Addiction,a complex and chronic neurobiological disorder,is characterized by compulsive substance use despite harmful consequences,leading to persistent alterations in brain function,particularly within the reward,mot...Addiction,a complex and chronic neurobiological disorder,is characterized by compulsive substance use despite harmful consequences,leading to persistent alterations in brain function,particularly within the reward,motivation,and decision-making systems.Despite the availability of a range of treatment options,including pharmacotherapy and behavioral therapies,relapse remains a major challenge,with many individuals struggling to maintain long-term recovery.Current treatments often show limited efficacy,underscoring the need for novel therapeutic strategies that can address the underlying neurobiological disruptions in addiction.展开更多
The prevalence of neuropsychiatric disorders,such as Alzheimer’s disease and major depressive disorder,has been rising annually,imposing a significant burden on social and economic development.Although current therap...The prevalence of neuropsychiatric disorders,such as Alzheimer’s disease and major depressive disorder,has been rising annually,imposing a significant burden on social and economic development.Although current therapeutic interventions can mitigate symptoms,a comprehensive understanding of the complex etiologies underlying these disorders remains elusive.This suggests that exploring the mechanisms of these disorders from a holistic perspective may lead to more effective therapeutic strategies.Traditional Chinese medicine(TCM)is primarily composed of natural compounds,often associated with fewer side effects,and its holistic treatment philosophy.These advantages have led to its widespread use in alleviating neuropsychiatric disorders.However,the specific mechanisms through which orally administered TCM interacts with the nervous system to exert therapeutic effects remain undefined.Numerous studies have suggested that these effects may be linked to gastrointestinal absorption and metabolism,particularly the interactions between TCM and gut microbiota.On one hand,TCM can regulate the balance of the gut microbiome,which plays a critical role in the progression of many neuropsychiatric diseases.On the other hand,TCM is metabolized by gut microbiota into key bioactive molecules,which then exert their alleviating effects on neuropsychiatric disorders through specific signaling pathways.This review will elucidate the interactions between the microbiota-gut-brain axis and neuropsychiatric disorders through the perspectives of neurological,immune,and endocrine-metabolic pathways.Furthermore,it will summarize the current clinical applications and therapeutic potentials of single TCM herbs,herbal formulas,and bioactive compounds,based on the microbiota-gut-brain axis theory,in alleviating major neuropsychiatric conditions.展开更多
Non-right-handedness(NRH),encompassing left-handedness and mixed-handedness,has been frequently reported at elevated rates in individuals with various psychiatric disorders.The consistency of this association across m...Non-right-handedness(NRH),encompassing left-handedness and mixed-handedness,has been frequently reported at elevated rates in individuals with various psychiatric disorders.The consistency of this association across multiple conditions and its underlying mechanisms is the subject of ongoing investigation.This review synthesized current evidence to explore the association between NRH and psychiatric disorders from epidemiological,genetic,and neurobiological perspectives.We systematically identified and appraised relevant literature investigating NRH prevalence in psychiatric populations and potential explanatory mechanisms.Epidemiological evidence indicates an elevated prevalence of NRH,particularly within neurodevelopmental disorders.Potential contributing mechanisms identified include early developmental disruptions,shared genetic predispositions,and atypical patterns of brain lateralization.While the association between NRH and psychiatric conditions,especially neurodevelopmental disorders,is evident,the causal pathways and relative contributions of identified mechanisms are complex and debated.This review highlighted key areas requiring further research to elucidate these relationships.展开更多
Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Alt...Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.展开更多
BACKGROUND Non-suicidal self-injury(NSSI)is common among adolescents with depressive disorders and poses a major public health challenge.Rumination,a key cognitive feature of depression,includes different subtypes tha...BACKGROUND Non-suicidal self-injury(NSSI)is common among adolescents with depressive disorders and poses a major public health challenge.Rumination,a key cognitive feature of depression,includes different subtypes that may relate to NSSI through distinct psychological mechanisms.However,how these subtypes interact with specific NSSI behaviors remains unclear.AIM To examine associations between rumination subtypes and specific NSSI behaviors in adolescents.METHODS We conducted a cross-sectional study with 305 hospitalized adolescents diagnosed with depressive disorders.The subjects ranged from 12-18 years in age.Rumi-nation subtypes were assessed using the Ruminative Response Scale,and 12 NSSI behaviors were evaluated using a validated questionnaire.Network analysis was applied to explore symptom-level associations and identify central symptoms.RESULTS The network analysis revealed close connections between rumination subtypes and NSSI behaviors.Brooding was linked to behaviors such as hitting objects and burning.Scratching emerged as the most influential NSSI symptom.Symptomfocused rumination served as a key bridge connecting rumination and NSSI.CONCLUSION Symptom-focused rumination and scratching were identified as potential intervention targets.These findings highlight the psychological significance of specific cognitive-behavioral links in adolescent depression and suggest directions for tailored prevention and treatment.However,the cross-sectional,single-site design limits causal inference and generalizability.Future longitudinal and multi-center studies are needed to confirm causal pathways and verify the generalizability of the findings to broader adolescent populations.展开更多
Musculoskeletal injuries are among the most common causes of disability worldwide,with early detection and appropriate intervention critical to minimizing long-term complications.Infrared thermography(IRT)has emerged ...Musculoskeletal injuries are among the most common causes of disability worldwide,with early detection and appropriate intervention critical to minimizing long-term complications.Infrared thermography(IRT)has emerged as a noninvasive,real-time imaging modality that captures superficial temperature changes reflecting underlying physiological processes such as inflammation and vascular alterations.This review explores the fundamental principles of medical thermography,differentiates between passive and active approaches,and outlines key technological advancements including artificial intelligence integration.The clinical utility of IRT is discussed in various contexts–ranging from acute soft tissue injuries and overuse syndromes to chronic pain and rehabilitation monitoring.Comparative insights with conventional imaging techniques such as ultrasound and magnetic resonance imaging are also presented.While IRT offers functional imaging capabilities with advantages in portability,safety,and speed,its limitations–such as lack of deep-tissue penetration and protocol standardization–remain significant barriers to broader adoption.Future directions include the integration of IRT with other imaging modalities and digital health platforms to enhance musculoskeletal assessment and injury prevention strategies.展开更多
Traditional psychiatric diagnosis relies on subjective symptom assessment,lacking objective biomarkers that hinder early detection and personalized treatment.Plasma proteins and polygenic risk score(PRS),as potential ...Traditional psychiatric diagnosis relies on subjective symptom assessment,lacking objective biomarkers that hinder early detection and personalized treatment.Plasma proteins and polygenic risk score(PRS),as potential predictive tools,hold promise for advancing early diagnosis of mental disorders.This study aims to evaluate the predictive potential of proteomic features and PRS in multiple mental illnesses(depression,schizophrenia,and post-traumatic stress disorder(PTSD)).Using participant data from the UK Biobank-Pharma Proteomics Project,we screen protein associations with mental disorders through least absolute shrinkage and selection operator(LASSO)analysis and construct a Cox regression risk prediction model by integrating the PRS.Additionally,we evaluate predictive performance using 6 machine learning methods and Kaplan-Meier survival curves.Our findings reveal distinct predictive patterns across dis-orders.For depression,integrating plasma proteins with PRS significantly improves prediction beyond the clinical model(C-index=0.6322).For schizophrenia,adding plasma proteins enhances predictive performance,whereas PRS provides no significant improvement.For PTSD,neither plasma proteins nor PRS add substantial predictive value beyond clinical variables.Risk stratification analysis demonstrat that all three mental disorders models can clearly distinguish high-risk from low-risk groups(depression:HR=2.34,P<0.001;schizophrenia:HR=5.47,P<0.001;PTSD:HR=3.02,P<0.001).Al-though it shows good performance in short-term prediction,its long-term prediction ability has decreased,and it needs to be further optimized in the future.This study underscores the differential utility of biomarkers across mental disorders and provides a rationale for disorder-specific predictive modeling in precision psychiatry.展开更多
Inflammasomes,a category of protein complexes,recognize exogenous pathogens and endogenous tissue damage.In response,they induce inflammatory responses and pyroptosis,and are involved in both innate immunity and the r...Inflammasomes,a category of protein complexes,recognize exogenous pathogens and endogenous tissue damage.In response,they induce inflammatory responses and pyroptosis,and are involved in both innate immunity and the regulation of adaptive immunity,with significant effects in disease and health.Neuroinflammation is closely related to neurological disorders.Nervous system homeostasis is primarily regulated by glial cells,with microglia and astrocytes playing a dual role in both neuroprotection and neurotoxicity.Recent studies highlight the importance of microglia and astrocytes within the central nervous system in mediating neuroinflammation associated with neuropsychiatric diseases.In particular,the role of inflammasomes in glial cells and neuroinflammation has garnered growing attention.This review classifies inflammasomes and their activation mechanisms as well as explores their involvement in the activation of microglia and astrocytes in various neurological diseases,aiming to contribute a deeper understanding of the pathogenesis of neurodegenerative disease and brain injury and identification of novel therapeutic targets.展开更多
BACKGROUND Timely and accurate evaluation of mental disorders in adolescents using appropriate mental health literacy assessment tools is essential for improving their mental health literacy levels.AIM To develop an e...BACKGROUND Timely and accurate evaluation of mental disorders in adolescents using appropriate mental health literacy assessment tools is essential for improving their mental health literacy levels.AIM To develop an evaluation index system for the mental health literacy of adolescent patients with mental disorders,providing a scientific,comprehensive,and reliable tool for the monitoring and intervention of mental health literacy of such patients.METHODS From December 2022 to June 2023,the evaluation index system for mental health literacy of adolescents with mental disorders was developed through literature reviews,semi-structured interviews,expert letter consultations,and the analytic hierarchy process.Based on this index system,a self-assessment questionnaire was compiled and administered to 305 adolescents with mental disorders to test the reliability and validity of the index system.RESULTS The final evaluation index system for mental health literacy of adolescents with mental disorders included 4 first-level indicators,10 second-level indicators,and 52 third-level indicators.The overall Cronbach’sαcoefficient of the index system was 0.957,with a partial reliability of 0.826 and a content validity index of 0.975.The cumulative variance contribution rate of 10 common factors was 66.491%.The correlation coefficients between each dimension and the total questionnaire ranged from 0.672 to 0.724,while the correlation coefficients in each dimension ranged from 0.389 to 0.705.CONCLUSION The evaluation index system for mental health literacy of adolescents with mental disorders,developed in this study,demonstrated notable reliability and validity,making it a valuable tool for evaluating mental health literacy in this population.展开更多
Functional gastrointestinal disorders(FGIDs),including irritable bowel syndrome(IBS),functional dyspepsia(FD),and gastroesophageal reflux disease(GERD),present persistent diagnostic and therapeutic challenges due to s...Functional gastrointestinal disorders(FGIDs),including irritable bowel syndrome(IBS),functional dyspepsia(FD),and gastroesophageal reflux disease(GERD),present persistent diagnostic and therapeutic challenges due to symptom heterogeneity and the absence of reliable biomarkers.Artificial intelligence(AI)enables the integration of multimodal data to enhance FGID management through precision diagnostics and preventive healthcare.This minireview summarizes recent advancements in AI applications for FGIDs,highlighting progress in diagnostic accuracy,subtype classification,personalized interventions,and preventive strategies inspired by the traditional Chinese medicine concept of“treating the undiseased”.Machine learning and deep learning algorithms have demonstrated value in improving IBS diagnosis,refining FD neuro-gastrointestinal subtyping,and screening for GERD-related complications.Moreover,AI supports dietary,psychological,and integrative medicine-based interventions to improve patient adherence and quality of life.Nonetheless,key challenges remain,including data heterogeneity,limited model interpretability,and the need for robust clinical validation.Future directions emphasize interdisciplinary collaboration,the development of multimodal and explainable AI models,and the creation of patientcentered platforms to facilitate a shift from reactive treatment to proactive prevention.This review provides a systematic framework to guide the clinical application and theoretical innovation of AI in FGIDs.展开更多
Objective Cerebral venous outflow disorders(CVOD)can impair cerebral perfusion and produce diverse,often debilitating symptoms,substantially reducing quality of life.Intermittent hypoxiahyperoxia training(IHHT)has dem...Objective Cerebral venous outflow disorders(CVOD)can impair cerebral perfusion and produce diverse,often debilitating symptoms,substantially reducing quality of life.Intermittent hypoxiahyperoxia training(IHHT)has demonstrated therapeutic potential across various pathologies and may represent a promising non-pharmacological approach for CVOD management.Methods Patients with imaging-confirmed CVOD underwent 14 IHHT sessions,each comprising four cycles of 10-minute hypoxia(11%O_(2))stimulation and 20-minute hyperoxia(38%O_(2)).Physiological parameters and adverse events were monitored throughout the intervention.Clinical scales,24-hour ambulatory blood pressure,blood tests,jugular ultrasound,and perfusion imaging were assessed preand post-intervention.Results No participants experienced intolerable discomfort or severe adverse events;vital signs remained within normal ranges.No significant changes were observed in 24-hour blood pressure,blood cell counts,lipid profiles,or other blood markers.Notably,60%of patients(n=12)reported overall symptom improvement on the Patient Global Impression of Change scale.Headache severity,as measured by the visual analogue scale,significantly decreased(6.33±1.22 vs.4.89±2.03,P=0.016).In patients with internal jugular vein(IJV)stenosis,significant improvements were observed in regional cerebral blood flow(including the insula,occipital lobe,internal capsule,and lenticula)and left J3-segment IJV flow volume(107.27[47.50,160.00]vs.140.83[55.00,210.00]mL/min,P=0.011).Conclusion The current IHHT protocol is safe and well-tolerated in patients with CVOD.IHHT may alleviate CVOD-related symptoms by improving oxygen saturation,cerebral perfusion,and venous outflow pattern,supporting its potential as a non-invasive therapeutic strategy.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
Objective To investigate methods for constructing a high-quality instructional dataset for traditional Chinese medicine(TCM)mental disorders and to validate its efficacy.Methods We proposed the Fine-Med-Mental-T&P...Objective To investigate methods for constructing a high-quality instructional dataset for traditional Chinese medicine(TCM)mental disorders and to validate its efficacy.Methods We proposed the Fine-Med-Mental-T&P methodology for constructing high-quality instruction datasets in TCM mental disorders.This approach integrates theoretical knowledge and practical case studies through a dual-track strategy.(i)Theoretical track:textbooks and guidelines on TCM mental disorders were manually segmented.Initial responses were generated using DeepSeek-V3,followed by refinement by the Qwen3-32B model to align the expression with human preferences.A screening algorithm was then applied to select 16000 high-quality instruction pairs.(ii)Practical track:starting from over 600 real clinical case seeds,diagnostic and therapeutic instruction pairs were generated using DeepSeek-V3 and subsequently screened through manual evaluation,resulting in 4000 high-quality practiceoriented instruction pairs.The integration of both tracks yielded the Med-Mental-Instruct-T&P dataset,comprising a total of 20000 instruction pairs.To validate the dataset’s effectiveness,three experimental evaluations(both manual and automated)were conducted:(i)comparative studies to compare the performance of models fine-tuned on different datasets;(ii)benchmarking to compare against mainstream TCM-specific large language models(LLMs);(iii)data ablation study to investigate the relationship between data volume and model performance.Results Experimental results demonstrate the superior performance of T&P-model finetuned on the Med-Mental-Instruct-T&P dataset.In the comparative study,the T&P-model significantly outperformed the baseline models trained solely on self-generated or purely human-curated baseline data.This superiority was evident in both automated metrics(ROUGEL>0.55)and expert manual evaluations(scoring above 7/10 across accuracy).In benchmark comparisons,the T&P-model also excelled against existing mainstream TCM LLMs(e.g.,HuatuoGPT and ZuoyiGPT).It showed particularly strong capabilities in handling diverse clinical presentations,including challenging disorders such as insomnia and coma,showcasing its robustness and versatility.Data ablation studies showed that T&P-model performance had an overall upward trend with minor fluctuations when training data increased from 10%to 50%;beyond 50%,performance improvement slowed significantly,with metrics plateauing and approaching a saturation point.展开更多
Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure pro...Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure proper protein folding,the addition of post-translational modifications,and delive ring to intracellular and extracellular destinations.Astrocytes are fundamental homeostatic cells,controlling multiple aspects of the central nervous system physiology,such as ion balance,nutrients,blood flow,neurotransmitte rs,and responses to insults.Astrocytes are polarized cells,and,such as neurons,extensively use the secretory pathway for secreting factors and exposing functional receptors,channels,and transporte rs on the plasma membrane.In this review,we will underline the importance of studying the Golgi apparatus and the secretory pathway in astrocytes,based on the possible tight connection between the Golgi apparatus and astrocytes'homeostatic function.Given the topic of this review,we will provide examples mostly about the Golgi apparatus structure,function,localization,and its involvement in astrocytes'homeostatic response,with an insight into congenital glycosylation disorders,as an example of a potential future field in the study of astrocyte homeostatic failu re and Golgi apparatus alteration.展开更多
Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure pro...Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure proper protein folding,the addition of post-translational modifications,and delivering to intracellular and extracellular destinations.Astrocytes are fundamental homeostatic cells,controlling multiple aspects of the central nervous system physiology,such as ion balance,nutrients,blood flow,neurotransmitters,and responses to insults.Astrocytes are polarized cells,and,such as neurons,extensively use the secretory pathway for secreting factors and exposing functional receptors,channels,and transporters on the plasma membrane.In this review,we will underline the importance of studying the Golgi apparatus and the secretory pathway in astrocytes,based on the possible tight connection between the Golgi apparatus and astrocytes’homeostatic function.Given the topic of this review,we will provide examples mostly about the Golgi apparatus structure,function,localization,and its involvement in astrocytes’homeostatic response,with an insight into congenital glycosylation disorders,as an example of a potential future field in the study of astrocyte homeostatic failure and Golgi apparatus alteration.展开更多
Psychiatric disorders have emerged as significant contributors to the global burden of disease in recent decades.The endocannabinoid system(ECS)influences a range of physiological and pathophysiological processes,incl...Psychiatric disorders have emerged as significant contributors to the global burden of disease in recent decades.The endocannabinoid system(ECS)influences a range of physiological and pathophysiological processes,including nociception,cognition,appetite,memory,and behavior,serving as a crucial mediator in psychiatric disorders.Imaging the ECS provides valuable insights into the pathophysiological mechanisms underlying psychiatric disorders and enhances clinical management strategies.As an advanced noninvasive molecular imaging modality,positron emission tomography(PET)enables the in vivo exploration of biological processes at the cellular and molecular levels.Recent advancements have led to the development of numerous PET tracers that target various components of the ECS,offering opportunities to visualize,characterize,and quantify ECS activity in psychiatric disorders in vivo.In this review,we summarize the existing PET tracers for ECS imaging and discuss their applications in diverse psychiatric conditions,including cannabis use disorder,alcohol use disorder,post-traumatic stress disorder,schizophrenia,and eating disorders.展开更多
Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables th...Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.展开更多
Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century.However,the inaccessibility and complexity of the human brain have always represented a challeng...Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century.However,the inaccessibility and complexity of the human brain have always represented a challenge in understanding the pathophysiology of the central nervous system.Brain organoids are self-assembled threedimensional aggregates derived from pluripotent stem cells with cell types and structures similar to the embryonic human brain,giving them potential for investigating the atypical cellular,molecular,and genetic characteristics characteristic of central nervous system disorders.Brain organoids also provide a platform for drug screening and serve as a potential source for transplantation therapy for brain injuries.However,the broad application of brain organoids is hampered by several limitations,such as the lack of high-fidelity cell types,insufficient maturation,and considerable heterogeneity,undermining their reliability in specific applications.This review summarizes brain organoid evolution,discusses recent technological and methodological innovations,and reviews their applications in drug screening,transplantation therapy,and disease modeling,as well as clinical research progress.Additionally,we emphasize the limitations of current brain organoid research and explore the potential for advancing the technology to enhance its applicability.展开更多
The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral bloo...The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.展开更多
Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and disea...Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and diseased processes.Owing to their operability and sample accessibility,brain organoids serve as a bridge between in vitro monolayer cell culture models and in vivo animal models.An increasing number of induction protocols for brain organoids have been developed over the preceding decade.A key future research direction will focus on ensuring the complexity and quality of brain organoids.The integration of powerful technologies,such as the CRISP R/Cas9 genome editing and lineage tra cing systems,shall precipitate practical and broad applications of brain organoids.In this review,we discuss the generation and application of brain organoids,as well as their integration with genome editing technologies,in the study of neural development,disease modeling,and mechanistic investigations.The innovative combination of these two technologies may offer a fresh perspective for exploring the fundamental aspects of the human nervous system and related diseases.展开更多
基金supported by the National Natural Science Foundation of China(T2350008)the STI2030-Major Projects[2021ZD0203000(2021ZD0203003)]the Open Research Fund of the State Key Laboratory of Brain-Machine Intelligence,Zhejiang University(BMI2400014).
文摘Addiction,a complex and chronic neurobiological disorder,is characterized by compulsive substance use despite harmful consequences,leading to persistent alterations in brain function,particularly within the reward,motivation,and decision-making systems.Despite the availability of a range of treatment options,including pharmacotherapy and behavioral therapies,relapse remains a major challenge,with many individuals struggling to maintain long-term recovery.Current treatments often show limited efficacy,underscoring the need for novel therapeutic strategies that can address the underlying neurobiological disruptions in addiction.
基金supported by Henan Provincial Medical Science and Technology Research Project(LHGJ20240430).
文摘The prevalence of neuropsychiatric disorders,such as Alzheimer’s disease and major depressive disorder,has been rising annually,imposing a significant burden on social and economic development.Although current therapeutic interventions can mitigate symptoms,a comprehensive understanding of the complex etiologies underlying these disorders remains elusive.This suggests that exploring the mechanisms of these disorders from a holistic perspective may lead to more effective therapeutic strategies.Traditional Chinese medicine(TCM)is primarily composed of natural compounds,often associated with fewer side effects,and its holistic treatment philosophy.These advantages have led to its widespread use in alleviating neuropsychiatric disorders.However,the specific mechanisms through which orally administered TCM interacts with the nervous system to exert therapeutic effects remain undefined.Numerous studies have suggested that these effects may be linked to gastrointestinal absorption and metabolism,particularly the interactions between TCM and gut microbiota.On one hand,TCM can regulate the balance of the gut microbiome,which plays a critical role in the progression of many neuropsychiatric diseases.On the other hand,TCM is metabolized by gut microbiota into key bioactive molecules,which then exert their alleviating effects on neuropsychiatric disorders through specific signaling pathways.This review will elucidate the interactions between the microbiota-gut-brain axis and neuropsychiatric disorders through the perspectives of neurological,immune,and endocrine-metabolic pathways.Furthermore,it will summarize the current clinical applications and therapeutic potentials of single TCM herbs,herbal formulas,and bioactive compounds,based on the microbiota-gut-brain axis theory,in alleviating major neuropsychiatric conditions.
文摘Non-right-handedness(NRH),encompassing left-handedness and mixed-handedness,has been frequently reported at elevated rates in individuals with various psychiatric disorders.The consistency of this association across multiple conditions and its underlying mechanisms is the subject of ongoing investigation.This review synthesized current evidence to explore the association between NRH and psychiatric disorders from epidemiological,genetic,and neurobiological perspectives.We systematically identified and appraised relevant literature investigating NRH prevalence in psychiatric populations and potential explanatory mechanisms.Epidemiological evidence indicates an elevated prevalence of NRH,particularly within neurodevelopmental disorders.Potential contributing mechanisms identified include early developmental disruptions,shared genetic predispositions,and atypical patterns of brain lateralization.While the association between NRH and psychiatric conditions,especially neurodevelopmental disorders,is evident,the causal pathways and relative contributions of identified mechanisms are complex and debated.This review highlighted key areas requiring further research to elucidate these relationships.
文摘Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.
基金Supported by Key Research and Development Program of Shaanxi Province,China,No.2024SF-YBXM-078.
文摘BACKGROUND Non-suicidal self-injury(NSSI)is common among adolescents with depressive disorders and poses a major public health challenge.Rumination,a key cognitive feature of depression,includes different subtypes that may relate to NSSI through distinct psychological mechanisms.However,how these subtypes interact with specific NSSI behaviors remains unclear.AIM To examine associations between rumination subtypes and specific NSSI behaviors in adolescents.METHODS We conducted a cross-sectional study with 305 hospitalized adolescents diagnosed with depressive disorders.The subjects ranged from 12-18 years in age.Rumi-nation subtypes were assessed using the Ruminative Response Scale,and 12 NSSI behaviors were evaluated using a validated questionnaire.Network analysis was applied to explore symptom-level associations and identify central symptoms.RESULTS The network analysis revealed close connections between rumination subtypes and NSSI behaviors.Brooding was linked to behaviors such as hitting objects and burning.Scratching emerged as the most influential NSSI symptom.Symptomfocused rumination served as a key bridge connecting rumination and NSSI.CONCLUSION Symptom-focused rumination and scratching were identified as potential intervention targets.These findings highlight the psychological significance of specific cognitive-behavioral links in adolescent depression and suggest directions for tailored prevention and treatment.However,the cross-sectional,single-site design limits causal inference and generalizability.Future longitudinal and multi-center studies are needed to confirm causal pathways and verify the generalizability of the findings to broader adolescent populations.
文摘Musculoskeletal injuries are among the most common causes of disability worldwide,with early detection and appropriate intervention critical to minimizing long-term complications.Infrared thermography(IRT)has emerged as a noninvasive,real-time imaging modality that captures superficial temperature changes reflecting underlying physiological processes such as inflammation and vascular alterations.This review explores the fundamental principles of medical thermography,differentiates between passive and active approaches,and outlines key technological advancements including artificial intelligence integration.The clinical utility of IRT is discussed in various contexts–ranging from acute soft tissue injuries and overuse syndromes to chronic pain and rehabilitation monitoring.Comparative insights with conventional imaging techniques such as ultrasound and magnetic resonance imaging are also presented.While IRT offers functional imaging capabilities with advantages in portability,safety,and speed,its limitations–such as lack of deep-tissue penetration and protocol standardization–remain significant barriers to broader adoption.Future directions include the integration of IRT with other imaging modalities and digital health platforms to enhance musculoskeletal assessment and injury prevention strategies.
基金The National Natural Science Foundation of China-Regional Science“Identification of novel drug targets for lung cancer via Mendelian randomization analysis based on blood proteomics”(62362062)The 2025 Xinjiang University Excellent Graduate Innovation Project“Research on identification of therapeutic targets and predictive factors for mental disorders based on proteomics”(XJDX2025YJS151)。
文摘Traditional psychiatric diagnosis relies on subjective symptom assessment,lacking objective biomarkers that hinder early detection and personalized treatment.Plasma proteins and polygenic risk score(PRS),as potential predictive tools,hold promise for advancing early diagnosis of mental disorders.This study aims to evaluate the predictive potential of proteomic features and PRS in multiple mental illnesses(depression,schizophrenia,and post-traumatic stress disorder(PTSD)).Using participant data from the UK Biobank-Pharma Proteomics Project,we screen protein associations with mental disorders through least absolute shrinkage and selection operator(LASSO)analysis and construct a Cox regression risk prediction model by integrating the PRS.Additionally,we evaluate predictive performance using 6 machine learning methods and Kaplan-Meier survival curves.Our findings reveal distinct predictive patterns across dis-orders.For depression,integrating plasma proteins with PRS significantly improves prediction beyond the clinical model(C-index=0.6322).For schizophrenia,adding plasma proteins enhances predictive performance,whereas PRS provides no significant improvement.For PTSD,neither plasma proteins nor PRS add substantial predictive value beyond clinical variables.Risk stratification analysis demonstrat that all three mental disorders models can clearly distinguish high-risk from low-risk groups(depression:HR=2.34,P<0.001;schizophrenia:HR=5.47,P<0.001;PTSD:HR=3.02,P<0.001).Al-though it shows good performance in short-term prediction,its long-term prediction ability has decreased,and it needs to be further optimized in the future.This study underscores the differential utility of biomarkers across mental disorders and provides a rationale for disorder-specific predictive modeling in precision psychiatry.
基金National Natural Science Foundation of China,Nos.82371405(to HZ),82203683(to YH)the Hubei Provincial Key Research Projects,No.2022BCA027.
文摘Inflammasomes,a category of protein complexes,recognize exogenous pathogens and endogenous tissue damage.In response,they induce inflammatory responses and pyroptosis,and are involved in both innate immunity and the regulation of adaptive immunity,with significant effects in disease and health.Neuroinflammation is closely related to neurological disorders.Nervous system homeostasis is primarily regulated by glial cells,with microglia and astrocytes playing a dual role in both neuroprotection and neurotoxicity.Recent studies highlight the importance of microglia and astrocytes within the central nervous system in mediating neuroinflammation associated with neuropsychiatric diseases.In particular,the role of inflammasomes in glial cells and neuroinflammation has garnered growing attention.This review classifies inflammasomes and their activation mechanisms as well as explores their involvement in the activation of microglia and astrocytes in various neurological diseases,aiming to contribute a deeper understanding of the pathogenesis of neurodegenerative disease and brain injury and identification of novel therapeutic targets.
基金Supported by Inter Disciplinary Direction Cultivation Project of Hunan University of Chinese Medicine,No.2025JC01032025 Hunan Province Science and Technology Innovation Plan Project,No.2025RC9012+2 种基金2022"Unveiling and Leading"Project of Discipline Construction at Hunan University of Chinese Medicine,No.22JBZ044Changsha Municipal Natural Science Foundation,No.kq2402174Hunan Provincial Science Popularization Fund Project,No.2025ZK4223.
文摘BACKGROUND Timely and accurate evaluation of mental disorders in adolescents using appropriate mental health literacy assessment tools is essential for improving their mental health literacy levels.AIM To develop an evaluation index system for the mental health literacy of adolescent patients with mental disorders,providing a scientific,comprehensive,and reliable tool for the monitoring and intervention of mental health literacy of such patients.METHODS From December 2022 to June 2023,the evaluation index system for mental health literacy of adolescents with mental disorders was developed through literature reviews,semi-structured interviews,expert letter consultations,and the analytic hierarchy process.Based on this index system,a self-assessment questionnaire was compiled and administered to 305 adolescents with mental disorders to test the reliability and validity of the index system.RESULTS The final evaluation index system for mental health literacy of adolescents with mental disorders included 4 first-level indicators,10 second-level indicators,and 52 third-level indicators.The overall Cronbach’sαcoefficient of the index system was 0.957,with a partial reliability of 0.826 and a content validity index of 0.975.The cumulative variance contribution rate of 10 common factors was 66.491%.The correlation coefficients between each dimension and the total questionnaire ranged from 0.672 to 0.724,while the correlation coefficients in each dimension ranged from 0.389 to 0.705.CONCLUSION The evaluation index system for mental health literacy of adolescents with mental disorders,developed in this study,demonstrated notable reliability and validity,making it a valuable tool for evaluating mental health literacy in this population.
基金Supported by The Natural Science Foundation of China,No.82374292the Plans for Major Provincial Science and Technology Projects of Anhui Province,No.202303a07020003the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine,No.ZYYCXTD-C-202401.
文摘Functional gastrointestinal disorders(FGIDs),including irritable bowel syndrome(IBS),functional dyspepsia(FD),and gastroesophageal reflux disease(GERD),present persistent diagnostic and therapeutic challenges due to symptom heterogeneity and the absence of reliable biomarkers.Artificial intelligence(AI)enables the integration of multimodal data to enhance FGID management through precision diagnostics and preventive healthcare.This minireview summarizes recent advancements in AI applications for FGIDs,highlighting progress in diagnostic accuracy,subtype classification,personalized interventions,and preventive strategies inspired by the traditional Chinese medicine concept of“treating the undiseased”.Machine learning and deep learning algorithms have demonstrated value in improving IBS diagnosis,refining FD neuro-gastrointestinal subtyping,and screening for GERD-related complications.Moreover,AI supports dietary,psychological,and integrative medicine-based interventions to improve patient adherence and quality of life.Nonetheless,key challenges remain,including data heterogeneity,limited model interpretability,and the need for robust clinical validation.Future directions emphasize interdisciplinary collaboration,the development of multimodal and explainable AI models,and the creation of patientcentered platforms to facilitate a shift from reactive treatment to proactive prevention.This review provides a systematic framework to guide the clinical application and theoretical innovation of AI in FGIDs.
基金sponsored by the National Natural Science Foundation of China(Nos.82027802,82101389,82274401,and 81971114)Beijing Nova Program(No.20230484286)+1 种基金Beijing Natural Science Foundation(7254366)the General Project of Science and Technology of Beijing Municipal Education Commission(No.KM202110025018).
文摘Objective Cerebral venous outflow disorders(CVOD)can impair cerebral perfusion and produce diverse,often debilitating symptoms,substantially reducing quality of life.Intermittent hypoxiahyperoxia training(IHHT)has demonstrated therapeutic potential across various pathologies and may represent a promising non-pharmacological approach for CVOD management.Methods Patients with imaging-confirmed CVOD underwent 14 IHHT sessions,each comprising four cycles of 10-minute hypoxia(11%O_(2))stimulation and 20-minute hyperoxia(38%O_(2)).Physiological parameters and adverse events were monitored throughout the intervention.Clinical scales,24-hour ambulatory blood pressure,blood tests,jugular ultrasound,and perfusion imaging were assessed preand post-intervention.Results No participants experienced intolerable discomfort or severe adverse events;vital signs remained within normal ranges.No significant changes were observed in 24-hour blood pressure,blood cell counts,lipid profiles,or other blood markers.Notably,60%of patients(n=12)reported overall symptom improvement on the Patient Global Impression of Change scale.Headache severity,as measured by the visual analogue scale,significantly decreased(6.33±1.22 vs.4.89±2.03,P=0.016).In patients with internal jugular vein(IJV)stenosis,significant improvements were observed in regional cerebral blood flow(including the insula,occipital lobe,internal capsule,and lenticula)and left J3-segment IJV flow volume(107.27[47.50,160.00]vs.140.83[55.00,210.00]mL/min,P=0.011).Conclusion The current IHHT protocol is safe and well-tolerated in patients with CVOD.IHHT may alleviate CVOD-related symptoms by improving oxygen saturation,cerebral perfusion,and venous outflow pattern,supporting its potential as a non-invasive therapeutic strategy.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
基金Key Scientific Research Project of the Hunan Provincial Department of Education(23A312).
文摘Objective To investigate methods for constructing a high-quality instructional dataset for traditional Chinese medicine(TCM)mental disorders and to validate its efficacy.Methods We proposed the Fine-Med-Mental-T&P methodology for constructing high-quality instruction datasets in TCM mental disorders.This approach integrates theoretical knowledge and practical case studies through a dual-track strategy.(i)Theoretical track:textbooks and guidelines on TCM mental disorders were manually segmented.Initial responses were generated using DeepSeek-V3,followed by refinement by the Qwen3-32B model to align the expression with human preferences.A screening algorithm was then applied to select 16000 high-quality instruction pairs.(ii)Practical track:starting from over 600 real clinical case seeds,diagnostic and therapeutic instruction pairs were generated using DeepSeek-V3 and subsequently screened through manual evaluation,resulting in 4000 high-quality practiceoriented instruction pairs.The integration of both tracks yielded the Med-Mental-Instruct-T&P dataset,comprising a total of 20000 instruction pairs.To validate the dataset’s effectiveness,three experimental evaluations(both manual and automated)were conducted:(i)comparative studies to compare the performance of models fine-tuned on different datasets;(ii)benchmarking to compare against mainstream TCM-specific large language models(LLMs);(iii)data ablation study to investigate the relationship between data volume and model performance.Results Experimental results demonstrate the superior performance of T&P-model finetuned on the Med-Mental-Instruct-T&P dataset.In the comparative study,the T&P-model significantly outperformed the baseline models trained solely on self-generated or purely human-curated baseline data.This superiority was evident in both automated metrics(ROUGEL>0.55)and expert manual evaluations(scoring above 7/10 across accuracy).In benchmark comparisons,the T&P-model also excelled against existing mainstream TCM LLMs(e.g.,HuatuoGPT and ZuoyiGPT).It showed particularly strong capabilities in handling diverse clinical presentations,including challenging disorders such as insomnia and coma,showcasing its robustness and versatility.Data ablation studies showed that T&P-model performance had an overall upward trend with minor fluctuations when training data increased from 10%to 50%;beyond 50%,performance improvement slowed significantly,with metrics plateauing and approaching a saturation point.
文摘Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure proper protein folding,the addition of post-translational modifications,and delive ring to intracellular and extracellular destinations.Astrocytes are fundamental homeostatic cells,controlling multiple aspects of the central nervous system physiology,such as ion balance,nutrients,blood flow,neurotransmitte rs,and responses to insults.Astrocytes are polarized cells,and,such as neurons,extensively use the secretory pathway for secreting factors and exposing functional receptors,channels,and transporte rs on the plasma membrane.In this review,we will underline the importance of studying the Golgi apparatus and the secretory pathway in astrocytes,based on the possible tight connection between the Golgi apparatus and astrocytes'homeostatic function.Given the topic of this review,we will provide examples mostly about the Golgi apparatus structure,function,localization,and its involvement in astrocytes'homeostatic response,with an insight into congenital glycosylation disorders,as an example of a potential future field in the study of astrocyte homeostatic failu re and Golgi apparatus alteration.
文摘Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure proper protein folding,the addition of post-translational modifications,and delivering to intracellular and extracellular destinations.Astrocytes are fundamental homeostatic cells,controlling multiple aspects of the central nervous system physiology,such as ion balance,nutrients,blood flow,neurotransmitters,and responses to insults.Astrocytes are polarized cells,and,such as neurons,extensively use the secretory pathway for secreting factors and exposing functional receptors,channels,and transporters on the plasma membrane.In this review,we will underline the importance of studying the Golgi apparatus and the secretory pathway in astrocytes,based on the possible tight connection between the Golgi apparatus and astrocytes’homeostatic function.Given the topic of this review,we will provide examples mostly about the Golgi apparatus structure,function,localization,and its involvement in astrocytes’homeostatic response,with an insight into congenital glycosylation disorders,as an example of a potential future field in the study of astrocyte homeostatic failure and Golgi apparatus alteration.
基金supported by the National Key Research and Development Program of China(2022YFE0118000,2021YFA1101700)the National Natural Science Foundation of China(82030049,32027802,82394433,82361148130,and 82302262)+2 种基金the Zhejiang Provincial Natural Science Foundation(LMS25H180002)the Postdoctoral Fellowship Program of CPSF(GZC20251313)the Fundamental Research Funds for the Central Universities of China(226-2024-00059).
文摘Psychiatric disorders have emerged as significant contributors to the global burden of disease in recent decades.The endocannabinoid system(ECS)influences a range of physiological and pathophysiological processes,including nociception,cognition,appetite,memory,and behavior,serving as a crucial mediator in psychiatric disorders.Imaging the ECS provides valuable insights into the pathophysiological mechanisms underlying psychiatric disorders and enhances clinical management strategies.As an advanced noninvasive molecular imaging modality,positron emission tomography(PET)enables the in vivo exploration of biological processes at the cellular and molecular levels.Recent advancements have led to the development of numerous PET tracers that target various components of the ECS,offering opportunities to visualize,characterize,and quantify ECS activity in psychiatric disorders in vivo.In this review,we summarize the existing PET tracers for ECS imaging and discuss their applications in diverse psychiatric conditions,including cannabis use disorder,alcohol use disorder,post-traumatic stress disorder,schizophrenia,and eating disorders.
文摘Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.
基金National Natural Science Foundation of China,No.82471415Jilin Province Medical and Health Talents Special Project,No.2024WSZX-D03the Natural Science Foundation of Jilin Province of China,No.YDZJ202401262ZYTS。
文摘Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century.However,the inaccessibility and complexity of the human brain have always represented a challenge in understanding the pathophysiology of the central nervous system.Brain organoids are self-assembled threedimensional aggregates derived from pluripotent stem cells with cell types and structures similar to the embryonic human brain,giving them potential for investigating the atypical cellular,molecular,and genetic characteristics characteristic of central nervous system disorders.Brain organoids also provide a platform for drug screening and serve as a potential source for transplantation therapy for brain injuries.However,the broad application of brain organoids is hampered by several limitations,such as the lack of high-fidelity cell types,insufficient maturation,and considerable heterogeneity,undermining their reliability in specific applications.This review summarizes brain organoid evolution,discusses recent technological and methodological innovations,and reviews their applications in drug screening,transplantation therapy,and disease modeling,as well as clinical research progress.Additionally,we emphasize the limitations of current brain organoid research and explore the potential for advancing the technology to enhance its applicability.
基金supported by Department of Defense grant HT9425-24-1-0030 a grant from the Stanley Medical Research Institute(to SS).
文摘The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.
基金Special Projectfor Clinical Research of Shanghai Municipal Health Commission,No.202140403Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai,No.PWZxq2022-05+2 种基金Natural Science Foundation of Ningxia Hui Autonomous Region,No.2024AAC05084Ningxia Hui Autonomous Region Key Research and Development Program,No.2021BEG03084National Natural Science Foundation of China,Nos.32370895,32070862。
文摘Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and diseased processes.Owing to their operability and sample accessibility,brain organoids serve as a bridge between in vitro monolayer cell culture models and in vivo animal models.An increasing number of induction protocols for brain organoids have been developed over the preceding decade.A key future research direction will focus on ensuring the complexity and quality of brain organoids.The integration of powerful technologies,such as the CRISP R/Cas9 genome editing and lineage tra cing systems,shall precipitate practical and broad applications of brain organoids.In this review,we discuss the generation and application of brain organoids,as well as their integration with genome editing technologies,in the study of neural development,disease modeling,and mechanistic investigations.The innovative combination of these two technologies may offer a fresh perspective for exploring the fundamental aspects of the human nervous system and related diseases.
