Objective:To analyze the risk factors for infection after surgery for complex kidney stones and to investigate their correlation with the expressions of microRNA (miRNA)-451 and miRNA-218, as well as the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.Methods:A total of 213 patients with complex kidney stones who were admitted to Ningbo Fourth Hospital from March 2021 to March 2024 were included in this study. All patients underwent percutaneous nephrolithotomy (PCNL), and the occurrence of postoperative infections was recorded. The expression levels of serum miRNA-145 and miRNA-218 were measured using quantitative real-time PCR (qRT-PCR), while the expression of PI3K and Akt proteins was determined using Western blot assay. Multivariate logistic regression was performed to analyze the risk factors associated with infection after surgery for complex kidney stones. The expression levels of serum miRNA-145 and miRNA-218, as well as the grayscale values of PI3K and Akt proteins, were compared between the infection and non-infection groups. Pearson correlation analysis was conducted to assess the correlation between the expression of miRNA-145, miRNA-218, PI3K, and Akt and the occurrence of postoperative infections.Results:Among the 213 patients with complex kidney stones, 46 (21.60%) developed infections after PCNL, while 167 (78.40%) did not. There were no statistically significant differences between the two groups in terms of sex, age, history of hypertension, history of coronary heart disease, and history of smoking (all P > 0.05). The proportion of patients in the infection group with stone diameters ≥ 3 cm was higher than that in the non-infection group [78.26% (36/46) vs. 47.31% (79/167)]. The proportion of patients with diabetes in the infection group was higher than that in the non-infection group [30.43% (14/46) vs. 10.79% (18/167)]. Moreover, the incidence of moderate to severe hydronephrosis in the infection group was higher than that in the non-infection group [ 89.13% (41/46) vs. 68.86% (115/167)]. The proportion of patients with a surgical duration of ≥ 60 minutes in the infection group was higher than that in the non-infection group [86.96% (40/46) vs. 61.68% (103/167)]. Additionally, the proportion of patients in the infection group with a duration of postoperative urinary catheterization of ≥ 7 days was significantly higher than that in the non-infection group [69.57% (32/46) vs. 23.95% (40/167)]. The differences in stone diameter ≥ 3 cm, presence of diabetes, moderate to severe hydronephrosis, surgical duration ≥ 60 minutes, and postoperative urinary catheterization duration ≥ 7 days between the two groups were statistically significant ( χ2 = 13.91, 10.91, 7.55, 10.44, 33.53, all P < 0.05). Factors such as stone diameter ≥ 3 cm, presence of diabetes, moderate to severe hydronephrosis, surgical duration ≥ 60 minutes, and postoperative urinary catheterization duration ≥ 7 days were identified as independent risk factors for infection after surgery for complex kidney stones ( OR = 7.192, 4.870, 5.089, 12.988, 9.007). In the infection group, the relative expression levels of serum miRNA-145 and miRNA-218 were (1.37 ± 0.38) and (0.76 ± 0.21), respectively, which were significantly lower than those in the non-infection group [(2.86 ± 0.62), (1.97 ± 0.38), t = 15.50, 20.71, both P < 0.001]. In the infection group, the grayscale values of PI3K protein expression and Akt protein expression were (1.23 ± 0.31) and (0.98 ± 0.23), respectively, which were significantly higher than those in the non-infection group [(0.68 ± 0.20), (0.42 ± 0.12), t = 14.49, 22.36, both P < 0.001]. Pearson correlation analysis revealed that the expressions of miRNA-145 and miRNA-218 were negatively correlated with postoperative infections, while the expressions of PI3K and Akt were positively correlated with postoperative infection ( r = -0.57, -0.48, 0.62, 0.59, all P < 0.001). Conclusions:Postoperative infection in complex kidney stones is influenced by multiple factors, among which stone diameter, presence of diabetes, degree of hydronephrosis, surgical duration, and duration of postoperative urinary catheterization are independent risk factors. Additionally, patients with postoperative infection exhibit low expression levels of miRNA-145 and miRNA-218, while PI3K and Akt proteins show high expression levels.

Objective:To analyze the risk factors for infection after surgery for complex kidney stones and to investigate their correlation with the expressions of microRNA (miRNA)-451 and miRNA-218, as well as the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.Methods:A total of 213 patients with complex kidney stones who were admitted to Ningbo Fourth Hospital from March 2021 to March 2024 were included in this study. All patients underwent percutaneous nephrolithotomy (PCNL), and the occurrence of postoperative infections was recorded. The expression levels of serum miRNA-145 and miRNA-218 were measured using quantitative real-time PCR (qRT-PCR), while the expression of PI3K and Akt proteins was determined using Western blot assay. Multivariate logistic regression was performed to analyze the risk factors associated with infection after surgery for complex kidney stones. The expression levels of serum miRNA-145 and miRNA-218, as well as the grayscale values of PI3K and Akt proteins, were compared between the infection and non-infection groups. Pearson correlation analysis was conducted to assess the correlation between the expression of miRNA-145, miRNA-218, PI3K, and Akt and the occurrence of postoperative infections.Results:Among the 213 patients with complex kidney stones, 46 (21.60%) developed infections after PCNL, while 167 (78.40%) did not. There were no statistically significant differences between the two groups in terms of sex, age, history of hypertension, history of coronary heart disease, and history of smoking (all P > 0.05). The proportion of patients in the infection group with stone diameters ≥ 3 cm was higher than that in the non-infection group [78.26% (36/46) vs. 47.31% (79/167)]. The proportion of patients with diabetes in the infection group was higher than that in the non-infection group [30.43% (14/46) vs. 10.79% (18/167)]. Moreover, the incidence of moderate to severe hydronephrosis in the infection group was higher than that in the non-infection group [ 89.13% (41/46) vs. 68.86% (115/167)]. The proportion of patients with a surgical duration of ≥ 60 minutes in the infection group was higher than that in the non-infection group [86.96% (40/46) vs. 61.68% (103/167)]. Additionally, the proportion of patients in the infection group with a duration of postoperative urinary catheterization of ≥ 7 days was significantly higher than that in the non-infection group [69.57% (32/46) vs. 23.95% (40/167)]. The differences in stone diameter ≥ 3 cm, presence of diabetes, moderate to severe hydronephrosis, surgical duration ≥ 60 minutes, and postoperative urinary catheterization duration ≥ 7 days between the two groups were statistically significant ( χ2 = 13.91, 10.91, 7.55, 10.44, 33.53, all P < 0.05). Factors such as stone diameter ≥ 3 cm, presence of diabetes, moderate to severe hydronephrosis, surgical duration ≥ 60 minutes, and postoperative urinary catheterization duration ≥ 7 days were identified as independent risk factors for infection after surgery for complex kidney stones ( OR = 7.192, 4.870, 5.089, 12.988, 9.007). In the infection group, the relative expression levels of serum miRNA-145 and miRNA-218 were (1.37 ± 0.38) and (0.76 ± 0.21), respectively, which were significantly lower than those in the non-infection group [(2.86 ± 0.62), (1.97 ± 0.38), t = 15.50, 20.71, both P < 0.001]. In the infection group, the grayscale values of PI3K protein expression and Akt protein expression were (1.23 ± 0.31) and (0.98 ± 0.23), respectively, which were significantly higher than those in the non-infection group [(0.68 ± 0.20), (0.42 ± 0.12), t = 14.49, 22.36, both P < 0.001]. Pearson correlation analysis revealed that the expressions of miRNA-145 and miRNA-218 were negatively correlated with postoperative infections, while the expressions of PI3K and Akt were positively correlated with postoperative infection ( r = -0.57, -0.48, 0.62, 0.59, all P < 0.001). Conclusions:Postoperative infection in complex kidney stones is influenced by multiple factors, among which stone diameter, presence of diabetes, degree of hydronephrosis, surgical duration, and duration of postoperative urinary catheterization are independent risk factors. Additionally, patients with postoperative infection exhibit low expression levels of miRNA-145 and miRNA-218, while PI3K and Akt proteins show high expression levels.

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.
Humans ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Cisplatin/metabolism* ; Esophageal Neoplasms/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Growth Differentiation Factor 15/therapeutic use* ; Receptor, Transforming Growth Factor-beta Type II/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic

0.05),but the rate of GG genotype in cerebral infarction group was significantly higher than that in normal control group(P