Identification and bioinformatics analysis of genes associated with pyroptosis in spinal cord injury of rat and mouse.

The mechanism of spinal cord injury (SCI) is highly complex, and an increasing number of studies have indicated the involvement of pyroptosis in the physiological and pathological processes of secondary SCI. However, there is limited bioinformatics research on pyroptosis-related genes (PRGs) in SCI. This study aims to identify and validate differentially expressed PRGs in the GEO database, perform bioinformatics analysis, and construct regulatory networks to explore potential regulatory mechanisms and therapeutic targets for SCI. We obtained high-throughput sequencing datasets of SCI in rats and mice from the GEO database. Differential analysis was conducted using the "limma" package in R to identify differentially expressed genes (DEGs). These genes were then intersected with previously reported PRGs, resulting in a set of PRGs in SCI. GO and KEGG enrichment analyses, as well as correlation analysis, were performed on the PRGs in both rat and mouse models of SCI. Additionally, a protein-protein interaction (PPI) network was constructed using the STRING website to examine the relationships between proteins. Hub genes were identified using Cytoscape software, and the intersection of the top 5 hub genes in rats and mice were selected for subsequent experimentally validated. Furthermore, a competing endogenous RNA (ceRNA) network was constructed to explore potential regulatory mechanisms. The gene expression profiles of GSE93249, GSE133093, GSE138637, GSE174549, GSE45376, GSE171441_3d and GSE171441_35d were selected in this study. We identified 10 and 12 PRGs in rats and mice datasets respectively. Six common DEGs were identified in the intersection of rats and mice PRGs. Enrichment analysis of these DEGs indicated that GO analysis was mainly focused on inflammation-related factors, while KEGG analysis showed that the most genes were enriched on the NOD-like receptor signaling pathway. We constructed a ceRNA regulatory network that consisted of five important PRGs, as well as 24 miRNAs and 34 lncRNAs. This network revealed potential regulatory mechanisms. Additionally, the three hub genes obtained from the intersection were validated in the rat model, showing high expression of PRGs in SCI. Pyroptosis is involved in secondary SCI and may play a significant role in its pathogenesis. The regulatory mechanisms associated with pyroptosis deserve further in-depth research.

The top 100 most-cited articles on adult spinal deformity: The most popular topics are still sagittal plane parameters and complications.

Purpose: This study aimed to summarize the characteristics of the 100 most-cited articles on adult spinal deformity (ASD) and to analyze past and current research hotspots and trends. Methods: Literature searches (from inception to 28 April 2022) using Web of Science databases were conducted to identify ASD-related articles. The top 100 most-cited articles were collected for further analysis. Meanwhile, author keywords from articles published in the last 5 years were selected for further analysis. Results: The top 100 most-cited articles on ASD were selected from 3,354 papers. The publication year ranged from 1979 to 2017, and all papers were written in English. The citation count among them ranged from 100 to 1,145, and the mean citation number was 215.2. The foremost productive first author was Schwab F. University of Washington had the largest number of publications. The United States of America had the largest number of published articles (n = 84) in this field. Spine was the most popular journal. Complications were the most studied themes. The visualization analysis of author keywords from the literature in the recent 5 years showed that complications, sagittal plane parameters, and surgical techniques are still the research hotspots, and minimally invasive surgery will continue to develop rapidly. Conclusion: Based on a comparative analysis of the results of bibliometric and visualization, complications and sagittal plane parameters are still the major topics of research at present and even later, and minimally invasive surgery has a growth trend in this field of ASD.

A Presumed Synonymous Mutation of PKD2 Caused Autosomal Dominant Polycystic Kidney Disease in a Chinese Family.

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by the pathogenic mutation of PKD1 or PKD2 gene and usually affects bilateral kidneys. Synonymous mutations are generally assumed to be neutral as they do not alter amino acids. Herein, we described an extremely rare ADPKD child caused by a heterozygous synonymous mutation of PKD2 gene accompanied by massive proteinuria and congenital solitary kidney. METHODS: Clinical characteristics of the patients were summarized. Whole-exome sequencing was performed to screen the disease-causing gene mutation, and reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing were applied to analyze the impact of the identified mutation on gene transcription and splicing. RESULTS: Polycystic changes were found in the solitary kidney of a girl initially presented with nephrotic-range proteinuria. Thereafter her mother and 2 other family members were diagnosed to be ADPKD. Whole-exome sequencing of the proband identified a heterozygous synonymous mutation (c.1716G>A, p.Lys572=) located in the splicing site of exon 7 in PKD2 gene, which was co-segregated with the PKD phenotype in the family. RT-PCR and direct sequencing of amplified products revealed that this heterozygous synonymous mutation led to exon7 skipping in PKD2 gene. CONCLUSION: We reported an extremely rare child case of ADPKD2 in combination with solitary kidney and nephrotic-range proteinuria, and firstly confirmed the pathogenicity of a heterozygous synonymous mutation (c.1716G>A) in PKD2 gene. The results indicate that synonymous mutations should not be excluded from disease-causing if they are located in splicing site of an exon.