Objectives:PI3K plays a pivotal role in the inflammatory response by modulating the production and release of inflammatory factors.Pik3cb is one of the subunits of PI3K,and its specific role in myocardium inflammation...Objectives:PI3K plays a pivotal role in the inflammatory response by modulating the production and release of inflammatory factors.Pik3cb is one of the subunits of PI3K,and its specific role in myocardium inflammation remains unelucidated.This study aimed to investigate the role of Pik3cb in the inflammatory response and to elucidate the underlying mechanism.Methods:An inflammation model was established using H9c2 cells treated with LPS and ATP,and Pik3cb expression was evaluated in this model system.Subsequently,an overexpression model was constructed by transfecting cells with a Pik3cb overexpression plasmid,after which the effects of Pik3cb overexpression on the PI3K/AKT and NF-κB/NLRP3 inflammatory signaling pathways were assessed.Results:These analyses revealed that the expression and distribution of Pik3cb were significantly reduced in the LPS/ATP-induced cellular inflammation model group,whereas plasmid-mediated overexpression of Pik3cb significantly inhibited the activation of the PI3K/AKT signaling pathway in response to LPS/ATP stimulation.Additionally,the LPS/ATP-induced activation of the NF-κB/NLRP3 axis was significantly inhibited following Pik3cb overexpression.Conclusion:This study demonstrates that Pik3cb acts as a negative regulator of LPS/ATP-induced inflammation in cardiomyocytes,exerting anti-inflammatory effects by inhibiting the PI3K/AKT/NF-κB/NLRP3 signaling axis.These findings provide a potential therapeutic target for the treatment of myocardial inflammation.展开更多
Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chine...Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy.Methods: Clinical data of patients with mRCC who received sorafenib(400 mg twice daily; 4 weeks) or sunitinib(50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival(OS), progression-free survival(PFS), adverse events(AEs), and QoL(SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL.Results: Medical records of 184 patients(110 in the sorafenib group and 74 in the sunitinib group) were reviewed.PFS and OS were comparable between the sorafenib and sunitinib groups(both P > 0.05).The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group(36.5% vs. 10.9%,P< 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group(62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs(P = 0.017 and 0.005).Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.展开更多
Background:Hypoalbuminemia adversely affects the clinical outcomes of various cancers.The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metast...Background:Hypoalbuminemia adversely affects the clinical outcomes of various cancers.The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metastatic renal cell carcinoma(mRCC) who received sorafenib or sunitinib as first-line treatment.Methods:In this single-center,retrospective study,we assessed the progression-free survival(PFS) and overall survival(OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment.PFS and OS were compared between patients with post-treatment hypoalbuminemia(post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level(albumin level≥36.4 g/L).The Memorial Sloan Kettering Cancer Center(MSKCC)risk model stratified mRCC patients into three risk categories.Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models.Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis.Results:The median PFS and OS of the 184 patients were 11 months(95%confidence interval[CI]9-12 months)and 23 months(95%CI 19-33 months),respectively.Patients with post-treatment hypoalbuminemia had significantly shorter median PFS(6 months[95%CI 5-7 months]) and OS(11 months[95%CI 9-15 months]) than patients who had normal post-treatment albumin levels(PFS:12 months[95%CI 11-16 months],P < 0.001;OS:31 months[95%CI24-42 months],P < 0.001),respectively.Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS(hazard ratio[HR],2.113;95%CI 1.390-3.212;P < 0.001) and OS(HR,2.388;95%CI 1.591-3.585;P < 0.001).Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS.The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS(c-index:0.68 and 0.73,respectively) compared with the basic MSKCC risk model(c-index:0.67 and 0.70,respectively).The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis(both P < 0.001).Conclusions:Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors.Additionally,integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.展开更多
基金supported by Medical and Health Technology Project of Shandong Province(202402020509)20 New Universities Funding Project of Jinan(202228121).
文摘Objectives:PI3K plays a pivotal role in the inflammatory response by modulating the production and release of inflammatory factors.Pik3cb is one of the subunits of PI3K,and its specific role in myocardium inflammation remains unelucidated.This study aimed to investigate the role of Pik3cb in the inflammatory response and to elucidate the underlying mechanism.Methods:An inflammation model was established using H9c2 cells treated with LPS and ATP,and Pik3cb expression was evaluated in this model system.Subsequently,an overexpression model was constructed by transfecting cells with a Pik3cb overexpression plasmid,after which the effects of Pik3cb overexpression on the PI3K/AKT and NF-κB/NLRP3 inflammatory signaling pathways were assessed.Results:These analyses revealed that the expression and distribution of Pik3cb were significantly reduced in the LPS/ATP-induced cellular inflammation model group,whereas plasmid-mediated overexpression of Pik3cb significantly inhibited the activation of the PI3K/AKT signaling pathway in response to LPS/ATP stimulation.Additionally,the LPS/ATP-induced activation of the NF-κB/NLRP3 axis was significantly inhibited following Pik3cb overexpression.Conclusion:This study demonstrates that Pik3cb acts as a negative regulator of LPS/ATP-induced inflammation in cardiomyocytes,exerting anti-inflammatory effects by inhibiting the PI3K/AKT/NF-κB/NLRP3 signaling axis.These findings provide a potential therapeutic target for the treatment of myocardial inflammation.
基金supported by the National Natural Science Foundation of China(Nos.81402084,81472378)the Shanghai Municipal Commission of Health and Family Planning(No.2013SY027)the Incubating Program for Clinical Research and Innovation of Renji Hospital(No.PYXJS16-008)
文摘Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy.Methods: Clinical data of patients with mRCC who received sorafenib(400 mg twice daily; 4 weeks) or sunitinib(50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival(OS), progression-free survival(PFS), adverse events(AEs), and QoL(SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL.Results: Medical records of 184 patients(110 in the sorafenib group and 74 in the sunitinib group) were reviewed.PFS and OS were comparable between the sorafenib and sunitinib groups(both P > 0.05).The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group(36.5% vs. 10.9%,P< 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group(62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs(P = 0.017 and 0.005).Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.
基金supported by the National Natural Science Foundation of China(Grant Nos.81402084,81472378,and 81672513)incubating program for clinical research and innovation of Renji hospital(Grant No.PYXJS16-008)the Shanghai Municipal Commission of Health and Family Planning(Grant No.2013SY027)
文摘Background:Hypoalbuminemia adversely affects the clinical outcomes of various cancers.The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metastatic renal cell carcinoma(mRCC) who received sorafenib or sunitinib as first-line treatment.Methods:In this single-center,retrospective study,we assessed the progression-free survival(PFS) and overall survival(OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment.PFS and OS were compared between patients with post-treatment hypoalbuminemia(post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level(albumin level≥36.4 g/L).The Memorial Sloan Kettering Cancer Center(MSKCC)risk model stratified mRCC patients into three risk categories.Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models.Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis.Results:The median PFS and OS of the 184 patients were 11 months(95%confidence interval[CI]9-12 months)and 23 months(95%CI 19-33 months),respectively.Patients with post-treatment hypoalbuminemia had significantly shorter median PFS(6 months[95%CI 5-7 months]) and OS(11 months[95%CI 9-15 months]) than patients who had normal post-treatment albumin levels(PFS:12 months[95%CI 11-16 months],P < 0.001;OS:31 months[95%CI24-42 months],P < 0.001),respectively.Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS(hazard ratio[HR],2.113;95%CI 1.390-3.212;P < 0.001) and OS(HR,2.388;95%CI 1.591-3.585;P < 0.001).Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS.The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS(c-index:0.68 and 0.73,respectively) compared with the basic MSKCC risk model(c-index:0.67 and 0.70,respectively).The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis(both P < 0.001).Conclusions:Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors.Additionally,integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.
