Objective To explore the differences in heartbeat-evoked response (HER) under drug-related cues and neutral cues in individuals with heroin use disorder (HUD), and analyze the correlation between HER potentials and immediate cue-induced craving scores. Methods Fifty HUD participants were recruited from the Chang’an Compulsory Isolation Drug Rehabilitation Center in Shaanxi Province from June to September 2024. Simultaneous acquisition of 64-channel electroencephalography (EEG) and electrocardiogram signals was performed. Twenty alternating segments of drug-related and neutral cue videos were presented, and participants rated their subjective craving after each segment using visual analogue scale (VAS) scores. Scalp EEG data were source analyzed to obtain cortical EEG signals and corresponding HER. Short-time Fourier transform was used to calculate the power spectral density (PSD) of EEG within a time window from 100 ms before the R-peak to 500 ms after it, using the R-peak as the time zero point. Cluster-based permutation testing was used to analyze PSD differences between drug-related and neutral cues in the HUD individuals. Pearson correlation analysis was performed to evaluate the correlation between HER potentials and VAS scores. Results In the 350–420 ms time window, HER potentials in the left posterior parietal, temporal, and posterior cingulate cortices were significantly lower under drug-related cues compared to neutral cues (P＜0.01); in the 140–210 ms time window, HER potentials in the right prefrontal cortex were significantly higher under drug-related cues compared to neutral cues (P＜0.01). Correlation analysis showed that HER potentials in the left temporal and left posterior cingulate cortices were significantly negatively correlated with VAS scores (P＜0.05). Drug-related cues enhanced PSD of γ power (30–100 Hz) in salience network (fronto-insular), parietal and occipital regions (P＜0.05). PSD integrations of low-γ power (40–60 Hz) in parietal region (350–400 ms) and high-γ power (70–100 Hz) in left salience network (fronto-parietal) and occipital regions (300–350 ms) were positively correlated with VAS scores (P＜0.05). Conclusions Drug-related cues may modulate cortical activity related to heartbeat perception in HUD individuals, and such dynamic changes in both time and frequency domains are stably associated with subjective craving.

Objective: To explore the nonlinear dynamic effects of social capital, adverse childhood experiences (ACEs) and depressive symptoms on suicidal behavior among vocational high school students, so as to provide theoretical basis and practical references for formulating suicide prevention strategies. Methods: A convenience sampling method was employed to include 668 students from a vocational high school from Wuhan in March 2023. Social capital was used as the asymmetry variable, while ACEs and depressive symptoms were used as bifurcation variables, a cusp catastrophe model was constructed to analyze the nonlinear changes in suicidal behavior among vocational high school students, and its fit was compared with linear and Logistic regression models. Results: Among students in the health vocational high school in Wuhan, only suicidal ideation accounted for 8.5%, only suicide attempt for 18.6%, neither accounted for 31.9%, and both for 41.0%. Gender, left behind experience, family economic status, parental parenting styles, depressive symptoms, social capital, and ACEs were all related factors influencing suicidal behavior among vocational high school students ( χ 2/H=19.03, 13.33, 21.11, 46.70, 144.38, 24.61, 118.77, all P <0.05). Violin plots showed a bimodal distribution of suicidal behavior, indicating nonlinear variation characteristics. The cusp catastrophe model results showed that social capital was negatively correlated with suicidal behavior, but the relationship was bifurcated by ACEs ( α social capital = -0.006 , β ACEs =0.075) and depressive symptoms ( α social capital =-0.013, β depressive =0.028) (all P <0.05). When both ACEs and depressive symptoms coexisted, the impact of ACEs was stronger ( β ACEs =0.077, β depressive =0.014) (both P <0.05). The cusp catastrophe model fitted ( R 2=0.886, 0.881, 0.882) better than the linear ( R 2=0.258, 0.219, 0.258) and Logistic regression models ( R 2= 0.242, 0.211 , 0.176). Gender stratified analysis results showed that bifurcation effect of ACEs was stronger in males than in females( β boys =0.224, β girls =0.086); in females, both ACEs and depressive symptoms had a bifurcation effect, with the former showing a stronger effect ( β ACEs =0.062, β depressive =0.015) (all P <0.05). Conclusions Suicidal behavior among vocational high school students exhibits nonlinear characteristics. Improving social capital to reducing ACEs and depressive symptoms may contribute to decreasing adolescent suicidal behaviors.

ObjectiveTo clarify whether epigallocatechin gallate （EGCG） is involved in the clearance of amyloid β-protein （Aβ） and autophagy induction by microglia， so as to explore the potential mechanisms of EGCG in the prevention and treatment of Alzheimer's disease （AD）. MethodsSix-month-old APP/PS1 mice were randomly divided into model and EGCG groups， with some additional wild type （WT） mice as the control group， each group consisting of 15 mice. The EGCG group received continuous gavage administration［5 mg/（kg·d）］ for 8 weeks， followed by the open field test and Y-maze to assess the learning and memory abilities of the mice. Thioflavin-S staining was used to evaluate the content and distribution of amyloid β-protein （Aβ）in the brain parenchyma of the mice， and immunofluorescence was employed to detect the expression levels of Aβ_1-42， glial fibrillary acidic protein （GFAP）， and ionized calcium-binding adapter molecule 1 （Iba1） in the hippocampal tissue of the mice. Additionally， N9 mouse microglial cells were induced with 20 µmol/L Aβ_1-42， and the cell viability was measured after treatment with different concentrations of EGCG （5 µmol/L， 10 µmol/L， 20 µmol/L）. Western blotting was used to detect the levels of Aβ_1-42， low density lipoprotein receptor-related protein 1（LRP1）， receptor for advanced glycation endproducts （RAGE）， amyloid precursor protein （APP）， insulin degrading enzyme （IDE）， neprilysin （NEP）， microtubule associated protein 1 hydrogen chain 3（LC3）-Ⅱ/LC3-Ⅰ， phosphatidylinositol 3-hydroxy kinase（PI3K）， p-PI3K， protein kinase B （AKT）， p-AKT， mammalian target of rapamycin （mTOR）， p-mTOR， and histone deacetylase 6（HDAC6）. Finally， through the co-culture of microglial cells and neuronal SH-SY5Y cells， cell viability and Caspase-3 levels were measured to verify the protective effect of EGCG-mediated Aβ clearance on neurons. ResultsEGCG increased the activity time and frequency of APP/PS1 mice in the central area of the open field （P<0.05）， and enhanced the percentage of alternation in the Y-maze test （P<0.01）； EGCG reduced Aβ deposition in the hippocampal tissue of APP/PS1 mice and increased the number of microglia； in vitro experiments showed that EGCG improved the survival rate of Aβ-induced N9 cells （P<0.01）， upregulated RAGE activity （P<0.05）， and promoted the internalization and phagocytosis of Aβ （P<0.01）. ECGC activated microglial autophagy by downregulating the level of HDAC6 （P<0.05）， inhibiting the phosphorylation of PI3K， AKT， mTOR （P<0.001）， and increasing the LC3-Ⅱ/LC3-I ratio （P<0.001）； EGCG improved the survival rate of SH-SY5Y cells （P<0.05） and reduced the activity of Caspase-3 （P<0.01） by clearing Aβ_1-42 through microglia， and had a protective effect on neurons. ConclusionEGCG activates microglial autophagy to clear Aβ by targeting and inhibiting the HDAC6-PI3K/AKT/mTOR axis.

ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

Objective: To explore the association between the Internet usage characteristics and suicidal ideation among vocational high school students, so as to provide a theoretical basis for precise intervention of suicide among vocational high school students. Methods: A total of 1 781 students were recruited from three vocational high schools in Wuhan and Xianning in March 2023 by using the cluster random sampling method. The Columbia-Suicide Severity Rating Scale and Revised Chen Internet Addiction Scale were used to measure suicidal ideation and Internet addiction, respectively. LASSO regression model was used to select influential factors related to suicidal ideation, and the gradient boosting decision tree algorithm XGBoost was used to develop prediction models and evaluate predictive performance. By calculating the SHAP values, the contribution of each influential factor was quantified. Results: The prevalence of suicidal ideation among vocational high school students was 42.22% and prevalence of Internet addiction was 26.39%. LASSO regression results indicated that age, gender, experience of being left behind, parental relationship, holding a class cadre position, using the Internet for learning, Internet use during dawn, morning and late night, Internet addiction, and depressive symptoms were all the influential factors of suicidal ideation among vocational high school students ( β= -0.05 , 0.29, 0.09, 0.27, 0.10, -0.01, 0.09, 0.05, 0.24, 0.28, 0.78, all P <0.05). The AUC of the prediction model was 0.75. The results based on SHAP values indicated that all influential factors identified through multivariate analysis contributed positively to the model predictions ( SHAP >0). Among these, depressive symptoms and parental relationship had the greatest impact on suicidal ideation ( SHAP =0.77, 0.26), and the joint effect of features with higher contribution could improve the prediction probability. Conclusions Depressive symptoms, parental relationships, Internet addiction, and time of Internet use are most important risk factors of suicidal behaviors for vocational high school students. Thus, effective interventions should be conducted to reduce their suicidal ideation.

ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People