1.Jianpi Xiaoai Prescription Ameliorates Chemotherapy Resistance in Colon Cancer by Targeting FGF2 to Inhibit PI3K/Akt Signaling Pathway
Xiaolan JIAN ; Kangwen NING ; Jiaxiang YANG ; Shenglan KOU ; Wanting KUANG ; Ziqi WANG ; Yuqin TAN ; Puhua ZENG ; Lingjuan TAN ; Wei PENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):120-130
ObjectiveTo explore the effect and mechanism of Jianpi Xiaoai prescription (JPXA) in ameliorating the 5-fluorouracil (5-FU) resistance of colon cancer. MethodsA HCT116/5-FU resistant cell line was established. Different concentrations (10%, 15%, 20%) of JPXA-containing serum and drug-free serum were used for intervention, and 10% fetal bovine serum (10% FBS), fibroblast growth factor receptor (FGFR) inhibitor (AZD4547), and recombinant fibroblast growth factor 2 (FGF2) were set as the control groups. Sensitive HCT116 cells were used in the FGF2 group, while HCT116/5-FU cells were used in other groups. Drug resistance, the level of FGF2 in the cell culture medium, the mRNA level of FGF2 in cells, and the protein levels of FGF2/FGFR and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) were determined. The drug-resistant cells were transplanted into the axilla of nude mice to establish a tumor model. The modeled mice were allocated into model, JPXA (15 g·kg-1), 5-FU (0.02 g·kg-1), JPXA+5-FU (15 g·kg-1+0.02 g·kg-1), AZD4547 (0.012 5 g·kg-1), and AZD4547+5-FU (0.012 5 g·kg-1+0.02 g·kg-1) groups. The tumor growth and the protein levels of FGF/FGFR and PI3K/Akt in each group were observed. ResultsThe survival rate of HCT116/5-FU cells decreased in all the JPXA groups with different concentrations. The cell survival rate was decreased most obviously in the 20% JPXA group. The level of FGF2 in the cell culture medium and the mRNA level of FGF2 in cells of each JXPA group decreased, and the decrease was the most significant in the 20% group (P<0.01). HCT116/5-FU cells showed up-regulated protein levels of FGF2 and phosphorylated fibroblast growth factor receptor 1 (p-FGFR1), but down-regulated protein level of FGFR1 (P<0.01). JPXA down-regulated the expression of FGF2 and p-FGFR1 and up-regulated the expression of FGFR1 (P<0.05). In addition, JPXA down-regulated the expression levels of phosphorylated protein kinase B (p-Akt) and phosphorylated mammalian target of rapamycin (p-mTOR), while up-regulating the expression levels of Akt and Bcl-2-asociated death promoter (Bad) (P<0.05). Animal experiments showed that the JPXA combined with 5-FU significantly inhibited the growth of drug-resistant tumors, reduced the protein levels of FGF2, p-FGFR1, phosphorylated phosphatidylinositol-3-kinase (p-PI3K), p-Akt, and p-mTOR, and increased the expression of Bad. It indicated that JPXA can inhibit the FGF2/FGFR1 signaling in colon cancer and regulate PI3K/Akt and downstream signaling pathways. ConclusionJPXA can ameliorate the chemotherapy resistance of colon cancer through down-regulating FGF2 expression and inhibiting the activation of the PI3K/Akt signaling pathway.
2.Development and validation of a risk prediction model for early postoperative delirium in lung transplant patients
Wanting KOU ; Yinghua CAI ; Haiqin ZHOU ; Xia WAN ; Qiong WU
Chinese Journal of Nursing 2025;60(19):2348-2356
Objective To understand the current situation and influencing factors of delirium in lung transplant patients in the early postoperative period,and to construct and verify a risk prediction model.Methods The convenience sampling method was used to select patients who were admitted to a tertiary general hospital in Jiangsu Province for lung transplantation from June 2023 to November 2024.Lasso regression was used to screen variables,and logistic regression analysis was used to explore the influencing factors of early postoperative delirium in lung transplantation patients,and the risk prediction model was constructed and nomogram was drawn.The area under the working curve(AUC)of the subjects and the Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model.Internal validation of the model was performed by repeated sampling 1000 times using Bootstrap method.Results A total of 228 lung transplant patients were included in this study,of which 76 developed delirium in the early postoperative period,with an incidence of 33.33%.Age≥51.5 years,hypertension combined with diabetes mellitus,the Lung Allocation System(LAS)score ≥ 75.63,the duration of mean arterial pressure less than 70 mmHg≥ 12.50 min,intraoperative red blood cell transfusion≥750 ml,and midazolam dosage≥102.50 mg were the independent risk factors for early postoperative delirium in lung transplantation(P<0.05).The AUC of the model was 0.771;the optimal cut-off value was 0.334;the sensitivity and specificity were both 0.724.The results of Hosmer-Lemeshow test showed that x2=5.677,P=0.683;the internal verification showed that the AUC of the model was 0.737,and the absolute error of the actual and predicted values of the calibration curve was 0.023,and the calibration curve was close to the ideal curve.Conclusion Age,hypertension combined with diabetes mellitus,LAS score,duration of mean arterial pressure less than 70 mmHg,amount of intraoperative red blood cell transfusion,and midazolam dosage are the influencing factors for early postoperative delirium in lung transplant patients.The risk prediction model constructed in this study has good predictive performance and can be used as a risk prediction tool for early postoperative delirium in lung transplant patients,helping to timely and accurately identify high-risk groups of delirium,helping to reduce the incidence of early postoperative delirium,and improve patient prognosis.
3.Development and validation of a risk prediction model for early postoperative delirium in lung transplant patients
Wanting KOU ; Yinghua CAI ; Haiqin ZHOU ; Xia WAN ; Qiong WU
Chinese Journal of Nursing 2025;60(19):2348-2356
Objective To understand the current situation and influencing factors of delirium in lung transplant patients in the early postoperative period,and to construct and verify a risk prediction model.Methods The convenience sampling method was used to select patients who were admitted to a tertiary general hospital in Jiangsu Province for lung transplantation from June 2023 to November 2024.Lasso regression was used to screen variables,and logistic regression analysis was used to explore the influencing factors of early postoperative delirium in lung transplantation patients,and the risk prediction model was constructed and nomogram was drawn.The area under the working curve(AUC)of the subjects and the Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model.Internal validation of the model was performed by repeated sampling 1000 times using Bootstrap method.Results A total of 228 lung transplant patients were included in this study,of which 76 developed delirium in the early postoperative period,with an incidence of 33.33%.Age≥51.5 years,hypertension combined with diabetes mellitus,the Lung Allocation System(LAS)score ≥ 75.63,the duration of mean arterial pressure less than 70 mmHg≥ 12.50 min,intraoperative red blood cell transfusion≥750 ml,and midazolam dosage≥102.50 mg were the independent risk factors for early postoperative delirium in lung transplantation(P<0.05).The AUC of the model was 0.771;the optimal cut-off value was 0.334;the sensitivity and specificity were both 0.724.The results of Hosmer-Lemeshow test showed that x2=5.677,P=0.683;the internal verification showed that the AUC of the model was 0.737,and the absolute error of the actual and predicted values of the calibration curve was 0.023,and the calibration curve was close to the ideal curve.Conclusion Age,hypertension combined with diabetes mellitus,LAS score,duration of mean arterial pressure less than 70 mmHg,amount of intraoperative red blood cell transfusion,and midazolam dosage are the influencing factors for early postoperative delirium in lung transplant patients.The risk prediction model constructed in this study has good predictive performance and can be used as a risk prediction tool for early postoperative delirium in lung transplant patients,helping to timely and accurately identify high-risk groups of delirium,helping to reduce the incidence of early postoperative delirium,and improve patient prognosis.
4.Effect of gender difference on the model of rheumatoid arthritis induced by bovine type Ⅱ collagen
Wenting SUN ; Yingying WAN ; Jiaxi YANG ; Wenqian WANG ; Haonan WANG ; Wanting YE ; Qiuai KOU
Chinese Journal of Comparative Medicine 2024;34(2):25-34
Objective To establish female and male bovine collagen-induced arthritis(CIA)models and compare the effects of gender differences on joint and extra-articular manifestations of the CIA model.Methods The CIA model was induced by injection of bovine type Ⅱ collagen and Freund's complete adjuvant into female and male SD rats.The general condition,arthritis index,foot swelling,serum proinflammatory factors and plasminogen activator inhibitor levels,spleen index,knee and ankle joint pathologies,right rear paw bone destruction,and pulmonary interstitial lesions were evaluated.Results The arthritis index of female CIA rats was significantly higher than that of male CIA rats on day 21 after initial immunization(P<0.05),but no significant difference was found in the degree of foot swelling between the two groups at any time point(P>0.05).Serum tumor necrosis factor α,interleukin-1β,and the spleen index of female CIA rats were significantly higher than those of male CIA rats(P<0.05,P<0.001).No significant difference was found in plasminogen activator inhibitor levels(P>0.05).The scores of inflammatory cell infiltration and synovial hyperplasia in the knee and ankle pathologies of female CIA rats were significantly higher than those of male CIA rats(P<0.05),and cartilage damage of the knee joint and bone damage of the right rear paw of female CIA rats were significantly higher than that of male rats(P<0.05).Both male and female CIA rats showed pulmonary interstitial inflammatory cell infiltration and mild fibrosis,but the pulmonary interstitial lesions in females were more severe than those in males.Conclusions Female and male CIA models established in SD rats have arthritis and pulmonary interstitial lesions,but the lesion degree in female CIA rats is more serious.When using CIA models for RA-related research,attention should be focused on the effect of gender differences.

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