the main arm intrathecally every 3 mo for a long term(3-5 years) according to the internal research protocol international medical institute of tissue engineering. Magnetic resonance imaging of the site of injury and urodyna-mic tests were performed every 6 mo. Motor evoked potentials(MEP), somatosensory evoked potentials(SSEP) were evaluated every 3 mo. The patients were evaluated with american spianl injury association(ASIA) index, functional independence measure index, the Medical Research Council Scale, the International Standards for Neurological Classification of Spinal Cord Injury(ISCSCI-92) and specifically developed scales. The function of bladder was evaluated by a specifically developed clinical scale. The long-term clinical outcomes were assessed for the SCI patients who received no less than 20 intrathecal transplantations of HSCs and hematopoietic precursors(HPs).RESULTS: The restoration of neurologic deficit after HSCs and HPs transplantations was proved stable and evident in 57.4% of the cases. In 42.6% cases no neurologic improvement has been observed. In 50% of the cases the motor restoration began after the first transplantation, which is confirmed in average by 9.9 points improvement in neurologic impairment as compared to the baseline(P < 0.05). Repair of the urinary system was observed in 47.7% of the cases. The sensitivity improved from baseline 124.3 points to 138.4 after the first and to 153.5 points after the second transplantations of HSCs and HPs(P < 0.05, between the stages of research). The evaluation with ASIA index demonstrated regress of neurologic symptoms in 23 cases. Motor progress was also assessed with the ISCISCI-92 motor and sensory scores, and the data coincided with those received with the specifically developed scale. The number of the patients with the signs of locomotive repair was 56.9%. No life threatening complications or adverse effects have been observed.CONCLUSION: The method is safe, effective and considerably improves the life quality of SCI patients. The therapy is approved for clinical use as the treatment of choice.
文摘Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment for ICAD is a crucial issue;data from recent trials indicate that aggressive medical management and life style modifications are better than endovascular treatments for prevention of recurrent stroke in high-risk patients with ICAD. Endovascular treatment is still an option for subgroup of patients who are not responded to optimal medical therapy.
基金National Natural Science Foundation of China,Grant/Award Number:82301715Wuxi Taihu Lake Talent Plan,Supports for Leading Talents in Medical and Health Profession,Grant/Award Number:2020THRC-DJ-SNW+1 种基金Jiangsu Province Double-Creation Doctoral Talent Plan,Grant/Award Number:JSSCBS20221995WuXi Municipal Health Commission,Grant/Award Number:Q202222。
文摘Oral microbiota is the second largest microbial colony in the body and forms a complex ecological community that influences oral and brain health.Impaired homeostasis of the oral microbiota can lead to pathological changes,resulting in central nervous system(CNS)diseases.However,the mechanisms and clinical value of how the oral microbiome influences the brain remain unclear.This review summarizes recent clinical findings on the role of the oral microbiota in CNS diseases and proposes potential approaches to understand the way the oral microbiota and brain communicate.We propose three underlying patterns involving neuroinflammation,neuroendocrine regulation,and CNS signaling between oral microbiota and CNS diseases.We also summarize the clinical characteristics and potential utilization of the oral microbiota in ischemic stroke,Alzheimer's and Parkinson's disease,intracranial aneurysms,and mental disorders.Although the current findings are preliminary and clinical evidence is incomplete,oral microbiota is a potential biomarker for the clinical diagnosis and treatment of CNS diseases.
基金This work was supported by the National Natural Science Foundation of China(Contract grant number:81471390 to N.M.,81371290 to Z.R.M.)Beijing High-level Personnel Funds(Contract grant number:2013-2-19 to Z.R.M.).
文摘background The outcome of acute ischaemic stroke due to tandem vertebrobasilar artery occlusion was poor.Endovascular revascularisation may be a positive approach for acute basilar artery occlusion combined with vertebral ostium stenosis or occlusion.We reported seven patients with acute vertebrobasilar tandem occlusion by using angioplasty or stenting for proximal lesion and thrombectomy for distal occlusion.Materials and methods Consecutive patients with acute tandem vertebrobasilar artery occlusion at two centres were included in this study.We retrospectively analysed the clinical,technical and functional outcomes of the patients.results From March 2016 to March 2017,seven patients were included.The mean age and National Institute of Health Stroke Scale score at admission was 57 years and 22,respectively.A reverse approach was used in five patients.The Thrombolysis in Cerebral Infarction score 2b-3 was acquired in all patients.There were no procedural complications.The modified Rankin Scale score was 1-2 for three patients and 4 for one patient at 3 months.Three patients died at 3 months of follow-up.Conclusions Endovascular revascularisation may be feasible for acute tandem vertebrobasilar artery occlusion,and more researches are needed.
基金This work was supported by the National Key R&D Program of China(2016YFC1307301)the National Natural Science Foundation of China(81820108012)This study was partially funded by Boehringer Ingelheim China.
文摘Background and purpose It remains controversial if endovascular treatment(EVT)can improve the outcome of patients with acute basilar artery occlusion(BAO).This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis(IVT)first in patients who had acute ischaemic stroke(AIS)due to BAO.Methods Patients who had AIS with BAO who underwent EVT within 24 hours of onset were enrolled in this multicentre cohort study,and the efficacy and safety were compared between IVT+EVT and direct EVT.The primary outcome was 90-day functional independence.All outcomes were assessed with adjusted OR(aOR)from the multivariable logistic regression.In addition,a meta-analysis was performed on all recently published pivotal studies on functional independence after EVT in patients with BAO.Results Of 310 enrolled patients with BAO,241(78%)were treated with direct EVT and 69(22%)with IVT+EVT.Direct EVT was associated with a worse functional outcome(aOR,0.46(95%CI 0.24 to 0.85),p=0.01).IVT+EVT was associated with a lower percentage of patients who needed≥3 passes of stent retriever(10.14%vs 20.75%).The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence(r=0.14(95%CI 0.05 to 0.24),p<0.01).Conclusions This study showed that compared with direct EVT,EVT with IVT first was associated with better functional outcomes in patients with BAO treated within 24 hours of onset.The meta-analysis demonstrated similar favourable efficacy of IVT first followed by EVT in patients with BAO.
基金The National Natural Science Foundation of China(contract grant number:81825012,81730048,81671126 to XL and contract grant number:81471390 to NM).
文摘Background and purpose We investigated the baseline demographics of patients with severe unilateral atherosclerotic stenosis of the middle cerebral artery(MCA)using multimodal MRI and evaluated the haemodynamic impairments and plaque characteristics of patients who had a recurrent stroke.Materials and methods We retrospectively recruited consecutive patients with severe unilateral atherosclerotic MCA stenosis who underwent arterial spin labelling(ASL)with postlabelling delay(PLD)of 1.5 and 2.5 s,and vessel wall MRI.For each PLD,cerebral blood flow(CBF)maps were generated.Hypoperfusion volume ratio(HVR)from 2 PLD CBF was calculated.An HVR value≥50%was considered as severe HVR.Plaque areas,plaque burden,plaque length and remodelling index were measured.Plaque enhancement at maximal lumen narrowing site were graded.Baseline clinical and imaging characteristics were compared between patients with(event+)and without(event?)1 year ischaemic events.Results Forty-three patients(47.23±12.15 years;28 men)were enrolled in this study.Seven patients had an HVR≥50%.During the 1-year follow-up,7 patients had experienced a recurrent stroke.HVR were significantly higher in the event+than event?(53.17%±29.82%vs 16.9%±15.57%,p=0.0002),whereas no significant difference was detected in plaque areas,plaque burden,remodelling index,plaque length and plaque enhancement grade.The multivariable analysis revealed that a severe HVR was significantly associated with a recurrent stroke(Odds ratio=12.93,95%confidence interval 1.57 to 106.24,p=0.017)after adjusted by hypertension and smoking.Conclusion HVR obtained from two PLD ASL may be a useful imaging predictor of recurrent stroke.
基金supported in part by research grants from the National Institutes of Health(No.CA226303 to TCH and No.DE030480 to RRR)the American Shoulder and Elbow Surgeons PJI Research Grant(LLS).JF was supported in part by research grants from the Natural Science Foundation of China(No.82102696)+4 种基金the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(China)(No.KJQN201900410)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)WW was supported by the Medical Scientist Training Program of the National Institutes of Health(No.T32 GM007281)This project was also supported in partby The University of Chicago Cancer Center Support Grant(No.P30CA014599)the National Center for Advancing Translational Sciences(NCATS)of the National Institutes of Health through Grant Number 5UL1TR002389.
文摘Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical pathway.Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling pathways.This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes.Dys-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic lethality.The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments.However,both stimulatory and inhibitory treatments come with potential risks that need to be addressed.This review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt signaling.It thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+pathway.Further description involved each of its components and their involvement in other cellular processes.Finally,this review explained the various other pathways and processes that crosstalk with Wnt signaling.
基金This work was supported by the National Key Research and Development Program of China,grant number 2016YFC1301501.
文摘Background and purpose Endovascular treatment could improve functional outcomes and reduce mortality in patients with intracranial large artery occlusion. This registry aims to evaluate the endovascular treatment delivery and to improve endovascular treatment algorithm in clinical practice for patients with stroke in China. Methods and analysis This multicentric, nationwide, prospective registry plans to include 20 stroke centres and recruit 900 consecutive AIS patients with large- artery occlusion under endovascular treatment. This registry will enrol acute large vessel occlusion patients suitable for endovascular treatment and the inclusion and exclusion criteria. In this study, 90 days functional independence (modified Rankin Scale score ≤2) is the primary efficacy endpoint. The procedural efficacy endpoint of this registry is target artery recanalisation defined by modified Thrombolysis in Cerebral Infarction score 2b or 3 after endovascular therapy. Symptomatic intracranial haemorrhage with 24±3 hours after the procedure is the primary safety endpoint of this registry. Ethics and dissemination Beijing Tiantan Hospital’s Ethics committee and all other participating centres approved the protocol and data collection of Acute Ischaemic Stroke Cooperation Group of Endovascular Treatment registry. Each participant or representative had a written informed consent.
基金This work is supported by National Natural Science Foundation of China(81371290),Beijing High-level Personnel Funds(2013-2-019)This study is also funded by the National Science and Technology Support Program of‘The 12th Five-Year Plan’of the Ministry of Science and Technology(2011BAI08B02).
文摘background and purpose A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis(ICAS)combined with poor collaterals in China showed that the short-term safety and efficacy of stenting was acceptable.However,it remained uncertain whether the low event rate could be of a long term.We reported the 1-year outcome of this registry study to evaluate the long-term efficacy of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Methods Patients with symptomatic ICAS caused by 70%-99% stenosis located at the intracranial internal carotid,middle cerebral,intracranial vertebral or basilar arteries combined with poor collaterals were enrolled.Balloon-mounted stent or balloon plus self-expanding stent were selected based on the ease of vascular access and lesion morphology determined by the operators.The primary outcome was the rate of 30-day stroke,transient ischaemic attack and death,and 12-month ischaemic stroke within the same vascular territory,haemorrhagic stroke and vascular death after stenting.results From September 2013 to January 2015,300 patients(ages 58.3±9.78 years)were recruited.Among them,159 patients were treated with balloon-mounted stent and 141 with balloon plus self-expanding stent.During the 1-year follow-up,25 patients had a primary end point event.The probability of primary outcome at 1 year was 8.1%(95% CI 5.3% to 11.7%).In 76 patients with digital subtraction angiography follow-up,27.6%(21/76)had re-stenosis≥50% and 18.4%(14/76)had re-stenosis≥70%.No baseline characteristic was associated with the primary outcome.Conclusion The event rate remains low over 1 year of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Further randomised trial of comparing individually tailored stenting with best medical therapy is needed.
基金supported in part by research grants from the Natural Science Foundation of China(No.82102696 to JF)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298 to JF)the National Institutes of Health(No.CA226303 to TCH,DE030480 to RRR).
文摘With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.
基金This study is sponsored and conducted by the Cerebrovascular Disease Center of Tiantan Hospital,which is also responsible for data analysis.This study is funded by the National Science and Technology Major Project of China(2011BAI08B02,2015BAI12B04 and 2015BAI12B02).
文摘Background and purpose:5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke(AIS)due to large vessel occlusion of the anterior circulation.This study aims to evaluate the safety and efficacy of Solitaire thrombectomy in patients with moderate-to-severe stroke in the Chinese population,which has a high prevalence of intracranial atherosclerosis.Methods and analysis:This multicentre prospective control study will involve 17 stroke centres in China,and plans to recruit 150 patients in the intervention group,and 150 patients in the medical group,in which patients meet enrolment criteria but refuse intervention.Patients with AIS due to large vessel occlusion indicated for treatment with Solitaire stent retriever within 12 hours of symptom onset,and who meet the inclusion and exclusion criteria,will be enrolled in this study.The primary efficacy endpoint is functional independence as defined by a modified Rankin Scale(mRS)score≤2 at 90 days or by functional improvement as defined by mRS,using shift analysis.The procedural efficacy endpoint is arterial recanalisation of the occluded target vessel measured by a modified Thrombolysis in Cerebral Infarction(mTICI)score equal or superior to 2b right following the use of the study device.The primary safety endpoint is symptomatic intracranial haemorrhage(sICH)within 24±3 hours postprocedure.Ethics and dissemination:The protocol was approved by the Ethics Committee at the coordinating centre and by the local Institutional Review Board of each participating centre.Trial registration number:NCT02350283.
基金supported in part by research grants from the National Institutes of Health(USA)(CA226303 to TCH,DE030480 to RRR)supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)+1 种基金the National Center for Advancing Translational Sciences of the National Institutes of Health(USA)(No.5UL1TR002389)supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund(USA).
文摘Adult neurogenesis occurs in two specialized regions of the mammalian brain,the subventricular zone(SVZ)and the subgranular zone(SGZ)of the dentate gyrus(DG).^(1)Adult hippocampal neural stem cells(NSCs),referred to as Type 1 cells represented by radial glia-like cells(RGLs),generate Type 2 cells that are divided into Type 2a and Type 2 b subpopulations,the latter of which give rise to Type 3 cells(neuroblasts).
文摘Objectives: Significant advances in neurosciences will result from research focused on the non‐contact treatment of the nervous tissue(NT).The objective of the article is to describe a novel non‐contact method of restoration of damaged NT of the human brain and spinal cord that was termed multi‐wave neuro‐bioengineering. Methods: The method includes a purposeful complex program of different therapeutic ionizing and non‐ionizing electromagnetic radiation effects on the damaged NT,which is approved for clinical practice. Exposure of the human brain to a stepwise algorithmized combination of different ionizing and non‐ionizing radiations and simultaneous application of various types of electromagnetic radiation at the specific site of restoration considerably reduce the adverse effects of all types of radiation on NT.Results: The technology for non‐contact restoration of the injured tissue of brain or spinal cord was appiled in 30 cases of neurological disorders using the stereotaxic system, structural resonance therapy, radiotherapy and focused ultrasound. The applied methods are approved for humans and theor programmed combination opens new perspective for the treatment of brain and spinal cord disorders. Conclusions: The approach provides quick restoration of the disordered function of damaged brain tissue and establishes a new paradigm of radio non‐contact neurorestoration of the brain and spinal cord.
基金National Health and Medical Research Council(NHMRC)of Australia,Grant/Award Numbers:APP2003904,GNT2022247NSW Cardiovascular Capacity Building Program,Grant/Award Number:Early-Mid Career Researcher Grant+7 种基金MRFF Cardiovascular Health Mission Grants,Grant/Award Numbers:APP2016165,APP2023977Ramaciotti Foundations,Grant/Award Number:2020HIG76National Heart Foundation,Grant/Award Numbers:106979,106879Office of Global and Research Engagement,Grant/Award Number:International Sustainable Development Goal ProgramSydney Nano Research Schemes,Grant/Award Number:Grand ChallengeNational Heart Foundation Future Leader Fellow Level 2,Grant/Award Number:105863Snow Medical Research Foundation Fellow,Grant/Award Number:2022SF176New South Wales Government。
文摘Cerebral venous sinus thrombosis(CVST)is a type of stroke associated with COVID-19 vaccine-induced immune thrombotic thrombocytopenia.The precise etiology of CVST often remains elusive due to the highly heterogeneous nature of its governing mechanisms,specifically,Virchow’s triad that involves altered blood flow,endothelial dysfunction,and hypercoagulability,which varies substantially amongst individuals.Existing diagnostic and monitoring approaches lack the capability to reflect the combination of these patient-specific thrombotic determinants.In response to this challenge,we introduce a Vein-Chip platform that recapitulates the CVST vascular anatomy from magnetic resonance venography and the associated hemodynamic flow profile using the“Chinese Movable Type-like”soft stereolithography technique.The resultant full-lumen personalized Vein-Chips,functionalized with endothelial cells,enable in-vitro thrombosis assays that can elucidate distinct thrombogenic scenarios between normal vascular conditions and those of endothelial dysfunction.The former displayed minimal platelet aggregation and negligible fibrin deposition,while the latter presented significant fibrin extrusion from platelet aggregations.The low-cost movable typing technique further enhances the potential for commercialization and broader utilization of personalized Vein-Chips in surgical labs and at-home monitoring.Future research and development in this direction will pave the way for improved management and prevention of CVST,ultimately benefiting both patients and healthcare systems.
文摘The retrospective study summarizes 28 years of cell therapy for neurotrauma of different origin. The four experimental groups were the groups of neurotrama that included traumatic disease of the spinal cord, traumatic disease of the brain and chronic vegetative post‐traumatic state. The first group received transplantations of the fetal cells of neural tissue. The second group received the tissue engineering surgery with the transplantation of the fetal cells of neural tissue. The third group were the cases of the bioengineering pasty of the damaged brain tissue;and fourth were the cases of neurotrauma that were treated with the transplantation of the hematopoietic stem cells (HSCs) and hematopoietic precursor cells (HPCs). The long‐term follow up proved the cell therapy with HSCs and HPCs to be the safest and most effective.
文摘Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction.
