Understanding the relationship between genetic variations and brain abnormalities is crucial for uncovering the cross-scale pathophysiological mechanisms underlying schizophrenia. This cross-sectional study identifies brain structural correlates of individual variation in gene expression in schizophrenia and its clinical implication. RNA-sequencing data from blood samples, magnetic resonance imaging scans and clinical assessments were collected from 43 patients with schizophrenia, together with data from 60 healthy controls. Using RNA-sequencing data we show alterations in both gene-level and isoform-level expression between patients with schizophrenia and healthy controls (1,836 genes and 1,104 isoforms, false-discover-rate-adjusted P < 0.05). We also show differential gene expression to be associated with schizophrenia-related genomic variations (based on genome-wide association study data on 76,755 patients and 243,649 controls; regression coefficient (beta) = 0.211, P = 0.001) and differential brain gene expression (P < 0.001, hypergeometric test). Multivariate correlation analysis combining gene expression and brain imaging shows that transcriptional levels of differentially expressed genes significantly correlate with gray matter volume in the frontal and temporal regions of cognitive brain networks in patients with schizophrenia (P < 0.001, permutation test). Findings show a significant association between gene expression, gray matter volume and cognitive performance in patients (P = 0.031, permutation test). Our results suggest that genomic variants in individuals with schizophrenia are associated with alterations in the transcriptome, which plays a role in individual variations in macroscale brain structure and cognition, contributing to building a comprehensive, multi-omics marker for the assessment of schizophrenia.

Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7–10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximately 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions. In vivo and in vitro results demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex likely through enhancing the voltage-gated K + and also the leak K + conductance. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising applications in other nervous system diseases.

Cognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia. 136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects’ cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia. Grouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P < 0.05). We found a negative correlation between the backward digit span task score and fALFF of the left IPL in healthy controls (r = − 0.388, P = 0.003), which was not seen in patients (r = 0.203, P = 0.020). In addition, none of the other analyses were statistically significant (P > 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia. Our study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment.

How genetic risk variants may relate to brain abnormalities is crucial for understanding cross-scale pathophysiological mechanisms underlying schizophrenia. The present study identifies brain structural correlates of variation in gene expression in schizophrenia and its clinical significance. Of 43 patients with schizophrenia, RNA-seq data from blood samples, MRI, and clinical assessments were collected, together with data from 60 healthy controls. Gene expression differentiation between schizophrenia and health controls was assessed and cross-referenced to schizophrenia-related genomic variations (GWAS on 76,755 patients and 243,649 controls and GWAS on 22,778 East Asian patients) and brain gene expressions (samples from 559 patients and 175 individuals). Multivariate correlation analysis was employed to examine associations across gene expression, brain volume, and clinical assessments. Differentially expressed genes in blood samples from patients with schizophrenia were significantly enriched for genes previously reported in genome-wide association studies on schizophrenia ( P = 0.002, false discovery rate corrected) and were associated with gene expression differentiation in the brain ( P = 0.016, 5,000 permutations). Transcriptional levels of differentially expressed genes were found to significantly correlate with gray matter volume in the frontal and temporal regions of cognitive brain networks in schizophrenia ( q < 0.05, false discovery rate corrected). A significant correlation was further observed between gene expression, gray matter volume, and performance in the Wechsler Adult Intelligence Scale test ( P = 0.031). Our findings suggest that genomic variations in schizophrenia are associated with differentiation in the blood transcriptome, which further plays a role in individual variations in macroscale brain structure and cognition.

Schizophrenia is a complex mental illness with genetic heterogeneity, which is often accompanied by alterations in brain structure and function. The neurobiological mechanism of schizophrenia associated with heredity remains unknown. Recently, the development of trans-scale and multi-omics methods that integrate gene and imaging information sheds new light on the nature of schizophrenia. In this article, we summarized the results of brain structural and functional changes related to the specific single-nucleotide polymorphisms (SNPs) in the past decade, and the SNPs were divided into non-coding regions and coding regions, respectively. It is hoped that the relationship between SNPs and cerebral alterations can be displayed more clearly and intuitively, so as to provide fresh approaches for the discovery of potential biomarkers and the development of clinical accurate individualized treatment decision-making.

目的 探讨PBL联合翻转课堂教学模式对解剖实验课学生知识、能力、综合素质培养的影响.方法 选择2018年5月至2019年6月我院校158名医学生,随机分为观察组与传统组,每组各79例;传统组采用传统带教模式进行教学,观察组采用PBL联合翻转课堂教学模式进行教学;对两组学生学习后对带教模式的满意度、学习效果、以及学习前后的评判思维做出比较与分析.结果 观察组学生学习后对所采用的带教模式满意度为94.94％,显著大于传统组72.15％,差异有统计学意义(P＜0.05);观察组学生在学习结束后理论认知和操作技能成绩均优于传统组(P＜0.05),综合成绩观察组(95.56±4.16)分,较传统组(85.12±3.97)分显著提高(P＜0.05);两组学生在学习前批判思维评分比较差异均无统计学意义(P＞0.05),在学习后批判思维评分较学习前比较两组学生均得到提高(P＜0.05),但是组间比较观察组批判思维能力的提高显著高于传统组(P＜0.05).结论 PBL联合翻转课堂教学模式在解剖实验课中可有效提高学生的专业知识和操作能力,使理论与实践相结合从而提高整体综合素质.

Background: Ambiguous or atypical phenotypes can make a definite diagnosis of primary immunodeficiency diseases based on biochemical indices alone challenging. Further, mortality in early life because of infections in patients with these conditions supports the use of genetic tests to facilitate rapid and accurate diagnoses. Methods: Genetic and clinical analyses of three unrelated Chinese children with clinical manifestations of recurrent infections, who were considered to have primary immunodeficiency diseases, were conducted. Patient clinical features and serum immunological indices were recorded. Next-generation sequencing was used to screen for suspected pathogenic variants. Family co-segregation and in silico analysis were conducted to evaluate the pathogenicity of identified variants, following the American College of Medical Genetics and Genomics guidance. Results: All three patients were found to have predominant antibody defects. Sequencing analysis revealed that one had two compound heterozygous variants, c.255C>A and c.295C>T, in the autosomal gene, activation-induced cytidine deaminase (AICDA). The other two patients were each hemizygous for the variants c.1185G>A and c.82C>T in the Bruton's tyrosine kinase (BTK) gene on the X chromosome. In silico analysis revealed that identified substituted amino acids were highly conserved and predicted to cause structural and functional damage to the proteins. Conclusion: Four pathogenic variants in AICDA and BTK were confirmed to cause different forms of hyper-IgM syndrome type 2 (HIGM2) and X-linked agammaglobulinemia (XLA); two were novel mutations that have never been reported previously. This is the first report of HIGM2 caused by AICDA deficiency in a patient from the Chinese mainland.