Objective To construct and validate a prediction model for urosepsis in patients after upper urinary tract stone surgery using various machine learning algorithms.Methods A total of 7 464 upper urinary tract stone patients who underwent surgery at the Sixth Affiliated Hospital of Guangxi Medical University from Jun.2018 to Jun.2023 were enrolled and randomly assigned to training(5 224 cases)or validation sets(2 240 cases)at a ratio of 7∶3.Among them,622(8.33%)cases developed urosepsis postoperatively.Six machine learning algorithms,including extreme gradient boosting(XGBoost),logistic regression,light gradient boosting machine(LightGBM),random forest(RF),adaptive boosting(AdaBoost),and gradient boosting decision tree(GBDT),were used to construct prediction models for postoperative urosepsis.The model's predictive ability and clinical benefits were evaluated using receiver operating characteristic(ROC)curves,Shapley additive explanation(SHAP)analysis,calibration curves,and decision curve analysis(DCA).Results The clinical features included body mass index(BMI),number of surgeries,heart rate,Barthel index,venous thrombo embolism(VTE)risk assessment,gender,American Society of Anesthesiologists(ASA)grade,urinary nitrite,and urinary leukocyte in the models.In the training set,the XGBoost,LightGBM,and RF models performed excellently,with area under curve(AUC)values of ROC curves reaching 1.00.In the validation set,the logistic regression model performed the best,with an AUC value of ROC curve of 0.76,showing good predictive stability and calibration.The AdaBoost and GBDT models followed with AUC values of 0.74 and 0.75,respectively,while the AUC values of the LightGBM,XGBoost,and RF models were 0.71,0.70,and 0.68.In terms of model interpretability,SHAP analysis showed the contribution of variables in a descending order as:heart rate,urinary leukocytes,gender,BMI,Barthel index,VTE risk assessment,urinary nitrite,number of surgeries,and ASA grade.Conclusion A logistic regression model for early risk prediction of postoperative urosepsis in upper urinary tract stone patients has been successfully constructed.This model has good predictive performance and calibration,and can effectively assist clinical diagnosis.

Objective:To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. Methods:A child diagnosed with CDCBM4 and epilepsy at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097).Results:The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c. 776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+ PS3+ PM2_Supporting+ PP3). Combining the child′s clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. Conclusion:Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c. 776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. METHODS: A child diagnosed with CDCBM4 and epilepsy at the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097). RESULTS: The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c.776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+PS3+PM2_Supporting+PP3). Combining the child's clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. CONCLUSION Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c.776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.
Humans ; Female ; Epilepsy/genetics* ; Malformations of Cortical Development/genetics* ; Infant ; Phenotype ; Exome Sequencing ; Microtubule-Associated Proteins/genetics*

WDFY1 is a member of the protein family containing the WD repeat and FYVE structural domains,acting as a junction that assists the recruitment of downstream molecules by Toll-like receptor 3/4(TLR3/TLR4)and promotes the body's natural anti-viral and anti-bacterial immune response.In recent years,the role of WDFY1 has been successively reported in various disease models,such as neurological diseases,autophagy and tumors.This paper aims to provide a comprehensive review of the current state of WDFY1 research,encompassing its expression distribution,cell biological function and its role in disease development,and take a prospect on the potential of WDFY1 as a target in rheumatoid arthritis.

WDFY1 is a member of the protein family containing the WD repeat and FYVE structural domains,acting as a junction that assists the recruitment of downstream molecules by Toll-like receptor 3/4(TLR3/TLR4)and promotes the body's natural anti-viral and anti-bacterial immune response.In recent years,the role of WDFY1 has been successively reported in various disease models,such as neurological diseases,autophagy and tumors.This paper aims to provide a comprehensive review of the current state of WDFY1 research,encompassing its expression distribution,cell biological function and its role in disease development,and take a prospect on the potential of WDFY1 as a target in rheumatoid arthritis.

Objective:To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. Methods:A child diagnosed with CDCBM4 and epilepsy at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097).Results:The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c. 776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+ PS3+ PM2_Supporting+ PP3). Combining the child′s clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. Conclusion:Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c. 776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.

Objective To establish a human tonsil organoid model and investigate the immunological effects of this tonsil organoid infected by influenza virus.Methods Human tonsil tissue removed by adenoid hypertrophy surgery were subjected to gradient centrifugation,and then the obtain cells were cultured in vitro with using a 2.5D-Transwell chamber in combination with IL-2 and B cell activating factor(Baff)to construct a human tonsil organoid.Single cell transcriptome sequencing(scRNA-seq)was used to analyze the distribution of influenza virus receptors in different cell subsets of the tonsil organoid.Immunofluorescence assay and flow cytometry were applied to detect the immunological effects of the tonsil organoid in 48 h after influenza virus infection.Results The tonsil organoids were established successfully using this 2.5D-Transwell culture technique.scRNA-seq analysis showed that the receptors for influenza virus were extensively distributed in nearly all of cell subsets of tonsil organoids.In 48 h after influenza virus infection,the tonsil organoids could generate a large amount of plasma cells and memory B cells to produce specific IgG antibodies.In addition,direct infection of the virus promoted the production of TNF-α and IL-2 from CD8+T cells and the secretion of TNF-α,IFN-γ and IL-2 by CD4+T cells.Conclusion The tonsil organoids can be established successfully and reach maturity at about the 6th day after culture.The receptors for influenza virus are widely distributed in human tonsil organoids.Influenza virus directly infects human T cells,leading to T cell activation and cytokine releasing.Moreover,influenza virus infection also promotes B cells differentiate into plasma cells and induce the secretion of IgG as well as the formation of memory B cells.

This study was designed to explore the transcription level,genome alteration,potential abnormal expression mechanism,prognostic value and the association with immune cells of the tetraspan MS4A6A(membrane-spanning 4A(MS4A)subfamily protein 6A)in pan-cancer.Public databases,such as UCSC Xena,cBioPortal and Timer2,were used to collect relative data,and thenbioinformatic approaches were used to analyze the correlation of MS4A6A genome and MS4A6A expression with immune infiltration,tumor mutation burden(TMB),microsatellite instability(MSI)etc.TMB and MSI were further calculated by R package maftools.Immune score,stromal score and ESTIMATE score were calculated by R package ESTIMATE.The correlation between immune score and MS4A6A expression was conducted based on Spearman correlation coefficient.Data showed that DNA methylation of MS4A6A in most cancer tissues was negatively correlated with its expression level,suggesting the possible relation of differential MS4A6A expression to the methylation level of its promoter region.Univariate Cox analysis revealed that high expression of MS4A6A was the risk factor for LGG,TGCT,UVM and THYM;MS4A6A expression was positively correlated with the immune score in 32 types of cancer;MS4A6A expression was positively correlated with the infiltration levels of various immune cells,such as tumor associated fibroblasts(CAF),regulatory T cells(Treg),B cells,neutrophils,macrophages,monocytes,and CD8+T cells.In conclusion,MS4A6A may participate in the development of cancer,suggesting it is a potential new biomarker for cancer treatment and prevention.

Background and objective Lung cancer is a leading cause of cancer-related deaths.Non-small cell lung cancer(NSCLC)is the most common pathological subtype,with adenocarcinoma being the predominant type.FAT atypical cadherin 1(FAT1)is a receptor-like protein with a high frequency of mutations in lung adenocarcinoma.The protein encoded by FAT1 plays a crucial role in processes such as cell adhesion,proliferation,and differentiation.This study aims to investigate the expression of FAT1 in lung adenocarcinoma and its relationship with immune infiltration.Methods Gene expression levels and relevant clinical information of 513 lung adenocarcinoma samples and 397 adjacent lung samples were obtained through The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)data.The mRNA expression levels of the FAT1 gene in lung adenocarcinoma tissues were analyzed,along with its association with the prognosis of lung adenocarcinoma patients.Pathway enrichment analysis was conducted to explore the signaling pathways regulated by the FAT1 gene.Immu-noblotting was used to detect the differential expression of FAT1 in lung epithelial cells and various lung cancer cell lines,while immunohistochemistry was employed to assess FAT1 expression in lung cancer and adjacent tissues.Results FAT1 gene muta-tions were identified in 14%of lung adenocarcinoma patients.TCGA database data revealed significantly higher FAT1 mRNA expression in lung adenocarcinoma tissues compared to adjacent lung tissues.Kaplan-Meier analysis indicated lower survival rates in lung adenocarcinoma patients with higher FAT gene expression.Pathway enrichment analysis suggested the involve-ment of FAT1 in tumor development pathways,and its expression was closely associated with immune cell infiltration.Immu-nohistochemical validation demonstrated significantly higher expression of FAT1 in cancer tissues compared to adjacent lung tissues.Conclusion FAT1 mRNA is highly expressed in lung adenocarcinoma tissues,and elevated FAT1 mRNA expression is associated with poor prognosis in lung adenocarcinoma patients.FAT1 may serve as a potential biomarker for lung cancer.

Background and objective Transcription factor(TF)can bind specific sequences that either promotes or represses the transcription of target genes,and exerts important effects on tumorigenesis,migration,invasion.Staphylococcal nuclease-containing structural domain 1(SND1),which is a transcriptional co-activator,is considered as a promising target for tumor therapy.However,its role in lung adenocarcinoma(LUAD)remains unclear.This study aims to explore the role of SND1 in LUAD.Methods Data from The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),Clinical Pro-teomic Tumor Analysis Consortium(CPTAC),and Human Protein Atlas(HPA)database was obtained to explore the associa-tion between SND1 and the prognosis,as well as the immune cell infiltration,and subcellular localization in LUAD tissues.Furthermore,the functional role of SND1 in LUAD was verified in vitro.EdU assay,CCK-8 assay,flow cytometry,scratch assay,Transwell assay and Western blot were performed.Results SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients.In addition,SND1 was predominantly present in the cytoplasm of LUAD cells.Enrichment analysis showed that SND1 was closely associated with the cell cycle,as well as DNA replication,and chro-mosome segregation.Immune infiltration analysis showed that SND1 was closely associated with various immune cell popula-tions,including T cells,B cells,cytotoxic cells and dendritic cells.In vitro studies demonstrated that silencing of SND1 inhib-ited cell proliferation,invasion and migration of LUAD cells.Besides,cell cycle was blocked at G,phase by down-regulating SND1.Conclusion SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.