Objectives: Digital refractory gangrene is rarely found in collagen diseases, including systemic sclerosis and is possibly caused by similar underlying vascular damage in peripheral arterial disease (PAD) such as arte...Objectives: Digital refractory gangrene is rarely found in collagen diseases, including systemic sclerosis and is possibly caused by similar underlying vascular damage in peripheral arterial disease (PAD) such as arteriosclerosis obliterans (ASO) and/or thromboangiitis obliterans (TAO) by unclarified mechanisms other than vasculitis and thrombosis. This study evaluated the radiological imaging in patients with digital gangrene associated with collagen disease and compared the images with those of PAD based on the results of laboratory and histopathological examinations. Methods: Angiography, MR angiography and/or CT angiography were performed on 6 patients with refractory gangrene or extensive ulcers accompanied by scleroderma-spectrum disorders;3 with diffuse systemic sclerosis, 1 with limited systemic sclerosis, 1 with overlap syndrome and 1 with Sj?gren’s syndrome. Results: Although the vascular alterations in collagen diseases were similar to those in PAD, the abnormal image findings (occlusion or stenosis of the arteries with smooth vessel walls) found in collagen diseases did not include atheromatous plaque, which are worm-like vessels that are characteristic of those observed in PAD. Conclusions: Some cases of digital gangrene seen in collagen diseases show similar vascular imaging patterns to those of PAD and comprehensive examinations including arterial imaging can be useful for the diagnosis of these unrecognized vascular changes other than vasculitis or digital thrombosis.展开更多
[Objectives]To investigate the potential causal relationship between psoriasis and common mental disorders,and to provide genetic epidemiological evidence for the early intervention of mental comorbidities.[Methods]Ba...[Objectives]To investigate the potential causal relationship between psoriasis and common mental disorders,and to provide genetic epidemiological evidence for the early intervention of mental comorbidities.[Methods]Based on publicly available large-scale GWAS data,a bidirectional Mendelian randomization(MR)approach was employed to assess the causal associations between psoriasis and major depressive disorder(MDD),bipolar disorder,schizophrenia,and anxiety disorders.The inverse variance weighted(IVW)method served as the primary analytical tool,supplemented by sensitivity analyses using MR-Egger and weighted median methods.Additionally,a subgroup analysis was conducted for psoriatic arthritis(PsA).[Results]Forward MR analysis revealed a significant positive causal association between the genetic predisposition to psoriasis and bipolar disorder as well as MDD,whereas no significant causal relationship was observed with schizophrenia or anxiety disorders.The reverse MR analysis found no causal effect of mental disorders on psoriasis.Subgroup analysis of PsA indicated that its genetic predisposition was significantly associated with the risk of bipolar disorder.The results of various sensitivity analyses and pleiotropy tests supported the robustness of the conclusions.[Conclusions]This study provides genetic evidence supporting a causal link between psoriasis and both MDD and bipolar disorder.In particular,patients with PsA are at a higher risk of developing bipolar disorder,highlighting the need to strengthen early screening and intervention for mental health in clinical management.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
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
Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review ...Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review integrates preclinical and clinical evidence to evaluate the ability of melatonin to reverseWarburg-effect-like metabolic reprogramming.Literature on neurodegeneration,age-related sarcopenia,type 2 diabetes,chronic kidney disease,heart failure and pulmonary arterial hypertension(PAH)has been reviewed and synthesised.In all of these conditions,hypoxia-inducible factor 1α(HIF-1α)and pyruvate dehydrogenase kinase 4(PDK4)inhibit the pyruvate dehydrogenase complex.This diverts pyruvate away fromthe tricarboxylic acid(TCA)cycle and promotes glycolysis.In cell and animal models,melatonin consistently inhibits PDK4,destabilizes HIF-1αunder normoxic conditions,activates SIRT1/3-dependentmitochondrial biogenesis andmitophagy,and eliminates reactive oxygen and nitrogen species.These actions reduce lactate production,restore oxidative phosphorylation and attenuate tissue damage.This appears to induce cognitive and synaptic improvements in Alzheimer’s and Parkinson’s disease models,increased muscle mass and function in ageing rodents,improved insulin sensitivity alongside suppression of hepatic gluconeogenesis in diabetic models,reduced fibrosis in nephropathy,and normalization of vascular remodeling in hypoxia-induced pulmonary arterial hypertension(PAH).Early-stage clinical trials corroborate a decrease in oxidative and inflammatorymarkers,improved sleep quality and modest cognitive benefits.However,they report conflicting effects on insulin sensitivity,which are largely related to the dose and timing of administration in relation to food intake.Overall,the current data suggest that melatonin is a pleiotropic metabolic modulator capable of counteracting the Warburg phenotype in multiple organs.However,human studies remain scarce,and well-designed randomised trials incorporating chronotherapy are needed before clinical adoption.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
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
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
INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depres...INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depression leads to social and occupational impairment,diminished quality of life and an elevated risk of death by suicide.展开更多
BACKGROUND Overweight children exhibit a higher prevalence of functional gastrointestinal disorders compared with their normal-weight peers,yet the underlying reasons remain unclear.Gastrointestinal motility,a key pat...BACKGROUND Overweight children exhibit a higher prevalence of functional gastrointestinal disorders compared with their normal-weight peers,yet the underlying reasons remain unclear.Gastrointestinal motility,a key pathophysiological factor in functional gastrointestinal disorders,may be influenced by body mass index(BMI).AIM To evaluate the impact of BMI on gastric motility parameters in children with functional abdominal pain disorders(FAPDs).METHODS We assessed gastric motility in 176 children with FAPDs(61.4%females,mean age 7.94 years,SD 1.96 years)and 63 healthy controls(57.1%females,mean age 9.17 years,SD 1.90 years)at the Gastroenterology Research Laboratory,University of Kelaniya,Sri Lanka.FAPDs were diagnosed and subtyped using the Rome IV criteria:Functional abdominal pain 97 patients;irritable bowel syndrome 39 patients,functional dyspepsia(FD)25 patients;and abdominal migraine 15 patients.Gastric motility was measured using a validated ultrasound method.Weight and height were measured using sensitive standard scales.RESULTS The BMIs of children with FAPDs and controls were 15.04 and 15.46 kg/m^(2),respectively(P=0.33).Fasting antral area(FAA)and antral area at 1 min(AA1)and 15 min(AA15)were significantly greater in patients with FAPD with a higher BMI(2.71 cm^(2),12.57 cm^(2),and 7.19 cm^(2),respectively)compared with those with a lower BMI(2.12 cm^(2),10.68 cm^(2),and 6.13 cm^(2),respectively)(P<0.01).BMI positively correlated with FAA and AA15(r=0.18 and r=0.19,respectively)(P<0.01)in those with FAPDs.In controls,only AA1 was greater in the higher BMI group(12.51 cm^(2)vs 9.93 cm^(2))and had a positive correlation(r=0.33)(P≤0.01).Subgroup analysis revealed that in patients with FD,BMI negatively correlated with gastric emptying rate(GER)(r=-0.59)and antral motility index(MI)(r=-0.49),while in functional abdominal pain,MI positively correlated(r=0.25)with BMI(P≤0.01).CONCLUSION In children with FAPDs,higher BMI was associated with increased gastric antral distention during fasting and postprandial periods(as indicated by FAA,AA1,and AA15)but not with contractility and transit(MI,GER).However,in the FD subgroup,high BMI correlated with reduced GER and MI.This indicates the possible role of BMI in gastric hypomotility and the pathophysiology of FD.These findings underscore the importance of lifestyle and dietary interventions aimed at optimizing BMI in the management of FAPDs,particularly FD.展开更多
Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can con...Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can contribute to ferroptosis,resulting in nerve cell dysfunction and death.The ubiquitin-proteasome system(UPS)refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome.In neuro-logical conditions,the UPS plays a significant role in regu-lating ferroptosis.In this review,we outline how the UPS regulates iron metabolism,ferroptosis,and their interplay in neurological diseases.In addition,we discuss the future application of small-molecule inhibitors and identify poten-tial drug targets.Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applica-tions in neurological diseases.展开更多
文摘Objectives: Digital refractory gangrene is rarely found in collagen diseases, including systemic sclerosis and is possibly caused by similar underlying vascular damage in peripheral arterial disease (PAD) such as arteriosclerosis obliterans (ASO) and/or thromboangiitis obliterans (TAO) by unclarified mechanisms other than vasculitis and thrombosis. This study evaluated the radiological imaging in patients with digital gangrene associated with collagen disease and compared the images with those of PAD based on the results of laboratory and histopathological examinations. Methods: Angiography, MR angiography and/or CT angiography were performed on 6 patients with refractory gangrene or extensive ulcers accompanied by scleroderma-spectrum disorders;3 with diffuse systemic sclerosis, 1 with limited systemic sclerosis, 1 with overlap syndrome and 1 with Sj?gren’s syndrome. Results: Although the vascular alterations in collagen diseases were similar to those in PAD, the abnormal image findings (occlusion or stenosis of the arteries with smooth vessel walls) found in collagen diseases did not include atheromatous plaque, which are worm-like vessels that are characteristic of those observed in PAD. Conclusions: Some cases of digital gangrene seen in collagen diseases show similar vascular imaging patterns to those of PAD and comprehensive examinations including arterial imaging can be useful for the diagnosis of these unrecognized vascular changes other than vasculitis or digital thrombosis.
文摘[Objectives]To investigate the potential causal relationship between psoriasis and common mental disorders,and to provide genetic epidemiological evidence for the early intervention of mental comorbidities.[Methods]Based on publicly available large-scale GWAS data,a bidirectional Mendelian randomization(MR)approach was employed to assess the causal associations between psoriasis and major depressive disorder(MDD),bipolar disorder,schizophrenia,and anxiety disorders.The inverse variance weighted(IVW)method served as the primary analytical tool,supplemented by sensitivity analyses using MR-Egger and weighted median methods.Additionally,a subgroup analysis was conducted for psoriatic arthritis(PsA).[Results]Forward MR analysis revealed a significant positive causal association between the genetic predisposition to psoriasis and bipolar disorder as well as MDD,whereas no significant causal relationship was observed with schizophrenia or anxiety disorders.The reverse MR analysis found no causal effect of mental disorders on psoriasis.Subgroup analysis of PsA indicated that its genetic predisposition was significantly associated with the risk of bipolar disorder.The results of various sensitivity analyses and pleiotropy tests supported the robustness of the conclusions.[Conclusions]This study provides genetic evidence supporting a causal link between psoriasis and both MDD and bipolar disorder.In particular,patients with PsA are at a higher risk of developing bipolar disorder,highlighting the need to strengthen early screening and intervention for mental health in clinical management.
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 Government of the Principado de Asturias through the Fundacion para el Fomento en Asturias de la Investigacion Cientifica Aplicada y a la Tecnologia(FICYT)and also co-founded by the European Union,GRUPIN(IDI/2024/000719).
文摘Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review integrates preclinical and clinical evidence to evaluate the ability of melatonin to reverseWarburg-effect-like metabolic reprogramming.Literature on neurodegeneration,age-related sarcopenia,type 2 diabetes,chronic kidney disease,heart failure and pulmonary arterial hypertension(PAH)has been reviewed and synthesised.In all of these conditions,hypoxia-inducible factor 1α(HIF-1α)and pyruvate dehydrogenase kinase 4(PDK4)inhibit the pyruvate dehydrogenase complex.This diverts pyruvate away fromthe tricarboxylic acid(TCA)cycle and promotes glycolysis.In cell and animal models,melatonin consistently inhibits PDK4,destabilizes HIF-1αunder normoxic conditions,activates SIRT1/3-dependentmitochondrial biogenesis andmitophagy,and eliminates reactive oxygen and nitrogen species.These actions reduce lactate production,restore oxidative phosphorylation and attenuate tissue damage.This appears to induce cognitive and synaptic improvements in Alzheimer’s and Parkinson’s disease models,increased muscle mass and function in ageing rodents,improved insulin sensitivity alongside suppression of hepatic gluconeogenesis in diabetic models,reduced fibrosis in nephropathy,and normalization of vascular remodeling in hypoxia-induced pulmonary arterial hypertension(PAH).Early-stage clinical trials corroborate a decrease in oxidative and inflammatorymarkers,improved sleep quality and modest cognitive benefits.However,they report conflicting effects on insulin sensitivity,which are largely related to the dose and timing of administration in relation to food intake.Overall,the current data suggest that melatonin is a pleiotropic metabolic modulator capable of counteracting the Warburg phenotype in multiple organs.However,human studies remain scarce,and well-designed randomised trials incorporating chronotherapy are needed before clinical adoption.
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).
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.
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funded by the Construction Project of the"Flagship"Department of Chinese and Western Medicine Coordination(LiuL/2024-221)the 2024 Medical Service and Security Capacity Improvement Project(National Clinical Key Specialty Construction)(LiuL/Huwei Medical/2024-65)+5 种基金the Shanghai Traditional Chinese Medicine Standardization Project(LiuL/No.2023JSP03)the Shanghai Key Discipline Construction Project of Traditional Chinese Medicine(Clinical)(LiuL/2024-No.3)the Shanghai Technical Standardization Management and Promotion Project(LiuL/No.SHDC22023212)the Shanghai Municipal Health Commission Traditional Chinese Medicine Research Project(2022)(LiuL/No.2022Cx004)Clinical research project of Shanghai Health Commission-Youth Project(LW/No.20214Y0056)Shanghai Institute of Traditional Chinese Medicine for Mental Health(LW/No.SZB2023201).
文摘INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depression leads to social and occupational impairment,diminished quality of life and an elevated risk of death by suicide.
基金Supported by The University of Kelaniya,Sri Lanka,Research Council Grant No.G23.
文摘BACKGROUND Overweight children exhibit a higher prevalence of functional gastrointestinal disorders compared with their normal-weight peers,yet the underlying reasons remain unclear.Gastrointestinal motility,a key pathophysiological factor in functional gastrointestinal disorders,may be influenced by body mass index(BMI).AIM To evaluate the impact of BMI on gastric motility parameters in children with functional abdominal pain disorders(FAPDs).METHODS We assessed gastric motility in 176 children with FAPDs(61.4%females,mean age 7.94 years,SD 1.96 years)and 63 healthy controls(57.1%females,mean age 9.17 years,SD 1.90 years)at the Gastroenterology Research Laboratory,University of Kelaniya,Sri Lanka.FAPDs were diagnosed and subtyped using the Rome IV criteria:Functional abdominal pain 97 patients;irritable bowel syndrome 39 patients,functional dyspepsia(FD)25 patients;and abdominal migraine 15 patients.Gastric motility was measured using a validated ultrasound method.Weight and height were measured using sensitive standard scales.RESULTS The BMIs of children with FAPDs and controls were 15.04 and 15.46 kg/m^(2),respectively(P=0.33).Fasting antral area(FAA)and antral area at 1 min(AA1)and 15 min(AA15)were significantly greater in patients with FAPD with a higher BMI(2.71 cm^(2),12.57 cm^(2),and 7.19 cm^(2),respectively)compared with those with a lower BMI(2.12 cm^(2),10.68 cm^(2),and 6.13 cm^(2),respectively)(P<0.01).BMI positively correlated with FAA and AA15(r=0.18 and r=0.19,respectively)(P<0.01)in those with FAPDs.In controls,only AA1 was greater in the higher BMI group(12.51 cm^(2)vs 9.93 cm^(2))and had a positive correlation(r=0.33)(P≤0.01).Subgroup analysis revealed that in patients with FD,BMI negatively correlated with gastric emptying rate(GER)(r=-0.59)and antral motility index(MI)(r=-0.49),while in functional abdominal pain,MI positively correlated(r=0.25)with BMI(P≤0.01).CONCLUSION In children with FAPDs,higher BMI was associated with increased gastric antral distention during fasting and postprandial periods(as indicated by FAA,AA1,and AA15)but not with contractility and transit(MI,GER).However,in the FD subgroup,high BMI correlated with reduced GER and MI.This indicates the possible role of BMI in gastric hypomotility and the pathophysiology of FD.These findings underscore the importance of lifestyle and dietary interventions aimed at optimizing BMI in the management of FAPDs,particularly FD.
基金supported by the 2024 Talent Project of Shandong First Medical University(045RC200008)the Taishan Scholars Program(tsqn202211225).
文摘Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can contribute to ferroptosis,resulting in nerve cell dysfunction and death.The ubiquitin-proteasome system(UPS)refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome.In neuro-logical conditions,the UPS plays a significant role in regu-lating ferroptosis.In this review,we outline how the UPS regulates iron metabolism,ferroptosis,and their interplay in neurological diseases.In addition,we discuss the future application of small-molecule inhibitors and identify poten-tial drug targets.Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applica-tions in neurological diseases.
