cNPAS2 inducedβcell dysfunction by regulating KANK1 expression in type 2 diabetes

BACKGROUND Diabetes mellitus type 2(T2DM)is formed by defective insulin secretion with the addition of peripheral tissue resistance of insulin action.It has been affecting over 400 million people all over the world.AIM To explore the pathogenesis of T2DM and to develop and implement new prevention and treatment strategies for T2DM.METHODS Receiver operating characteristic(ROC)curve analysis was used to conduct diagnostic markers.The expression level of genes was determined by reverse transcription-PCR as well as Western blot.Cell proliferation assays were performed by cell counting kit-8(CCK-8)tests.At last,T2DM mice underwent Roux-en-Y gastric bypass surgery.RESULTS We found that NPAS2 was significantly up-regulated in isletβcell apoptosis of T2DM.The ROC curve revealed that NPAS2 was capable of accurately diagnosing T2DM.NPAS2 overexpression did increase the level of KANK1.In addition,the CCK-8 test revealed knocking down NPAS2 and KANK1 increased the proliferation of MIN6 cells.At last,we found that gastric bypass may treat type 2 diabetes by down-regulating NPAS2 and KANK1.CONCLUSION This study demonstrated that NPAS2 inducedβcell dysfunction by regulating KANK1 expression in type 2 diabetes,and it may be an underlying therapy target of T2DM.

Cell cycle and complement inhibitors may be specific for treatment of spinal cord injury in aged and young mice: transcriptomic analyses

Previous studies have reported age-specific pathological and functional outcomes in young and aged patients suffering spinal cord injury,but the mechanisms remain poorly understood. In this study, we examined mice with spinal cord injury. Gene expression profiles from the Gene Expression Omnibus database （accession number GSE93561） were used, including spinal cord samples from 3 young injured mice （2–3-months old, induced by Impactor at Th9 level） and 3 control mice （2–3-months old, no treatment）, as well as 2 aged injured mice （15–18-months old, induced by Impactor at Th9 level） and 2 control mice （15–18-months old, no treatment）. Differentially expressed genes （DEGs） in spinal cord tissue from injured and control mice were identified using the Linear Models for Microarray data method,with a threshold of adjusted P 〈 0.05 and ｜logFC（fold change）｜ 〉 1.5. Protein–protein interaction networks were constructed using data from the STRING database, followed by module analysis by Cytoscape software to screen crucial genes. Kyoto encyclopedia of genes and genomes pathway and Gene Ontology enrichment analyses were performed to investigate the underlying functions of DEGs using Database for Annotation, Visualization and Integrated Discovery. Consequently, 1,604 and 1,153 DEGs were identified between injured and normal control mice in spinal cord tissue of aged and young mice, respectively. Furthermore, a Venn diagram showed that 960 DEGs were shared among aged and young mice, while 644 and 193 DEGs were specific to aged and young mice, respectively. Functional enrichment indicates that shared DEGs are involved in osteoclast differentiation, extracellular matrix–receptor interaction, nuclear factor-kappa B signaling pathway, and focal adhesion. Unique genes for aged and young injured groups were involved in the cell cycle （upregulation of PLK1） and complement （upregulation of C3） activation, respectively. These findings were confirmed by functional analysis of genes in modules （common, 4; aged, 2; young, 1） screened from protein–protein interaction networks. Accordingly, cell cycle and complement inhibitors may be specific treatments for spinal cord injury in aged and young mice, respectively.

A 2-year follow-up survey of 523 cases with peripheral nerve injuries caused by the earthquake in Wenchuan, China

We performed a 2-year follow-up survey of 523 patients with peripheral nerve injuries caused by the earthquake in Wenchuan, Sichuan Province, China. Nerve injuries were classiifed into three types： type I injuries were nerve transection injuries, type II injuries were nerve compression injuries, and type III injuries displayed no direct neurological dysfunction due to trauma. In this study, 31 patients had type I injuries involving 41 nerves, 419 had type II injuries involving 823 nerves, and 73 had type III injuries involving 150 nerves. Twenty-two patients had open tran-section nerve injury. The restoration of peripheral nerve function after different treatments was evaluated. Surgical decompression favorably affected nerve recovery. Physiotherapy was effective for type I and type II nerve injuries, but not substantially for type III nerve injury. Pharmaco-therapy had little effect on type II or type III nerve injuries. Targeted decompression surgery and physiotherapy contributed to the effective treatment of nerve transection and compression injuries. The Louisiana State University Health Sciences Center score for nerve injury severity de-clined with increasing duration of being trapped. In the ifrst year after treatment, the Louisiana State University Health Sciences Center score for grades 3 to 5 nerve injury increased by 28.2% to 81.8%. If scores were still poor （0 or 1） after a 1-year period of treatment, further treatment was not effective.

Effect of vision loss on plasticity of the head and neck proprioception

AIM:To investigate whether head and neck proprioception and motor control could be compensatory enhanced by long-term vision loss or impairment.METHODS:Individuals who were blind,low vision or sighted were included in the study,which would undergo the head repositioning test(HRT).The constant error(CE),absolute error(AE),variable error(VE)and root mean square error(RMSE)of each subject were statistically analyzed.Data were analyzed using the SAS 9.4.Tukey-Kramer for one-way ANOVA was used for comparison of blind,low vision,and sighted subjects,as well as to compare subjects with balanced vision,strong vision in the left eye and strong vision in the right eye.Independent sample t-test was used to compare subjects with congenital blindness and acquired blindness,as well as left and right hand dominance subjects.RESULTS:A total of 90 individuals(25 blind subjects,31 low vision subjects,and 34 sighted subjects)were included in the study.Among the blind subjects,14 cases had congenital blindness and 11 cases had acquired blindness.Among the blind and low vision subjects,21 cases had balanced binocular vision,17 cases had strong vision in the left eye and 18 cases had strong vision in the right eye.Among all subjects,11 cases were left hand dominance,and 79 cases were right hand dominance.There were significant differences in AE,VE,and RMSE in head rotation between blind,low vision,and sighted subjects(P<0.01),in AE,VE,and RMSE between blind and sighted(P<0.01),and in VE and RMSE between low vision and sighted(P<0.05).No significant difference between blind and low vision(P>0.05).Significant differences in CE and AE of head right rotation and CE of general head rotation between congenital and acquired(P<0.05).No significant differences between left and right hand dominance and in balance or not of binocular vision(P>0.05).CONCLUSION:Long-term vision loss or impairment does not lead to compensatory enhancement of head and neck proprioception and motor control.Acquired experience contributes to HRT performance in the blind and has long-lasting effects on plasticity in the development of proprioception and sensorimotor control.

Establishment of a rat model of chronic thoracolumbar cord compression with a flat plastic screw

Previous studies of animal models of chronic mechanical compression of the spinal cord have mainly focused on cervical and thoracic lesions, but few studies have investigated thoracolumbar injury. The specific pathophysiological mechanism of chronic thoracolumbar cord injury has not yet been elucidated. The purpose of this study was to improve animal models of chronic thoracolumbar cord compression using the progressive screw. A custom-designed flat plastic screw was implanted in the spinal cord between thoracic vertebrae 12 and lumbar 1 of rats. The screw was tightened one complete turn（0.5 mm） every 7 days for 4 weeks to create different levels of chronic spinal cord compression. Following insertion of the screw, there was a significant decline in motor function of the hind limbs, and severe stenosis of micro-computed tomography parameters in the spinal cord. Cortical somatosensory evoked potential amplitudes were reduced remarkably, and latencies were prolonged at 30 minutes after surgery. The loss of motor neurons in the gray matter was marked. Demyelination and cavitation were observed in the white matter. An appropriate rat model of chronic thoracolumbar cord compression was successfully created using the progressive screw compression method, which simulated spinal cord compression injury.