背景:3D打印技术可根据患者实际病情和治疗需求设计构建模型、手术导板和个性化植入体或固定物,在创伤性骨折修复中展示了巨大的应用前景。目的:综述3D打印技术在创伤性骨折中的应用。方法:检索Web of science、PubMed和中国知网数据库2...背景:3D打印技术可根据患者实际病情和治疗需求设计构建模型、手术导板和个性化植入体或固定物,在创伤性骨折修复中展示了巨大的应用前景。目的:综述3D打印技术在创伤性骨折中的应用。方法:检索Web of science、PubMed和中国知网数据库2020-2024年发表的创伤骨科领域3D打印技术应用的相关文献,英文检索词为“traumatic fracture,3D printing technology,digital model,surgical guide”,中文检索词为“创伤性骨折,3D打印技术,数字模型,手术导板”,经筛选和分析,最终纳入60篇文献进行分析。结果与结论:①创伤性骨折是各种致伤因素导致的骨骼连续性中断和完整性破坏的骨折现象,以可靠方案提高复位愈合效果,已成为骨外科相关研究领域亟需解决的热点问题;②3D打印技术是以数字模型数据为基础的,运用粉末状金属或聚合物等可黏合成型材料以立体光刻、沉积建模和光聚合物喷射等形式制造满足需求三维实体的技术,在数字骨科生物医学领域应用广泛;③3D打印技术在疾病诊断、术前规划、重建骨折三维模型、定制骨科植入体、定制固定支具及假肢、手术导板制作和骨缺损修复等方面发挥了显著的优势,可根据患者实际病情和治疗需求设计构建模型、手术导板和个性化植入体或固定物,为创伤性骨折的治疗提供了新的思路。展开更多
背景:梯度人工骨修复支架模拟了骨骼系统中的独特特征,在骨骼系统再生中具有巨大的应用潜力。目的:综述梯度人工骨修复支架在骨骼系统组织工程中的最新研究进展,并阐述了其优势与制造策略。方法:由第一作者检索Web of Science和PubMed...背景:梯度人工骨修复支架模拟了骨骼系统中的独特特征,在骨骼系统再生中具有巨大的应用潜力。目的:综述梯度人工骨修复支架在骨骼系统组织工程中的最新研究进展,并阐述了其优势与制造策略。方法:由第一作者检索Web of Science和PubMed数据库2000-2023年发表的文献,英文检索词为“gradient,bone regeneration,scaffold”,最终筛选后对76篇文献进行分析总结。结果与结论:①作为骨骼系统组织高效、高质量修复的重要手段,梯度人工骨修复支架目前针对骨组织、骨-软骨、肌腱-骨组织的天然梯度特征进行了仿生设计,这些支架能够一定程度地从结构、成分上模拟原生组织的细胞外基质,从而促进细胞黏附、迁移、增殖和分化,促进受损组织向原生状态再生恢复。②先进制造技术为梯度人工骨修复支架制备提供了更多可能;目前已经开发了通过空间差异化纤维排布和生物活性物质加载构建的梯度电纺纤维支架;分层叠加、分级孔隙率与生物3D打印技术制造的梯度3D打印支架;原位分层注射、简单逐层叠加、冷冻干燥法制造的梯度水凝胶支架;另外还包括其他方式或多方法联用的支架;这些支架在体外实验中展示了良好的生物相容性,在小型动物实验中能够加速组织再生并且观察到组织学结构明显改善。③目前开发的梯度人工骨修复支架仍需进一步优化,提高在梯度尺度上的匹配性,进一步明确材料与组织相互作用,避免降解产物导致的副反应等问题,未来需要结合相关学科优势与临床需求进一步优化。展开更多
Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregati...Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.展开更多
Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which mi...Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.展开更多
Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Cu...Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.展开更多
文摘背景:梯度人工骨修复支架模拟了骨骼系统中的独特特征,在骨骼系统再生中具有巨大的应用潜力。目的:综述梯度人工骨修复支架在骨骼系统组织工程中的最新研究进展,并阐述了其优势与制造策略。方法:由第一作者检索Web of Science和PubMed数据库2000-2023年发表的文献,英文检索词为“gradient,bone regeneration,scaffold”,最终筛选后对76篇文献进行分析总结。结果与结论:①作为骨骼系统组织高效、高质量修复的重要手段,梯度人工骨修复支架目前针对骨组织、骨-软骨、肌腱-骨组织的天然梯度特征进行了仿生设计,这些支架能够一定程度地从结构、成分上模拟原生组织的细胞外基质,从而促进细胞黏附、迁移、增殖和分化,促进受损组织向原生状态再生恢复。②先进制造技术为梯度人工骨修复支架制备提供了更多可能;目前已经开发了通过空间差异化纤维排布和生物活性物质加载构建的梯度电纺纤维支架;分层叠加、分级孔隙率与生物3D打印技术制造的梯度3D打印支架;原位分层注射、简单逐层叠加、冷冻干燥法制造的梯度水凝胶支架;另外还包括其他方式或多方法联用的支架;这些支架在体外实验中展示了良好的生物相容性,在小型动物实验中能够加速组织再生并且观察到组织学结构明显改善。③目前开发的梯度人工骨修复支架仍需进一步优化,提高在梯度尺度上的匹配性,进一步明确材料与组织相互作用,避免降解产物导致的副反应等问题,未来需要结合相关学科优势与临床需求进一步优化。
基金supported by the Research Foundation for Talented Scholars of Fujian Medical University,No.XRCZX2018014(to DZ)Startup Fund for Scientific Research,Fujian Medical University,No.2019QH1017(to CW)the Natural Science Foundation of Fujian Province,China,Nos.2021J01693(to DZ),2021J02032(to ZCY)。
文摘Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.
基金supported by grants from the National Key Research and Development Program of China,No.2017YFA0105400(to LR)the Key Research and Development Program of Guangdong Province,No.2019B020236002(to LR)the National Natural Science Foundation of China,Nos.81972111(to LZ),81772349(to BL).
文摘Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.
基金supported by the National Natural Science Foundation of China,No.82071254(to WZ).
文摘Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.
