Shandong Mental Health Center

High-definition transcranial alternating current stimulation (HD-tACS) is an emerging neuromodulatory intervention for major depressive disorder (MDD). Here, we evaluate the efficacy and safety of a portable, low-intensity (1.6 mA), 10 Hz HD-tACS protocol targeting the bilateral dorsolateral prefrontal cortex (DLPFC) in adults with MDD. This randomized clinical trial was conducted including 120 adult MDD participants. Participants underwent 20 sessions (5 sessions/week for 4 weeks) of either active 10 Hz HD-tACS (1.6 mA) or sham stimulation a ratio of 1:1 and were followed for an additional 4 weeks. The primary outcome was the percentage reduction in 17-item Hamilton Depression Rating Scale scores at week 4. The active group showed significantly greater improvement in depression than the sham group (48% ± 14% vs 24% ± 13%, p < 0.001), sustained through the 4-week follow-up period. Additionally, significant improvements in the active group were also found in anxiety, sleep efficiency, quality of life components of physical, vitality, social functioning, and mental health. Adverse events including two cases of new-onset hypomania occurred, but no serious adverse events were observed. Thus, this trial supported the efficacy and good tolerability of 10 Hz HD-tACS for patients with MDD. Further research requires more focus on the underlying neural mechanisms and the optimized stimulation protocols. Trial Registration: China Clinical Trial Registry Identifier: ChiCTR2500103570. ClinicalTrials.gov Identifier: NCT06891326.

To explore the novel mutations associated with asthma in core family lines of Han Chinese children by using GWAS and transmission disequilibrium test. Core family lines with a proband affected with asthma were recruited for the family-based genome-wide association studies (GWAS). Peripheral blood samples were collected from the core family lines, and DNA was extracted for genotyping. TDT was used to analyze associations between asthma. Susceptibility genes were further assessed by gene-based analysis using ANNOVAR. Enrichment analysis was performed according to the differentially expressed genes. Three hundred eighty-seven single nucleotide polymorphism loci were identified in the samples from 89 core family lines of children with asthma, which could be annotated to the genes LINC01310, LRRC4C, and UTRN. Results of the TDT analysis showed the rs79186957 locus of the LRRC4C gene is associated with the development of asthma (P = 2.23 × 10−9, OR = 0.025, 95% CI: 0.003437–0.1819); the G allele was protective against asthma. The rs78742926, located in the intergenic between UTRN and EPM2A, is associated with susceptibility to asthma (P = 5.22 × 10−9), and the correlation between HLA-DRB1, HLA-DQA1, IL4R, and IL1RL1 and asthma was verified. rs79186957 in the LRRC4C intron and rs78742926 in the UTRN intergenic region are associated with asthma in Chinese Han children, and the G allele at the rs79186957 locus is a protective factor for asthma.

Abstract Background Adolescents with major depressive disorder (MDD) and non-suicidal self-injury (NSSI) face serious challenges to their mental and physical health. The development of this condition is influenced by genetic, environmental, and brain development factors. This study aimed to explore brain structural network abnormalities and their transcriptional mechanisms in adolescents with MDD and NSSI using the Morphometric Inverse Divergence Gradient Network for the first time. Methods A total of 241 adolescents with MDD participated in this study, including 134 individuals with a history of non-suicidal self-injury and 107 without. Using high-resolution T1-weighted magnetic resonance imaging, we constructed the principal morphometric gradient network, which reflects the similarity of cortical morphology between different brain regions. Partial least squares regression analysis was conducted to link imaging findings with neurotransmitter receptor distributions and gene expression patterns. Results Adolescents with NSSI showed higher morphometric gradient values in the left caudal middle frontal gyrus and bilateral inferior temporal gyri, and lower values in the left lingual gyrus and right superior parietal lobule. These structural changes were slightly associated with functional alterations in the dorsal attention network. Further analysis revealed associations with the distribution of nine neurotransmitter receptor types, including serotonin 5-HT1A, GABAa, glutamate, and dopamine receptors. The first component of partial least squares regression analysis explained 39.53% of the spatial variance in the morphometric gradient and identified key genes related to NSSI, such as GABRA5 and MGST1. Enrichment analysis showed that positively correlated genes were involved in synaptic signaling, neurodevelopment, and mood disorder pathways, and were enriched in astrocytes and cortical layers I, II, and V. Negatively correlated genes were linked to chromatin regulation and cytoskeletal metabolism, and were mainly expressed in cortical layers III and IV. Conclusions Adolescents with MDD and non-suicidal self-injury display specific abnormalities in brain structural gradients that are closely associated with neurotransmitter receptor distributions and gene expression profiles. These findings provide multi-level evidence for understanding the neurobiological mechanisms underlying non-suicidal self-injury.

ObjectiveTo evaluate the safety and effectiveness of lurasidone in Chinese patients with schizophrenia in a 12-week post-marketing study.MethodsThis 12-week, multicenter, prospective, open-label, single-arm study included schizophrenia patients from 36 sites in Mainland China, who initiated lurasidone between September 2019 and December 2023. Adverse events (AEs) and adverse drug reactions (ADRs) were primary safety endpoints. Other safety assessments included extrapyramidal symptoms (EPS) and weight gain. Effectiveness was evaluated using the Brief Psychiatric Rating Scale (BPRS) at baseline and week 12. Patients were also stratified to assess differences across ages.ResultsA total of 3170 patients were included in the Full Analysis Set (FAS) and 3178 in the Safety Set (SS). The mean daily lurasidone dose was 59.9±20.93 mg. ADRs occurred in 7.9% of patients, with incidences of 8.1%, 8.9%, 5.9%, and 2.3% in the <18, 18–45, 45–65, and >65-year age groups, respectively. EPS was the most common ADR (3.2%), typically emerging in weeks 3–4. Metabolic-related AEs occurred in 4.3% and 2.2% of patients with and without metabolic affecting agents. BPRS scores significantly improved at weeks 2/4, 6/8, and 12 compared with baseline (all P < 0.05): total score (−8.9 ± 9.62, −14.0 ± 12.16, −17.5 ± 13.61), anxiety-depression (−1.5 ± 2.37, −2.5 ± 2.88, −3.3 ± 3.31), anergia (−1.5 ± 2.34, −2.4 ± 2.83, −3.1 ± 3.11), thought disturbance (−2.4 ± 2.98, −3.8 ± 3.72, −4.7 ± 4.07), activation (−1.2 ± 1.97, −1.7 ± 2.38, −2.1 ± 2.63), and hostility-suspiciousness (−2.4 ± 2.81, −3.6 ± 3.44, −4.3 ± 3.76). In <18 years group, BPRS total score also significantly decreased from 46.1±15.10 at baseline to 26.3±9.72 at week 12.ConclusionThis real-world study demonstrated a favorable safety profile and significant clinical effectiveness of lurasidone in both adult and adolescent population with schizophrenia in China in real-world clinical settings, supporting its use across diverse patient populations.Trial RegistrationShanghai Clinical Research Center for Mental Health (SCRC-MH) NCT04432688. URL: www.smhc.org.cn/.

Postoperative nausea and vomiting (PONV) are still significant issues in the perioperative care that impact patient recovery and satisfaction, but the underlying molecular pathways that lead to personal predisposition are not comprehensively understood. In order to fill this gap we performed a multi-omics study incorporating bulk RNA sequencing, single cell transcriptomics, circRNA profiling, and alternative splicing evaluation and genotype expression colocalization analyses to detail regulatory networks of PONV. Analysis of differential expression showed inflammatory pathways and neurotransmission pathways as key driving factors in the development of symptoms, and HIF1A and STAT3 were found to be prominent central nodes in a variety of data layers. Cell type-specific transcriptional signatures indicative of neuroimmune interaction as a driving force were identified at the single-cell level with regulatory noncoding elements including differentiation of back-splice junction support of circPTGS2 and circGABRA3 and alternative splicing of GABRA3 indicating further post-transcriptional regulation. Convergent molecular signals were observed between matched datasets of patients with Integration of bulk and single-cell expression with BisqueRNA deconvolution and Harmony batch correction. These results present the initial transcriptomics-wide multi-dimensional model to integrate genetic variation, RNA organization and cellular heterogeneity to describe PONV susceptibility. The paper is supporting the sale of potential biomarker(s) that promise to inform any future clinical prediction framework and tailored antiemetic alternatives, which forms the basis of translating to diagnostic and therapeutic uses. Clinical implementation will be provided with further validation, such as protein-level validation and splice variants PCR confirmation and increased multicentric cohorts.

Background: Human noroviruses are the leading cause of foodborne gastroenteritis worldwide. Accumulating evidence suggests that food matrices containing fucosylated or histo-blood group antigen (HBGA)-like glycans may facilitate viral attachment and persistence, yet the molecular mechanisms underlying these interactions remain unclear. Methods: In this study, we performed a comparative computational analysis of norovirus–glycan interactions by integrating AlphaFold3-based structure prediction, molecular docking, and molecular dynamics simulations. A total of 182 P-domain models representing all genotypes across five human norovirus genogroups (GI, GII, GIV, GVIII, and GIX) were predicted and docked with a lettuce-derived core-fucosylated hexasaccharide (H2N2F2) previously identified by our group. The three complexes exhibiting the most favorable docking energies were further examined using 40 ns molecular dynamics simulations, followed by MM/GBSA binding free energy calculations and per-residue decomposition analyses. Results: Docking results indicated that the majority of modeled P proteins were able to adopt energetically favorable interaction poses with H2N2F2, with predicted binding energies ranging from −3.7 to −7.2 kcal·mol−1. The most favorable docking energies were observed for GII.6_S9c_KC576910 (−7.2 kcal·mol−1), GII.3_MX_U22498 (−7.1 kcal·mol−1), and GII.4_CARGDS11182_OR700741 (−6.8 kcal·mol−1). Molecular dynamics simulations suggested stable ligand engagement within canonical HBGA-binding pockets, with recurrent residues such as Asp374, Gln393, and Arg345 contributing to electrostatic and hydrophobic interactions, consistent with previously reported HBGA-binding motifs. MM/GBSA analyses revealed comparatively favorable binding tendencies among these complexes, particularly for globally prevalent genotypes including GII.3, GII.4, and GII.6. Conclusions: This work provides a large-scale structural and energetic assessment of the potential interactions between a naturally occurring lettuce-derived fucosylated hexasaccharide and human norovirus P domains. The results support the notion that core-fucosylated food-associated glycans can serve as interaction partners for diverse norovirus genotypes and offer comparative molecular insights into glycan recognition patterns relevant to foodborne transmission. The integrative AlphaFold3–docking–dynamics framework presented here may facilitate future investigations of virus–glycan interactions within food matrices.

摘要： 自发性知觉经络反应(autonomous sensory meridian response, ASMR)作为一种特殊的视听诱发体验, 为探究人脑加工与响应情感刺激的机制提供了独特窗口。现有研究表明, ASMR会暂时抑制个体的认知控制, 但这种影响是状态性的还是特质性的、具体作用于认知控制的哪个阶段及其认知神经基础为何, 尚不清楚。为此, 本研究旨在从青少年心理发展和神经加工动态两个视角, 深入揭示ASMR的发生发展机制。这一工作不仅能为理解人脑加工情感刺激的认知控制过程提供新证据, 深化对青少年认知控制发展的认识, 也将为促进有异常情感反应青少年的心理健康, 以及ASMR的临床实践应用提供理论指导。

Abstract Early detection of Alzheimer’s disease (AD) is critical, as neuropathologic change and modifiable social behavioral risks accumulate years before diagnosis. Identifying higher-risk individuals earlier enables prevention, timely care, and more equitable resource allocation. We study prediction of cognitive performance from social determinants of health (SDOH) using the NIH NIA supported PREPARE Challenge Phase 2 dataset, derived from the nationally representative Mex-Cog cohort within the 2003 and 2012 Mexican Health and Aging Study (MHAS). The target is a validated composite cognitive score covering orientation, immediate and delayed memory, attention, language, constructional praxis, and executive function, which derived from 2021 and 2016 MHAS. We curated features across demographic, socioeconomic, health, lifestyle, psychosocial, and healthcare access domains to capture multidimensional social and behavioral influences on cognitive aging. Substantial missingness was addressed with a singular value decomposition (SVD)-based imputation pipeline, treating continuous and categorical variables separately. This leverages latent feature correlations to recover missing values while balancing reliability and scalability. To better understand the relationship between input features and the composite cognitive score, we conducted a thorough post hoc analysis of the top contributing features, examining the mechanism of these features are associated with cognitive scores. The study further stratified the analysis by age group to explore whether the most predictive features differ across life stages. The proposed framework demonstrates robustness, interpretability, and computational efficiency, underscoring its potential as a practical modeling strategy for MHAS data in AD and MCI detection with substantial missingness across both continuous and categorical features.

Better mental health service engagement (MHSE) was identified to be an effective way to prevent relapse and worsening of the severe mental disorders (SMDs). There is a lack of evidence on the relationships between family function and MHSE among people with SMD. To understand the current status of family function and MHSE among people with SMD and to explore the associations between family function and MHSE. A cross-sectional study involving 486 people with SMD was conducted in Shandong province, China. Family function (the family adaptation, partnership, growth, affection, resolve [APGAR] scale) and MHSE (service engagement scale [SES]) were measured. The results indicated that the family function of the study sample was good, and the MHSE was low. Family function was negatively associated with the SES scores (β = -0.36, p = 0.002), indicating that better family function was associated with high engagement levels (since higher SES scores indicate lower engagement). The findings of this study provided epidemiological evidence for the association between family function and MHSE, and helped us further understand the significance of family in mental disease management. Some interventions for family function are helpful to improve MHSE among people with SMD, and some family-oriented policies may be useful to promote MHSE.