The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzh...The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.展开更多
Central venous catheterization(CVC)is a fundamental clinical procedure widely performed across medical specialties.However,the complication rate of subclavian vein catheterization ranges from 6%to 11%.[1]Common compli...Central venous catheterization(CVC)is a fundamental clinical procedure widely performed across medical specialties.However,the complication rate of subclavian vein catheterization ranges from 6%to 11%.[1]Common complications include hemothorax,pneumothorax,air embolism,arterial puncture,and aortic perforation.[2]Herein,we report a rare case of accidental puncture of the aorta during subclavian CVC,which was successfully managed with a ventricular septal defect(VSD)occluder.展开更多
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
Background:That Central and Eastern Europe and Central Asia(CEECA)experienced a major mortality crisis in the 1990s is a well-established finding,with most analyses focusing on singular causes like alcohol-related dea...Background:That Central and Eastern Europe and Central Asia(CEECA)experienced a major mortality crisis in the 1990s is a well-established finding,with most analyses focusing on singular causes like alcohol-related deaths.However,the utility of the integrated“deaths of despair”framework,which views alcohol,drug,and suicide deaths as a unified socio-economic phenomenon,remains under-explored in this context.Crucially,the long-term evolution of the composition of despair within the region remains a largely unexplored area of inquiry.Therefore,this study aims to analyze the long-term trends,changing composition,and regional heterogeneity of deaths from despair in the CEECA region from 1980 to 2021.Methods:Using 2021 Global Burden of Disease(GBD)data(1980–2021),we analyzed deaths of despair mortality trends in 29 CEECA countries.We employed Joinpoint regression to identify significant trend changes and conducted stratified analyses by cause,gender,and age group.Results:The CEECA deaths of despair crisis began as an alcohol and suicide driven phenomenon concentrated in middle-aged men(50–74 years)during the 1990s,with mortality rates for alcohol use disorders and self-harm surging annually by 30.35%(p=0.002)and 13.44%(p=0.001),respectively,between 1991 and 1994.It has since evolved,marked by a contrasting and emerging threat in the 21st century:a rising proportion of drug-related deaths among the younger(15–49 years)male cohort,where the share of drug use disorders increased from 6.9%in 2000 to 11.8%in 2008.Conclusion:The deaths of despair crisis in the CEECA region is not a past event but an ongoing,evolving phenomenon.Its changing nature demands a shift in public health focus from solely historical drivers to new,generation-specific threats,particularly the rise of drug-related despair among youth.展开更多
Central Asia is characterized by an arid climate and widespread desert distribution,with its sustainable development severely constrained by dust events.An objective understanding of the spatiotemporal patterns and dr...Central Asia is characterized by an arid climate and widespread desert distribution,with its sustainable development severely constrained by dust events.An objective understanding of the spatiotemporal patterns and driving forces of dust weather is highly important in this area.Based on the meteorological observations from 2000 to 2020,we examined the spatiotemporal characteristics of dust weather in the five Central Asian countries(Kazakhstan,Uzbekistan,Kyrgyzstan,Turkmenistan,and Tajikistan)via Theil-Sen trend analysis and Geodetector modeling method,quantitatively revealing the influence of environmental factors,such as temperature,precipitation,and vegetation,on the frequency of dust weather.The results showed that:(1)dust weather in Central Asia was mainly distributed in a large''dust belt''extending from west to east from northern part of the Caspian lowland desert,and concentrated in basins,plains,and other low-altitude areas.Strong dust weather mainly occurred in northern areas of the Aral Sea and southern edge of Central Asia,with a maximum annual frequency of 21.9%;(2)strong dust weather in Central Asia has fluctuated and slightly decreased since 2001.The highest frequency(1.1%)occurred in spring(from March to June);(3)from 2000 to 2020,changes such as spot shifting and shrinking occurred in the four main source areas(north of the Aral Sea,Kyzylkum Desert,Karakum Desert,and Garabogazköl Bay region),where sandstorms occurred in Central Asia,and northern Caspian lowland desert became the most important low-emission dust source in Central Asia;and(4)the combined effect of soil moisture and air temperature has the most significant influence on dust weather in Central Asia.This study provides a theoretical basis for sand prevention and sand control in Central Asia.In the future,Central Asia should focus on the rational utilization of land and water resources,and implement human interventions such as vegetation restoration and optimization of irrigation methods to curb further desertification in this area.展开更多
AIM:To compare the intravitreal brolucizumab and bevacizumab injections for chronic central serous chorioretinopathy(cCSC).METHODS:Patients with cCSC were classified into bevacizumab and brolucizumab group.The proport...AIM:To compare the intravitreal brolucizumab and bevacizumab injections for chronic central serous chorioretinopathy(cCSC).METHODS:Patients with cCSC were classified into bevacizumab and brolucizumab group.The proportion of complete resolution of subretinal fluid(SRF),best-corrected visual acuity(BCVA),central macular thickness(CMT),and subfoveal choroidal thickness(SFCT)were compared between the two groups.RESULTS:A total of 40 eyes from 40 patients with aged 34-59y were enrolled in the study.Twenty eyes in bevacizumab group(17 males)and 20 eyes(18 males)in brolucizumab group.Comparing the proportion of complete resolution of SRF,the brolucizumab group was statistically significantly higher than the bevacizumab group(P<0.05).In 1mo,CMT was significantly reduced in the brolucizumab group compared to the bevacizumab group(265±69 vs 319±70μm;P=0.021).However,there was no significant difference in CMT between the two groups at 2 and 3mo(P>0.05).CONCLUSION:Brolucizumab is anatomically and functionally superior to bevacizumab in the treatment of patients with cCSC.展开更多
AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCT...AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCTA)parameters,including optic disc vessel density(VD;including whole-disc VD,intra-disc VD,and peripapillary VD),superficial/deep capillary plexus(SCP/DCP)VD,and central macular thickness(CMT)were analyzed.Additional assessments included best-corrected visual acuity(BCVA)via Early Treatment Diabetic Retinopathy Study(ETDRS)chart and hemorheological profiling.CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months.Pre-and post-treatment parameters were statistically compared.RESULTS:The study comprised 60 CRVO-ME patients(28 males;32 females),aged 50-78y(mean 63.3±7.6y)and 60 age-/sex-matched healthy controls.As compared with participants exhibiting normal funduscopic findings,CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity(LSR-WBV),high-shearrate whole blood viscosity(HSR-WBV),and aggregation index(AI,all P<0.05).In CRVO-affected eyes,vertical cupto-disc(C/D)ratio and optic cup volume were significantly smaller,whereas retinal nerve fiber layer(RNFL)thickness was significantly greater,compared to both unaffected contralateral eyes and normal control eyes(all P<0.05).Following treatment,VD of the entire optic disc(P<0.05),intra-disc VD(P<0.05),and peripapillary VD(P<0.05)all increased significantly relative to baseline.CMT decreased significantly(P<0.05),whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions(P>0.05).At baseline,BCVA of CRVO eyes correlated with whole-disc VD(r=-0.276,P=0.033),intra-disc VD(r=-0.342,P=0.009),and peripapillary VD(r=-0.335,P=0.007),with intra-disc VD demonstrating the strongest association.Besides,BCVA improvement,after the treatment,correlated positively with whole-disc VD(r=0.342,P=0.008)and intradisc VD(r=0.396,P=0.002).CONCLUSION:Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion,suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO.Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula.CRVO patients shows higher hemorheological parameters than those with normal fundi.Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence,potentially acting as susceptibility factors.展开更多
Convex feasibility problems are widely used in image reconstruction, sparse signal recovery, and other areas. This paper is devoted to considering a class of convex feasibility problem arising from sparse signal recov...Convex feasibility problems are widely used in image reconstruction, sparse signal recovery, and other areas. This paper is devoted to considering a class of convex feasibility problem arising from sparse signal recovery. We first derive the projection formulas for a vector onto the feasible sets. The centralized circumcentered-reflection method is designed to solve the convex feasibility problem. Some numerical experiments demonstrate the feasibility and effectiveness of the proposed algorithm, showing superior performance compared to conventional alternating projection methods.展开更多
Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic He...Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic Hedgehog signaling pathway is crucial in the central nervous system,with implications in a diverse range of diseases,including Parkinson's disease,Alzheimer's disease,spinal cord injury,traumatic brain injury,depression,Sonic Hedgehog medulloblastoma,and stroke.In this comprehensive review,we examined Sonic Hedgehog from the perspective of canonical and non-canonical pathways,elucidating their complex connections to the central nervous system.Subsequently,we summarize the latest advancements in drug therapies that offer novel strategies for treating neurological diseases by modulating the Sonic Hedgehog protein.Finally,we summarize and extend the technologies and tools for studying the Sonic Hedgehog signaling field,with the aim of providing new research ideas and methods.展开更多
This study makes an in-depth exploration of the core pathogenesis of chronic atrophic gastritis,Qi Deficiency with Stagnation,to systematically interpret it within the theoretical framework of Achieving Central Harmon...This study makes an in-depth exploration of the core pathogenesis of chronic atrophic gastritis,Qi Deficiency with Stagnation,to systematically interpret it within the theoretical framework of Achieving Central Harmony,and to provide a treatment plan.Professor Li Tingquan believes that the occurrence and development of chronic atrophic gastritis(CAG)is fundamentally a process of harmony imbalance of the spleen and stomach.Its specific manifestation lies in the interaction between qi deficiency and stagnation,namely,spleen deficiency as the root cause,and qi stagnation,phlegm-dampness,and blood stasis obstructing the middle energizer as the secondary manifestations.These factors are mutually causal and interact with one another.Based on this,he proposed a four-step method to treat the disease:eliminating pathogenic factors,harmonizing the spleen and stomach,activating blood circulation to resolve stasis,and tonifying the kidney to generate blood(metaphorically described as"closing the mountains to cultivate forests and thicken the soil,breeding seeds and irrigating for stomach recovery").This approach aims to restore the harmonious state of the middle energizer,providing a complete clinical framework of theory,principle,formula,and herbs for the prevention and treatment of CAG.展开更多
AIM:To construct an intelligent segmentation scheme for precise localization of central serous chorioretinopathy(CSC)leakage points,thereby enabling ophthalmologists to deliver accurate laser treatment without navigat...AIM:To construct an intelligent segmentation scheme for precise localization of central serous chorioretinopathy(CSC)leakage points,thereby enabling ophthalmologists to deliver accurate laser treatment without navigational laser equipment.METHODS:A dataset with dual labels(point-level and pixel-level)was first established based on fundus fluorescein angiography(FFA)images of CSC and subsequently divided into training(102 images),validation(40 images),and test(40 images)datasets.An intelligent segmentation method was then developed,based on the You Only Look Once version 8 Pose Estimation(YOLOv8-Pose)model and segment anything model(SAM),to segment CSC leakage points.Next,the YOLOv8-Pose model was trained for 200 epochs,and the best-performing model was selected to form the optimal combination with SAM.Additionally,the classic five types of U-Net series models[i.e.,U-Net,recurrent residual U-Net(R2U-Net),attention U-Net(AttU-Net),recurrent residual attention U-Net(R2AttUNet),and nested U-Net(UNet^(++))]were initialized with three random seeds and trained for 200 epochs,resulting in a total of 15 baseline models for comparison.Finally,based on the metrics including Dice similarity coefficient(DICE),intersection over union(IoU),precision,recall,precisionrecall(PR)curve,and receiver operating characteristic(ROC)curve,the proposed method was compared with baseline models through quantitative and qualitative experiments for leakage point segmentation,thereby demonstrating its effectiveness.RESULTS:With the increase of training epochs,the mAP50-95,Recall,and precision of the YOLOv8-Pose model showed a significant increase and tended to stabilize,and it achieved a preliminary localization success rate of 90%(i.e.,36 images)for CSC leakage points in 40 test images.Using manually expert-annotated pixel-level labels as the ground truth,the proposed method achieved outcomes with a DICE of 57.13%,an IoU of 45.31%,a precision of 45.91%,a recall of 93.57%,an area under the PR curve(AUC-PR)of 0.78 and an area under the ROC curve(AUC-ROC)of 0.97,which enables more accurate segmentation of CSC leakage points.CONCLUSION:By combining the precise localization capability of the YOLOv8-Pose model with the robust and flexible segmentation ability of SAM,the proposed method not only demonstrates the effectiveness of the YOLOv8-Pose model in detecting keypoint coordinates of CSC leakage points from the perspective of application innovation but also establishes a novel approach for accurate segmentation of CSC leakage points through the“detect-then-segment”strategy,thereby providing a potential auxiliary means for the automatic and precise realtime localization of leakage points during traditional laser photocoagulation for CSC.展开更多
Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes...Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.展开更多
Dear Editor,Central retinal artery occlusion(CRAO)is a devastating ocular event caused by obstruction of the central retinal artery,leading to a sudden and significant loss of vision.A hallmark of CRAO on funduscopic ...Dear Editor,Central retinal artery occlusion(CRAO)is a devastating ocular event caused by obstruction of the central retinal artery,leading to a sudden and significant loss of vision.A hallmark of CRAO on funduscopic examination is a characteristic“cherry-red spot”at the fovea surrounded by a pale retina[1].The anterior segment typically appears unremarkable.展开更多
BACKGROUND Peripherally inserted central catheters(PICCs)are crucial for patients requiring long-term intravenous therapy,especially within digestive surgery under bundled care protocols.AIM To evaluate and compare th...BACKGROUND Peripherally inserted central catheters(PICCs)are crucial for patients requiring long-term intravenous therapy,especially within digestive surgery under bundled care protocols.AIM To evaluate and compare the efficacy,safety,and patient-reported outcomes of single-lumen vs double-lumen PICCs among patients undergoing digestive surgery within a structured bundled care framework.METHODS This retrospective cohort study analyzed data from 249 patients who underwent digestive surgery and utilized either single-lumen(n=117)or double-lumen(n=132)PICCs between January 2021 and June 2024.Clinical outcomes,patient satisfaction,catheterization duration,and complication rates were compared using statistical analysis via SPSS(version 29.0).The bundled care protocol was consistently applied,focusing on standardized procedures,staff training,and patient support.RESULTS Single-lumen PICCs were associated with a significantly lower thrombosis rate(0.85%)than double-lumen PICCs(6.82%,P=0.039).The single-lumen group experienced shorter catheterization durations(12.5±3.14 days vs 13.6±4.50 days,P=0.025)and higher successful infusion rates(92.7%±5.32%vs 90.4%±6.60%,P=0.003).This group also reported higher comfort scores(8.40±1.20 vs 7.90±1.50,P=0.004)and lower pain levels(2.90±0.70 vs 3.20±0.80,P=0.002).Aside from thrombosis,complication rates showed no significant difference between the groups.CONCLUSION Within bundled care context,single-lumen PICCs demonstrated advantages in reducing thrombosis risk,procedural efficiency,patient comfort,and satisfaction compared with double-lumen PICCs.The findings underscore the importance of considering patient-specific needs and clinical scenarios in catheter choice.展开更多
Central retinal artery occlusion(CRAO)is an acute ophthalmic emergency,characterized by sudden vision loss due to retinal ischemia in areas corresponding to arterial occlusion sites.Diagnosis primarily relies on fundu...Central retinal artery occlusion(CRAO)is an acute ophthalmic emergency,characterized by sudden vision loss due to retinal ischemia in areas corresponding to arterial occlusion sites.Diagnosis primarily relies on fundus fluorescein angiography(FFA)and optical coherence tomography(OCT),which show delayed retinal artery filling time hours to days after occlusion and increased hyperreflectivity of the inner retina.展开更多
Objective:Patients after radical gastrectomy often require medium-to long-term intravenous therapy.However,traditional central venous catheters(CVCs)have issues such as high infection risk and poor comfort.This study ...Objective:Patients after radical gastrectomy often require medium-to long-term intravenous therapy.However,traditional central venous catheters(CVCs)have issues such as high infection risk and poor comfort.This study aims to deeply explore the clinical application value of peripherally inserted central catheters(PICCs)after radical gastrectomy,providing a scientific basis for optimizing intravenous access selection.Methods:Fifty patients requiring catheterization after radical gastrectomy at the Friendship Hospital of Ili Kazak Autonomous Prefecture from December 2022 to May 2024 were selected.Catheterization site selection was based on patients’preferences,dividing them into two groups:the experimental group receiving PICCs and the control group receiving CVCs,with 25 patients in each group.Multi-dimensional comparative analysis was conducted,including catheterization operation time,catheter indwelling time,success rates of first and second catheterizations,and complication rates.Statistical methods such as t-tests and chi-square tests were used for in-depth analysis.Results:Compared to the control group,the experimental group had longer catheterization operations and catheter indwelling times,and a higher success rate of first catheterization(P<0.05).The incidence of catheterization complications in the experimental group was 12.00%,lower than the 40.00%in the control group(P<0.05).Conclusion:Although PICC catheterization after radical gastrectomy has relatively longer catheterization operation and indwelling times,it has a high success rate of first catheterization and a low complication rate,demonstrating high clinical application value and worth promoting in clinical practice.展开更多
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central ne...Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)re...Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.展开更多
基金supported by ANR(ANR-21CE16-0008-01)ANR(ANR-21-CE16-0008-02 and ANR-23CE52-0007)+1 种基金UNADEV(A22018CS)(to HN)UNADEV(A22020CS)(to SB)。
文摘The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.
基金supported by a grant from the Beijing Union Medical College Foundation-Rui E Emergency Medicine Research Fund in 2025。
文摘Central venous catheterization(CVC)is a fundamental clinical procedure widely performed across medical specialties.However,the complication rate of subclavian vein catheterization ranges from 6%to 11%.[1]Common complications include hemothorax,pneumothorax,air embolism,arterial puncture,and aortic perforation.[2]Herein,we report a rare case of accidental puncture of the aorta during subclavian CVC,which was successfully managed with a ventricular septal defect(VSD)occluder.
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金supported by grants from the National Research Foundation of Korea(NRF)under the Ministry of Science and Information and Communication Technology(grant number:RS-2023-00249082)Korea University(grant number:K2225791).
文摘Background:That Central and Eastern Europe and Central Asia(CEECA)experienced a major mortality crisis in the 1990s is a well-established finding,with most analyses focusing on singular causes like alcohol-related deaths.However,the utility of the integrated“deaths of despair”framework,which views alcohol,drug,and suicide deaths as a unified socio-economic phenomenon,remains under-explored in this context.Crucially,the long-term evolution of the composition of despair within the region remains a largely unexplored area of inquiry.Therefore,this study aims to analyze the long-term trends,changing composition,and regional heterogeneity of deaths from despair in the CEECA region from 1980 to 2021.Methods:Using 2021 Global Burden of Disease(GBD)data(1980–2021),we analyzed deaths of despair mortality trends in 29 CEECA countries.We employed Joinpoint regression to identify significant trend changes and conducted stratified analyses by cause,gender,and age group.Results:The CEECA deaths of despair crisis began as an alcohol and suicide driven phenomenon concentrated in middle-aged men(50–74 years)during the 1990s,with mortality rates for alcohol use disorders and self-harm surging annually by 30.35%(p=0.002)and 13.44%(p=0.001),respectively,between 1991 and 1994.It has since evolved,marked by a contrasting and emerging threat in the 21st century:a rising proportion of drug-related deaths among the younger(15–49 years)male cohort,where the share of drug use disorders increased from 6.9%in 2000 to 11.8%in 2008.Conclusion:The deaths of despair crisis in the CEECA region is not a past event but an ongoing,evolving phenomenon.Its changing nature demands a shift in public health focus from solely historical drivers to new,generation-specific threats,particularly the rise of drug-related despair among youth.
基金funded by the National Natural Science Foundation of China(42571311).
文摘Central Asia is characterized by an arid climate and widespread desert distribution,with its sustainable development severely constrained by dust events.An objective understanding of the spatiotemporal patterns and driving forces of dust weather is highly important in this area.Based on the meteorological observations from 2000 to 2020,we examined the spatiotemporal characteristics of dust weather in the five Central Asian countries(Kazakhstan,Uzbekistan,Kyrgyzstan,Turkmenistan,and Tajikistan)via Theil-Sen trend analysis and Geodetector modeling method,quantitatively revealing the influence of environmental factors,such as temperature,precipitation,and vegetation,on the frequency of dust weather.The results showed that:(1)dust weather in Central Asia was mainly distributed in a large''dust belt''extending from west to east from northern part of the Caspian lowland desert,and concentrated in basins,plains,and other low-altitude areas.Strong dust weather mainly occurred in northern areas of the Aral Sea and southern edge of Central Asia,with a maximum annual frequency of 21.9%;(2)strong dust weather in Central Asia has fluctuated and slightly decreased since 2001.The highest frequency(1.1%)occurred in spring(from March to June);(3)from 2000 to 2020,changes such as spot shifting and shrinking occurred in the four main source areas(north of the Aral Sea,Kyzylkum Desert,Karakum Desert,and Garabogazköl Bay region),where sandstorms occurred in Central Asia,and northern Caspian lowland desert became the most important low-emission dust source in Central Asia;and(4)the combined effect of soil moisture and air temperature has the most significant influence on dust weather in Central Asia.This study provides a theoretical basis for sand prevention and sand control in Central Asia.In the future,Central Asia should focus on the rational utilization of land and water resources,and implement human interventions such as vegetation restoration and optimization of irrigation methods to curb further desertification in this area.
基金Supported by research fund from Chosun University Hospital,2022.
文摘AIM:To compare the intravitreal brolucizumab and bevacizumab injections for chronic central serous chorioretinopathy(cCSC).METHODS:Patients with cCSC were classified into bevacizumab and brolucizumab group.The proportion of complete resolution of subretinal fluid(SRF),best-corrected visual acuity(BCVA),central macular thickness(CMT),and subfoveal choroidal thickness(SFCT)were compared between the two groups.RESULTS:A total of 40 eyes from 40 patients with aged 34-59y were enrolled in the study.Twenty eyes in bevacizumab group(17 males)and 20 eyes(18 males)in brolucizumab group.Comparing the proportion of complete resolution of SRF,the brolucizumab group was statistically significantly higher than the bevacizumab group(P<0.05).In 1mo,CMT was significantly reduced in the brolucizumab group compared to the bevacizumab group(265±69 vs 319±70μm;P=0.021).However,there was no significant difference in CMT between the two groups at 2 and 3mo(P>0.05).CONCLUSION:Brolucizumab is anatomically and functionally superior to bevacizumab in the treatment of patients with cCSC.
基金Central High-Level Traditional Chinese Medicine Hospital Project of Eye Hospital China Academy of Chinese Medical Science(No.GSP5-83,No.GSP4-02No.GSP5-06)+1 种基金Supported by National Natural Science Foundation of China(General ProgramNo.82474582).
文摘AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCTA)parameters,including optic disc vessel density(VD;including whole-disc VD,intra-disc VD,and peripapillary VD),superficial/deep capillary plexus(SCP/DCP)VD,and central macular thickness(CMT)were analyzed.Additional assessments included best-corrected visual acuity(BCVA)via Early Treatment Diabetic Retinopathy Study(ETDRS)chart and hemorheological profiling.CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months.Pre-and post-treatment parameters were statistically compared.RESULTS:The study comprised 60 CRVO-ME patients(28 males;32 females),aged 50-78y(mean 63.3±7.6y)and 60 age-/sex-matched healthy controls.As compared with participants exhibiting normal funduscopic findings,CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity(LSR-WBV),high-shearrate whole blood viscosity(HSR-WBV),and aggregation index(AI,all P<0.05).In CRVO-affected eyes,vertical cupto-disc(C/D)ratio and optic cup volume were significantly smaller,whereas retinal nerve fiber layer(RNFL)thickness was significantly greater,compared to both unaffected contralateral eyes and normal control eyes(all P<0.05).Following treatment,VD of the entire optic disc(P<0.05),intra-disc VD(P<0.05),and peripapillary VD(P<0.05)all increased significantly relative to baseline.CMT decreased significantly(P<0.05),whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions(P>0.05).At baseline,BCVA of CRVO eyes correlated with whole-disc VD(r=-0.276,P=0.033),intra-disc VD(r=-0.342,P=0.009),and peripapillary VD(r=-0.335,P=0.007),with intra-disc VD demonstrating the strongest association.Besides,BCVA improvement,after the treatment,correlated positively with whole-disc VD(r=0.342,P=0.008)and intradisc VD(r=0.396,P=0.002).CONCLUSION:Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion,suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO.Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula.CRVO patients shows higher hemorheological parameters than those with normal fundi.Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence,potentially acting as susceptibility factors.
基金Supported by the Natural Science Foundation of Guangxi Province(Grant Nos.2023GXNSFAA026067,2024GXN SFAA010521)the National Natural Science Foundation of China(Nos.12361079,12201149,12261026).
文摘Convex feasibility problems are widely used in image reconstruction, sparse signal recovery, and other areas. This paper is devoted to considering a class of convex feasibility problem arising from sparse signal recovery. We first derive the projection formulas for a vector onto the feasible sets. The centralized circumcentered-reflection method is designed to solve the convex feasibility problem. Some numerical experiments demonstrate the feasibility and effectiveness of the proposed algorithm, showing superior performance compared to conventional alternating projection methods.
基金supported by the National Natural Science Foundation of China,No.82474468the Science and Technology Innovation Program of Hunan Province,No.2024RC3200+3 种基金the Health Commission Talent Project of Hunan Province,No.20240304118the Scientific Research Project of Hunan Department of Education,No.23A0281the Open Fund for Chinese Medicine Powder and Innovative Drugs in the Cultivation Base of the Provincial-Ministry Jointly Established State Key Laboratory of Chinese Medicine,No.23PTKF1013the Training Plan of Outstanding Innovative Youth of Changsha,No.kq2009018(all to PM)。
文摘Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic Hedgehog signaling pathway is crucial in the central nervous system,with implications in a diverse range of diseases,including Parkinson's disease,Alzheimer's disease,spinal cord injury,traumatic brain injury,depression,Sonic Hedgehog medulloblastoma,and stroke.In this comprehensive review,we examined Sonic Hedgehog from the perspective of canonical and non-canonical pathways,elucidating their complex connections to the central nervous system.Subsequently,we summarize the latest advancements in drug therapies that offer novel strategies for treating neurological diseases by modulating the Sonic Hedgehog protein.Finally,we summarize and extend the technologies and tools for studying the Sonic Hedgehog signaling field,with the aim of providing new research ideas and methods.
基金Supported by General Project of Shanxi Administration of Traditional Chinese Medicine(2023ZYYA007&2024ZYY2D009)Young Scientists Project of Shanxi Provincial Department of Science and Technology(202203021212026)Scientific and Technological Innovation Capacity Cultivation Program for Basic and Clinical Cooperative Research Project of Shanxi University of Chinese Medicine(2024PY-JL-23-01).
文摘This study makes an in-depth exploration of the core pathogenesis of chronic atrophic gastritis,Qi Deficiency with Stagnation,to systematically interpret it within the theoretical framework of Achieving Central Harmony,and to provide a treatment plan.Professor Li Tingquan believes that the occurrence and development of chronic atrophic gastritis(CAG)is fundamentally a process of harmony imbalance of the spleen and stomach.Its specific manifestation lies in the interaction between qi deficiency and stagnation,namely,spleen deficiency as the root cause,and qi stagnation,phlegm-dampness,and blood stasis obstructing the middle energizer as the secondary manifestations.These factors are mutually causal and interact with one another.Based on this,he proposed a four-step method to treat the disease:eliminating pathogenic factors,harmonizing the spleen and stomach,activating blood circulation to resolve stasis,and tonifying the kidney to generate blood(metaphorically described as"closing the mountains to cultivate forests and thicken the soil,breeding seeds and irrigating for stomach recovery").This approach aims to restore the harmonious state of the middle energizer,providing a complete clinical framework of theory,principle,formula,and herbs for the prevention and treatment of CAG.
基金Supported by the Shenzhen Science and Technology Program(No.JCYJ20240813152704006)the National Natural Science Foundation of China(No.62401259)+2 种基金the Fundamental Research Funds for the Central Universities(No.NZ2024036)the Postdoctoral Fellowship Program of CPSF(No.GZC20242228)High Performance Computing Platform of Nanjing University of Aeronautics and Astronautics。
文摘AIM:To construct an intelligent segmentation scheme for precise localization of central serous chorioretinopathy(CSC)leakage points,thereby enabling ophthalmologists to deliver accurate laser treatment without navigational laser equipment.METHODS:A dataset with dual labels(point-level and pixel-level)was first established based on fundus fluorescein angiography(FFA)images of CSC and subsequently divided into training(102 images),validation(40 images),and test(40 images)datasets.An intelligent segmentation method was then developed,based on the You Only Look Once version 8 Pose Estimation(YOLOv8-Pose)model and segment anything model(SAM),to segment CSC leakage points.Next,the YOLOv8-Pose model was trained for 200 epochs,and the best-performing model was selected to form the optimal combination with SAM.Additionally,the classic five types of U-Net series models[i.e.,U-Net,recurrent residual U-Net(R2U-Net),attention U-Net(AttU-Net),recurrent residual attention U-Net(R2AttUNet),and nested U-Net(UNet^(++))]were initialized with three random seeds and trained for 200 epochs,resulting in a total of 15 baseline models for comparison.Finally,based on the metrics including Dice similarity coefficient(DICE),intersection over union(IoU),precision,recall,precisionrecall(PR)curve,and receiver operating characteristic(ROC)curve,the proposed method was compared with baseline models through quantitative and qualitative experiments for leakage point segmentation,thereby demonstrating its effectiveness.RESULTS:With the increase of training epochs,the mAP50-95,Recall,and precision of the YOLOv8-Pose model showed a significant increase and tended to stabilize,and it achieved a preliminary localization success rate of 90%(i.e.,36 images)for CSC leakage points in 40 test images.Using manually expert-annotated pixel-level labels as the ground truth,the proposed method achieved outcomes with a DICE of 57.13%,an IoU of 45.31%,a precision of 45.91%,a recall of 93.57%,an area under the PR curve(AUC-PR)of 0.78 and an area under the ROC curve(AUC-ROC)of 0.97,which enables more accurate segmentation of CSC leakage points.CONCLUSION:By combining the precise localization capability of the YOLOv8-Pose model with the robust and flexible segmentation ability of SAM,the proposed method not only demonstrates the effectiveness of the YOLOv8-Pose model in detecting keypoint coordinates of CSC leakage points from the perspective of application innovation but also establishes a novel approach for accurate segmentation of CSC leakage points through the“detect-then-segment”strategy,thereby providing a potential auxiliary means for the automatic and precise realtime localization of leakage points during traditional laser photocoagulation for CSC.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.
文摘Dear Editor,Central retinal artery occlusion(CRAO)is a devastating ocular event caused by obstruction of the central retinal artery,leading to a sudden and significant loss of vision.A hallmark of CRAO on funduscopic examination is a characteristic“cherry-red spot”at the fovea surrounded by a pale retina[1].The anterior segment typically appears unremarkable.
文摘BACKGROUND Peripherally inserted central catheters(PICCs)are crucial for patients requiring long-term intravenous therapy,especially within digestive surgery under bundled care protocols.AIM To evaluate and compare the efficacy,safety,and patient-reported outcomes of single-lumen vs double-lumen PICCs among patients undergoing digestive surgery within a structured bundled care framework.METHODS This retrospective cohort study analyzed data from 249 patients who underwent digestive surgery and utilized either single-lumen(n=117)or double-lumen(n=132)PICCs between January 2021 and June 2024.Clinical outcomes,patient satisfaction,catheterization duration,and complication rates were compared using statistical analysis via SPSS(version 29.0).The bundled care protocol was consistently applied,focusing on standardized procedures,staff training,and patient support.RESULTS Single-lumen PICCs were associated with a significantly lower thrombosis rate(0.85%)than double-lumen PICCs(6.82%,P=0.039).The single-lumen group experienced shorter catheterization durations(12.5±3.14 days vs 13.6±4.50 days,P=0.025)and higher successful infusion rates(92.7%±5.32%vs 90.4%±6.60%,P=0.003).This group also reported higher comfort scores(8.40±1.20 vs 7.90±1.50,P=0.004)and lower pain levels(2.90±0.70 vs 3.20±0.80,P=0.002).Aside from thrombosis,complication rates showed no significant difference between the groups.CONCLUSION Within bundled care context,single-lumen PICCs demonstrated advantages in reducing thrombosis risk,procedural efficiency,patient comfort,and satisfaction compared with double-lumen PICCs.The findings underscore the importance of considering patient-specific needs and clinical scenarios in catheter choice.
基金Supported by National Natural Science Foundation of China(No.82070991).
文摘Central retinal artery occlusion(CRAO)is an acute ophthalmic emergency,characterized by sudden vision loss due to retinal ischemia in areas corresponding to arterial occlusion sites.Diagnosis primarily relies on fundus fluorescein angiography(FFA)and optical coherence tomography(OCT),which show delayed retinal artery filling time hours to days after occlusion and increased hyperreflectivity of the inner retina.
基金The Ili Kazakh Autonomous Prefecture Science and Technology Plan Project(Project No.:YJC2023A28)。
文摘Objective:Patients after radical gastrectomy often require medium-to long-term intravenous therapy.However,traditional central venous catheters(CVCs)have issues such as high infection risk and poor comfort.This study aims to deeply explore the clinical application value of peripherally inserted central catheters(PICCs)after radical gastrectomy,providing a scientific basis for optimizing intravenous access selection.Methods:Fifty patients requiring catheterization after radical gastrectomy at the Friendship Hospital of Ili Kazak Autonomous Prefecture from December 2022 to May 2024 were selected.Catheterization site selection was based on patients’preferences,dividing them into two groups:the experimental group receiving PICCs and the control group receiving CVCs,with 25 patients in each group.Multi-dimensional comparative analysis was conducted,including catheterization operation time,catheter indwelling time,success rates of first and second catheterizations,and complication rates.Statistical methods such as t-tests and chi-square tests were used for in-depth analysis.Results:Compared to the control group,the experimental group had longer catheterization operations and catheter indwelling times,and a higher success rate of first catheterization(P<0.05).The incidence of catheterization complications in the experimental group was 12.00%,lower than the 40.00%in the control group(P<0.05).Conclusion:Although PICC catheterization after radical gastrectomy has relatively longer catheterization operation and indwelling times,it has a high success rate of first catheterization and a low complication rate,demonstrating high clinical application value and worth promoting in clinical practice.
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
文摘Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by the National Natural Science Foundation of China(82204634,82174047,81622051)the Zhejiang Provincial Natural Science Foundation of China(LQ22H280010)the Foundation of Zhejiang Chinese Medical University(2021ZR03).
文摘Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.
