Résumé
Immunosuppressant is one of the main preventive measures for rejection after organ transplantation, whereas it may reduce the host response capability to pathogens and increase the risk of infection. In recent years, the application of mesenchymal stem cell (MSC) therapy in the field of solid organ transplantation has attracted widespread attention. Preclinical studies have shown that MSC therapy may prolong the survival time of transplant kidney, induce immune tolerance, accelerate the repair of acute kidney injury and promote the recovery of renal function. Clinical trials have confirmed the safety, tolerance and effectiveness of MSC therapy. Consequently, general characteristics, immunomodulation and tissue repair function of MSC, and the application of MSC in clinical trials of kidney transplantation were reviewed, the unresolved issues were briefly discussed and the prospects for subsequent research were predicted, aiming to provide reference for promoting the application of MSC therapy in clinical kidney transplantation.
Résumé
Objective:To evaluate the diagnostic performance of the prostate imaging reporting and data system version 2.1 (PI-RADS v2.1) based on multiparametric MRI (mpMRI) in the detection of clinically significant prostate cancer (csPCa).Methods:A total of 561 patients who underwent prostate mpMRI in the First Affiliated Hospital of Guangxi Medical University from June 2015 to December 2020 due to elevated prostate specific antigen were collected ambispectively. The patients were divided into csPCa group (276 cases) and non-csPCa group (285 cases) according to pathological findings. Prostate were scored according to the PI-RADS v2.1 scoring standard by a junior and a senior radiologist. The prostate volume was measured and the prostate specific antigen density (PSAD) was calculated. The diffusion-weighted imaging and dynamic contrast-enhanced MRI images were processed to measure the quantitative parameters of the index lesion, including apparent diffusion coefficient (ADC), volume transfer constant (K trans) and rate constant (K ep) values. The Mann-Whitney U test was used to compare the difference in parameters between the two groups. The predictors of csPCa were screened by logistic regression analysis. Predictive model of multi-parameter was established. The receiver operator characteristic curves were used to evaluate the efficacy of PI-RADS v2.1 and the model in diagnosing csPCa, and the comparisons of area under the curve (AUC) were conducted by DeLong test. Results:Compared with non-csPCa group, the patients in csPCa group had higher PI-RADS score of senior physician, PSAD, K trans and K ep value, lower ADC value ( Z=-16.69, -12.49, -3.43, -4.67, 13.91, all P<0.001). The PI-RADS scores of senior physician (OR=3.064, 95%CI 2.428-3.866, P<0.001), PSAD (OR=1.554, 95%CI 1.170-2.064, P=0.002) and ADC value (OR=0.095, 95%CI 0.032-0.288, P<0.001) were the predictors of csPCa. The AUC of junior, senior physician PI-RADS and combined prediction model were 0.861 (95%CI 0.830-0.892), 0.895 (95%CI 0.868-0.922) and 0.923 (95%CI 0.898-0.944). The pairwise difference was statistically significant (the PI-RADS score between the junior and senior physicians Z=3.24, P=0.001, the difference between the PI-RADS score of junior physician and prediction model Z=5.54, P<0.001, the difference between the PI-RADS score of senior physician and prediction model Z=4.20, P<0.001). Conclusion:Based on mpMRI, the application of PI-RADS v2.1 by junior and senior radiologists has the high diagnostic efficacy for csPCa, and the multi-parameter model has the best diagnostic efficacy for csPCa.
Résumé
OBJECTIVE@#To explore the driving gene of hepatocellular carcinoma (HCC) occurrence and progression and its potential as new therapeutic target of HCC.@*METHODS@#The transcriptome and genomic data of 858 HCC tissues and 493 adjacent tissues were obtained from TCGA, GEO, and ICGC databases. Gene Set Enrichment Analysis (GSEA) identified EHHADH (encoding enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase) as the hub gene in the significantly enriched differential pathways in HCC. The downregulation of EHHADH expression at the transcriptome level was found to correlate with TP53 mutation based on analysis of the TCGA- HCC dataset, and the mechanism by which TP53 mutation caused EHHADH downregulation was explored through correlation analysis. Analysis of the data from the Metascape database suggested that EHHADH was strongly correlated with the ferroptosis signaling pathway in HCC progression, and to verify this result, immunohistochemical staining was used to examine EHHADH expression in 30 HCC tissues and paired adjacent tissues.@*RESULTS@#All the 3 HCC datasets showed signficnatly lowered EHHADH expression in HCC tissues as compared with the adjacent tissues (P < 0.05) with a close correlation with the degree of hepatocyte de-differentiation (P < 0.01). The somatic landscape of HCC cohort in TCGA dataset showed that HCC patients had the highest genomic TP53 mutation rate. The transcriptomic level of PPARGC1A, the upstream gene of EHHADH, was significantly downregulated in HCC patients with TP53 mutation as compared with those without the mutation (P < 0.05), and was significantly correlated with EHHADH expression level. GO and KEGG enrichment analyses showed that EHHADH expression was significantly correlated with abnormal fatty acid metabolism in HCC. The immunohistochemical results showd that the expression level of EHHADH in HCC tissues was down-regulated, and its expression level was related to the degree of hepatocytes de-differentiation and the process of ferroptosis.@*CONCLUSION@#TP53 mutations may induce abnormal expression of PPARGC1A to cause downregulation of EHHADH expression in HCC. The low expression of EHHADH is closely associated with aggravation of de-differentiation and ferroptosis escape in HCC tissues, suggesting the potential of EHHADH as a therapeutic target for HCC.