Clinically differentiating bipolarⅡdisorder(BD-Ⅱ)from major depressive disorder(MDD)remains a significant challenge in modern psychiatry.These two conditions share substantial clinical symptomatology,making accurate...Clinically differentiating bipolarⅡdisorder(BD-Ⅱ)from major depressive disorder(MDD)remains a significant challenge in modern psychiatry.These two conditions share substantial clinical symptomatology,making accurate diagnosis difficult in routine clinical practice.Misdiagnosis may lead to inappropriate treatment strategies,increased psychological and physical burdens,reduced quality of life,and impaired social functioning.Genetic overlap may partially explain the clinical similarities between MDD and BD-Ⅱ,and biomarkers along with neuroimaging techniques are receiving increasing attention as tools to aid in diagnosis.For example,electroencephalography has been shown to effectively distinguish between unipolar depression and bipolar depression;serum levels of glycogen synthase kinase-3 have also been investigated as a potential tool for differentiating between the two disorders.A comprehensive assessment integrating clinical characteristics,genetic basis research,and multimodal evaluations using neuroimaging and biomarkers through a multidisciplinary approach will help enhance clinicians'ability to distinguish between MDD and BD-Ⅱ.By improving diagnostic accuracy,more personalized and effective treatment strategies can be developed,ultimately improving patients'health outcomes and quality of life.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
Recent advances in geoscience have underscored the critical role of abiogenic processes in petroleum formation,especially the formation and polymerization of methane.However,whether a direct carbon-H_(2) reaction can ...Recent advances in geoscience have underscored the critical role of abiogenic processes in petroleum formation,especially the formation and polymerization of methane.However,whether a direct carbon-H_(2) reaction can produce C_(2+)hydrocarbons(e.g.,ethane and propane)beyond methane remains an open question.Here,we demonstrate the direct synthesis of ethane and propane via reactions between amorphous carbon and H_(2) under upper mantle conditions(2-10 GPa and 800-1200℃).A systematic investigation reveals that increasing structural disorder in carbon precursors,from graphite to glassy carbon-Ⅱ and carbon black,enhances the production of C_(2)-C_(3) hydrocarbons.Through integrated X-ray diffraction and reverse Monte Carlo simulations,we establish that the continuous random atomic network structures in amorphous carbon enable one-step synthesis of heavy hydrocarbons with H_(2).These models establish a direct link between atomic-scale carbon structures and the one-step synthesis of C_(2+) hydrocarbons under H_(2)-rich,high-pressure,and high-temperature conditions—potentially revealing an efficient mechanism for the abiotic production of C_(2+) hydrocarbons in the upper mantle.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
Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association betw...Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association between body fat mass(FM)and OCD.Methods Summary statistics from genome-wide association studies of European ancestry were utilized to conduct two-sample Mendelian randomization analysis.Heterogeneity,horizontal pleiotropy,and sensitivity analyses were performed to assess the robustness.Results The inverse variance weighting method demonstrated that a genetically predicted decrease in FM was causally associated with an increased OCD risk[odds ratio(OR)=0.680,95%confidence interval(CI):0.528–0.875,P=0.003].Similar estimates were obtained using the weighted median approach(OR=0.633,95%CI:0.438–0.915,P=0.015).Each standard deviation increases in genetically predicted body fat percentage corresponded to a reduced OCD risk(OR=0.638,95%CI:0.455–0.896,P=0.009).The sensitivity analysis confirmed the robustness of these findings with no outlier instrument variables identified.Conclusion The negative causal association between FM and the risk of OCD suggests that the prevention or treatment of mental disorders should include not only the control of BMI but also fat distribution and body composition.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
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
Premenstrual dysphoric disorder(PMDD),a subtype of premenstrual syndrome(PMS),involves physical and emotional symptoms that impact patients'daily lives and productivity.A reliable,side-effect-free clinical interve...Premenstrual dysphoric disorder(PMDD),a subtype of premenstrual syndrome(PMS),involves physical and emotional symptoms that impact patients'daily lives and productivity.A reliable,side-effect-free clinical intervention is needed.Shuyu capsule is an effective traditional Chinese medicine preparation for PMDD used in the clinics,but its therapeutic mechanism remains unclear.Previous research has suggested that theγ-aminobutyric acidergic(GABAergic)system in the periaqueductal gray(PAG)may play a role in treating PMDD with traditional Chinese medicine,but there is a lack of functional verification.This study aims to reveal the potential mechanism of the Shuyu capsule in treating PMDD.The study employed an experimental design using female C57BL/6J and Vgat-Cre mice to assess the effects of Shuyu capsules on PMDD,with a focus on the GABAergic system in the dorsal PAG(dPAG).Assessments were conducted using the forced swimming test(FST)to gauge depression-like behaviors and western blot(WB)and immunofluorescence(IF)to measure the numbers of active GABAergic neurons and theγ-aminobutyric acid type A receptor(GABA,R)δsubunit(GABRD)expression.Chemogenetic techniques and adeno-associated virus were specifically used to activate GABAergic neurons and knock down the expression of subunits,respectively,providing insights into the neurobiological mechanisms underpinning the therapeutic effects of Shuyu capsules in treating PMDD.After being stressed by FST,the immobility duration of PMDD mice in the late dioestrus(LD)phase decreased after the Shuyu capsule intervention,implying that it can improve the estrous cycle-dependent depression-like phenotype in PMDD mice.Additionally,the application of Shuyu capsule can downregulate the expression of GABRD and reverse the downtrend of activated GABAergic neurons in the dPAG of PMDD model mice.We also found that single-target manipulation was enough to improve the depressionlike behavior of PMDD model mice.Transgenic mice with GABRD knockout were established,and their behaviors were tested,revealing changes in their exploratory behaviors,indicating that the GABRD may be closely related to anxiety disorders.Shuyu capsule plays an anti-PMDD role by activating GABAergic neurons and downregulating the expression of GABRD in the dPAG.This provides a theoretical basis for the clinical treatment of PMDD with traditional Chinese medicine and promotes the development of drugs for treating PMDD.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
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
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
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
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
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
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
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
Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarke...Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.展开更多
Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at...Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.展开更多
In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release f...In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.展开更多
文摘Clinically differentiating bipolarⅡdisorder(BD-Ⅱ)from major depressive disorder(MDD)remains a significant challenge in modern psychiatry.These two conditions share substantial clinical symptomatology,making accurate diagnosis difficult in routine clinical practice.Misdiagnosis may lead to inappropriate treatment strategies,increased psychological and physical burdens,reduced quality of life,and impaired social functioning.Genetic overlap may partially explain the clinical similarities between MDD and BD-Ⅱ,and biomarkers along with neuroimaging techniques are receiving increasing attention as tools to aid in diagnosis.For example,electroencephalography has been shown to effectively distinguish between unipolar depression and bipolar depression;serum levels of glycogen synthase kinase-3 have also been investigated as a potential tool for differentiating between the two disorders.A comprehensive assessment integrating clinical characteristics,genetic basis research,and multimodal evaluations using neuroimaging and biomarkers through a multidisciplinary approach will help enhance clinicians'ability to distinguish between MDD and BD-Ⅱ.By improving diagnostic accuracy,more personalized and effective treatment strategies can be developed,ultimately improving patients'health outcomes and quality of life.
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.
基金mainly supported by the Natural Science Foundation of China (Grant Nos. 52288102, 52090020, and 52372261)the Natural Science Foundation of Hebei Province (Grant No. E202403045)+1 种基金the S&T Program of Hebei (Grant No. 225A1102D)the Ministry of Education Chang Jiang Scholar Professor Program (Grant No. T2022241)
文摘Recent advances in geoscience have underscored the critical role of abiogenic processes in petroleum formation,especially the formation and polymerization of methane.However,whether a direct carbon-H_(2) reaction can produce C_(2+)hydrocarbons(e.g.,ethane and propane)beyond methane remains an open question.Here,we demonstrate the direct synthesis of ethane and propane via reactions between amorphous carbon and H_(2) under upper mantle conditions(2-10 GPa and 800-1200℃).A systematic investigation reveals that increasing structural disorder in carbon precursors,from graphite to glassy carbon-Ⅱ and carbon black,enhances the production of C_(2)-C_(3) hydrocarbons.Through integrated X-ray diffraction and reverse Monte Carlo simulations,we establish that the continuous random atomic network structures in amorphous carbon enable one-step synthesis of heavy hydrocarbons with H_(2).These models establish a direct link between atomic-scale carbon structures and the one-step synthesis of C_(2+) hydrocarbons under H_(2)-rich,high-pressure,and high-temperature conditions—potentially revealing an efficient mechanism for the abiotic production of C_(2+) hydrocarbons in the upper mantle.
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 the Yanzhao Gold Talent Project of Hebei Province(NO.HJZD202506)。
文摘Objective Previous studies link lower body mass index(BMI)with increased obsessive-compulsive disorder(OCD)risk,yet other body mass indicators may be more etioloically relevant.We dissected the causal association between body fat mass(FM)and OCD.Methods Summary statistics from genome-wide association studies of European ancestry were utilized to conduct two-sample Mendelian randomization analysis.Heterogeneity,horizontal pleiotropy,and sensitivity analyses were performed to assess the robustness.Results The inverse variance weighting method demonstrated that a genetically predicted decrease in FM was causally associated with an increased OCD risk[odds ratio(OR)=0.680,95%confidence interval(CI):0.528–0.875,P=0.003].Similar estimates were obtained using the weighted median approach(OR=0.633,95%CI:0.438–0.915,P=0.015).Each standard deviation increases in genetically predicted body fat percentage corresponded to a reduced OCD risk(OR=0.638,95%CI:0.455–0.896,P=0.009).The sensitivity analysis confirmed the robustness of these findings with no outlier instrument variables identified.Conclusion The negative causal association between FM and the risk of OCD suggests that the prevention or treatment of mental disorders should include not only the control of BMI but also fat distribution and body composition.
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.
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.
基金supported by the National Natural Science Foundation of China(No.81974553)the High Level Key Disciplines of Traditional Chinese Medicine:Basic Theory of Traditional Chinese Medicine,National Administration of Traditional Chinese Medicine(No.zyyzdxk-2023118)+3 种基金the Special Funding for the Taishan Scholars Project(Nos.tsqn202211137,tsqn201909186,and tsqn202211355)the Natural Science Foundation of Shandong Province(Nos.ZR2020ZD17 and ZR2021LZY018)the City-School Integration Development Strategy Project of Jinan City(No.JNSX2023056)the Chinese Medicine and Brain Science Youth Scientific Research Innovation Team,Shandong University of Traditional Chinese Medicine(No.22202101),China.
文摘Premenstrual dysphoric disorder(PMDD),a subtype of premenstrual syndrome(PMS),involves physical and emotional symptoms that impact patients'daily lives and productivity.A reliable,side-effect-free clinical intervention is needed.Shuyu capsule is an effective traditional Chinese medicine preparation for PMDD used in the clinics,but its therapeutic mechanism remains unclear.Previous research has suggested that theγ-aminobutyric acidergic(GABAergic)system in the periaqueductal gray(PAG)may play a role in treating PMDD with traditional Chinese medicine,but there is a lack of functional verification.This study aims to reveal the potential mechanism of the Shuyu capsule in treating PMDD.The study employed an experimental design using female C57BL/6J and Vgat-Cre mice to assess the effects of Shuyu capsules on PMDD,with a focus on the GABAergic system in the dorsal PAG(dPAG).Assessments were conducted using the forced swimming test(FST)to gauge depression-like behaviors and western blot(WB)and immunofluorescence(IF)to measure the numbers of active GABAergic neurons and theγ-aminobutyric acid type A receptor(GABA,R)δsubunit(GABRD)expression.Chemogenetic techniques and adeno-associated virus were specifically used to activate GABAergic neurons and knock down the expression of subunits,respectively,providing insights into the neurobiological mechanisms underpinning the therapeutic effects of Shuyu capsules in treating PMDD.After being stressed by FST,the immobility duration of PMDD mice in the late dioestrus(LD)phase decreased after the Shuyu capsule intervention,implying that it can improve the estrous cycle-dependent depression-like phenotype in PMDD mice.Additionally,the application of Shuyu capsule can downregulate the expression of GABRD and reverse the downtrend of activated GABAergic neurons in the dPAG of PMDD model mice.We also found that single-target manipulation was enough to improve the depressionlike behavior of PMDD model mice.Transgenic mice with GABRD knockout were established,and their behaviors were tested,revealing changes in their exploratory behaviors,indicating that the GABRD may be closely related to anxiety disorders.Shuyu capsule plays an anti-PMDD role by activating GABAergic neurons and downregulating the expression of GABRD in the dPAG.This provides a theoretical basis for the clinical treatment of PMDD with traditional Chinese medicine and promotes the development of drugs for treating PMDD.
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.
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.
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.
文摘Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.
基金supported by Postdoc Fellowship from the Foundation for Angelman Syndrome Therapeutics(FT2022-005 to JM,PD2023-001 to XY,and FT2024-001 to YAH)STTR R41 MH118747(to JM)。
文摘Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.
基金supported by the National Natural Science Foundation of China,No.81971269 (to DP)the Science and Technology Commission of Shanghai,No.YDZX20213100001003 (to DP)。
文摘In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.
