Objective: To investigate the molecular mechanism of NOD-like receptor(NLR) signaling pathway induced cellular focal death in mouse kidney tissues under plateau hypoxia based on transcriptomic sequencing technology. Methods: Animal models were constructed in high-altitude kidney test group(HKT group) and plain kidney control group(PKC group),and C57/BL6 mice were bred at an altitude of 4 200 m and 400 m,respectively.Kidney tissues were aseptically taken out after 30 d and used for observation of renal histopathological changes and transcriptomics sequencing,respectively,and then differentially expressed genes(DEGs) were enriched by KEGG and GO analysis.Key gene and protein expression levels were verified by reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot analysis. Results: Hematoxylin-eosin(HE) staining showed that the renal tubules of HKT mice were disorganized,and the tubular epithelial cells were edematous with inflammatory cell aggregation.Transcriptomics sequencing analysis revealed that a total of 3 007 DEGs were identified in the HKT group,and KEGG analysis showed that DEGs were significantly enriched in the NLR signaling pathway.The mRNA expression of the key differentially expressed genes,CASP1,CASP11,GSDMD,IFI16,NAIP5,IRF9,and the downstream inflammatory factors,IL-1β and IL-18,was upregulated,and protein expression of CASP1,CASP11,and GSDMD was up-regulated. Conclusion The plateau hypoxic environment induces cellular pyroptosis by regulating the expression of NLR signaling pathway and releases downstream inflammatory factors to cause inflammatory responses.

Objective·To develop a nomogram prediction model and an online risk calculator,and to predict the continence of patients after robot-assisted laparoscopic radical prostatectomy(RARP).Methods·A total of 604 prostate cancer patients who underwent RARP and had preoperative prostate magnetic resonance imaging at the Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to December 2024 were analyzed and included.All patients were randomly resampled and divided into a training set(n=420)and a validation set(n=184)at a ratio of 7∶3.The patients'continence was followed up every month from the first month after the operation.The least absolute shrinkage and selection operator(LASSO)model was applied to screen the features.A Logistic multivariate regression analysis was used to establish a prediction model integrating the features selected from the LASSO analysis.The receiver operator characteristic(ROC)curve was drawn to predict the recovery of continence in patients after RARP,and the areas under the curve were compared by the DeLong test to evaluate the discrimination of the model.Calibration curves and decision curve analysis(DCA)were used to evaluate the calibration and clinical utility the model.Results·According to the postoperative continence follow-up data of the patients,the continence rate of the patients at 3 months after the operation was 58.28%(352/604).The length of the membranous urethra,the thickness of the right levator ani muscle,and blood loss were identified as independent predictors of early postoperative(3-month)incontinence by Logistic multivariate regression analysis of the training set.The area under the ROC curve was calculated as 0.976(0.954,0.998)for the training set and 0.977(0.945,1.000)for the validation set,demonstrating good discrimination of this model.No significant difference between the ROC curves of the training set and the validation set was confirmed by the DeLong test(P=0.949).A good goodness of fit of this model was demonstrated by the Hosmer-Lemeshow test(P=0.179).The clinical utility of the nomogram prediction model was indicated by the DCA plot.This nomogram prediction model was incorporated into an online calculator(https://yitingd.shinyapps.io/DynNomapp).Conclusion·This study developed and validated a nomogram prediction model that can effectively predict the early continence of patients after RARP.The length of the membranous urethra,the thickness of the right levator ani muscle,and the intraoperative blood loss are significant independent predictors of early postoperative incontinence.

Objective·To develop a nomogram prediction model and an online risk calculator,and to predict the continence of patients after robot-assisted laparoscopic radical prostatectomy(RARP).Methods·A total of 604 prostate cancer patients who underwent RARP and had preoperative prostate magnetic resonance imaging at the Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to December 2024 were analyzed and included.All patients were randomly resampled and divided into a training set(n=420)and a validation set(n=184)at a ratio of 7∶3.The patients'continence was followed up every month from the first month after the operation.The least absolute shrinkage and selection operator(LASSO)model was applied to screen the features.A Logistic multivariate regression analysis was used to establish a prediction model integrating the features selected from the LASSO analysis.The receiver operator characteristic(ROC)curve was drawn to predict the recovery of continence in patients after RARP,and the areas under the curve were compared by the DeLong test to evaluate the discrimination of the model.Calibration curves and decision curve analysis(DCA)were used to evaluate the calibration and clinical utility the model.Results·According to the postoperative continence follow-up data of the patients,the continence rate of the patients at 3 months after the operation was 58.28%(352/604).The length of the membranous urethra,the thickness of the right levator ani muscle,and blood loss were identified as independent predictors of early postoperative(3-month)incontinence by Logistic multivariate regression analysis of the training set.The area under the ROC curve was calculated as 0.976(0.954,0.998)for the training set and 0.977(0.945,1.000)for the validation set,demonstrating good discrimination of this model.No significant difference between the ROC curves of the training set and the validation set was confirmed by the DeLong test(P=0.949).A good goodness of fit of this model was demonstrated by the Hosmer-Lemeshow test(P=0.179).The clinical utility of the nomogram prediction model was indicated by the DCA plot.This nomogram prediction model was incorporated into an online calculator(https://yitingd.shinyapps.io/DynNomapp).Conclusion·This study developed and validated a nomogram prediction model that can effectively predict the early continence of patients after RARP.The length of the membranous urethra,the thickness of the right levator ani muscle,and the intraoperative blood loss are significant independent predictors of early postoperative incontinence.

Objective To investigate the molecular mechanism of lipid metabolism disorder in mouse spleen tissues due to high-altitude hypoxia.Methods Ten C57BL/6 male mice were randomly divided into normoxia group(maintained at an altitude of 400 m)and high-altitude hypoxia group(maintained at 4200 m)for 30 days(n=5).Lipidomics and metabolomics analyses of the spleen tissue of the mice were conducted using liquid chromatography-mass spectrometry(LC-MS)to identify the differential metabolites,which were further analyzed by KEGG enrichment and pathway analyses,and the differential genes were screened through transcriptome sequencing.Bioinformatics analysis was conducted to identify the upstream target genes of the differential metabolites in specific metabolic pathways.RT-qPCR and Western blotting were used to detect mRNA expressions of 11β-hydroxysteroid dehydrogenase 1(HSD11B1),steroid 5α reductase 1(SRD5A1),prostaglandin-endoperoxide synthase 1(PTGS1),hematopoietic prostaglandin D synthetase(HPGDS),xanthine dehydrogenase(XDH),purine nucleoside phosphorylase(PNP),hypoxanthine guanine-phosphoribosyltransferase(HPRT)and extracellular 5'-nucleotidase(NT5E)and protein expressions of HSD11B1,SRD5A1,XDH,PNP and HPRT in the mouse spleens.Results We identified a total of 41 differential lipid metabolites in the mouse spleens,and these metabolites and the differential genes were enriched in steroid hormone biosynthesis,arachidonic acid metabolism,and purine metabolism pathways.Compared to the mice kept in normoxic conditions,the mice exposed to high-altitude hypoxia showed significantly upregulated expressions of adrenosterone,androsterone,prostaglandin D2,prostaglandin J2,xanthine,xanthosine,and uric acid in the spleen with also changes in the expression levels of HSD11B1,SRD5A1,PTGS1,HPGDS,XDH,PNP,HPRT,and NT5E.Conclusion High-altitude hypoxia can result in lipid metabolism disorder in mouse spleen tissue by affecting steroid hormone biosynthesis,arachidonic acid metabolism,and purine metabolism pathways.

Objective To investigate the molecular mechanism of lipid metabolism disorder in mouse spleen tissues due to high-altitude hypoxia.Methods Ten C57BL/6 male mice were randomly divided into normoxia group(maintained at an altitude of 400 m)and high-altitude hypoxia group(maintained at 4200 m)for 30 days(n=5).Lipidomics and metabolomics analyses of the spleen tissue of the mice were conducted using liquid chromatography-mass spectrometry(LC-MS)to identify the differential metabolites,which were further analyzed by KEGG enrichment and pathway analyses,and the differential genes were screened through transcriptome sequencing.Bioinformatics analysis was conducted to identify the upstream target genes of the differential metabolites in specific metabolic pathways.RT-qPCR and Western blotting were used to detect mRNA expressions of 11β-hydroxysteroid dehydrogenase 1(HSD11B1),steroid 5α reductase 1(SRD5A1),prostaglandin-endoperoxide synthase 1(PTGS1),hematopoietic prostaglandin D synthetase(HPGDS),xanthine dehydrogenase(XDH),purine nucleoside phosphorylase(PNP),hypoxanthine guanine-phosphoribosyltransferase(HPRT)and extracellular 5'-nucleotidase(NT5E)and protein expressions of HSD11B1,SRD5A1,XDH,PNP and HPRT in the mouse spleens.Results We identified a total of 41 differential lipid metabolites in the mouse spleens,and these metabolites and the differential genes were enriched in steroid hormone biosynthesis,arachidonic acid metabolism,and purine metabolism pathways.Compared to the mice kept in normoxic conditions,the mice exposed to high-altitude hypoxia showed significantly upregulated expressions of adrenosterone,androsterone,prostaglandin D2,prostaglandin J2,xanthine,xanthosine,and uric acid in the spleen with also changes in the expression levels of HSD11B1,SRD5A1,PTGS1,HPGDS,XDH,PNP,HPRT,and NT5E.Conclusion High-altitude hypoxia can result in lipid metabolism disorder in mouse spleen tissue by affecting steroid hormone biosynthesis,arachidonic acid metabolism,and purine metabolism pathways.