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Objective To explore the gene expression profile in paraspinal muscle degeneration (PMD) and identify key ferroptosis genes. Methods RNA sequencing was performed on paraspinal muscle tissue of 3 normal and 3 PMD patients respectively to obtain differentially expressed genes. Through protein-protein interaction (PPI) and gene functional enrichment analysis, the intersection of ferroptosis genes was identified to identify key hub genes associated with ferroptosis. The diagnostic value for PMD disease was analyzed by receiver operating characteristic (ROC) curves. Results A total of 292 differentially expressed genes were identified in PMD. Among them, 125 genes were significantly downregulated and 167 genes were significantly upregulated. Bioinformatics analysis revealed that 14 differentially expressed genes were associated with ferroptosis. Among them, ferroptosis genes MUC1, ATF3 and CDKN1A were key hub genes with good specificity and sensitivity for diagnosing PMD. Functional enrichment analysis revealed that they may mediate the occurrence and progression of PMD by regulating cell apoptosis, ferroptosis and skeletal muscle tissue development and differentiation. Conclusion Ferroptosis genes MUC1, ATF3 and CDKN1A can serve as biomarkers for diagnosing PMD, providing theoretical basis for decoding the pathological mechanism of PMD and developing new drugs. [ABSTRACT FROM AUTHOR]

Copyright of Traditional Chinese Drug Research & Clinical Pharmacology is the property of Traditional Chinese Drug Research & Clinical Pharmacology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To explore the key genes related to patients with recurrent implantation failure (RIF) using bioinformatics analysis, to identify cell subpopulations and cell-cell communications in human endometrium, and to discuss the impact on endometrial receptivity. Methods: The GSE103465 dataset, GSE183837 dataset and GSE223672 dataset were downloaded from the Gene Expression Omnibus (GEO) database as research samples. Endometrial tissue data from RIF patients and control females were utilized. R language and Perl scripts were employed to conduct the quality analysis on the raw data, and the limma package was utilized for differential gene selection. The selected differentially expressed genes were subjected to gene ontology (GO) and Kyoto encyclopedia of genes and genome (KEGG) analysis, Protein-Protein Interaction Networks (PPI) construction and core gene selection. Using R language-related packages, single-cell annotation and classification were performed, followed by the construction of an intercellular communication map. Results: The identified key genes included RPF2, DDX27, PWP2, CDC5L, NOP2, DCAF13, CEBPZ, FTSJ1, GNL3L, and NSUN2. The main cell types in the endometrium of patients with RIF were identified as epithelial cells, NK cells, granulocyte-monocyte progenitors, endothelial cells, and smooth muscle cells. The enriched pathways involving GRN, SPP1, PTN, MIF, MK signaling pathways participate in the intercellular communication through receptor-ligand pairs. Conclusions: The impaired endometrial receptivity in RIF patients is associated with aberrant RNA modification and processing and epigenetic modification errors, as well as inflammatory response and decreased metabolism. Intercellular communication reveals that endometrial epithelial cells in RIF patients have a decreased capacity for osteoblastin -integrin - mediated adhesion and invasion, which may be the cause of embryo implantation failure. [ABSTRACT FROM AUTHOR]

Objective To explore the regulatory mechanism of emodin on pain behavior in a mouse model of osteoarthritis based on mitochondrial key genes. Methods Thirty C57BL/6J mice were randomly divided into the control group, the osteoarthritis (OA) model group and the emodin-treated (OA+emodin) group, 10 mice per each group. The mice in the OA group and the OA+emodin group were intra-articular injection of complete Freund’s adjuvant (20 µL) in knee to establish the OA model, and mice in the OA+emodin group were treated by intraperitoneal emodin (10 mg/kg) injection. After behavioral testing, knee tissue of mice was collected for hematoxylin-eosin staining. Western blot analysis was used to detect expression levels of proinflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and mitochondriarelated proteins NADH dehydrogenase (ubiquinone) flavoprotein 1 (NDUFV1), cytochrome C oxidase subunit 5B (COX5B), cytochrome C oxidase assembly protein COX15 homolog (COX15), NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 10 (NDUFA10) in knee tissue. Results Compared with the control group, mice in the OA group showed decreased mechanical nociceptive threshold (PWT), reduced latency and distance in rotarod test (P＜0.05). Compared with the OA group, mice in the OA+emodin group showed increased PWT, latency, and distance (P＜0.05). In the control group, the structures of cartilage and subchondral bone were intact, while in the OA group, the cartilage was thinner and the subchondral trabeculae was deteriorated. The treatment with emodin alleviated cartilage degeneration. The expression levels of IL-1β, TNF-α, COX15 and NDUFA10 were increased while expression levels of NDUFV1 and COX5B were decreased in the OA group compared with the control group. The emodin treatment restored the above-mentioned protein expression levels (P＜0.05). Conclusion Emodin can alleviate pain behavior in OA mice by regulating the expressions of inflammatory factors and mitochondrial related proteins. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression of Augmin like complex subunit 5 (HAUS5) gene and its prognostic significance in renal clear cell carcinoma (RCCC), elucidating its potential mechanisms in the occurrence and development of RCCC through bioinformatics methods and various analytical approaches. Methods Pan-cancer analysis was conducted using the TIMER2 website. Human protein atlas database was utilized to obtain immunohistochemistry-based antibody-specific staining scores for RCCC. Additionally, gene mRNA expression levels and related clinical data for RCCC were downloaded from the Cancer Genome Atlas database, mRNA expression levels and associated clinical data of HAUS5 gene in RCCC were organized using R and Excel software. Patients were categorized into the high and the low expression groups based on the median HAUS5 expression level. SPSS27.0 and R software were used for survival analysis, functional analysis. and visualization. Results HAUS5 exhibited high expression in both RCCC tissues and cells. Higher expression of HAUS5 in RCCC was associated with an increased risk of mortality, with statistically significant differences (hazard ratio=1.744,95% confidence interval: 1. 286-2.365,P<0.001). Other clinical variables significantly associated with overall survival [such as distant metastasis (M stage), clinical stage, and primary tumor status (T stage) also had an impact (hazard ratio=1.550,1.866,1.891,95% confidence interval: 1.302-1.846.1.637-2.126,1.608-2.225, P<0.001). Conclusion HAUS5 is highly expressed in both RCCC tissues and cells and is closely associated with the progression and adverse prognosis of RCCC. suggesting it as a potential target for clinical treatment of RCCC. [ABSTRACT FROM AUTHOR]

Objective To explore autophagy-related genes (ARGs) in lung adenocarcinoma and construct a prognostic model for lung adenocarcinoma based on ARGs. Methods RNA high-throughput transcriptome data of lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database and HADb database to acquire ARGs. A prognostic model for lung adenocarcinoma was constructed and validated based on differentially expressed ARGs, followed by the construction of column line graphs and calibration curves to explore the clinical application value of the model. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on differentially expressed ARGs. Lasso regression analysis was conducted on differentially expressed ARGs with prognostic significance to construct the prognostic model for lung adenocarcinoma. Kaplan-Meier survival curves were plotted. Results A total of 31 differentially expressed ARGs were obtained, and 10 differentially expressed ARGs with prognostic significance were selected. Patients in the high-risk group were significantly associated with poorer overall survival, with statistical significance (P<0.05). T stage, N stage and risk score was an independent prognostic factor for patients with lung adenocarcinoma. The global consistency of the calibration curve column line graph was 0.710,indicating a high level of agreement between the model's predicted results and actual outcomes. Conclusion The risk model constructed based on differentially expressed ARGs can serve as a prognostic feature for patients with lung adenocarcinoma or provide a reference for individualized treatment for patients with lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objective To investigate the sperm proteomics of asthenospermia patients using the tandem mass tag(TMT) labeling technique and ingenuity pathway analysis (IPA) platform for better understanding the pathogenesis of asthenospermia. Methods Sperm samples were collected from 30 male healthy subjects and 30 patients with asthenospermia and their proteomics were comparatively analyzed by TMT technology. Differentially expressed proteins were identified based on the criteria of fold change >1.7 or < 0. 588 and P value < 0. 05. The IPA bioinfbrmatics analysis platform was employed to analyze all the differential proteins. Results A total of 89 differentially expressed proteins were obtained, including 73 upregulated proteins and 16 downregulated proteins. IPA analysis revealed that 4 differential proteins were associated with apoptosis f 2 differential proteins with autophagy, 1 differential protein with androgens, 10 differential proteins with immune responses and 2 differential proteins with inflammation. The differentially expressed proteins were primarily involved in the endoplasmic reticulum localization of proteins and mRNA breakdown of nuclear transcription. The typical signaling pathways involved were the Sirtuins, protein kinase A, and mTOR signaling pathway. Four candidate disease markers related to asthenospermia were obtained. Conclusions The occurrence of asthenospermia is closely related to changes in apoptosis, autophagy, androgen abnormality, immunity and inflammation, but it needs to be further verified. Meanwhile, the differential proteins of sperm in patients with asthenospermia involve complex biological processes, molecular functions and signaling pathways, which lays a foundation for the study of its pathogenesis. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression of COL6A1 in sarcoma tissue and its significance based on bioinformatics analysis. Methods The GEO database was used to download the GSE16088, GSE21122, and GSE49972 datasets to analyze the expression level of COL6A1-3. The Kaplan-Meier survival curves were used to analyze the impact of the expression level of COL6A1-3 on the prognosis of patients with sarcoma. A Spearman correlation analysis was performed using GSVA package to investigate the correlation between the expression level of COL6A1 and immune cell infiltration. The LinkedOmics database was used to analyze the genes co-expressed with COL6A1, and the ggstatsplot package of R software was used to investigate the correlation between COL6A1 and COL6A2. The ClusterProfiler package of R software was used to perform GO functional enrichment analysis and KEGG pathway analysis of the genes co-expressed with COL6A1. The GSEA analysis was used to investigate the important kinase, miRNA, and transcription factor targets of the genes co-expressed with COL6A1. Results Compared with normal tissue, there was a significant increase in the expression level of COL6A1 in osteosarcoma, soft tissue sarcoma, and clear cell sarcoma of the kidney. The survival analysis showed that the high expression of COL6A1 was associated with low overall survival rate and di-sease-specific survival rate (χ2=6.37,4.57,P

Objective To lay the groundwork for formulating novel immunotherapies through understanding the regulatory role of ferroptosis and its function in immune microenvironment in ANCA-associated vasculitis (AAV) with renal injury. Methods Kidney data sets on AAV were downloaded from the database of Gene Expression Omnibus (GEO). Based upon the results of differential expression, consensus clustering algorithm was employed for identifying the subtypes of iron mortality. Single sample gene set enrichment analysis (ssGSEA) and gene set variation analysis (GSVA) were performed for evaluating the immune invasion and signaling pathways of subtypes. Key ferroptosis-related genes (FRGs) were further screened by LASSO and SVM-RFE algorithms and verified by independent data sets. CIBERSORT was utilized for assessing the abundance of infiltrating immune cells for FRGs. Finally a clinical diagnostic model of FRGs was constructed by rsm package. And the correlation between FRGs and renal function was examined by Nephroseq V5 database. Results Twenty-four ferroptosis related genes were significantly differentially expressed in AAV with kidney injury. Unsupervised cluster analysis revealed the regulatory patterns of two different ferroptosis subtypes with significant differences in gene expression, immune infiltration and biological functional pathways. A set of FRGs composed of ALOX5, CD44, CRYAB, TP53, and FTH1 was selected by two machine learning algorithms. It could effectively distinguish AAV with kidney injury from normal control group. CCR, macrophage and HLA were correlated positively with FRGs. Area under ROC curve of clinical diagnostic model constructed by FRGs was 0. 961. FRGs were correlated negatively with glomerular filtration rate (GFR). However, except for CRYAB and FTH1, other FRGs were correlated positively with serum creatinine (Scr). It implicated their potential relevance to renal injury in ANCA-associated vasculitis (AAV) and their potential as prognostic biomarkers. Conclusions Ferroptosis in AAV with kidney injury is correlated closely with immune microenvironment. It provides rationales for devising new treatments for AAV with kidney injury through a better understanding the pattern of ferroptosis.

Objective To prepare a whole-cell vaccine for murine Lewis lung carcinoma (LLC), and to investigate the role of this vaccine in enhancing the anti-LLC ability of immune system in C57BL/6N mice. Methods TCGA database was used to analyze the changes in the infiltration level of immune cells within human lung adenocarcinoma (LUAD) tissue in the context of MYC amplification, and the optimal duration of ultraviolet irradiation was explored for the preparation of LLC whole-cell vaccine. A mouse model was used to assess the effect of LLC whole-cell vaccine with targeted inhibition of Myc on resistance to LLC. Results In human LUAD tissue samples, compared with the low N-MYC expression group, the high N-MYC expression group had a significant reduction in the infiltration abundance of activated CD4+ memory T cells and activated NK cells (W=28 233,27 990,P

Objective To investigate the differentially expressed genes (DEGs) in the substantia nigra of mice with Parkinson’s disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) based on bioinformatics, as well as their role in the pathological and progression of PD. Methods GEO database was used to obtain the gene expression microarray data in the substantia nigra of mice in the normal group and the PD model group, and the bioinformatics method was used to screen for DEGs in the substantia nigra between the normal group and the PD model. Metascape tool was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis. Quantitative real-time PCR was used to measure the mRNA expression levels of key functional genes regulating neuronal apoptosis and prion transmission. Results There were 174 upregulated DEGs and 173 downregulated DEGs in the substantia nigra of mice with MPTP-induced PD (P0.26). The upregulated genes were significantly enriched in the pathways regulating prion transmission, neuronal development, iron homeostasis, and export across the plasma membrane, while the downregulated genes were significantly enriched in the pathways regulating synaptic vesicle release, transsynaptic complex transmission, neuronal apoptosis, and actin in cytoskeleton. Compared with the normal group, the PD model group had significant reductions in the expressions of Bdnf and Fbxw7 in the substantia nigra of mice (t=2.25,2.39,P0.05). Conclusion There are significant changes in the key functional genes Bdnf and Fbxw7 that regulate neuronal apoptosis in PD model, which lays a foundation for further clarifying their role in the pathological progression of PD.

Objective To identify key genes associated with the prognosis of oral squamous cell carcinoma (OSCC) by RNA sequencing integrated bioinformatics. Methods Carcinoma and adjacent tissues of 3 OSCC patients admitted to the Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University from February to October 2019 were collected. RNA was extracted and DNA libraries were constructed, and Illumina high-throughput sequencing was performed to screen out differentially expressed genes (DEGs) by integrating the data. The biological processes, signal pathways and interaction network of DEGs were analyzed, and the visualization and module analysis of DEGs were conducted. Candidate genes were identified by survival analysis of TCGA database of the module gene with the highest score, and key genes were further screened by GSE41613 data set for survival analysis of candidate genes. The human Protein Atlas database was used to verify the protein expression of key genes in OSCC. Gene set enrichment analysis (GSEA website) was used to predict the possible signaling pathways of key genes in OSCC. Results According to the sequencing data from the three pairs of OSCC, a total of 1818 DEGs were screened out, including 824 upregulated and 994 downregulated genes. They were mainly enriched in mitotic nuclear division, extracellular regions and calcium signaling pathways. TCGA data identified three candidate genes, including ASPM, CENPF and KIF15. The survival analysis of GSE41613 data identified CENPF as the key gene of OSCC. Its expression in OSCC tissues was higher (P＜0. 05). OSCC with higher CENPF expression had worse prognosis (P＜0. 05). The protein expression of CENPF in OSCC was higher. The samples with high expression of CENPF were enriched in gene sets of multiple pathways such as basic transcription factors and cell cycle (P＜0. 05). Conclusion A total of 1 818 DEGs are screened by transcriptional sequencing, among which the prognosis is worse when CENPF is higher in OSCC, which may be related to the occurrence, development and prognosis of OSCC. [ABSTRACT FROM AUTHOR]

Objective: Autophagy is a recirculation system of lysosomal degradation of its own structure, which plays an important role in the development of tumors. The purpose of this study was to explore the functions of autophagy-related genes （ARGs） in gastric cancer （GC） to improve the current prognostic staging system. Methods: The differential survival ARGs in GC was identified by R language, and the risk scoring model of ARGs was constructed by univariate Cox and Lasso regression analysis, and its efficacy was verified by survival analysis and ROC curve. Results: Survival analysis showed that high risk score predicted poor prognosis （all P<0.05）. ROC curve confirmed that the model had reliable predictive performance （AUCmax=0.843）. Univariate and multivariate independent prognostic analysis showed that this score was an independent risk factor for GC （P<0.001）. Pearson correlation analysis showed that the model could reflect multiple types of immune cell infiltration （P<0.001）. Conclusion: This study constructed a risk scoring model based on 5 ARGs labels（ CXCR4, GRID2, HSPB8, IRGM, TSC1）, which can be combined with existing clinicopathology to provide more accurate prognosis for GC patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression and clinical significance of nucleolar and spindle associated protein 1 (NUSAP1) in lung adenocarcinoma. Methods By searching Oncomine, GEPIA, UALCAN, TIMER,STRING and other databases, the expression of NUSAP1 gene and protein in lung adenocarcinoma, the influence of NUSAP1 expression on the prognosis of patients, the relationship between NUSAP1 gene and tumor immune cell infiltration, and the physiological process involved in protein network pattern enrichment were analyzed. Results NUSAP1 was highly expressed in lung adenocarcinoma tissues, and the higher the gene expression was, the worse the prognosis was, the difference was statistically significant (P <0.05).The expression level of NUSAP1 in lung adenocarcinoma was negatively correlated with B lymphocytes,CD4+ T lymphocytes and dendritic cells in tumor microenvironment(P <0.05),and positively correlated with CD8+T lymphocytes, macrophages and neutrophils(P <0.05).NUSAP1 was mainly involved in the regulation of cell cycle, positive regulation of mitotic cell cycle, nuclear division and other biological processes. Conclusion NUSAP1 is highly expressed in lung adenocarcinoma tissues and is associated with the occurrence and development of lung adenocarcinoma, which may be used as a biomarker for diagnosis and prognosis evaluation of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objective To investigate the association of physical fitness levels with gut microbiota and find out the bacterial taxa with potential of improving physical fitness. Methods 44 healthy adult men were recruited for this study and the data on physical fitness was obtained. They were assigned to a high or low physical fitness group by using latent profile analysis. High-throughput sequencing was used to detect 16S rDNA collected from the fecal samples of volunteers before physical test. The alpha or beta diversity of intestinal flora was analyzed to determine the differences in gut flora between the two groups. Linear discriminant analysis Effect Size was applied to screen the taxa contributing more to the diversity, which were considered as closely related to physical fitness level. Spearman correlation analysis was used to determine the correlation among the richness of taxa that contribute more to diversity and indexes related to physical fitness. Results There wahs no significant difference in the alpha diversity of gut flora between the two groups, whereas the beta diversity differed significantly. Lachnospiraceae ND3007 group and Clostridia UCG-014 were related to higher level of physical fitness, while Olsenella, Bacteroides stercoris and Eubacterium ventriosum group were associated with lower lever of physical fitness. The richness of taxa related to better physical fitness condition appeared to be negatively correlated with that of worse physical fitness condition, and the latter showed a stronger correlation with indexes related to physical fitness than the former. Conclusions The composition of microbiota planted in gastrointestinal tract was associated with physical fitness. Lachnospiraceae ND3007 group could be considered as latent taxa to help improve physical fitness condition. [ABSTRACT FROM AUTHOR]

Objective To screen hub genes and miRNA interaction in aging osteoporosis. Methods The GSE35956 gene chip data set was downloaded from GEO database, and the differentially expressed genes (Degs) in bone marrow mesenchymal stem cells were screened by R language in patients with osteoporosis. GO enrichment and KEGG pathway were analyzed in Degs using DAVID database. String database and Cytoscape software were used to analyze the protein interaction network and screen hub genes. The mirnas interacting with hub genes were predicted by Targetscan database, and the predicted mirnas were enriched by funrich database. Bone marrow mesenchymal stem cells from 3 to 4 month-old (the young group) and 18 to 20 month-old (the old group) in C57BL/6 mice were extracted and cultured. The expression levels of miRNA in bone marrow mesenchymal stem cells were verified by qPCR technique in the young and the old groups. Results A total of 982 up-regulated Degs and 99 down-regulated degs were identified in patients with osteoporosis. Degs were mainly enriched in plasma membrane adhesion molecule-mediated homologous cell adhesion and calcium ion binding, and were mainly involved in neuroactive ligand-receptor interaction signaling pathways. PPI interaction network analysis identified eight core genes: leptin (LEP), lymphocyte-specific protein tyrosine kinase (LCK), WT1 transcription factor (WT1), SRY-box transcription factor 10 (SOX10), integrin subunit beta 2 (ITGB2), albumin (ALB), cholecystokinin (CCK) and bone morphogenetic protein 7（BMP7). The interaction between 105 miRNA and 6 core genes was predicted by Trargetscan qPCR results showed that BMP7, CCK, ITGB2 and SOX10 genes in bone marrow mesenchymal stem cells were significantly up regulated in the old group compared with those of the young group. It is consistent with the results of bioinformatics analysis. Conclusion The expression levels of the selected core genes are related to the differentiation degree of bone marrow mesenchymal stem cells in aged mice. The identified miRNA may be a diagnostic marker and a therapeutic target for aging osteoporosis [ABSTRACT FROM AUTHOR]

Bioinformatics is widely used in the studies of reproductive system at various technical levels, including genome, transcriptome, proteome and metabolome. Through systematic data collection and visual processing, the mechanisms of key molecules in the reproductive process have been gradually discovered and elucidated. The application of bioinformatics technology in reproductive system not only has effectively promoted the development and innovation of reproductive system research on the basis of ensuring preciseness and scientificity, such as analyses of the normal functions, abnormal and pathological phenomena of different reproduction organs at the different levels of genome, transcriptome, proteome and metabolome, but also has enhanced the progress of clinical diagnosis and treatment of the related diseases in reproductive system, such as the discoveries of new disease markers and drug targets for the diagnosis and treatment. In this review, we mainly introduced the latest bioinformatics technologies in the reproductive medicine in recent years. Meanwhile, we also summarized the current research progress in reproductive system using bioinformatics, which may provide some key guidance and ideas for future research. [ABSTRACT FROM AUTHOR]

Objective To screen core genes and related signal pathways of benign prostatic hyperplasia using Gene Expression Omnibus (GEO) database and bioinformatics methods. Methods Through screening the GEO database, the gene chip data set GSE119195 containing 5 prostate hyperplasia tissues and 3 normal prostate tissues was obtained. The R tool was used to normalize the gene expression data of prostate hyperplasia tissue and prostate tissue, and the differentially expressed genes (DEGs) were screened and visualized. Gene function annotation (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, gene set enrichment analysis (GSEA) were performed by using the cluster Profiler package and a protein-protein interaction (PPI) network was constructed by using the STRING database. The core genes were found by using Cytoscape software and cytohubb and MCODE plug-in. Results A total of 186 differential genes were obtained through the limma package, of which 64 were up-regulated genes and 122 were down-regulated genes in the BPH group. GO enrichment analysis showed that DEGs were mainly involved in smooth muscle cell proliferation, transfonning growth factor 13 response, extracellular matrix, glandular receptor activation, and signal pathway receptor activator activity. The enrichment analysis of KEGG signaling pathway revealed that DEGs were enriched in MAPK signaling pathway, renin secretion, EGFR tyrosine kinase inhibitor resistance, and PPAR signaling pathway, and the biological pathways analyzed by GSEA showed that DEGs were mainly involved in epithelial mesenchymal transition, MTORCl signaling pathway, fatty acid metabolism, oxidative phosphorylation. Ten hub genes, such as F ABP3, IGFl, MYLl, TTN, NEB, JUN, LPL, CD36, F ABP4, DMD were obtained in PPI analysis and screening. Conclusion The obtained target genes, from the bioinformatics analysis of GEO database including multi-dimensional enrichment analysis and construction of protein interaction network, the differentially expressed genes, biological processes and enrichment signal pathways, may become potential target molecules for the treatment of BPH. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Clinical Healthcare is the property of Chinese Journal of Clinical Healthcare and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To screen the differentially expressed genes of lung metastasis of osteosarcoma by bioinformatics, and explore their functions and regulatory networks., Methods: The data set of GSE14359 was screened from GEO database(http://www.ncbi.nlm.nih.gov/gds) and the differentially expressed gene(DEG) was identified using GEO2R online tool. Download osteosarcoma disease related miRNAs from the online HMMD database(http://www.cuilab.cn/hmdd) and then FunRich software was used to predict the target gene, intersects with DEG to obtains the target gene. The miRNA-mRNA relationship pairs were formed according to the targeted joints, then the data was imported into Cytoscape for visualization, DAVID was used to performe GO and KEGG analysis on target genes, STRING was used to construct PPI network, Cytoscape visualization, CytoHubba plug-in screening central genes and online website for expression and survival analysis., Results: Total 704 DEGs were identified, consisting of 477 up-regulated genes and 227 down regulated genes. FunRich predicted 7 888 mRNAs and 343 target genes were obtained through intersection of the two. KEGG analysis showed that it was mainly involved in focal adhesion, ECM receptor interaction, TNF signal pathway, PI3K-Akt signal pathway, IL-17 signal pathway and MAPK signal pathway. Ten central genes (CCNB1, CHEK1, AURKA, DTL, RRM2, MELK, CEP55, FEN1, KPNA2, TYMS) were identified as potential key genes. Among them, CCNB1, DTL, MELK were highly correlated with poor prognosis., Conclusion: The key genes and functional pathways identified in this study may be helpful to understand the molecular mechanism of the occurrence and progression of lung metastases from osteosarcoma, and provide potential therapeutic targets.

Objective To analyze the relationship between protein phosphatase 2A catalytic subunit alpha (PPP2CA) expression and prognosis and immune infiltration in colorectal cancer (CRC) patients, and further explore the mechanism about the development and progression of CRC. Methods The differences in PPP2CA expression levels between CRC tissues and normal tissues were analyzed using the gene chip database Oncomine and The Tumor Immune Estimation Resource (TIMER) database. The impact of PPP2CA expression levels on the prognosis of CRC patients was analyzed using The University of Alabama at Birmingham Cancer data analysis portal (UALCAN) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. To further understand the role of PPP2CA in CRC, the co-expression network of PPP2CA was constructed using LinkedOmics platform, followed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Besides, the correlation between PPP2CA and immune infiltration was analyzed using TIMER and GEPIA databases. The gene mutation of PPP2CA in colon adenocarcinoma (COAD) were analyzed using c-BioPortal platform. Results PPP2CA was down-regulated in CRC tissues compared with normal tissues, and higher PPP2CA expression indicated better Overall Survival (OS) and Progression-Free Survival (PFS). In COAD, the expression level of PPP2CA was positively correlated with immune infiltrating cells including CD8 + T cells, neutrophils and dendritic cells. However, certain immune cell markers including CD19 and CD38 in B cells, NOS2 in M1 macrophages, Arginase 1 (ARG1) and Mannose Receptor C-Type 1 (MRC1) in M2 macrophages, Human Leukocyte Antigen G (HLA-G) and CD80 in Tumor Associated Macrophage (TAM) and CD14 and Fc Gamma Receptor 3A (FCGR3A) in monocytes, showed a different pattern of PPP2CA-associated immune infiltration. In other words, PPP2CA expression level was significantly associated with B cells, macrophages, monocytes, TAM, Th1 cells, Th2 cells, regulatory T cells, exhausted T cells and neutrophils in both COAD and rectum adenocarcinoma (READ). Conclusion PPP2CA is down-regulated in CRC tissues and closely correlated with immune infiltration.

Objective To explore the potential of the cell surface receptor c-Met as an effective target for chimeric antigen receptor T-cell (CAR-T) therapy in colorectal cancer. Methods The bioinformatics was used to analyze the specific expression of c-Met in colorectal adenocarcinoma (COAD) and its clinical significance. c-Met protein expression was detected by immunohistochemistry in tumor tissues obtained from colorectal cancer patients. Flow cytometry was utilized to assess the expression of c-Met in the HCT116 human colorectal cancer cell line. Additionally, primary T cells isolated from human peripheral blood mononuclear cells (PBMCs) were transduced with a lentivirus to generate second-generation CAR-T cells targeting c-Met, followed by an observation of the inhibitory effects of these c-Met-targeted CAR-T cells on HCT116 cells. Results Immunohistochemistry and bioinformatics data both demonstrated that c-Met was over-expressed in COAD, with patients exhibiting relatively lower expression showing better prognosis. In normal colonic tissue, c-Met was either expressed at low levels or not expressed. Flow cytometry revealed high expression of c-Met in HCT116 cells as well. The c-Met-targeted CAR-T cells were capable of specifically recognizing and targeting antigen-expressing tumor cells. CAR-T cells proliferated specifically under antigenic stimulation, exerting cytotoxic effects on cancer cells and releasing cytokines interleukin 2 (IL-2) and interferon-gamma (IFN-γ), thereby demonstrating the biological functions. Conclusion c-Met may be a promising therapeutic target in COAD; c-Met-targeted CAR-T cells demonstrate inhibitory effects on colorectal cancer cells in vitro.

Lectin receptor-like kinase(LecRLK) is a class of phytokinase with lectin conserved domain, which plays an important role in plant resistance to biological and abiotic stresses, as well as plant growth and development. Cannabis sativa is an important multi-purpose plant, widely used in food, textile, medicine, and other fields. Genome-wide screening and expression analysis of the LecRLK family of C. sativa were performed in this paper, so as to provide scientific reference for functional analysis of the LecRLK family of C. sativa. Based on BLAST and HMM methods, 93 LecRLKs were identified in the whole genome of C. sativa, including 69 G types, 23 L types, and one C types. Subsequently, a series of bioinformatics analyses were performed on the LecRLK family members, and the physicochemical properties of the protein of the LecRLK family members were initially revealed. The prediction of cis-acting elements of promoters in family members showed that family members were regulated by hormones and stress response. The expression analysis showed that some family members were highly expressed in the roots, which may participate in the process of stress resistance. Several members were highly expressed in female flowers and may be involved in female flower development. This study provides a theoretical basis for further study of LecRLK gene function. Meanwhile, the expression analysis screens candidate LecRLK members who may participate in the resistance of C. sativa, which provides a theoretical basis for the subsequent selection of C. sativa varieties against resistance.

Objective To conduct comparative proteomics study between the stenotic and the normal ureteral tissues adjacent to the stenotic ureter in children with ureteropelvic junction ( UPJ) stenosis, and explore the etiology and pathogenesis of congenital UPJ stenosis. Methods 30 children with congenital UPJ stenosis underwent Anderson-Hynes operation. The ureteral tissue of the narrow segment (group A) and the normal ureteral tissue adjacent to the distal end of the stenosis ( group B) were taken immediately after the operation. A relative quantitative method of high-throughput proteomics based on tandem mass tag ( TMT) was used to screen the differentially expressed proteins in these two groups. And then the targeted proteomics quantitative verification of the screened differential proteins was carried out by parallel reaction monitoring ( PRM) . Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of genes and genomics (KEGG) pathway were enriched and analyzed by bioinformatics method, and protein-protein interaction ( PPI) network was analyzed. Results A total of 6093 proteins were identified in the two groups of specimens, including 160 differential proteins, of which 65 were up-regulated and 95 were down-regulated. Among the 9 target proteins subjected to PRM relative quantitative analysis, the ratio of protein content of 7 proteins including carbonic anhydrase 1 in group A and group B was less than 1 in the quantitative results of PRM and TMT; Glypican The ratio of protein content of -6 and RNA-binding proteins with multiple splicing in group A to group B was greater than 1 in the quantitative results of PRM and TMT. GO functional enrichment analysis found that the GO functional enrichment of differentially expressed proteins in the two groups in biological processes such as humoral immune response, anti-microbial humoral response, response to fungi, defense response to fungi, and defense response to bacteria were significantly higher. High level of significance( P < 0. 05) . The results of KEGG pathway enrichment analysis showed that the enrichment of 20 signaling pathways including nitrogen metabolism and PPAR signaling pathway had a high significant level ( P < 0. 05) . In the PPI network, the most connected proteins were: neutrophil elastase (connectivity of 9) and cathepsin antimicrobial peptide (connectivity of 8) . Conclusion The results of comparative proteomics suggest that the pathogenesis of congenital UPJ stenosis is related to microbial infection, which provides a reference for further study on the etiology and pathogenesis of this disease. [ABSTRACT FROM AUTHOR]

Nervous system diseases are associated with complexity and diversity. As a result, the prognosis of patients deeply depends on physicians' clinical experience and their diagnosis and treatment level. With the exponential growth of medical big data and the development of statistical analysis tools, more researchers discover the pathogenesis of diseases and assist clinical process through the mining of big data, so as to improve the diagnosis, treatment, and prognosis of nervous system diseases. This paper elaborates the application of three kinds of medical big data in nervous system diseases, including structured data, radiomics, and bioinformatics. doi：10.3969/j.issn.1672⁃6731.2021.03.002

Objective To explore the differences in gene expression and altered biological processes in patients with tuberculosis based on bioinformatics methods,and to provide a basis for the diagnosis and treatment of tuberculosis.Methods The National Center for Biotechnology Information′s Gene Expression Database was searched in March 2021 for tuberculosis-related gene microarrays,and GSE29536 and GSE42834 microarray data were downloaded.Differential genes were analyzed online using GEO2 Rand bioinformatics.R language package was used to conduct gene ontology functional analysis and kyoto encyclopedia of genomes（KEGG）pathway enrichment.Protein interactions were analyzed using the STRING database,and key（hub）genes were analyzed using the Cytoscape software.Results A total of 166 differential genes were obtained,including 114 up-regulated genes and 52 down-regulated genes.They were mainly enriched in biological processes such as defense against viruses,immune response and innate immune response,mediated molecular functions such as protein binding and adenosine triphosphate binding,and they were enriched in cytoplasm,cytosol,plasma membrane and cell components such as mitochondria.The KEGG pathway was mainly enriched in signalling pathways such as influenza A,herpes simplex and measles.Signal transducer and activator of transcription 1（STAT1）,ISG15 and OAS1 expression were up-regulated,with statistically significant differences（P<0.05）.Conclusion STAT1,CXCL10,interferon regulatory factor 7,ISG15,IFIH1,IFIT1,IFIT3,GBP1,OAS1 and OAS2 are the most relevant characteristic genes in TB patients.Signaling pathways such as immune response and defense against viruses are closely related to TB.Upregulation of STAT1,ISG15 and OAS1 expression provides important ideas for subsequent studies [ABSTRACT FROM AUTHOR]

Objective: To explore the expression and its clinical significance of MECOM in ovarian cancer. Methods: The data about MECOM was collected from Oncomine and GEPIA databases; cBioportal, Coexpedia and STRING database were used to analyze the mutation, co-expression and interacting proteins of MECOM in ovarian cancer. Kaplan-Meier Plotter was used to analyze the relationship between the expression level of MECOM mRNA and the prognosis of patients with ovarian cancer. Results: With different types of cancer in Oncomine database, there were 353 studies related to MECOM, and 99 of them showed statistically significance (33 high-regulated and 99 low-regulated), including 10 studies on ovarian cancer, both show high MECOM expression. This result was also confirmed in the GEPIA database. Mutation analysis showed that 30% of ovarian cancer patients had mutations in MECOM gene, including missense mutation, fusion mutation and truncation mutation. Co-expression analysis showed that 275 genes were co-expressed. MECOM may interact with NR2E1, MTA1, HDAC1, TP53, PPARG, EZH2, JUN, MBD3, HDAC2 and CTBP1. The total survival rate of ovarian cancer patients in the group with high MECOM mRNA expression was lower than that with low MECOM mRNA expression (P=0.013). Conclusions: MECOM gene is overexpression in ovarian cancer, and its translated proteins interact with various proteins to exert biological effects. The expression level of MECOM mRNA is related to the survival prognosis of ovarian cancer patients, which is expected to provide a new idea for molecular targeted therapy of ovarian cancer. [ABSTRACT FROM AUTHOR]

Objective To elucidate the role and expression pattern of COL6A5 in lung adenocarcinoma (LUAD). Methods The expression pattern of COL6A5 in LUAD was detected through Oncomine database. The relationship between COL6A5 and the prognosis of LUAD patients was analyzed by GEPIA database. The qPCR assay was used to detect the expression of RNA demethylase ALKBH5 in lung adenocarcinoma tissue. The m6A sites on COL6A5 was confirmed by bioinformatics analysis and MeRIP-qPCR experiment. The inhibitory effect of ALKBH5 on COL6A5 was detected by qPCR and Western blot assy. Bioinformatics analysis and Transwell assay were performed to determine the role of COL6A5 in LUAD. Results Oncomine analysis of the online database showed that the expression of COL6A5 was significantly reduced in LUAD. GEPIA database analysis showed that the level of COL6A5 mRNA expression was significantly lower in LUAD tissue than that of normal tissue (P＜0.05). qPCR result showed that COL6A5 mRNA expression was lower in LUAD tissues than that of adjacent normal tissues in 27 LUAD patients. Compared to normal pulmonary epithelial cells, COL6A5 mRNA was significantly inhibited in LUAD cells (P＜0.05). Furthermore, bioinformatics analysis and MeRIP-qPCR assay confirmed that there were m6A sites on COL6A5 mRNA. The expression level of ALKBH5 mRNA was higher in LUAD than that of adjacent normal tissues, and it was negatively correlated with COL6A5 mRNA expression (r=-0.599, P＜0.01). Knocking down ALKBH5 significantly enhanced COL6A5 expression in H1299 cells. After the analysis of co-expressed genes with COL6A5, it was found that COL6A5 may be involved in the regulation of life activities including epithelial transition, hemostasis, and cell surface interaction in LUAD cells. Results of Transwell assay and Western blot assay confirmed that the over-expression of COL6A5 could inhibit the invasion of H1299 cells. Conclusion The down regulated COL6A5 by ALKBH5 can inhibit the invasion metastasis of LUAD cells. [ABSTRACT FROM AUTHOR]

Objective To screen and clarify the mechanism of long non-coding RNA CD48-AS (lncRNA CD48-AS) and the antisense complementary molecule CD48 in the process of N-3-oxododecanoyl-L-homoserine lactone (3-O-C12- HSL) hampering the maturation of human monocyte-induced dendritic cells (Mo-DCs). Methods Mo-DCs were extracted from the peripheral blood of healthy individuals, and the immature Mo-DCs were divided into three groups for lncRNA chip analysis: the negative control group (0.1% DMSO), the lipopolysaccharide (LPS) positive control group (100 μg/L LPS) and the treatment group (100 μg/L LPS+40 μmol/L 3-O-C12-HSL). The natural antisense lncRNA expressed more than 5 times in the lncRNA expression profile were screened for Cluster analysis. The natural antisense lncRNA CD48-AS was screened. Immature Mo-DCs were divided into the negative control group, the LPS positive control group, and the 3-O-C12-HSL treatment group (5, 10, 25 μmol/L 3-O-C12-HSL). The expression of lncRNA CD48-AS and antisense molecule CD48 were measured using quantitative PCR in each group. The complementary regions of lncRNA CD48-AS and CD48 and the protein coding function of lncRNA CD48-AS were analyzed through bioinformatics. Whether lncRNA CD48-AS affected the expression of CD48 by forming a dimer with CD48 was verified through the ribonuclease protection experiment (RPA). Preliminary experiments were carried out on the localization of lncRNA CD48-AS in cells. Results The lncRNA expression profile of Mo-DCs showed specific changes after 3-O-C12-HSL treatment. 3-O-C12-HSL down-regulated the expression of lncRNA CD48-AS and its antisense target molecule CD48 induced by LPS. Bioinformatics analysis showed that lncRNA CD48-AS was a non-coding RNA without protein coding function. lncRNA CD48-AS may form RNA dimers with CD48 to reduce the degradation of CD48 by RNase and increase the expression of CD48. lncRNA CD48-AS was mainly located in the nucleus in Mo-DCs, with less expression in cytoplasm. Conclusion 3-O-C12-HSL can inhibit the maturation of Mo-DCs by down-regulating lncRNA CD48-AS and then affecting the expression of CD48. [ABSTRACT FROM AUTHOR]

Objective To screen out and validate the abnormally expressed circular RNAs (circRNAs) in intrahepatic cholangiocarcinoma (iCCA) by comparing the circRNA microarray results of iCCA tissue and adjacent tissue, and to investigate their potential mechanism in iCCA. Methods Tumor tissue specimens were collected from three patients with iCCA who were admitted from July to December, 2019, and microarray hybridization was used to measure the differential expression of circRNAs between iCCA tissue and adjacent tissue. A total of 15 patients with iCCA who were treated during the same period of time were enrolled, and quantitative real-time PCR was used for validation of differentially expressed circRNAs. A bioinformatics analysis was performed to identify the downstream molecules of differentially expressed circRNAs, and quantitative real-time PCR was used for validation of potential molecules. The paired samples t-test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results With 1.5-fold as the cut-off value for differential expression, there were 171 upregulated circRNAs and 104 downregulated circRNAs in iCCA tissue compared with the adjacent tissue. With 3-fold as the cut-off value for differential expression, there were 10 upregulated circRNAs (circRNA_002172, circRNA_002144, circRNA_001588, circRNA_000166, circRNA_000585, circRNA_000167, circRNA_402608, circRNA_006853, circRNA_001589, and circRNA_008882) and 3 downregulated circRNAs (circRNA_406083, circRNA_104940, and circRNA_006349) compared with the adjacent tissue. Pathologically confirmed iCCA tissue samples and adjacent tissue samples were collected from 15 patients, and quantitative real-time PCR was used for the validation of differentially expressed circRNAs; the results showed that circRNA_000585 was significantly upregulated in iCCA tissue (t=3.607, P=0.003). Further bioinformatics analysis showed that circRNA_000585/miR-615-5p/AMOT/YAP might be the potential pathway involved in the pathogenesis of iCCA, and quantitative real-time PCR showed that for this pathway, miR-615-5p was significantly downregulated in iCCA (t=5.724, P < 0.001) and AMOT and YAP were significantly upregulated in iCCA (t=2.664 and 2.986, P=0.019 and 0.009 8). Conclusion Abnormal expression of various circRNAs is observed in iCCA, among which circRNA_000585 is significantly upregulated in iCCA and may play an important role in the pathogenesis of iCCA via the circRNA_000585/miR-615-5p/AMOT/YAP pathway. [ABSTRACT FROM AUTHOR]

Objective To investigate the possible pathogenesis and clinical feature of mitochondrial encephalomyopathy with lactic acidemia and stroke ⁃ like episodes (MELAS) on the molecular level by bioinformatics analysis of differential expression genes. Methods The microarray information ofthe wild ⁃ type cell lines and the mutant cell line with high expression of mtDNA A3243G locus was downloaded from the GEO database, and the differential expression genes were obtained by the R platform. Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed, and paired comparison of gene microarray analysis to screen out the same differently expressed genes, and the protein ⁃ protein interaction (PPI) network was used to find the relation of key genes between MELAS and clinical symptoms. Results A total of 563 differential expression genes were obtained, of which 250 genes were up ⁃ regulated and 313 genes were down ⁃ regulated. GO enrichment analysis showed that the differential expression genes were mainly involved in the extracellular matrix (ECM) binding biological process, and KEGG pathway involved in phosphatidylinositol 3 ⁃ kinase (PI3K) ⁃ serine/threonine kinase (AKT) signaling pathway, tranforming growth factor ⁃ β ( TGF ⁃ β ) sign a ling pathw ay, ECM receptor interaction pathway. Using the STRING platform, 9 hubs genes including GNG2 , SDC2 , ANXA1 , FN1, TNC, CYR61, IGFBP3, LTBP1 , SERPIND1 had been found. PAMR1 , GLRX5 , SNCA other common differential genes were obtained by paired comparison of 3 groups of gene microarrays. Conclusions According to the above results, the PI3K⁃AKT signaling pathway, TGF⁃β signaling pathway, ECM receptor interaction pathway and the biological processes of ECM binding were involved in the process of the mitochondrial energy metabolism, which might be related to the pathogenesis of MELAS. GNG2, TNC , LTBP1, PAMR1, GLRX5, SNCA and other hubs genes might be related to the clinical manifestations of MELAS. DOI：10.3969/j.issn.1672⁃6731.2020.04.015

Objective: To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs. Methods: Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing. Results: An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P =0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes ( CTSC , LAMB3 , CYP2S1 , TRPV4 , ARHGAP21 , PTHLH , CDH26 , MRPS6 , TENM4 , FAM110C , NCKAP5 , SAMD3 , and PTCHD4 ). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P =0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC + cells in CRS. Conclusion: This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.

This study aims to explore the diagnostic value of inflammation-related genes in peripheral blood mononuclear cells in bronchopulmonary dysplasia (BPD). By using bioinformatics analysis, three datasets including GSE32472, GSE125873, and GSE220135, which contain whole-genome expression profile data of 251 neonates, were included. The GSE32472 dataset was used as a training dataset to detect differentially expressed genes between non-BPD and BPD neonates in peripheral blood mononuclear cells. The gene enrichment analysis (GSEA) was used to detect the pathway enrichment of up-regulated genes in BPD newborns. The main regulatory factors analysis (MRA) algorithm was used to filter the main regulatory genes in the inflammation-related pathway (GO:0006954). After obtaining the main regulatory genes, the expression of the main regulatory genes in the GSE32472, GSE125873, and GSE220135 datasets was detected. Through the logistic regression model, risk scoring was conducted for neonates, and the risk scores of non-BPD and BPD neonates were compared. Lastly, the classification performance of the model was evaluated using the area under the curve (AUC). The results showed that compared with non-BPD neonates, there were 486 up-regulated genes and 433 down-regulated genes in the peripheral blood mononuclear cells of BPD neonates. The inflammation-related pathway was highly enriched in the up-regulated genes. Ultimately, phospholipase C beta 1 (PLCB1), nidogen 1 (NID1), serum response factor binding protein 1 (SRFBP1), centrosomal protein 72 (CEP72), excision repair cross complementation group 6 like (ERCC6L), and peptidylprolyl isomerase like 1 (PPIL1) were identified as the main regulatory genes. The prediction model's calculation formula for risk score was PLCB1×0.26+NID1×0.97+SRFBP1×1.58+CEP72×(-0.36)+ERCC6L×2.14+PPIL1×0.67. The AUCs in the GSE32472 test dataset, GSE125873 dataset, and GSE220135 dataset were 0.88, 0.86, and 0.89, respectively. This prediction model could distinguish between non-BPD and BPD neonates. In conclusion, the prediction model based on inflammation-related pathway genes has a certain diagnostic value for BPD.

Objective: To explore differentially expressed endoplasmic reticulum stress-associated genes (ERSAGs) in aortic dissection (AD) and their correlations with immune cell infiltration to identify new therapeutic targets for AD., Methods: Two AD mRNA expression datasets (GSE190635 and GSE98770) were downloaded from GEO database for analysis of differentially expressed genes between the aorta of AD patients and normal aorta using R software. ERSAGs dataset was downloaded from GeneCards website, and GeneMANIA database was used to analyze the protein-protein interaction network of the differentially expressed ERSAGs and the proteins interacting with these genes. Based on GSE98770 dataset we analyzed the distributions of 22 immune cells within the aortic wall of AD patients using CIBERSORT package of R software. Surgical aortic wall specimens were obtained from 10 AD patients and 10 non-AD patients for detecting AGER mRNA expression using qRTPCR, and the upstream transcriptional factors, miRNAs, and chemicals targeting AGER were analyzed using the TRRUST database and NetworkAnalyst database., Results: Bioinformatic analysis suggested significant differential expression of AGER in AD, which interacted with 20 proteins involved in pattern recognition receptor signaling pathway, positive regulation of DNA-binding transcription factor activity, myeloid leukocyte migration, leukocyte migration, and regulation of the I-κB kinase/NF-κB signaling. In AD, AGER expression level was positively correlated with Treg cell abundance ( r =0.59, P < 0.05). The results of qRT-PCR demonstrated significantly lower expression of AGER mRNA in AD than in non-AD patients (1.00±0.30 vs 1.76±0.68, P < 0.05). ROC curve analysis showed that at the cut-off value of 1.335, AGER had an AUC of 0.86 (95% CI : 0.67-1.00, P = 0.0073) for predicting AD. Three transcriptional factors, 3 miRNAs, and 27 chemicals were predicted in the AGER regulatory network., Conclusion: AGER is lowly expressed in the aorta of AD patients and may influence the occurrence of AD through Treg cells.

Objectives: To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE -/- mice., Methods: The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE -/- mice. Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers., Results: Proteomic analysis showed that there were 43 significantly up-regulated and 58 significantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group. Among them, GBP2, TAOK3, TFR1 and UCP1 were biomarkers with great diagnostic potential. KEGG pathway enrichment analysis indicated that ferroptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model. The mmu&#95;circ&#95;0001567 / miR-7a / Tfr-1 and mmu&#95;circ&#95;0001042 / miR-7a / Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model., Conclusions: Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferroptosis. Four potential biomarkers are selected for myocardial injury diagnosis, providing a new direction for sudden cardiac death (SCD) caused by hyperlipidemia combined with the restraint stress.

Objective: To investigate the genetic and expression characteristics of transcription factor IIH (TFIIH) in pre-initiationcomplex in prostate cancer (PCa) and its relationship with prostate cancer progression. Methods: Analyzing the expression characteristics and clinical signification of TFIIH subunits about 495 cases of PCa and 52 cases of adjacent cancer in The Cancer Genome Atlas-Prostate adenocarcinoma (TCGA-PRAD) database. PCa microarray chip was used to verify the correlation between the key factor General Transcription Factor IIH Subunit 4 (GTF2H4) in TFIIH and clinical features. Results: The 495 patients with PCa were (61.01±6.82) years old.The mRNA expression of ERCC3、GTF2H4 and MNAT1 were high in PCa tissues with GS≥8( P <0.05). The expression of GTF2H4 and MNAT1 were relevant to the pathological stages( P <0.05). High expression of GTF2H4 has higher biochemical recurrence (BCR) rate in PCa patients( HR =2.47, 95% CI :1.62-3.77, P <0.001), which has better predictive effect of BCR in PCa patients(The 3rd, 5th, and 7th year AUC all>0.7) than other subunits, and it has been verified in four additional databases. Single-factor Cox regression analysis showed that GTF2H4 were risk factors for BCR ( HR =2.470, 95% CI :1.620-3.767, P <0.001) and GTF2H5 were protective factors( HR =0.506,95% CI : 0.336-0.762, P =0.001). The results of immunohistochemical staining showed that the protein expression of GTF2H4 was correlated with the clinical features of PCa patients.The differences of the above results were statistically significant. Conclusion: GTF2H4, the key factor of TFIIH, is highly expressed in PCa and indicates a poor prognosis.

Pulmonary arterial hypertension (PAH) is a severe disease characterized by abnormal pulmonary vascular remodeling and increased right ventricular pressure load, posing a significant threat to patient health. While some pathological mechanisms of PAH have been revealed, the deeper mechanisms of pathogenesis remain to be elucidated. In recent years, bioinformatics has provided a powerful tool for a deeper understanding of the complex mechanisms of PAH through the integration of techniques such as multi-omics analysis, artificial intelligence, and Mendelian randomization. This review focuses on the bioinformatics methods and technologies used in PAH research, summarizing their current applications in the study of disease mechanisms, diagnosis, and prognosis assessment. Additionally, it analyzes the existing challenges faced by bioinformatics and its potential applications in the clinical and basic research fields of PAH in the future.

Objective: To explore the genetic basis for a patient with autosomal dominant retinitis pigmentosa (RP)., Methods: A male patient with RP treated at Gansu Provincial Maternal and Child Health Care Hospital in September 2019 was selected as the study subject. Clinical data was collected. Peripheral blood samples of the patient and his parents were subjected to whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis., Results: The patient, a 29-year-old male, developed night blindness, amblyopia, visual field defects and optic disc abnormalities since childhood. Gene sequencing revealed that he has harbored a heterozygous c.942G>C (p.Lys314Asn) variant of the IMPDH1 gene, which was inherited from his mother, whilst his father was of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.942G>C variant was predicted as likely pathogenic (PM1+PM2&#95;Supporting+PP3+PP1)., Conclusion: The c.942G>C (p.Lys314Asn) variant in the IMPDH1 gene probably underlay the RP in this patient.

In the new stage of trans-omics and trans-subjects for medicinal plants, it is an urgent need to integrate big data, provide interactive applications, and form a unified and multi-level research system and big data platform. Dao-di medicinal material, as an important source of medicinal plants, is a unique quality concept and comprehensive standard of tranditional Chinese medicine(TCM). Several databases have been developed in China and abroad, such as the Encyclopedia of Traditional Chinese Medicine(ETCM) and the Global Pharmacopoeia Genome Database(GPGD). Yet, most databases do not provide multi-dimensional data, including geographic data, phenotype data, compound data, and genetic data. Sichuan, known as the hometown of TCM therapies and the treasure trove of TCM, is the most representative region of medicinal plant diversity in China. According to the latest data of the fourth national survey of TCM resources, there are more than 8 000 TCM and 86 Dao-di medicinal materials in Sichuan province. Based on resource census data and relevant achievements, this study constructed the bioinformatics database of medicinal plants and the visual analysis platform of production layout by taking the Dao-di medicinal materials in Sichuan province as an example, covering geographic data, phenotype data, compound data, and genetic data. It effectively integrates multi-dimensional data of Dao-di medicinal materials and provides different levels of data interaction applications. The platform is the first large-scale multi-dimensional database and visual platform of Dao-di medicinal materials in Sichuan province, which serves as an essential resource for germplasm resources identification, decomposition of biosynthetic pathways, molecular breeding of varieties and provides medicinal plant resource information and data support for development and utilization of medicinal plants in China and abroad.

This study investigated the anti-aging mechanism of Xiyangshen Sanqi Danshen Granules based on metabonomics, network pharmacology, and molecular docking. The aging mice model was induced by intraperitoneal injection of D-galactose(D-gal). Mice were randomly divided into a control group, model group, melatonin group(MT group), and low, medium, and high dose groups of Xiyangshen Sanqi Danshen Granules(XSD-L, XSD-M, and XSD-H). An open-field experiment was conducted, and the expression of cell cycle arrest proteins(p16) and phosphorylated histone family 2A variant(γH2AX) in the brain tissue was detected by immunofluorescence. The expression of interleukin-1β(IL-1β) and interleukin-6(IL-6) in the brain tissue was detected by enzyme-linked immunosorbent assay(ELISA). Metabolomics analysis was performed on the serum of mice in control, model, and XSD-H groups to obtain metabolic processes and metabolites. The effective chemical components and potential targets of Xiyangshen Sanqi Danshen Granules were predicted through network pharmacology, and the network diagram of &quot;drug-effective chemical components-key targets&quot; was constructed. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were carried out, and a protein-protein interaction(PPI) network was constructed to clarify the anti-aging mechanism of Xiyangshen Sanqi Danshen Granules. The results showed that the Xiyangshen Sanqi Danshen Granules could significantly improve the aging degree of D-gal mice, significantly improve the total motion distance and the mean motion speed of D-gal mice, and reduce the rest time. In addition, Xiyangshen Sanqi Danshen Granules could significantly reduce the protein levels of IL-6 and IL-1β and the expression of p16 and γH2AX in D-gal mice. Compared with the model group, 66 differential metabolites(DMs) were significantly up-regulated, and 91 DMs were down-regulated in the XSD-H group. Moreover, four key metabolic pathways(tryptophan metabolism, glycerophospholipid metabolism, pyrimidine metabolism, and lysine degradation) and 16 biomarkers(lysine, tryptophan, indoleacetaldehyde, PCs, LysoPCs, 3-hydroxyanthranilic acid, melatonin, etc) were screened out. 58 main active components and 62 key targets of Xiyangshen Sanqi Danshen Granules were screened by network pharmacology. The GO functional enrichment analysis found the positive regulation of gene expression, drug response, etc. KEGG pathway enrichment screening involved diabetic complications-related AGE-RAGE signaling pathway, hypoxia inducible factor-1 signaling pathway, etc. Through the PPI network and molecular docking, six potential core targets of STAT3, MAPK1, MAPK14, EGFR, FOS, and STAT1 were screened.

Objective To investigate the expression of long non-coding RNA (lncRNA) brain cytoplasmic RNA 1 (BCYRN1) in lung adenocarcinoma cell lines A549 and H1299 and its effects on cell cycle, apoptosis, invasion and migration, then to analyze the relationship between the expression of BCYRN1 and clinicopathological features and prognosis of patients with lung adenocarcinoma. Methods Normal lung epithelial cells BEAS-2B and lung adenocarcinoma cells GGAGCGAA549 and H1299 were cultured. Real-time quantitative polymerase chain reaction (qPCR) was used to detect the expression level of BCYRN1 in normal cells and lung adenocarcinoma cells. BCYRN1 down-regulation and control plasmid were transfected into H1299 lung adenocarcinoma cells, respectively. The cell cycle and apoptosis were analyzed by flow cytometry. Changes of cell invasion and migration ability were detected by scratch test and Transwell test. Combined with the Cancer Genome Atlas (TCGA) database, the correlation between BCYRN1 expression and clinicopathological characteristics of patients with lung adenocarcinoma was analyzed. Cox regression was used to analyze the relationship between BCYRN1 expression and patient prognosis by using the lncRNAs from cancer arrays (lnCAR) database. Results The expression level of BCYRN1 was significantly higher in lung adenocarcinoma cells than that in normal lung epithelial cells (P＜0.05). Flow cytometry analysis indicated that S phase arrest and the proportion of cells in the apoptotic phase increased in the BCYRN1 knockdown cells. The scratch test and Transwell test showed that the invasion and migration of H1299 cells reduced in BCYRN1 knockdown group. Bioinformatics analysis showed that the expression of BCYRN1 was associated with N stage and tumor stage (P＜0.05), and the overall survival of patients with high BCYRN1 expression was significantly shortened. Conclusion BCYRN1 is highly expressed in lung adenocarcinoma cells. BCYRN1 knockdown inhibits the invasion and migration of lung adenocarcinoma and causes cell cycle arrest. The high expression of BCYRN1 is associated with N stage and tumor stage of lung adenocarcinoma. The prognosis of patients with high expression of BCYRN1 is poor. [ABSTRACT FROM AUTHOR]

To investigate the expression of the nucleolar spindle - associated protein 1 ( NUSAPl ) gene in hepatocellular carcinoma ( HCC) and its effect on clinical prognosis. Methods HCC microarray datasets GSE57957, GSE14520, GSE22058, GSE46444, GSE54236, GSE36376, GSE64041, GSE76297, GSE76427, and GSE102079 were downloaded from the Gene Expression Omnibus (GEO) database, and HCC RNA - Seq data were downloaded from The Cancer Genome Atlas ( TCGA ) . R software 4. 0 was used to investigate the difference in the expression of NUSAPl between HCC tissue and adjacent tissue. The t - distributed stochastic neighbour embedding ( t - SNE) method was used to perform dimensionality reduction of single - cell sequencing data and analyze the difference in the expression of NUSAPl between HCC tissue and adjacent tissue. HCC tissue samples and adjacent tissue samples were collected from 42 patients with hepatitis B - related HCC who underwent liver transplantation in The Affiliated Hospital of Qingdao University from January 2018 to November 2019, and related clinical and pathological data were collected to analyze their correlation with the expression of the NUSAPl gene. The chi - square test was used for comparison of paired data. The Kaplan - Meier method was used to analyze the correlation of the expression level of NUSAPl with overall survival rate and disease - free survival, and the log - rank test was used for survival difference analysis; the results were visualized using Graphpad prim 7. Results NUSAPl was highly expressed in HCC tissue in GEO and TCGA datasets ( P < 0. 001). The cells from HCC tissue had a significantly higher proportion of cells with high NUSAPl expression than those from adjacent tissue. NUSAPl showed high expression in HCC tissue of 29 patients and low expression in HCC tissue of 13 patients, and there were significant differences in Child - Pugh class, TNM stage, and Okuda stage between the high - expression group and the low - expression group (x² = 5. 469,6. 836 and 4. 617, all P < 0. 05). The HCC patients with high expression of NUSAPl had significantly lower overall survival rate and disease - free survival rate than those with low expression; compared with the patients with high expression, the patients with low expression had significantly higher 1 -, 3 -, and 5 - year survival rates (92. 96%/83. 80%/76. 76% vs 76. 76%/67. 60%/64. 78%, P < 0. 05), and the patients with high expression had a significantly shorter median survival time than those with low expression ( 61. 7 months vs 108. 6 months, P <0. 05). Conclusion NUSAPl is highly expressed in cells from HCC tissue and may be used as a potential marker for poor prognosis of patients with hepatitis B - related HCC. [ABSTRACT FROM AUTHOR]

Objective To investigate the changes and potential effects of differentially expressed microRNAs (miRNAs) in the development and progression of liver injury in a mouse model of autoimmune hepatitis (AIH) induced by concanavalin A (ConA). Methods Eight healthy male specific pathogen - free C57BL/6 mice were randomly divided into model group and control group, with four mice in each group. The mice in the model group were given tail vein injection of ConA 15 mg/kg, and those in the control group were given an equal volume of normal saline. All mice were sacrificed after 8 hours of modeling, Total RNA in liver tissue was extracted, gene microarray was used to screen out differentially expressed miRNAs, and target prediction and function analysis were performed for upregulated and downregulated miRNAs. The independent samples t - test was used for comparison of differentially expressed miRNAs between two groups. Results The principal component analysis showed that the inter - group difference of the data extracted by gene microarray met the conditions for further analysis. Compared with the control group, the model group had 31 upregulated miRNAs and 18 downregulated miRNAs in mouse liver, which had a regulatory relationship with 959 target genes (601 upregulated genes and 358 downregulated genes). GO analysis showed that in the model group, the target genes of the upregulated miRNAs mainly had the molecular functions such as “DNA binding” (P = 1. 47 × 10-6),participated in the biological processes such as “transcription, DNA - templated” (P = 2. 36 ×10-7),and were mainly enriched in the cellular components such as “neuronal cell body” (P = 5. 99 ×10-6),while the target genes of the downregulated miRNAs had the molecular functions such as “RNA polymerase II proximal promoter sequence - specific DNA binding” (P = 2. 49 ×10-6), participated in the biological processes such as “regulation of transcription, DNA - templated” (P = 1. 64 ×10-11), and were mainly enriched in the cellular components such as “nucleoplasm” (P = 4. 30 ×10-10). KEGG pathway enrichment analysis showed that the target genes of the upregulated miRNAs were mainly enriched in “Endocytosis” (P = 0. 000 4), while the target genes of the downregulated miRNAs were mainly enriched in the “Hippo signaling pathway” (P = 0. 004), and the above functional analysis results were statistically significant (P < 0. 05). Conclusion There are differentially expressed miRNAs in the pathogenesis of AIH, and these differentially expressed miRNAs can provide new targets for the clinical treatment of AIH. [ABSTRACT FROM AUTHOR]

Objective To investigate the differentially expressed proteins in the plasma exosome of acute - on - chronic liver failure ( ACLF) patients with different prognoses, to analyze their functions and biological processes, and to provide a basis for clinical diagnosis. Methods A prospective study was performed for 10 ACLF patients who were hospitalized and diagnosed in Beijing YouAn Hospital, Capital Medical University, from July 2019 to October 2019, and the patients were followed up for 90 days. The patients who died or received liver transplantation were enrolled as liver transplantation/ death group ( 5 patients), and the patients who survived were enrolled as survival group (5 patients). The Mann - Whitney U test was used for comparison of general data between the two groups. The label -free quantitative proteomic method was used for identification and quantitative analysis of plasma exosome proteins to screen out differentially expressed proteins, and a functional enrichment analysis was performed. R - 3. 5. 1 software was used to perform a hierarchical cluster analysis of differentially expressed proteins to analyze the biological processes involving these proteins. Results A total of 860 proteins were identified by the exosome proteomic analysis, and according to the criteria of upregulation > 1. 2 folds or downregulation > 1. 2 folds ( P < 0. 05), there were 116 differentially expressed proteins. Compared with the liver transplantation/ death group, the survival group had 62 upregulated proteins and 54 downregulated proteins. The bioinformatics analysis showed that these differentially expressed proteins mainly participated in immune reaction, signal transduction, vesicle - mediated transport, cell death, and cell proliferation and were closely associated with the signaling pathways including inflammatory response, carbohydrate and amino acid metabolism, hepatocyte injury, and hepatocyte regeneration. Conclusion Differentially expressed proteins screened out by the label - free quantitative proteomic method can be used as serological markers for the early diagnosis and prognostic evaluation of ACLF. [ABSTRACT FROM AUTHOR]

Objective To investigate the relative expression of miRNA⁃210⁃5P in serum of patients with carotid atherosclerotic stenosis (CAS) and to explore the function of miRNA⁃210⁃5P and its target genes using bioinformatics methods. Methods We selected 146 patients with CAS from July 2015 to September 2018 in our hospital. Reverse transcriptase⁃polymerase chain reaction (RT⁃PCR) was used to detect the relative expression of miRNA⁃210⁃5P in peripheral blood of all enrolled patients. The target genes were predicted by using TargetScan and CoMeTa databases. The target genes of miRNA⁃210⁃5P were enriched by Gene Ontology (GO) using DAVID data and were performed with KEGG Pathway analysis. Results Compared with non⁃CAS patients or normal subjects (control group, N = 60), the relative expression of miRNA⁃210⁃5P in the serum of CAS group was significantly increased(t=14.759, P=0.000). The relative expressions of serum miRNA⁃210⁃5P in severe stenosis group(N=31; q=23.028, P=0.000), moderate stenosis group (N=53; q=6.657, P=0.000) and mild stenosis group (N=62; q=42.612, P= 0.000) were higher than that in control group. The relative expressions of serum miRNA⁃210⁃5P in moderate stenosis group (q =34.538, P =0.000) and severe stenosis group (q =11.914, P =0.000) were significantly higher than that in mild stenosis group. There lative expressions of serum miRNA⁃210⁃5P in severe stenosis group was significantly higher than thatin moderate stenosis group (q=16.983, P=0.000). Receive roperating characteristic (ROC) curve showed that the miRNA⁃210⁃5P predicted the area under the curve (AUC) of moderate to severe stenosis in CAS to be 0.943, the sensitivity was 90.33% and the specificity was 92.54% at the best cutoff value of 1.495. Bioinformatics analysis showed there were 54 potential target genes of miRNA⁃210⁃5P, such as VEGFA, KCMF1, HMGCS1, KLF12, EFNA3, GIT2, etc. GO analysis showed that the target genes of miRNA⁃210⁃5P were involved in angiogenesis, neuronal development, positive regulation of DNA transcription factor activity, endothelial cell chemotaxis, cell migration and differentiation and adhesion processes. KEGG Pathway analysis displayed miRNA⁃210⁃5P target genes were mainly enriched in synaptic⁃directed factor signal transduction pathways. Conclusions The expression of miRNA⁃210⁃5P inperipheral blood of CAS patients is upregulated,and it may participate in the process of CAS occurrence and development by regulating multiple target genes and acting on synaptic⁃directed signaling pathways.

Objectives: Abnormal programmed cell death in immune cells is associated with autoimmune diseases, but the patterns of programmed cell death in systemic lupus erythematosus (SLE) and especially lupus nephritis (LN) remain unclear. This study aims to explore the association between SLE, LN, and immune cell death patterns., Methods: Bulk RNA sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) database. Bioinformatic analysis was conducted to explore the expression levels of genes related to 3 cell death patterns in peripheral blood mononuclear cells of SLE patients. Key cell subsets involved in the imbalance of cell death patterns were identified through scRNA-seq. Immunofluorescence was used to detect the expression levels of receptor interacting serine/threonine kinase 3 (RIPK3), mixed-lineage kinase domain-like protein (MLKL), phosphorylated MLKL (pMLKL), caspase 1 (CASP1), CD1c molecule (CD1C), C-type lectin domain containing 9A (CLEC9A), and X-C motif chemokine receptor 1 (XCR1) in dendritic cells (DC). scRNA-seq was performed on kidney tissues collected from LN patients and healthy controls (HC) at the Third Xiangya Hospital of Central South University, followed by bioinformatic analysis to identify key cell subsets involved in the imbalance of cell death patterns. Pseudotime analysis and ligand-receptor analysis were used to explore the differentiation direction and cell communication of different DC subsets. Transient transfection was used to transfect RAW264.7 cells with empty plasmid, empty plasmid+dsDNA (HSV-DNA), empty plasmid+200 μmol/L tert-butyl hydroperoxide (TBHP), stimulator of interferon genes (STING) shRNA plasmid, STING shRNA plasmid+dsDNA (HSV-DNA), and STING shRNA plasmid+200 μmol/L TBHP. Annexin V-mCherry and SYTOX Green staining were used to detect cell death in each group. Western blotting was used to detect the activation of CASP1, gasdermin D (GSDMD), RIPK3, and MLKL in each group., Results: Bioinformatic analysis showed an imbalance in 3 cell death patterns in SLE and LN patients: Pro-inflammatory pyroptosis and necroptosis were activated, while anti-inflammatory apoptosis was inhibited. The key cell subsets involved were DC subsets, particularly focusing on CLEC9A +cDC1. Immunofluorescence results showed that the expression levels of RIPK3, MLKL, and CASP1 in DCs were higher in the SLE group compared to the HC group. pMLKL and CASP1 expression levels in renal cDC1 marked by CLEC9A and XCR1 were higher in the LN group than in the HC group. Pseudotime analysis and ligand-receptor analysis suggested that the CLEC9A +cDC1 subset in LN kidney tissues originated from peripheral circulation. Annexin V-mCherry and SYTOX Green staining results showed that the number of dead cells decreased in the STING shRNA transfection group compared to the empty plasmid group in RAW264.7 cells. Western blotting results showed that the activation of CASP1, GSDMD, RIPK3, and MLKL was decreased in the STING shRNA transfection group compared to the empty plasmid group., Conclusions: This study provides novel insights into the role of CLEC9A +cDC1 in the imbalance of cell death patterns in SLE and LN.

Objective: To explore the core genes related to the diagnosis and prognosis of gastric cancer (GC) based on Gene Expression Omnibus (GEO) database and screen the molecular targets involved in the occurrence and development of GC., Methods: GC microarray data GSE118916, GSE54129 and GSE79973 were downloaded from GEO database, and the differentially expressed genes (DEGs) were screened. Enrichment analysis of the signaling pathways and molecular functions were preformed and protein-protein interaction networks (PPI) were constructed to identify the hub genes, whose expression levels and diagnostic and prognostic values were verifies based on gastric adenocarcinoma data from TCGA. The expression levels of these core genes were also detected in different GC cell lines using qRT- PCR., Results: Seventy-seven DEGs were identified, which encodes proteins located mainly in the extracellular matrix and basement membrane with activities of oxidoreductase and extracellular matrix receptor and ligand, involving the biological processes of digestion and hormone metabolism and the signaling pathways in retinol metabolism and gastric acid secretion. Nine hub genes were obtained, among which SPARC , TIMP1 , THBS2 , COL6A3 and THY1 were significantly up- regulated and TFF1 , GKN1 , TFF2 and PGC were significantly down-regulated in GC. The abnormal expressions of SPARC , TIMP1 , THBS2 , COL6A3 , TFF2 and THY1 were significantly correlated with the survival time of GC patients. ROC curve analysis showed that aberrant expression of TIMP1 SPARC , THY1 and THBS2 had high diagnostic value for GC. High expressions of SPARC , TIMP1 , THBS2 and COL6A3 were detected in GC tissues. In the GC cell lines, qRT- PCR revealed different expression patterns of these hub genes, but their expressions were largely consistent with those found in bioinformatics analyses., Conclusion: SPARC , TIMP1 , THBS2 and other DEGs are probably involved in GC occurrence and progression and may serve as potential candidate molecular markers for early diagnosis and prognostic evaluation of GC.

Background: Lung squamous cell carcinoma (LUSC) is a subtypes of non-small cell lung cancer (NSCLC). It has been reported that members of the protocadherin γ family can regulate tumor cell growth by inhibiting the Wnt signaling pathway. Protocadherin-gamma subfamily B4 (PCDHGB4) as a family member in LUSC was rarely reported. The aim of this study was to investigate the role and potential prognostic value of PCDHGB4 in the development of LUSC using bioinformatics methods., Methods: The Cancer Genome Atlas (TCGA), cBioPortal and UALCAN databases were used to analyze the expression, prognosis, clinicopathological features, immune cell infiltration, immune regulatory genes, immune checkpoint inhibitors (ICIs), and methyltransferases of PCDHGB4 in LUSC. At the single cell level, we analyzed the clustering results of cell subtypes and the expression of PCDHGB4 in different immune cell subpopulations. In addition, we compared the promoter methylation levels of PCDHGB4 in LUSC tissues and normal tissues and performed protein-protein interaction and mutation analysis. Finally, enrichment analysis was performed based on the differentially expressed genes., Results: Bioinformatics analysis results showed that the expression level of PCDHGB4 in LUSC tissues was lower than that in normal tissues. Survival analysis showed that increased PCDHGB4 expression was associated with poor prognosis. Single-cell sequencing analysis showed that PCDHGB4 was expressed in T cells, monocytes or macrophages, and dendritic cells. It was further found that PCDHGB4 played an important role in tumor immunity and confirmed that PCDHGB4 was associated with immune checkpoints, immune regulatory genes, and methyltransferases. Besides, enrichment analysis revealed that PCDHGB4 was involved in multiple cancer-related pathways., Conclusions: The expression of PCDHGB4 was low in LUSC. PCDHGB4 was related to the poor prognosis of patients, and PCDHGB4 was closely related to the infiltration and pathway of tumor immune cells. PCDHGB4 may be a potential prognostic marker and a new target for immunotherapy in LUSC.

Objective: To report on a case of Kabuki syndrome (KS) due to a novel variant of KMT2D gene., Methods: A child diagnosed with KS at the Fujian Children's Hospital on July 25, 2022 was selected as the study subject. Whole exome sequencing was carried out for the child and her parents. Candidate variant was validated by Sanger sequencing and bioinformatic analysis., Results: The child, a 4-month-old female, had presented with distinctive facial features, growth retardation, cardiac malformations, horseshoe kidney, hypothyroidism, and recurrent aspiration pneumonia. Whole exome sequencing revealed that she has harbored a heterozygous c.6285dup (p.Lys2096Ter) variant of the KMT2D gene. Sanger sequencing confirmed that neither of her parents had carried the same variant. The variant was previously unreported and may result in a truncated protein and loss of an enzymatic activity region. The corresponding site of the variant is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PS2+PM2&#95;Supporting)., Conclusion: The c.6285dup variant of the KMT2D gene probably underlay the KS in this child.

Objective: To explore the clinical phenotype and genetic characteristics of a child with Hypotrichosis 14., Methods: A child who had presented at the Henan Provincial People's Hospital on May 4, 2020 due to hair thinning was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples were collected from the child and her parents. Genomic DNA was extracted and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis., Results: The child, a 5-year-old female, had presented with thin, soft lanugo-like hair which was easy to fall off. The child was found to harbor compound heterozygous missense variants of the LSS gene, namely c.1609G>A (p.V537M) in exon 17 and c.802T>G (p.F268V) in exon 8, which were respectively inherited from her father and mother. Both variant sites were highly conserved, though based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as variants of unknown significance (PM2&#95;Supporting+PP3+PP4)., Conclusion: The c.1609G>A (p.V537M) and c.802T>G (p.F268V) compound heterozygous variants of the LSS gene probably underlay the clinical phenotype in this patient.