Objective To investigate the role of microRNA-106a and microRNA-106b (miR-106a/b) in diagnosis and prognosis of hepatocellular carcinoma (HCC).Methods In this study,108 HCC patients and 54 age-and sex-matched healthy controls were enrolled.Blood samples were collected from each participant,and total RNA was extracted from the plasma.We determined miR-106a/b expression levels using quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results The miR-106a/b expression levels in HCC patients were elevated compared with the healthy controls (P＜ 0.001).The ROC curve analysis showed that miR-106a/b expression levels could be used to predict the risk of HCC,with AUC values of 0.670 (95％ CI:0.573-0.768) and 0.684 (95％ CI:0.593-0.776),respectively.The miR-106a expression level in HCC patients correlated positively with hepatitis B surface antigen (HBsAg) presence (P =0.028),differentiation (P =0.025),tumor size (P =0.002),lymph node metastasis (P =0.028),and TNM stage (P =0.037).The miR-106b expression level correlated positively with HBsAg presence (P =0.003),alpha-fetoprotein (AFP) level (P =0.031),and tumor size (P =0.005).To further investigate the correlation of miR-106a/b expression levels with overall survival (OS),Kaplan-Meier curves were plotted.The results showed that HCC patients with high miR-106a expression displayed shorter OS (P =0.013).In addition,univariate and multivariate Cox proportional hazards regression showed that miR-106a was an independent risk factor for HCC prognosis.Conclusion Circulating miR-106a/b expression levels could be used as diagnostic biomarkers for HCC,and a high circulating miR-106a expression level is an independent risk factor for poor prognosis of HCC patients.

AIM:To investigate the expression of CUE domain-containing 2 (CUEDC2) in hepatocellular car-cinoma ( HCC) and to analyze its clinical prognostic significance .METHODS:Total 186 formalin-fixed paraffin-embed-ded tissues obtained from surgical HCC with detailed clinicopathological and follow -up data were used .The expression of CUEDC2 was detected by immunohistochemistry .The relationships between the expression of CUEDC 2 and clinicopatholog-ical characteristics and prognosis were analyzed .RESULTS: The positive rate of CUEDC 2 in HCC was 85.5% ( 159/186), among which, the low expression was 52.2%(97/186) and the high expression was 47.8%(89/186).CUEDC2 expression was correlated with serum alpha-fetal protein (AFP) level, tumor size, tumor number, tumor differentiation and TNM stage (P<0.05).Kaplan-Meier survival curves showed that the patients with high expression of CUEDC 2 were asso-ciated with significantly shorter overall survival and recurrence-free survival than those with low CUEDC 2 expression ( P<0.05).Multivariate Cox regression analysis revealed 3 independent prognostic factors including CUEDC 2 expression, ser-um AFP and tumor number .CONCLUSION:CUEDC2 was expressed in most HCC tissues , which was relevant to tumor growth, tumor differentiation and prognosis .CUEDC2 could be a novel valuable molecular marker to predict the HCC prog-nosis.

Objective To identify M1 macrophage-related genes in rejection after kidney transplantation and construct a risk prediction model for renal allograft survival. Methods GSE36059 and GSE21374 datasets after kidney transplantation were downloaded from Gene Expression Omnibus (GEO) database. GSE36059 dataset included the samples from the recipients with rejection and stable allografts. Using this dataset, weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted to screen the M1 macrophage-related differentially expressed gene (M1-DEG). Then, GSE21374 dataset (including the follow-up data of graft loss) was divided into the training set and validation set according to a ratio of 7∶3. In the training set, a multivariate Cox's model was constructed using the variables screened by least absolute shrinkage and selection operator (LASSO), and the ability of this model to predict allograft survival was evaluated. CIBERSORT was employed to analyze the differences of infiltrated immune cells between the high-risk group and low-risk group, and the distribution of human leukocyte antigen (HLA)-related genes was analyzed between two groups. Gene set enrichment analysis (GSEA) was used to further clarify the biological process and pathway enrichment in the high-risk group. Finally, the database was employed to predict the microRNA (miRNA) interacting with the prognostic genes. Results In the GSE36059 dataset, 14 M1-DEG were screened. In the GSE21374 dataset, Toll-like receptor 8 (TLR8), Fc gamma receptor 1B (FCGR1B), BCL2 related protein A1 (BCL2A1), cathepsin S (CTSS), guanylate binding protein 2(GBP2) and caspase recruitment domain family member 16 (CARD16) were screened by LASSO-Cox regression analysis, and a multivariate Cox's model was constructed based on these 6 M1-DEG. The area under curve (AUC) of receiver operating characteristic of this model for predicting the 1- and 3-year graft survival was 0.918 and 0.877 in the training set, and 0.765 and 0.736 in the validation set, respectively. Immune cell infiltration analysis showed that the infiltration of rest and activated CD4⁺ memory T cells, γδT cells and M1 macrophages were increased in the high-risk group (all P < 0.05). The expression level of HLA I gene was up-regulated in the high-risk group. GSEA analysis suggested that immune response and graft rejection were enriched in the high-risk group. CTSS interacted with 8 miRNA, BCL2A1 and GBP2 interacted with 3 miRNA, and FCGR1B interacted with 1 miRNA. Conclusions The prognostic risk model based on 6 M1-DEG has high performance in predicting graft survival, which may provide evidence for early interventions for high-risk recipients.

Objective:To explore the temporal distribution of high level of BK virus(BKV) viruria after kidney transplantation(KT)and the association of high level of viruria with clinical factors and specific human leukocyte antigen(HLA)sites in donors and recipients.Methods:From January 1, 2017 to December 31, 2019, clinical data were retrospectively reviewed for 212 recipients of cadaveric KT.A high level of urinary BKV viruria was defined as urinary BKV-DNA quantification>10 7(copies/ml)after KT while 212 recipients with the same gender composition below the threshold during the same period were selected as low-level controls.Clinical data and HLA sites of two groups were statistically analyzed and risk factors for high level of viruria screened by univariate and multifactorial Logistic regressions. Results:The median time to initial high-level BKV infection in urine after RT was 125.5 days.Based upon univariate Logistic analysis, delayed graft function(DGF)and HLA-A24 of recipient were risk factors for high-level BKV infection in urine while HLA-DQ9 of donor acted as a protective factor.Through multivariate Logistic analysis, DGF( OR=2.18, 95% CI 1.18~4.01, P=0.012)and HLA-A24( OR=1.63, 95% CI 1.06~2.53, P=0.027)of recipient were independent risk factors for high-level BKV infection in urine.And HLA-DQ9 of donors( OR=0.58, 95% CI 0.36~0.91, P=0.019)was an independent protective factor. Conclusions:High level of BKV viruria after RT is associated with donor/recipient-specific HLA sites.Early risk factor stratification and protective factors of recipients can aid in tailoring postoperative immunosuppression and screening program and developing T cell-associated vaccines.

Objective To investigate the characteristics of adverse drug event (ADE) related to tacrolimus (Tac) in pediatric solid organ transplant recipients. Methods The data were retrieved from the US Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the second quarter of 2023. The ADE data of pediatric organ transplant recipients with Tac as the primary suspected drug were extracted. The relationship between Tac and ADE was quantitatively analyzed by proportional imbalance method. Basic characteristics and signal strength of ADE related to Tac were analyzed. ADE related to Tac in children of different ages and different types of organ transplantation were analyzed. Results A total of 1 443 children's ADE reports involving Tac were screened, including 188 cases (13.0%) of heart transplantation, 668 cases (46.3%) of liver transplantation, 531 cases (36.8%) of kidney transplantation and 56 cases (3.9%) of lung transplantation. The median age of children was 10 years old. The top three countries with ADE reporting were the United States, France and the United Kingdom. China reported 26 cases, accounting for 1.8%. Infection and infectious diseases accounted for the highest proportion (20.96%) in ADE related to Tac, including EB virus and cytomegalovirus infection, etc. Infection and infectious diseases occupied the largest proportion of ADE related to Tac in children of different ages, whereas the pathogen types were different. Rejection, unstable immunosuppression level and renal function damage were also common ADE related to Tac in children of all ages. Nervous system disease was the main ADE in heart transplant recipients, while infection and infectious diseases were more common in liver and kidney transplant recipients. Rejection was the most common ADE in lung transplant recipients. Conclusions ADE related to Tac possess different distribution characteristics in different types of organ transplantation. Extensive attention should be paid to individualized drug monitoring and risk assessment in pediatric organ transplant recipients, thereby optimizing Tac treatment and reducing the risk of ADE.

Objective To explore the molecular mechanisms and cell-cell interactions in the injury process of pancreatic islet transplantation. Methods Single-cell transcriptome data from mouse islets treated with inflammatory factors were used, and data processing was performed using the Seurat package, with integrated data to remove batch effects. Cell subpopulations were annotated based on known markers. Cell-cell interactions in the inflammatory factor-treated group were analyzed using the CellChat package, and inferred based on the expression of cell surface receptors and ligands. Gene set enrichment analysis was used to clarify the biological processes enriched in β-cells after treatment with inflammatory factors. Finally, differentially expressed transcription factors were identified and verified using microarray datasets of donor islet ischemic injury and Western blotting. Results A total of 7 different cell subpopulations were found in mouse islets, with β-cells being the most abundant. Cell-cell interaction network analysis showed that the number and strength of interactions between ductal cells and other cells were the highest. Gene set enrichment analysis showed that after treatment with inflammatory factors, the immune response was positively enriched in β-cells, while peptide hormone metabolism, bile acid metabolism, and ion homeostasis were downregulated. The common differential transcription factors identified in the mouse single-cell transcriptome and the microarray dataset of donor islet ischemic injury were early growth response 1 (EGR1), nuclear factor-κB inhibitor α (NFKBIA), and activating transcription factor 3 (ATF3). Among them, NFKBIA and ATF3 were upregulated, while EGR1 was downregulated. The expression of EGR1 protein was downregulated after 24 h, 48 h, and 72 h of cold ischemia. Conclusions EGR1 is a transcription factor closely related to islet cold ischemia, and future research should focus on the specific mechanisms of EGR1 and its downstream target genes, in order to provide more effective strategies for clinical treatment of islet transplantation.