ABSTRACT
Object: The purpose of this study was to describe the longitudinal dynamic hemoglobin trajectories in patients undergoing cardiac surgery and to explore whether they provide a broader perspective in predicting AKI compared to traditional threshold values. Additionally, the interaction of red blood cell transfusion was also investigated. Methods: The MIMIC-IV database was searched to identify patients undergoing cardiac surgery with cardiopulmonary bypass. Group-based trajectory modeling (GBTM) was used to determine the hemoglobin trajectories in the first 72â h after ICU admission. The correlation between hemoglobin trajectories and AKI was evaluated using multivariable logistic regression and inverse probability of treatment weighting. Receiver operating characteristic (ROC) curves were created in the dataset to further validate previously reported thresholds. Results: A total of 4,478 eligible patients were included in this study. Three hemoglobin trajectories were identified by GBTM, which were significantly different in the initial hemoglobin level and evolution pattern. Compared to the "the lowest, rising, and then declining" trajectory, patients in the "the highest, declining" and "medium, declining" trajectory groups had significantly lower AKI risk (OR 0.56; 95% CI 0.48, 0.67) and (OR 0.70; 95% CI 0.55, 0.90), respectively. ROC analysis yielded a disappointing result, with an AUC of 0.552, sensitivity of 0.25, and specificity of 0.86 when the hemoglobin threshold was set at 8â g/dl in the entire cohort. In the subgroup analysis of red blood cell transfusion, hemoglobin levels above 10â g/dl predicted higher AKI risk, and there was no correlation between hemoglobin trajectories and AKI in the non-red blood cell transfusion subgroup. Conclusion: This study identified a hemoglobin trajectory that is associated with an increased risk of AKI after cardiac surgery. It is noteworthy that fixed hemoglobin thresholds should not be applied to all patient types. In patients receiving red blood cell transfusion, maintaining hemoglobin levels above 10â g/dl through transfusion was associated with an increased risk of AKI.
ABSTRACT
BACKGROUND: Vincristine (VCR) is a chemotherapeutic drug commonly used in the treatment of Colorectal Cancer (CRC). However, VCR drug resistance may result in reduced efficacy and even failure of chemotherapy in CRC treatment. MiRNA has been demonstrated to be associated with the sensitivity of tumor cells to chemotherapy. OBJECTIVES: This study aimed to identify a novel miRNA-14669 that can reverse vincristine resistance and sensitize drug-resistant colorectal cancer cells. METHODS: High-throughput sequencing was performed to screen miRNAs that are associated with VCR drug resistance, and qRT-PCR was used for further validation. The miRNA mimic and inhibitor were designed and transfected into HCT-8,HCT-116 and HCT-8/VCR cells. Wound healing test examined the effect of the miRNA on the migration of colorectal cancer cells. Flow cytometry was used to evaluate cell apoptosis of HCT-8 cells. Survivin, Bcl-2, GST3, MDR1 and MRP1 expressions were detected by Western blot. RESULTS: The expression of miRNA-14669 in HCT-8/VCR cells was 1.925 times higher than that of the HCT-8 cells. After transfecting with mimic miRNA, HCT-8 and HCT-116 cells showed an increased survival rate. The survival rate of HCT-8/VCR cells decreased by transfection of inhibitor. The inhibitor also sensitized HCT-8 and HCT-116 cells to VCR or 5-Fluorouracil (5-FU). The migratory ability of HCT-8 and HCT-116 cells increased by miRNA mimic while reduced by miRNA inhibitor. Overexpression of miRNA-14669 reduced apoptosis, while downregulation of miRNA- 14669 increased cell apoptosis in HCT-8 cells. The mechanism of the miRNA involved in drug resistance may be attributed to apoptosis of tumor cells, detoxification of GST3 and drug efflux induced by MDR1 and MRP1. PI3K / AKT is the signaling pathway related to drug resistance. CONCLUSION: We identified a novel miRNA-14669 that may be associated with the chemotherapeutic resistance in CRC cells.
