Objective:To evaluate the oncological outcomes of ductal adenocarcinoma of the prostate(DAC)managed with radical prostatectomy(RP)or radiotherapy(RT)and optimize the proper treatment modality to DAC comprehensively.Me...Objective:To evaluate the oncological outcomes of ductal adenocarcinoma of the prostate(DAC)managed with radical prostatectomy(RP)or radiotherapy(RT)and optimize the proper treatment modality to DAC comprehensively.Methods:The cohorts included a total of 528 patients from the Surveillance,Epidemiology and End Results(SEER)database,354 receiving RP and 174 receiving RT.Cox proportional hazards regressions were performed to assess cancer specific mortality(CSM)and overall mortality(OM)between treatment groups.A competing risk analysis was further conducted.Subgroup analyses by age and level of prostate-specific antigen(PSA)were performed.Propensity score matching was implemented.Results:Patients managed with RP had lower risks of CSM and OM compared with RT(before matching:Hazard ratio[HR]=0.24,95%confidence interval[CI]0.13-0.47 and HR=0.26,95%CI 0.17-0.40,respectively;after matching:HR=0.18,95%CI 0.04-0.82 and HR=0.28,95%CI 0.11-0.70,accordingly).Subgroup analyses demonstrated that patients in the middle tertile of the age or with lower tertile PSA level managed with RP took lower risks of OM significantly(HR=0.18,95%CI 0.06-0.57,p<0.01 and HR=0.17,95%CI 0.06-0.54,p<0.01).Conclusion:Among patients with DAC,treatment with RP was associated with better survival outcomes in comparison with RT.Patients with DAC in the middle tertile of the age and with lower tertile PSA level benefited the most from RP.展开更多
Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment costs.To date,tumor cells with intrinsic softness have been identified to function as cancer s...Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment costs.To date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types.Nonetheless,the existence of soft tumor cells in bladder tumors remains elusive.Thus,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3D Matrigel culture system was to maintain the softness of tumor cells.Expression patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)were determined by Western blotting.Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TRIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.Results:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer cells.More importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor relapse.Furthermore,we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells.Simultaneously,we detected a remarkable up-regulation in ITGB8,TRIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness.Meanwhile,the soft tumor cells become more sensitive to chemotherapy after stiffening,that offers new insights for hampering tumor progression and recurrence.展开更多
3D microgels with various mechanical properties have been important platforms tumor metastasis analysis,and widely adjustable stiffness is crucial for deeper researches.Herein,by mixing biodegradable polylactic acid(P...3D microgels with various mechanical properties have been important platforms tumor metastasis analysis,and widely adjustable stiffness is crucial for deeper researches.Herein,by mixing biodegradable polylactic acid(PLA)nanofibers in the modified alginate with different concentrations of Ca^(2+),we significantly enhance the stiffness range of microgels while retaining the pore size,which provides bionic microenvironment for tumor analysis.As a proof of concept,we simulated the mechanical characteristics of breast tumors by encapsulating cells in 3D microgels with diverse stiffness,and analyzed cellular behaviors of two typical breast cancer cell lines:MCF-7 and SUM-159.Results showed that with the addition of 2.0%(w/v)PLA short nanofibers,the Young’s modulus of modified alginate increased more than three-fold.Besides preserving high survival and proliferation rates,both cells also displayed stronger migration ability in soft microgel spheres,where RT-qPCR analysis revealed the underlying changes at the genetic level.This systematic study demonstrated our method is powerful for creating widely adjustable 3D mechanical microenvironment,and the results of cellular behavior analysis shows its promising application prospects in tumorigenesis and progression.展开更多
Background:Studies have classified muscle-invasive bladder cancer(MIBC)into primary(initially muscle-invasive,PMIBC)and secondary subtypes(initially non-muscle-invasive but progresses,SMIBC),for which controversial su...Background:Studies have classified muscle-invasive bladder cancer(MIBC)into primary(initially muscle-invasive,PMIBC)and secondary subtypes(initially non-muscle-invasive but progresses,SMIBC),for which controversial survival outcomes were demonstrated.This study aimed to compare the survival outcomes between PMIBC and SMIBC patients in China.Methods:Patients diagnosed with PMIBC or SMIBC at West China Hospital from January 2009 to June 2019 were retrospectively included.Kruskal-Wallis and Fisher tests were employed to compare clinicopathological characteristics.Kaplan-Meier curves and Cox competing proportional risk model were used to compare survival outcomes.Propensity score matching(PSM)was employed to reduce the bias and subgroup analysis was used to confirm the outcomes.Results:A total of 405 MIBC patients were enrolled,including 286 PMIBC and 119 SMIBC,with a mean follow-up of 27.54 and 53.30 months,respectively.The SMIBC group had a higher proportion of older patients(17.65%[21/119]vs.9.09%[26/286]),chronic disease(32.77%[39/119]vs.22.38%[64/286]),and neoadjuvant chemotherapy(19.33%[23/119]vs.8.04%[23/286]).Before matching,SMIBC had a lower risk of overall mortality(OM)(hazard ratios[HR]0.60,95%confidence interval[CI]0.41-0.85,P=0.005)and cancer-specific mortality(CSM)(HR 0.64,95%CI 0.44-0.94,P=0.022)after the initial diagnosis.However,higher risks of OM(HR 1.47,95%CI 1.02-2.10,P=0.038)and CSM(HR 1.58,95%CI 1.09-2.29,P=0.016)were observed for SMIBC once it became muscle-invasive.After PSM,the baseline characteristics of 146 patients(73 for each group)were well matched,and SMIBC was confirmed to have an increased CSM risk(HR 1.83,95%CI 1.09-3.06,P=0.021)than PMIBC after muscle invasion.Conclusions:Compared with PMIBC,SMIBC had worse survival outcomes once it became muscle-invasive.Specific attention should be paid to non-muscle-invasive bladder cancer with a high progression risk.展开更多
Electrochemical nitrogen reduction reaction(NRR)has been considered as an appealing and sustainable method to produce ammonia from N_(2) under ambient conditions,attracting increasing interest.Limited by low solubilit...Electrochemical nitrogen reduction reaction(NRR)has been considered as an appealing and sustainable method to produce ammonia from N_(2) under ambient conditions,attracting increasing interest.Limited by low solubility of N_(2) in water and high stability of Ntriple bondN triple bond,developing NRR electrocatalysts with both strong N_(2) adsorption/activation and high electrical conductivity remain challenging.Here,we demonstrate an efficient strategy to develop NRR electrocatalyst with synergistically enhanced N_(2) adsorption/activation and electrical conductivity by heteroatom doping.Combining computational and experimental study,the DFT-designed Ti-doped SnO_(2) exhibits significantly enhanced NRR performance with ammonia yield rate of 13.09µg h^(-1) mg^(-1) at −0.2 V vs.RHE.Particularly,the Faradaic efficiency reaches up to 42.6%,outperforming most of Sn-based electrocatalysts.The fundamental mechanism for improving NRR performance of SnO_(2) by Ti doping is also revealed.Our work highlights a powerful strategy for developing high-activity electrocatalysts for NRR and beyond.展开更多
Nitrogen reduction reaction (NRR) is a clean mode of energy conversion and the development of highly efficient NRR electrocatalysts under ambient conditions for industrial application is still a big challenge. Metal-n...Nitrogen reduction reaction (NRR) is a clean mode of energy conversion and the development of highly efficient NRR electrocatalysts under ambient conditions for industrial application is still a big challenge. Metal-nitrogen-carbon (M-N-C) has emerged as a class of single atom catalyst due to the unique geometric structure, high catalytic activity, and clear selectivity. Herein, we designed a series of dual metal single atom catalysts containing adjacent M-N-C dual active centers (MN_(4)/M'N_(4)-C) as NRR electrocatalysts to uncover the structure-activity relationship. By evaluating structural stability, catalytic activity, and selectivity using density functional theory (DFT) calculations, 5 catalysts, such as CrN_(4)/M'N_(4)-C (M’ = Cr, Mn, Fe, Cu and Zn), were determined to exhibit the best NRR catalytic performance with the limiting potential ranging from -0.64 V to -0.62 V. The CrN_(4) center acted as the main catalytic site and the adjacent M'N_(4) center could enhance the NRR catalytic activity by modulation effect based on the analysis of the electronic properties including the charge density difference, partial density of states (PDOS), and Bader charge variation. This study offers useful insights on understanding the structure-activity relationship of dual metal single atom catalysts for electrochemical NRR.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.SQ2017YFC0908003)National Natural Science Foundation of China(Grant No.81702536,81770756)+3 种基金the Sichuan Science and Technology Program(2017HH0063)China Postdoctoral Science Foundation(2017M612971)Post-Doctor Research Project,West China Hospital,Sichuan University(2018HXBH085)National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(Z2018C01).
文摘Objective:To evaluate the oncological outcomes of ductal adenocarcinoma of the prostate(DAC)managed with radical prostatectomy(RP)or radiotherapy(RT)and optimize the proper treatment modality to DAC comprehensively.Methods:The cohorts included a total of 528 patients from the Surveillance,Epidemiology and End Results(SEER)database,354 receiving RP and 174 receiving RT.Cox proportional hazards regressions were performed to assess cancer specific mortality(CSM)and overall mortality(OM)between treatment groups.A competing risk analysis was further conducted.Subgroup analyses by age and level of prostate-specific antigen(PSA)were performed.Propensity score matching was implemented.Results:Patients managed with RP had lower risks of CSM and OM compared with RT(before matching:Hazard ratio[HR]=0.24,95%confidence interval[CI]0.13-0.47 and HR=0.26,95%CI 0.17-0.40,respectively;after matching:HR=0.18,95%CI 0.04-0.82 and HR=0.28,95%CI 0.11-0.70,accordingly).Subgroup analyses demonstrated that patients in the middle tertile of the age or with lower tertile PSA level managed with RP took lower risks of OM significantly(HR=0.18,95%CI 0.06-0.57,p<0.01 and HR=0.17,95%CI 0.06-0.54,p<0.01).Conclusion:Among patients with DAC,treatment with RP was associated with better survival outcomes in comparison with RT.Patients with DAC in the middle tertile of the age and with lower tertile PSA level benefited the most from RP.
基金supported by the National Natural Science Foundation of China(Nos.81902578,81974098,8197032158)China Postdoctoral Science Foundation(No.2020M670057ZX)+3 种基金Programs from Science and Technology Department of Sichuan Province(No.2021YJ0462)Post-doctoral Science Research Foundation of Sichuan University(No.2020SCU12041)Post-Doctor Research Project,West China Hospital,Sichuan University(Nos.2018HXBH084,2019HXBH092)the National key research and development program of China(No.2020YFC2008601)
文摘Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment costs.To date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types.Nonetheless,the existence of soft tumor cells in bladder tumors remains elusive.Thus,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3D Matrigel culture system was to maintain the softness of tumor cells.Expression patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)were determined by Western blotting.Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TRIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.Results:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer cells.More importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor relapse.Furthermore,we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells.Simultaneously,we detected a remarkable up-regulation in ITGB8,TRIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness.Meanwhile,the soft tumor cells become more sensitive to chemotherapy after stiffening,that offers new insights for hampering tumor progression and recurrence.
基金supported by the National Natural Science Foundation of China(Nos.22034005,81973569,and 21621003).
文摘3D microgels with various mechanical properties have been important platforms tumor metastasis analysis,and widely adjustable stiffness is crucial for deeper researches.Herein,by mixing biodegradable polylactic acid(PLA)nanofibers in the modified alginate with different concentrations of Ca^(2+),we significantly enhance the stiffness range of microgels while retaining the pore size,which provides bionic microenvironment for tumor analysis.As a proof of concept,we simulated the mechanical characteristics of breast tumors by encapsulating cells in 3D microgels with diverse stiffness,and analyzed cellular behaviors of two typical breast cancer cell lines:MCF-7 and SUM-159.Results showed that with the addition of 2.0%(w/v)PLA short nanofibers,the Young’s modulus of modified alginate increased more than three-fold.Besides preserving high survival and proliferation rates,both cells also displayed stronger migration ability in soft microgel spheres,where RT-qPCR analysis revealed the underlying changes at the genetic level.This systematic study demonstrated our method is powerful for creating widely adjustable 3D mechanical microenvironment,and the results of cellular behavior analysis shows its promising application prospects in tumorigenesis and progression.
基金China Post-doctoral Science Foundation(No.2021M692306,No.2022T150455)PostDoctor Re-search Project of West China Hospital of Sichuan University(No.2021HXBH025)
文摘Background:Studies have classified muscle-invasive bladder cancer(MIBC)into primary(initially muscle-invasive,PMIBC)and secondary subtypes(initially non-muscle-invasive but progresses,SMIBC),for which controversial survival outcomes were demonstrated.This study aimed to compare the survival outcomes between PMIBC and SMIBC patients in China.Methods:Patients diagnosed with PMIBC or SMIBC at West China Hospital from January 2009 to June 2019 were retrospectively included.Kruskal-Wallis and Fisher tests were employed to compare clinicopathological characteristics.Kaplan-Meier curves and Cox competing proportional risk model were used to compare survival outcomes.Propensity score matching(PSM)was employed to reduce the bias and subgroup analysis was used to confirm the outcomes.Results:A total of 405 MIBC patients were enrolled,including 286 PMIBC and 119 SMIBC,with a mean follow-up of 27.54 and 53.30 months,respectively.The SMIBC group had a higher proportion of older patients(17.65%[21/119]vs.9.09%[26/286]),chronic disease(32.77%[39/119]vs.22.38%[64/286]),and neoadjuvant chemotherapy(19.33%[23/119]vs.8.04%[23/286]).Before matching,SMIBC had a lower risk of overall mortality(OM)(hazard ratios[HR]0.60,95%confidence interval[CI]0.41-0.85,P=0.005)and cancer-specific mortality(CSM)(HR 0.64,95%CI 0.44-0.94,P=0.022)after the initial diagnosis.However,higher risks of OM(HR 1.47,95%CI 1.02-2.10,P=0.038)and CSM(HR 1.58,95%CI 1.09-2.29,P=0.016)were observed for SMIBC once it became muscle-invasive.After PSM,the baseline characteristics of 146 patients(73 for each group)were well matched,and SMIBC was confirmed to have an increased CSM risk(HR 1.83,95%CI 1.09-3.06,P=0.021)than PMIBC after muscle invasion.Conclusions:Compared with PMIBC,SMIBC had worse survival outcomes once it became muscle-invasive.Specific attention should be paid to non-muscle-invasive bladder cancer with a high progression risk.
基金supported by the National Natural Science Foundation of China(No.U2067216)。
文摘Electrochemical nitrogen reduction reaction(NRR)has been considered as an appealing and sustainable method to produce ammonia from N_(2) under ambient conditions,attracting increasing interest.Limited by low solubility of N_(2) in water and high stability of Ntriple bondN triple bond,developing NRR electrocatalysts with both strong N_(2) adsorption/activation and high electrical conductivity remain challenging.Here,we demonstrate an efficient strategy to develop NRR electrocatalyst with synergistically enhanced N_(2) adsorption/activation and electrical conductivity by heteroatom doping.Combining computational and experimental study,the DFT-designed Ti-doped SnO_(2) exhibits significantly enhanced NRR performance with ammonia yield rate of 13.09µg h^(-1) mg^(-1) at −0.2 V vs.RHE.Particularly,the Faradaic efficiency reaches up to 42.6%,outperforming most of Sn-based electrocatalysts.The fundamental mechanism for improving NRR performance of SnO_(2) by Ti doping is also revealed.Our work highlights a powerful strategy for developing high-activity electrocatalysts for NRR and beyond.
基金supported by the open project of State Key Laboratory of Advanced Welding and Joining,Harbin Institute of Technology (No. AWJ-19M07)the National Natural Science Foundation of China (No. U2067216)。
文摘Nitrogen reduction reaction (NRR) is a clean mode of energy conversion and the development of highly efficient NRR electrocatalysts under ambient conditions for industrial application is still a big challenge. Metal-nitrogen-carbon (M-N-C) has emerged as a class of single atom catalyst due to the unique geometric structure, high catalytic activity, and clear selectivity. Herein, we designed a series of dual metal single atom catalysts containing adjacent M-N-C dual active centers (MN_(4)/M'N_(4)-C) as NRR electrocatalysts to uncover the structure-activity relationship. By evaluating structural stability, catalytic activity, and selectivity using density functional theory (DFT) calculations, 5 catalysts, such as CrN_(4)/M'N_(4)-C (M’ = Cr, Mn, Fe, Cu and Zn), were determined to exhibit the best NRR catalytic performance with the limiting potential ranging from -0.64 V to -0.62 V. The CrN_(4) center acted as the main catalytic site and the adjacent M'N_(4) center could enhance the NRR catalytic activity by modulation effect based on the analysis of the electronic properties including the charge density difference, partial density of states (PDOS), and Bader charge variation. This study offers useful insights on understanding the structure-activity relationship of dual metal single atom catalysts for electrochemical NRR.