Construction and clinical validation of a nomogram-based predictive model for diabetic retinopathy in type 2 diabetes.

OBJECTIVE: This study aimed to identify risk factors for diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and construct a nomogram prediction model for DR. METHODS: T2DM patients (n = 520) who underwent funduscopic examinations from June 2020 to June 2022 were included. Of these patients, 220 had DR, yielding a disease rate of 40.38%. Patients were divided into a training set (n = 364) and a validation set (n = 156) at a 7:3 ratio. Feature variables were selected using LASSO regression, random forests, and decision trees. Venn diagrams identified common DR feature variables. The prediction model's validity was assessed using the C-index, decision curve analysis (DCA), receiver operating characteristic (ROC) curves, and calibration curves. RESULTS: Factors influencing DR were age, Diabetic Peripheral Neuropathy (DPN), Hemoglobin A1C (HbA1C) levels, High-Density Lipoprotein (HDL) cholesterol, Low-Density Lipoprotein (LDL) cholesterol, Neutrophil-to-Lymphocyte Ratio (NLR), Triglycerides (TG), Blood Urea Nitrogen (BUN), and disease duration. Univariate analysis excluded LDL as being unrelated to DR. The DR prediction model, constructed using the remaining eight variables, showed internal validation metrics with a C-index of 0.937, area under the ROC curve (AUC) of 0.773, and DCA net benefit of 11%-95%. The external validation metrics demonstrated a C-index of 0.916, AUC of 0.735, and DCA net benefit of 17%-93%. Calibration curves indicated high consistency. CONCLUSION: This study developed a nomogram prediction model to assess the risk of DR in patients with T2DM. The model demonstrated high precision through internal validation.

Overexpressed lncRNA FTX promotes the cell viability, proliferation, migration and invasion of renal cell carcinoma via FTX/miR­4429/UBE2C axis.

The present study aimed to explore the role of long non­coding (lnc)RNA FTX and ubiquitin­conjugating enzyme E2C (UBE2C) in promoting the progression of renal cell carcinoma (RCC) and the underlying regulatory mechanism. Relative levels of lncRNA FTX, UBE2C, AKT, CDK1 and CDK6 in RCC cell lines were detected by reverse transcription­quantitative (RT­q). Expression levels of UBE2C, phosphorylated (p)­AKT/AKT, p­CDK1/CDK1 and p­CDK6/CDK6 in RCC and paracancerous specimens and RCC cells were measured by western blot or immunohistochemistry assay. In addition, the proliferative rate, cell viability, cell cycle progression, migratory rate and invasive rate of RCC cells overexpressing lncRNA FTX by lentivirus transfection were determined by a series of functional experiments, including the colony formation assay, MTT assay, flow cytometry, Transwell assay and wound healing assay. The targeted binding relationship in the lncRNA FTX/miR­4429/UBE2C axis was validated by dual­luciferase reporter assay. By intervening microRNA (miR)­4492 and UBE2C by the transfection of miR­4429­mimics or short interfering UBE2C­2, the regulatory effect of lncRNA FTX/miR­4429/UBE2C axis on the progression of RCC was evaluated. Finally, a xenograft model of RCC in nude mice was established by subcutaneous implantation, thus evaluating the in vivo function of lncRNA FTX in the progression of RCC. The results showed that lncRNA FTX and UBE2C were upregulated in RCC specimens and cell lines. The overexpression of lncRNA FTX in RCC cells upregulated UBE2C. In addition, the overexpression of lncRNA FTX promoted the cell viability and proliferative, migratory and invasive capacities of RCC cells and accelerated the cell cycle progression. A dual­luciferase reporter assay validated that lncRNA FTX exerted the miRNA sponge effect on miR­4429, which was bound to UBE2C 3'UTR. Knockdown of UBE2C effectively reversed the regulatory effects of overexpressed lncRNA FTX on the abovementioned phenotypes of RCC cells. In the xenograft model of RCC, the mice implanted with RCC cells overexpressing lncRNA FTX showed a larger tumor size and higher tumor weight than those of controls, while the in vivo knockdown of UBE2C significantly reduced the size of RCC lesions, indicating the reversed cancer­promoting effect of lncRNA FTX. Overall, the present study showed that lncRNA FTX was upregulated in RCC and could significantly promote the proliferative, migratory and invasive capacities, enhancing the viability and accelerating the cell cycle progression of RCC cells by exerting the miRNA sponge effect on miR­4429 and thus upregulating UBE2C. lncRNA FTX and UBE2C are potential molecular biomarkers and therapeutic targets of RCC.