Association of SOX11 Polymorphisms in distal 3'UTR with Susceptibility for Schizophrenia.

BACKGROUND: Diverse and circumstantial evidence suggests that schizophrenia is a neurodevelopmental disorder. Genes contributing to neurodevelopment may be potential candidates for schizophrenia. The human SOX11 gene is a member of the developmentally essential SOX (Sry-related HMG box) transcription factor gene family and mapped to chromosome 2p, a potential candidate region for schizophrenia. METHODS: Our previous genome-wide association study (GWAS) implicated an involvement of SOX11 with schizophrenia in a Chinese Han population. To further investigate the association between SOX11 polymorphisms and schizophrenia, we performed an independent replication case-control association study in a sample including 768 cases and 1348 controls. RESULTS: After Bonferroni correction, four SNPs in SOX11 distal 3'UTR significantly associated with schizophrenia in the allele frequencies: rs16864067 (allelic P = .0022), rs12478711 (allelic P = .0009), rs2564045 (allelic P = .0027), and rs2252087 (allelic P = .0025). The haplotype analysis of the selected SNPs showed different haplotype frequencies for two blocks (rs4371338-rs7596062-rs16864067-rs12478711 and rs2564045-rs2252087-rs2564055-rs1366733) between cases and controls. Further luciferase assay and electrophoretic mobility shift assay (EMSA) revealed the schizophrenia-associated SOX11 SNPs may influence SOX11 gene expression, and the risk and non-risk alleles may have different affinity to certain transcription factors and can recruit divergent factors. CONCLUSIONS: Our results suggest SOX11 as a susceptibility gene for schizophrenia, and SOX11 polymorphisms and haplotypes in the distal 3'UTR of the gene might modulate transcriptional activity by serving as cis-regulatory elements and recruiting transcriptional activators or repressors. Also, these SNPs may potentiate as diagnostic markers for the disease.

Study of the Anatomical Structure of the Nasopharyngeal Cavity and Distribution of the Air Flow Field.

To build a biomechanical numerical model of the nasopharynx, construct an accurate computerized numerical description of its specific anatomical structures, analyze the distribution of air flow field, starting with the anatomical structure of the pharyngeal recess, correlate its anatomical characteristics with the occurrence and development of nasopharyngeal carcinoma from the perspective of biomechanics. In this study, the nasal and nasopharyngeal cavities of healthy male adult, with the pharyngeal recess in an open state, were scanned by CT to obtain DICOM imaging data. Then, they were imported into Mimics 20.0 to build a model which was recorded in binary STL format. Each file was imported into Geomagic studio 12.0 to construct a 3D model saved in an IGES format. Then, it was imported into ANSYS Workbench for numerical simulation of air flow field. The authors found that:Above all, the causes and pathogenesis of nasopharyngeal carcinoma can be identified from the perspective of biomechanics through the construction of a 3D model and analysis of the characteristics of air flow field. With more in-depth research, it is expected that a more solid scientific foundation will be created for related quantitative analysis.

Fluid-solid coupling model and biological features of large vestibular aqueduct syndrome.

Objective: Computed tomography (CT) images of the temporal bone of large vestibular aqueduct syndrome (LVAS) patients were used to establish 3D numerical models based on the structure of the inner ear, which are, in turn, used to construct inner ear fluid-solid coupling models. The physiological features and pathophysiology of LVAS were analyzed from a biomechanical perspective using finite element analysis. Methods: CT images of the temporal bone were collected from five children attending the Second Hospital of Dalian Medical University in 2022. The CT images were used to build 3D models of the inner ear containing the vestibular aqueduct (VA) by Mimics and Geomagic software, and round window membrane models and fluid-solid coupling models were built by ANSYS software to perform fluid-solid coupling analysis. Results: By applying different pressure loads, the deformation of the round window membranes occurred, and their trend was basically the same as that of the load. The deformation and stress of the round window membranes increased with the increase in load. Under the same load, the deformation and stress of the round window membranes increased with the expansion of the midpoint width of the VA. Conclusion: CT images of the temporal bone used clinically could establish a complete 3D numerical model of the inner ear containing VA. Fluctuations in cerebrospinal fluid pressure could affect inner ear pressure, and VA had a limiting effect on the pressure from cerebrospinal fluid. The larger the VA, the smaller the limiting effect on the pressure.

Evaluation of Rabbits Liver Fibrosis Using Gd-DTPA-BMA of Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

OBJECTIVE: To evaluate the different pharmacokinetic parameters of the DCE-MRI method on diagnosing and staging of rabbits' liver fibrosis. METHODS: We had performed DCE-MRI for rabbits that had been divided into the experiment group and the control group. Then, rabbits' images were transferred to a work station to get three parameters such as K trans, K ep, and V e, which had been measured to calculate. After data were analyzed, ROC analyses were performed to assess the diagnostic performance of K trans, K ep, and V e to judge liver fibrosis. RESULTS: The distribution of the different liver fibrosis group was as follows: F1, n = 8; F2, n = 9; F3, n = 6; F4, n = 5. No fibrosis was deemed as F0, n = 6. K ep is statistically significant (P < 0.05) for F0 and mild liver fibrosis stage, and the K ep shows AUC of 0.814. Three parameters are statistically significant for F0 and advanced liver fibrosis stage (K trans and K ep, P < 0.01; V e, P < 0.05), and the K trans shows AUC of 0.924; the K ep shows AUC of 0.909; the V e shows AUC of 0.848; K trans and K ep are statistically significant for mild and advanced liver fibrosis stages (K trans, P < 0.01; K ep, P < 0.05), and the K trans shows AUC of 0.840; the K ep shows AUC of 0.765. Both K trans and K ep are negatively correlated with the liver fibrosis stage. V e is positively correlated with the liver fibrosis stage. CONCLUSION: K trans is shown to be the best DCE parameter to distinguish the fibrotic liver from the normal liver and mild and advanced fibrosis. On the contrary, K ep is moderate and V e is worst. And K ep is a good DCE parameter to differentiate mild fibrosis from the normal liver.

The biomechanical characteristics of human vestibular aqueduct: a numerical-based model construction and simulation.

Vestibular aqueduct is a precise structure embedded in the temporal bone and plays a key role in the physiological function of inner ear by maintaining the endolymphatic circulation and buffering the impact from intracranial pressure. Although the alterations on the morphology or volume of vestibular aqueduct result in variety of diseases, the approaches of evaluating the condition of vestibular aqueduct are still unsatisfing because the pathological sections utilized for the 3D construction model most likely undergoes morphological changes. In this study, the vestibular aqueduct images obtained by CT scanning were processed by finite element method to construct the 3D model. To assess if this numerical model reflects the actual biomechanical properties of vestibular aqueduct, the fluid-solid coupling calculation was applied to simulate the endolymphatic flow in the vestibular aqueduct. By measuring the dynamics of endolymphatic flow, and the pressure and displacement on round membrane under external pressure, we found the numerical 3D model recapitulated the biomechanical characteristics of the real vestibular aqueduct. In summary, our approach of 3D model construction for vestibular aqueduct will provide a powerful method for the research of vestibular aqueduct-related diseases.

Pilot study of pressure-flow properties in a numerical model of the middle ear.

Background: Constructing a three-dimensional (3D) model through non-invasive techniques will greatly benefit the diagnosis and treatment of otitis media. However, such a model should reflect the physiological characteristics of the middle ear; in particular, the pressure-flow responses determine the validity of the model. Objectives: A 3D model of the middle ear was constructed by digital scanning and simulation. The pressure-flow properties in the model were measured to evaluate whether the model could reflect the real middle ear under physiological and pathological conditions. Materials and methods: Computed tomography (CT) scanning data from a healthy woman were input into Mimics 20.0 to construct 3D images of the middle ear. The 3D images were treated with Ansys 15.0 for finite element mesh generation. Msc Nastran 2014 were used for the fluid-solid coupling calculations. Results: The pressure-flow rate in the model resembled a Venturi tube, namely, the pressure decreased with increasing flow velocity, especially in the Eustachian tube. In the absence of the right mastoid process, the differences in air pressure and the maximal velocity in the model were reduced. Conclusions: This numerical model based on CT images of the middle ear recapitulates the biomechanical characteristics of the real middle ear. Significance: This study provides an easy and rapid approach to constructing a middle ear model for diagnosis and treatment of otitis media.

Inhibition of Ezrin suppresses cell migration and invasion in human nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most severe types of malignant cancer of the head and neck as it is difficult to treat. Ezrin is highly expressed in numerous types of cancer. However, the role of Ezrin in NPC has not been fully investigated and further studies are required in order to uncover its therapeutic potential in the treatment of NPC. The aim of the present study was to investigate the expression of Ezrin in human NPC and to evaluate the effect of knockdown of Ezrin using small interfering (si)-RNA on NPC cell migration and invasion. The expression levels of Ezrin were determined using reverse transcription-quantitative polymerase chain reaction, immunohistochemical staining and western blotting. Following transfection of Ezrin-siRNA into NPC cells, cell invasion and migration were analyzed and the mRNA expression levels of matrix metalloproteinase(MMP)-2 and MMP9 were determined. The results revealed that the expression of Ezrin was markedly increased in human NPC tissue samples compared with normal adjacent nasopharyngeal tissue samples. Ezrin was also highly expressed in the NPC cell lines 6-10B and C6661 when compared with the normal nasopharyngeal cell line NP69. Transfection of NPC cell lines with siRNA targeting Ezrin significantly inhibited NPC cell migration and invasion, and downregulated the mRNA expression level of MMP2; however, no effect was observed on MMP9 mRNA expression. At the same time, knockdown of Ezrin significantly decreased the expression levels of phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt), which downregulated the mRNA expression of MMP2. In conclusion, the results revealed that knockdown of Ezrin suppressed NPC migration and invasion by reducing the mRNA expression of MMP2 via the PI3K/Akt signaling pathway. These results highlight the important role of Ezrin in NPC cell migration and invasion. In addition, they indicate that silencing of Ezrin may serve as a potential therapeutic strategy to treat human NPC.