OBJECTIVE: To investigate the clinical manifestations and genetic etiology of a fetus with Neurodevelopmental disorders with deformed facial features and distal skeletal abnormalities (NEDDFSA). METHODS: Clinical data of a NEDDFSA fetus diagnosed at the Affiliated Women and Children's Hospital Affiliated to Ningbo University in March 2025 was selected as the study subject. Whole-exome sequencing (WES) was carried out on the amniotic fluid and parental peripheral blood samples, and candidate variants was verified by Sanger sequencing. The pathogenicity of candidate variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: At 30 weeks of gestation, the fetus was found to have microcephaly, short femur and intrauterine growth restriction. WES revealed that the fetus harbored a de novo heterozygous frameshift variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene, which was rated as pathogenic (PM2_Supporting+PS2_Supporting+PVS1). Combined with 25 cases from the literature, the main manifestations of patients have included intellectual disability, growth retardation and cranio-limb skeletal dysplasia, albeit without clear genotype-phenotype correlation. CONCLUSION The de novo variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene probably underlay the NEDDFSA in this fetus. Genetic testing has enabled accurate prenatal diagnosis and provided evidence for genetic counseling and reproductive guidance of this family.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/genetics* ; Transcription Factors/genetics* ; Fetus/abnormalities* ; Exome Sequencing ; Prenatal Diagnosis

This study explores the impact of perceived stress on the academic performance of orthopaedic surgery residents in the Philippines. Conducted as a cross-sectional investigation, it involved 126 residents who participated in the 2024 Philippine Board of Orthopaedics In-Service Training Examination (ITE). Stress levels were assessed using the Perceived Stress Scale-10 (PSS-10), while ITE scores served as the measure of academic performance. A significant negative correlation was identified between stress and academic performance (r = -0.3138, p = 0.00010). Residents experiencing high stress achieved lower scores (55.2%) compared to those with low to moderate stress (61.8%). Other demographic variables such as sex, age, marital status and type of training institution (public and private) were not significantly associated with stress level findings. On the other hand, key factors contributing to elevated stress included insufficient sleep (0–4 hours nightly; OR = 5.83, p = 0.0289) and limited awareness of mental health issues (OR = 13.34, p = 0.0014). These results highlight the pressing need for stress reduction initiatives, improved mental health education and strategies to address challenges posed by sleep deprivation and extensive work hours. This study provides a foundation for improving both academic outcomes and overall well-being in residency programs.

Human ; Male ; Female ; Adult: 25-44 Yrs Old ; World Health Organization ; Sleep Deprivation ; Internship And Residency ; Health Education ; Cross-sectional Studies ; Marital Status

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused significant mental distress in populations globally. At the frontline of the pandemic, emergency departments (EDs) are the prime setting to observe the effects of the pandemic on the mental health of the population. We aimed to describe the trend of mental health-related ED attendances at an acute hospital in Singapore before and during the various stages of the COVID-19 pandemic. METHODS: This is a retrospective, descriptive study of patients who presented to the ED between 1 January 2019 and 31 December 2020. Patients diagnosed with mental health-related systematised nomenclature of medicine who visited the ED during this period were identified and were placed into mental health diagnosis categories for analysis. A comparison was made between patients who presented before the pandemic (2019) and during the pandemic (2020). RESULTS: During the study periods, we identified 1,421 patients, of whom 27 were excluded due to non-mental health-related diagnoses, leaving 1,394 patients for analysis. There was a 36.7% increase in mental health-related ED presentations from 2019 to 2020. The proportion of higher-acuity mental health-related ED attendances and number of suicide attempts also increased. CONCLUSION Our study described an increase in the proportion of high-acuity mental health-related ED attendances during the COVID-19 pandemic. Emergency physicians must be cognisant of the effects of the pandemic on mental health. Further research should be conducted to better equip the healthcare system for handling all aspects of the pandemic.
Humans ; COVID-19/psychology* ; Emergency Service, Hospital/statistics & numerical data* ; Retrospective Studies ; Singapore/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Mental Disorders/diagnosis* ; Mental Health ; SARS-CoV-2 ; Tertiary Care Centers ; Pandemics ; Aged ; Suicide, Attempted/statistics & numerical data* ; Young Adult ; Adolescent

Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual developmental disorder (IDD), are highly prevalent and lack effective treatments, posing significant health challenges. These disorders are frequently comorbid with disruptions in sleep rhythms, and sleep-related indicators are often used to assess disease severity and treatment efficacy. Recent evidence has highlighted the crucial roles of circadian rhythm disturbances and circadian clock gene mutations in the pathogenesis of NDDs. This review focuses on the mechanisms by which circadian rhythm disruptions and circadian clock gene mutations contribute to cognitive, behavioral, and emotional disorders associated with NDDs, particularly through the dysregulation of dopamine system. Additionally, we discussed the potential of targeting the circadian system as novel therapeutic strategies for the treatment of NDDs.
Humans ; Neurodevelopmental Disorders/genetics* ; Attention Deficit Disorder with Hyperactivity/genetics* ; Circadian Rhythm/genetics* ; Autism Spectrum Disorder/genetics* ; Mutation ; Intellectual Disability/genetics* ; Circadian Clocks/physiology* ; Dopamine/metabolism*

Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

Cardiovascular diseases and psychological disorders represent two major threats to human physical and mental health. Research on electrocardiogram (ECG) signals offers valuable opportunities to address these issues. However, existing methods are constrained by limitations in understanding ECG features and transferring knowledge across tasks. To address these challenges, this study developed a multi-resolution feature encoding network based on residual networks, which effectively extracted local morphological features and global rhythm features of ECG signals, thereby enhancing feature representation. Furthermore, a model compression-based continual learning method was proposed, enabling the structured transfer of knowledge from simpler tasks to more complex ones, resulting in improved performance in downstream tasks. The multi-resolution learning model demonstrated superior or comparable performance to state-of-the-art algorithms across five datasets, including tasks such as ECG QRS complex detection, arrhythmia classification, and emotion classification. The continual learning method achieved significant improvements over conventional training approaches in cross-domain, cross-task, and incremental data scenarios. These results highlight the potential of the proposed method for effective cross-task knowledge transfer in ECG analysis and offer a new perspective for multi-task learning using ECG signals.
Humans ; Electrocardiography/methods* ; Mental Health ; Algorithms ; Signal Processing, Computer-Assisted ; Machine Learning ; Arrhythmias, Cardiac/diagnosis* ; Cardiovascular Diseases ; Neural Networks, Computer ; Mental Disorders

BACKGROUND: Exposure to environmental noise may have a negative impact on a population's mental health. We estimated the prevalence of exposure perception to high environmental noise in the Valencian Community, a region on the Mediterranean coast of Spain, and analysed its association with poor mental health risk, adjusting for demographic, socioeconomic and health status variables. METHODS: Cross-sectional study based on a sample of 5.485 subjects, aged 15 or above, of the 2016 Valencian Community Health Survey. The risk of poor mental health was assessed via Goldberg's questionnaire, a highly standardized self-reported questionnaire designed to screen for general psychological distress in the general population. Noise perception were determined in the home environment based on individuals' responses to the Valencian Survey question about external noise problems. Sociodemographic variables, such as sex, age, level of education, or country of birth, and health variables, such as self-perceived health, or chronic diseases, were also considered. Logistic regression was used to estimate the Odds Ratios and confidence intervals of association between variables according to sex. RESULTS: The prevalence of poor mental health was 26.2% [n = 2665; 95% CI: 24.5-27.9] in men and 33.6% [n = 2820; 95% CI: 31.9-35.3] in women. A total of 7.8% [n = 5485; 95% CI: 6.8-8.8] presented exposure to high noise perception, with no differences according to sex. Being at risk of poor mental health was significantly associated (p < 0.05) with high noise perception after adjusting for the rest of the variables (OR: 2.16 [95% CI: 1.46-3.19] in men; 2.46 [95% CI: 1.72-3.50] in women). CONCLUSIONS Although the prevalence of exposure perception to high noise was not very high, population subgroups presenting high values were detected. High noise perception was related to the risk of poor mental health, regardless of other variables. Poor mental health risk was associated with exposure perception to high noise, other socioeconomic determinants, and health status. Improving noise exposure conditions could reduce the risk of poor mental health.
Humans ; Spain/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Noise/adverse effects* ; Cross-Sectional Studies ; Young Adult ; Adolescent ; Environmental Exposure/adverse effects* ; Aged ; Mental Health/statistics & numerical data* ; Prevalence ; Mental Disorders/epidemiology* ; Risk Factors

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

Neuropsychiatric disorders arise from complex interactions between genetic and environmental factors. DNA methylation, a reversible and environmentally responsive epigenetic regulatory mechanism, serves as a crucial bridge linking environmental exposure, gene expression regulation, and neurobehavioral outcomes. During long-duration deep-space missions, astronauts face multiple stressors-including microgravity, cosmic radiation, circadian rhythm disruption, and social isolation, which can induce alterations in DNA methylation and increase the risk of neuropsychiatric disorders. Genome-wide DNA methylation research can be divided into 3 major methodological stages: Study design, sample preparation and detection, and data analysis, each of which can be applied to astronaut neuropsychiatric health monitoring. Systematic comparison of the Illumina MethylationEPIC array and whole-genome bisulfite sequencing reveals their complementary strengths in terms of genomic coverage, resolution, cost, and application scenarios: the array method is cost-effective and suitable for large-scale population studies and longitudinal monitoring, whereas sequencing provides higher resolution and coverage and is more suitable for constructing detailed methylation maps and characterizing individual variation. Furthermore, emerging technologies such as single-cell methylation sequencing, nanopore long-read sequencing, and machine-learning-based multi-omics integration are expected to greatly enhance the precision and interpretability of epigenetic studies. These methodological advances provide key support for establishing DNA-methylation-based monitoring systems for neuropsychiatric risk in astronauts and lay an epigenetic foundation for safeguarding neuropsychiatric health during future long-term deep-space missions.
DNA Methylation ; Humans ; Space Flight ; Mental Disorders/genetics* ; Epigenesis, Genetic ; Astronauts/psychology* ; Weightlessness/adverse effects* ; Epigenomics

OBJECTIVES: To explore the molecular mechanism by which miR-124 affects cognitive function of sleep-deprived rats. METHODS: Fifty-four adult male SD rats were randomized into 6 groups (n=9), including a normal control group, a sleep deprivation (SD) model group, and 4 intracerebral microinjection groups in which the rats were subjected to stereotactic injection of miR-124 agomir, miR-124 agomir NC, miR-124 antagomir, or miR-124 antagomir into the lateral ventricle 7 days before SD modeling. The cognitive functions of the rats were evaluated with Morris water maze test, and pathological changes in the hippocampus were observed using HE staining. The expression level of miR-124 in hippocampal tissues of the rats was detected with qRT-PCR, and the expression level of apoptosis-related proteins and signaling pathway proteins were determined using Western blotting. RESULTS: In Morris water maze test, the SD rat models treated with miR-124 agomir showed a significantly shorter escape latency and fewer platform crossings with increased percentage of time and swimming distance in the fourth quadrant as compared with those in SD model group, while the rats treated with miR-124 antagomir exhibited worsened performance in the test. In the SD rat models, treatment with miR-124 agomir obviously lessened pathological changes in the hippocampus, while treatment with miR-124 antagomir significantly worsened the pathological changes. Compared with those in SD model group, the miR-124 agomir-treated rats showed an increased hippocampal expression of miR-124 with upregulated protein expressions of PI3K, p-AKT/AKT, and Bcl-2 and downregulated expressions of Bax and caspase-3 proteins, while rats treated with miR-124 antagomir showed significantly decreased hippocampal expression of miR-124 with lowered expressions of PI3K, p-AKT/AKT and Bcl-2 proteins and increased Bax and caspase-3 protein expressions. CONCLUSIONS High expression of miR-124 alleviates SD-induced cognitive decline and neuronal apoptosis in rats by activating the PI3K/AKT signaling pathway.
Animals ; MicroRNAs/metabolism* ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Male ; Rats, Sprague-Dawley ; Hippocampus/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cognition ; Rats ; Sleep Deprivation/metabolism* ; Apoptosis ; Maze Learning