Background: Hypoxia-induced chemoresistance is recognized as a major obstacle to the successful treatment of gastric cancer (GC). Circular RNAs (circRNAs) have been proposed to implicate in resistance to chemotherapeutic drugs. However, whether circNRIP1 is involved in the development of hypoxia-induced 5-fluorouracil (5-FU) resistance remains largely unknown. Methods: Gene expression was evaluated using quantitative real-time polymerase chain reaction and Western blot. The impact of circNRIP1 on hypoxia-induced resistance to 5-FU was investigated by determining glucose consumption, lactate production and glucose-6-phosphate (G6P) levels. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide assay was performed to assess cell survival. Results: circNRIP1 was upregulated in GC cells. Hypoxia induced the upregulation of circNRIP1 and reduced the sensitivity of GC cells to 5-FU, as evidenced by the increase in multidrug resistance 1 gene, P-glycoprotein, hypoxia-inducible factor-1α (HIF-1α) and G6P levels, glucose consumption, lactate production, as well as cell survival. Silencing of circNRIP1 enhanced the sensitivity of GC cells to 5-FU under a hypoxic condition. microRNA (miR)-138-5p was confirmed as a downstream target gene of circNRIP1, and upregulation of miR-138-5p could reverse the effect of circNRIP1 on hypoxia-induced 5-FU resistance. Additionally, HIF-1α was a target gene of miR-138-5p. More significantly, the effect of circNRIP1 on hypoxia-induced 5-FU resistance was markedly blocked by 2-DG treatment. Conclusion: circNRIP1 functioned as a miR-138-5p sponge to enhance hypoxia-induced resistance to 5-FU through modulation of HIF-1α-dependent glycolysis, which provides a novel potential approach to overcome hypoxia-induced 5-FU resistance in GC.
Objective. To explore the causes of urogenic sepsis in patients after flexible ureteroscopic lithotripsy and analyze the preventive strategies. Methods. A total of 240 patients who underwent flexible ureteroscopic lithotripsy in our hospital from January 2019 to June 2022 were selected and divided into 2 groups according to whether postoperative ureteral sepsis occurred. 24 cases occurred in the observation group. Logistics multivariate regression analysis was used to analyze the risk factors of urogenic sepsis after flexible ureteroscopic lithotripsy, and the serum albumin (ALB), the peripheral blood neutrophil-to-lymphocyte ratio (NLR), and the level of procalcitonin (PCT) were correlated, and the ROC curve was used to analyze the predictive value of each index for urosepsis. Results. Univariate analysis showed that there were differences in gender, age, diabetes, stone diameter, and urine culture ratio between the two groups ( P < 0.05 ). The results of multivariate regression analysis showed that female, age ≥60 years, stone diameter >2.5 cm, and positive urine culture were the main influencing factors for the occurrence of urogenic sepsis. After operation, the ALB levels in the two groups were lower than those before operation, and the levels of NLR and PCT in the two groups were higher than those before operation; the ALB levels in the observation group were lower than those in the control group, and the NLR and PCT in the observation group were higher than those in the control group ( P < 0.05 ). According to Spearman’s correlation analysis, ALB was negatively correlated with the occurrence of uremia ( P < 0.05 ), r = −0.320, NLR and PCT were positively correlated with the occurrence of uremia ( P < 0.05 ), r = 0.313, respectively, and 0.417; in addition, Pearson’s correlation analysis showed that ALB was negatively correlated with NLR and PCT in the two groups ( P < 0.05 , r = −0.507, −0.605 in the control group, respectively, and r were −0.452 and −0.412 in the observation group). There was a positive correlation between NLR and PCT ( P < 0.05 ), r = 0.840, and there was no correlation between NLR and PCT in the observation group ( P > 0.05 ). According to the ROC curve analysis, the predictive value AUC of ALB, NLR, PCT and combined use were 0.808, 0.801, 0.901, and 0.925 ( P < 0.05 ). Conclusion. Gender, age, stone diameter, and urine culture results are the main influencing factors for the occurrence of urinary sepsis. Therefore, preventive measures should be strengthened for this group of patients. In addition, the combined use of postoperative ALT, NLR, and PCT level tests can be better.
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