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Objective·To explore the relationship between osteoarthritis and nicotinamide metabolism-related genes using bioinformatics analysis,and identify key genes with diagnostic value and therapeutic potential.Methods·By using"Osteoarthritis"as a search term,GSE12021,GSE55235,and GSE55457 were obtained from the GEO database,with GSE55457 being used as the validation set.After removing batch effects from the GSE12021 and GSE55235 datasets,the standardized combined dataset was obtained and used as the training dataset.Differentially expressed genes(DEGs)were identified from the training dataset.All nicotinamide metabolism-related genes(NMRGs)were obtained from the GeneCards and MSigDB databases.The intersection of DEGs and NMRGs was taken to obtain nicotinamide metabolism-related differentially expressed genes(NMRDEGs).Gene set enrichment analysis(GSEA)was performed on the training dataset,while gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis were performed on NMRDEGs.Key genes were selected by using least absolute shrinkage and selection operator(LASSO)and support vector machine(SVM)analysis in NMRDEGs to build an osteoarthritis diagnosis model which was validated by using the GSE55457 dataset.Single sample gene set enrichment analysis(ssGSEA)was used to analyze the immune cell infiltration type.Interactions networks and drug molecule predictions were obtained for these key genes'mRNA with the DGIdb,ENCORI,and CHIPBase databases.siRNA was used to knock down the key genes in chondrocytes,and then real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of chondrogenesis-related genes.Results·Seven NMRDEGs,including NAMPT,TIPARP,were discovered.GO and KEGG analysis enriched some signaling pathways,such as nuclear factor-κB signaling pathway and positive regulation of interleukin-1-mediated signaling pathway.GSEA enriched pathways such as Hif1 Tfpathway and syndecan 1 pathway.Key genes NPAS2,TIPARP,and NAMPT were identified through LASSO and SVM analysis,and used to construct an osteoarthritis diagnostic model.The validated results showed that the diagnostic model had high accuracy.Immune infiltration analysis results obtained by ssGSEA showed significant differences(all P<0.05)in 15 types of immune cells,including macrophages.Seven potential small molecules targeting key genes were identified,along with 19 miRNAs with the sum of upstream and downstream>10,19 transcription factors with upstream and downstream>7,and 27 RNA binding proteins with clusterNum>19.The results of RT-qPCR showed that knocking down key genes reduced the expression of chondrogenesis-related genes.Conclusion·Through bioinformatics analysis,key genes related to nicotinamide metabolism,NPAS2,TIPARP,and NAMPT,are discovered,and an osteoarthritis diagnostic model is constructed.
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Objective:To analyze the apply effect of radiofrequency ablation assisted associating liver partition and portal vein ligation for staged hepatectomy (RALPPS) in liver cancer patients with insufficient future liver remnant (FLR).Methods:The data of 29 patients who underwent RALPPS in the First Affiliated Hospital of the Army Military Medical University from June 2014 to July 2020 were analyzed, including 25 males and 4 females, aged (46.6±9.9) years. The patients were divided into the second stage group (completed the second stage operation, n=18) and the first stage group (completed only the first stage operation, n=11) according to whether they had successfully completed the second stage operation. FLR, percentage of FLR in standard liver volume (percentage of FLR), growth rate of FLR, liver function after operation, operation time and radiofrequency ablation time of first stage operation, surgical complications were compared between the two groups. Results:The percentage of FLR before the first stage operation was (30.0±7.0)% in 29 patients, and the second stage operation was completed in 18 patients (62.1%). After the first stage operation, the aspartate aminotransferase and alanine aminotransferase in the second stage group were 519.0 (362.9, 696.0) U/L and 391.8 (297.2, 591.1) U/L, which were better than those of the first stage group 931.0 (711.7, 1131.9) U/L and 851.3 (426.6, 888.0) U/L (both P<0.05). There was no significant difference between the two groups in FLR and percentage of FLR before the first stage operation, duration time, amount of bleeding and time of radiofrequency ablation of the first stage operation (all P>0.05). In the second stage group, the interval between two operations was (21.6±6.7) days, the FLR before the second stage operation was (623.2±101.8) cm 3, the FLR percentage was (49.0±7.0)%, and the FLR growth rate was (19.0±5.0)%. In the first stage group, there were 11 patients (100.0%) who developed complication after first stage operation, induding 7 patients (63.6%) with complication above Clavien-Dindo grade Ⅲb. In the second stage group, 18 patients (100.0%) developed complication after the first stage operation. There were no complication above grade Ⅲb. The causes of 11 patients who did not completed secondary surgery included poor liver function and insufficient FLR in 4 patients, tumor progression in 6 patients, and death in 1 patient. Conclusion:RALPPS is a therapeutic option for liver cancer patients with insufficient FLR, and the therapeutic effect is reasonable.
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After more than a hundred years of development,hepatic surgery has gradually developed from a traditional rough model to a precise model in the 21st century.The era of precision liver surgery,and even precision medicine has come.Under the guidance of precise concept,the therapeutic effect of all liver diseases,especially liver malignant tumors,has been significantly improved,and the quality of life of patients has been significantly improved.Precise hepatectomy,precise radiofrequency ablation and precise transcatheter arterial chemoembolization are the three magic weapons of precise treatment in liver surgery.The precise concept will be the future development direction of medicine.This article reviews the research progress of precise treatment in liver surgery in order to further promote the concept of precise treatment in liver surgery.