ObjectiveThis study aims to quantitatively assess the efficacy of exosome therapy for epilepsy through a systematic review and meta-analysis of preclinical animal experiments. We seek to clarify its overall effects on seizure reduction, cognitive function preservation, and neuroinflammation suppression.MethodsA systematic search was conducted across four English-language and four Chinese databases to include epilepsy animal studies. Continuous outcomes were synthesized using standardized mean differences (SMD) and 95% confidence intervals (CI), with fixed or random effects models selected based on heterogeneity.ResultsA total of eight preclinical studies were included. The overall meta-analysis revealed that exosome treatment significantly reduced the duration of seizures (SMD = −2.30, 95% CI −4.24 to −0.36), decreased the frequency of spontaneous recurrent seizures (SMD = −1.38, 95% CI −2.17 to −0.58), and prolonged the seizure latency (SMD = 1.49, 95% CI 0.08–2.90). In terms of cognitive function, exosomes significantly shortened the escape latency in the Morris water maze (SMD = −1.38, 95% CI −2.17 to −0.58), increased the percentage of time spent in the target quadrant (SMD = 3.69, 95% CI 0.30–7.08), and enhanced the number of platform crossings (SMD = 1.41, 95% CI 0.60–2.21), with no significant changes in swimming speed. Neuropathological analysis indicated that exosome treatment significantly increased the number of hippocampal neurons (SMD = 4.48, 95% CI 1.46–7.49) and markedly reduced levels of glial fibrillary acidic protein (GFAP) (SMD = −3.61, 95% CI −7.08 to −0.14), ionized calcium-binding adaptor molecule 1 (IBA-1) (SMD = −10.27, 95% CI −20.29 to −0.25), tumor necrosis factor-alpha (TNF-α) (SMD = −2.95, 95% CI −4.21 to −1.69), and interleukin-1 beta (IL-1β) (SMD = −7.39, 95% CI −14.64 to −0.13). Although some outcomes exhibited heterogeneity and publication bias, the corrected primary effects remained statistically significant. The source of exosomes, administration route, and dosage may be critical variables influencing their efficacy.ConclusionExosome therapy improves seizure phenotypes and protects cognitive function in epilepsy models by suppressing neuroinflammation to promote neuronal survival, providing evidence for further mechanistic and clinical translation studies.
Autonomic dysreflexia: the concealed killer behind recurrent cerebral hemorrhage in spinal cord injury—a case report with management insights
Autonomic dysreflexia (AD) is a potentially life-threatening complication of high-level spinal cord injury (SCI), marked by paroxysmal hypertension. Although cerebrovascular events can be triggered by severe hypertension, the direct association between AD and intracerebral hemorrhage (ICH) necessitates increased clinical awareness. We present a case of a 71-year-old male with a complete C3 SCI (American Spinal Injury Association Impairment Scale grade A). On May 24, 2025, the patient developed an acute episode of AD following defecation, characterized by a sudden, severe headache and transient loss of consciousness, with elevated blood pressure (BP) of 178/101 mmHg. Emergency computed tomography revealed a right occipital ICH (3.6 × 1.8 cm) with concomitant subarachnoid hemorrhage. A follow-up cranial imaging examination on June 21, 2025, revealed a new contralateral hematoma (3.4 × 3.0 cm) in the left frontal lobe. Notably, a follow-up 24-h ambulatory blood pressure monitoring performed between the two hemorrhagic events (on June 20, 2025) revealed markedly elevated blood pressure variability, with a systolic BP standard deviation of 32.7 mmHg (compared with 31.8 mmHg recorded before the initial hemorrhage). Pre-event 24-h ambulatory blood pressure monitoring performed on March 21, 2025, had already demonstrated marked blood pressure variability (BPV), which may reflect the patient’s underlying autonomic dysregulation. The association between this extreme BPV and the subsequent ICH remains a subject for hypothesis generation. The hematomas resolved following a regimen of antihypertensive therapy (nitrendipine), osmotic diuresis (mannitol), and meticulous management of triggering factors. This case demonstrates that AD in high cervical SCI can precipitate severe ICH, with extreme BPV potentially serving as a synergistic risk factor. Clinicians should maintain high vigilance for new-onset severe headache in patients with SCI at or above T6, ensuring prompt BP assessment and identification of AD triggers. Future studies are required to investigate whether long-term BPV stabilization could mitigate hemorrhagic risk in this population.
Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review
The autophagy-lysosomal pathway (ALP) is a critical intracellular protein degradation system responsible for maintaining proteostasis and metabolic balance within cells. Dysfunction of this pathway has been increasingly recognized as a key pathological basis underlying various neurodegenerative diseases (NDs). This review provides a comprehensive overview of the molecular mechanisms by which ALP impairment contributes to defective protein degradation in neurodegeneration. We focus on the impact of lysosomal structural integrity and functional imbalance on cellular fate, highlighting the interplay between protein oxidative damage and degradation system dysregulation. Furthermore, we summarize the current therapeutic strategies aimed at lysosomal repair, evaluating their potential clinical applications and efficacy. By integrating the latest research advances, this review aims to deepen the understanding of the pathological mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases, clarify the key molecular targets of lysosomal damage and repair, and provide theoretical basis for target screening and validation and practical reference for the development of targeted drugs for neurodegenerative diseases.
RNA editing in Parkinson’s disease: emerging mechanisms, translational potential, and current challenges
Parkinson’s disease (PD) is a major neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and accumulation of α-synuclein. Current treatments primarily focus on symptom alleviation, highlighting the necessity for identifying novel molecular therapeutic targets. RNA editing, as a post-transcriptional process that modifies RNA sequences without altering genomic DNA, is increasingly recognized as an important contributor to the neuronal development and synaptic regulation. Among known RNA editing types, ADAR-mediated adenine-to-inosine (A-to-I) editing is the predominant form in the brain. Accumulating evidence suggests that RNA editing patterns undergo significant alterations in PD patients. This review synthesizes current evidence within a three-layer framework: (1) evidence for RNA editing dysregulation in PD, emphasizing tissue-specific and context-dependent patterns; (2) downstream mechanistic pathways stratified by evidence strength; and (3) experimental models, translational applications, and limitations. A distinction between what is known versus what remains speculative is emphasized throughout. RNA editing changes in PD appear heterogeneous and context-dependent, with brain and peripheral blood showing distinct patterns. Whether editing changes represent disease drivers, compensatory responses, or downstream phenomena remains largely unresolved.
Glypican-1: a modulator of neurodegenerative and tumorigenic pathways
A hierarchical machine learning model for predicting self-harm and suicidal behaviour in hospitalised patients with schizophrenia using clinical history and nursing observations
ObjectiveThis study aimed to develop and evaluate a two-layered machine learning framework that combines admission clinical information with longitudinal nursing observations to identify schizophrenia inpatients at high risk of self-harm or suicidal acts.MethodsWe retrospectively reviewed the records of 477 patients with schizophrenia hospitalised in Liaoning Province between July 2021 and July 2024. According to whether at least one self-injurious or suicidal episode was documented during the index admission, 159 individuals were assigned to a high-risk group and 318 to a non-high-risk group. At admission, 18 baseline variables (including age, sex, history of self-harm, hopelessness/depression, and educational attainment) were extracted from electronic medical records, and 39 nurse-rated behavioural items were scored weekly using the Psychiatric Patient Nursing Observation Scale. Static and dynamic feature sets were used to train six classifiers [regularized logistic regression (LR), support vector machine (SVM), extreme gradient boosting, random forest, multi-layer perceptron, and K-nearest neighbours]. The best static model (regularized LR) and the best dynamic model (SVM) were combined through probability-level weighted fusion to generate a hierarchical risk score.ResultsMultivariable analysis of admission features showed that previous self-harm [odds ratio (OR) = 4.323], hopelessness/depression (OR = 3.090), younger age (OR = 0.938), and higher educational level (OR = 1.357) were independent predictors of self-harm/suicidal behaviour. Among dynamic indicators, negative self-evaluation (OR = 2.303), self-reported depression (OR = 1.812), insomnia (OR = 1.768), talking to oneself (OR = 1.733), crying (OR = 1.700), and reduced conversation with others (OR = 1.422) remained significant. The optimised static LR model achieved an area under the curve (AUC) of 0.7564, and the dynamic SVM model reached an AUC of 0.8531. Their fusion further improved performance (AUC = 0.9048; sensitivity 0.8542; specificity 0.7789; accuracy 0.8042). This hierarchical model outperformed the best flat combined-feature model (SVM; AUC = 0.9022) in sensitivity (0.8542 vs. 0.6667), indicating a more clinically appropriate detection of high-risk patients.ConclusionA hierarchical machine learning approach that integrates baseline clinical history with repeated nursing assessments can effectively flag schizophrenia inpatients at high risk for self-harm and suicidal behaviour, supporting timely and individualised preventive strategies in psychiatric wards.
Context-dependent interaction between oxytocin gene polymorphisms and alcohol dependence in modulating negative emotions during acute alcohol withdrawal in adult males
ObjectiveThe importance of multiple gene-environment interaction (G × E) has been highlighted in understanding the etiology of negative emotions. This study examines the impact of oxytocin (OXT) polymorphisms (rs2740210, rs6133010, and rs2740209) in combination with alcohol dependence on anxiety and depression symptoms during acute alcohol withdrawal under different social and environmental contexts.MethodA total of 414 Chinese Han male adults undergoing acute alcohol withdrawal were recruited. Participants provided blood samples for genotyping, self-reported measures of depression and anxiety, assessments of alcohol dependence severity, and demographic information regarding social and environmental contexts.ResultsResults revealed a positive correlation between severity of alcohol dependence and symptoms of depression and anxiety, while oxytocin polymorphism did not have a direct effect on depressive and anxiety symptoms. A significant interaction between OXT polymorphism (rs2740210 and rs2740209) and alcohol dependence in relation to anxiety symptoms solely among adults living with family and/or those who were married was observed. Further analyses indicate that the GG and CC genotypes are risk genotypes, while the T allele (rs2740210) and G allele (rs2740209) are non-risk alleles in the interaction between OXT genotypes (rs2740210, rs2740209) and alcohol dependence on anxiety among the aforementioned participants.ConclusionsThese findings provide evidence for distinct G × E interaction effects on anxiety and depression symptoms during acute alcohol withdrawal, supporting the weak diathesis-stress model. Furthermore, the study highlights the importance of considering environmental factors when investigating the role of oxytocin as a biological substrate underlying social bonding and the regulation of negative emotions.
Validation of a criterion-based screening and triage pathway for adult ADHD: a prospective observational study of safety and operational efficiency
BackgroundThe increasing demand for adult attention-deficit hyperactivity disorder (ADHD) assessments has required the development of efficient triage pathways. This study provides a formal assessment of a criterion-based screening model designed to prioritise patient safety and operational efficiency within a National Health Service (NHS) specialist secondary care setting.MethodsA prospective observational validation design was employed, involving 49 consecutive adults referred for ADHD assessment none of whom had a previous ADHD diagnosis. The Comprehensive ADHD Screening Questionnaire (CASQ), a clinician-administered instrument based on DSM-5 criteria, was utilised by four trained Physician Assistants. To ensure an assessment of triage safety, a universal assessment model was adopted: all participants received a blinded, gold-standard diagnostic assessment (NICE-compliant) regardless of the initial triage recommendation thereby eliminating verification bias. The primary outcome measure was the Number Needed to Harm (NNH), defined as the number of people screened before a single false-negative result occurs.ResultsOf the 48 participants who completed the diagnostic process, six (12.5%) received an ADHD diagnosis. The triage pathway correctly identified all six cases, resulting in a sensitivity of 100.0% (95% CI: 61.0%–100.0%) and an infinite NNH. Specificity was 45.2% (95% CI: 31.2%–59.9%), with a positive predictive value of 20.7%. The pathway permitted 39.6% (n = 19) of referrals to be triaged to alternative pathways rather than full ADHD assessment, potentially saving significant specialist clinician time. Exploratory analyses indicated that score magnitude did not reliably distinguish between true and false positives within the group triaged as appropriate for further assessment.ConclusionsThese preliminary findings suggest that criterion-based screening conducted by appropriately trained non-specialist clinicians can achieve high levels of safety whilst improving service efficiency. The findings support the feasibility of task-shifting models in adult ADHD services, provided that triage thresholds are calibrated to prioritise sensitivity. These results require replication in adequately powered multi-site studies before firm conclusions regarding pathway safety can be drawn. Further research is required to establish inter-rater reliability and cost-effectiveness across diverse clinical settings.
Protracted encephalopathy and subacute combined degeneration associated with chronic nitrous oxide use: a case report
Nitrous oxide is a dissociative hallucinogen that is increasingly used recreationally, in part due to its widespread availability. Its use is known to cause subacute combined degeneration via inactivation of vitamin B12; it may also result in acute delirium and chronic progressive encephalopathy. Though current practice guidelines call for treatment of neurological sequelae of nitrous oxide use with vitamin B12 supplementation, a paucity of long-term outcome data limits our ability to guide extended courses of treatment. In this report, we discuss a case of protracted encephalopathy associated with nitrous oxide use. We track the response to vitamin B12 supplementation in the hospital setting using the Mini-Mental Status Exam to assess the severity and improvement of cognitive impairment. We also review the patient’s comorbid medical and psychiatric conditions, which complicate diagnosis and treatment planning in this patient population.
Shifting the Overton Window: enhancing therapeutic outcomes for Māori experiencing Ngā Māuiui kai (eating disorders) through the integration of traditional Māori and Western healing systems in Aotearoa New Zealand
Ngā māuiui kai (eating disorders) are understood within a Māori worldview as a manifestation of imbalance across hinengaro (mind), tinana (body), wairua (spirit) and whānau (family or support system). Prevailing Western treatment, which prioritise biopsychosocial interventions, do not address the cultural and spiritual determinants of health for Māori, creating a gap in culturally responsive care for Māori. This gap is rooted in and sustained by the enduring impacts of colonisation, which marginalised mātauranga Māori (Māori knowledge) and disrupted traditional healing systems. This paper proposes that Specialist Supportive Clinical Management, a flexible, patient-centred psychotherapy, provides a unique point of alignment for the integration of Rongoā Māori, the traditional Māori healing system. Rongoā Māori encompasses modalities such as rongoā rākau (herbal remedies), mirimiri/romiromi (physical therapies), puku kōrero (talk therapy), and karakia (incantations/prayer) and offers a framework embedded within Māori knowledge systems. We argue that rongoā-informed Specialist Supportive Clinical Management, where puku kōrero aligns with Specialist Supportive Clinical Management patient-led dialogue, can synergistically support biopsychosocial goals while ensuring a holistic, culturally grounded approach. This conceptual analysis proposes a culturally adapted intervention to enhance therapeutic engagement, improve health outcomes, and honour the treatment aspirations of Māori by addressing the whole person within their cultural context.