This paper aims at analyzing the shapes of the bounded traveling wave solu- tions for a class of nonlinear wave equation with a quintic term and obtaining its damped oscillatory solutions. The theory and method of pla...This paper aims at analyzing the shapes of the bounded traveling wave solu- tions for a class of nonlinear wave equation with a quintic term and obtaining its damped oscillatory solutions. The theory and method of planar dynamical systems are used to make a qualitative analysis to the planar dynamical system which the bounded traveling wave solutions of this equation correspond to. The shapes, existent number, and condi- tions are presented for all bounded traveling wave solutions. The bounded traveling wave solutions are obtained by the undetermined coefficients method according to their shapes, including exact expressions of bell and kink profile solitary wave solutions and approxi- mate expressions of damped oscillatory solutions. For the approximate damped oscillatory solution, using the homogenization principle, its error estimate is given by establishing the integral equation, which reflects the relation between the exact and approximate so- lutions. It can be seen that the error is infinitesimal decreasing in the exponential form.展开更多
BACKGROUND Aberrant expression of stanniocalcin 2 (STC2) is implicated in colon adenocarcinoma (COAD). A previous study identified that STC2 functions as a tumor promoter to drive development of some cancers, but the ...BACKGROUND Aberrant expression of stanniocalcin 2 (STC2) is implicated in colon adenocarcinoma (COAD). A previous study identified that STC2 functions as a tumor promoter to drive development of some cancers, but the role of its overexpression in the development of COAD remains unclear. AIM To evaluate the regulation mechanism of STC2 overexpression in COAD. METHODS The expression of STC2 in COAD was assessed by TCGA COAD database and GEO (GSE50760). Methylation level of the STC2 promoter was evaluated with beta value in UALCAN platform, and the correlation between STC2 expression and survival rate was investigated with TCGA COAD. Transcription binding site prediction was conducted by TRANSFAC and LASAGNA, and a luciferase reporter system was used to identify STC2 promoter activity in several cell lines, including HEK293T, NCM460, HT29, SW480, and HCT116. Western blotting was performed to evaluate the role of Sp1 on the expression of STC2. RESULTS The central finding of this work is that STC2 is overexpressed in COAD tissues and positively correlated with poor prognosis. Importantly, the binding site of the transcription factor Sp1 is widely located in the promoter region of STC2. A luciferase reporter system was successfully constructed to analyze the transcription activity of STC2, and knocking down the expression of Sp1 significantly inhibited the transcription activity of STC2. Furthermore, inhibition of Sp1 remarkably decreased protein levels of STC2. CONCLUSION Our data provide evidence that the transcription factor Sp1 is essential for the overexpression of STC2 in COAD through activation of promoter activity. Taken together, our finding provides new insights into the mechanism of oncogenic function of COAD by STC2.展开更多
Hepatic arterial infusion chemotherapy(HAIC)using a combination of oxaliplatin,fluorouracil,and leucovorin(FOLFOX)has shown promise for hepatocellular carcinoma(HCC)patients classified under Barcelona Clinic Liver Can...Hepatic arterial infusion chemotherapy(HAIC)using a combination of oxaliplatin,fluorouracil,and leucovorin(FOLFOX)has shown promise for hepatocellular carcinoma(HCC)patients classified under Barcelona Clinic Liver Cancer(BCLC)stage C.In China,the combined therapy of camrelizumab and apatinib is now an approved first-line approach for inoperable HCC.This study(NCT04191889)evaluated the benefit of combining camrelizumab and apatinib with HAIC-FOLFOX for HCC patients in BCLC stage C.Eligible patients were given a maximum of six cycles of HAIC-FOLFOX,along with camrelizumab and apatinib,until either disease progression or intolerable toxicities emerged.The primary outcome measured was the objective response rate(ORR)based on the Response Evaluation Criteria in Solid Tumors(RECIST)v1.1.Thirty-five patients were enrolled.Based on RECIST v1.1 criteria,the confirmed ORR stood at 77.1%(95%CI:59.9%to 89.6%),with a disease control rate of 97.1%(95%CI:85.1%to 99.9%).The median progression-free survival was 10.38 months(95%CI:7.79 to 12.45).Patient quality of life had a transient deterioration within four cycles of treatment,and generally recovered thereafter.The most frequent grade≥3 or above treatment-related adverse events included reduced lymphocyte count(37.1%)and diminished neutrophil count(34.3%).The combination of camrelizumab,apatinib,and HAIC demonstrated encouraging results and manageable safety concerns for HCC at BCLC stage C.展开更多
The exact parametric representations of the traveling wave solutions for a nonlinear elastic rod equation are considered. By using the method of planar dynamical systems, in different parameter regions, the phase port...The exact parametric representations of the traveling wave solutions for a nonlinear elastic rod equation are considered. By using the method of planar dynamical systems, in different parameter regions, the phase portraits of the corresponding traveling wave system are given. Exact explicit kink wave solutions, periodic wave solutions and some unbounded wave solutions are obtained.展开更多
For the planar Z2-equivariant cubic systems having two elementary focuses, the characterization of a bi-center problem and shortened expressions of the first six Lyapunov constants are completely solved. The necessary...For the planar Z2-equivariant cubic systems having two elementary focuses, the characterization of a bi-center problem and shortened expressions of the first six Lyapunov constants are completely solved. The necessary and sufficient conditions for the existence of the bi-center are obtained. On the basis of this work, in this paper, we show that under small Z2-equivariant cubic perturbations, this cubic system has at least 13 limit cycles with the scheme 1 6 ∪ 6.展开更多
Background:The presence of delayed treatment effects(DTE)is common in immuno-oncology trials.However,conventional trial designs often overlook the potential presence of DTE,which can result in an underestimation of th...Background:The presence of delayed treatment effects(DTE)is common in immuno-oncology trials.However,conventional trial designs often overlook the potential presence of DTE,which can result in an underestimation of the required sample size and loss of statistical power.Conversely,when there is actually no apparent delay in treatment effects,alternative trial designs for addressing DTE may lead to an over-estimation of sample size and unnecessary prolongation of the trial duration.To mitigate this challenge,we propose the use of a DTE predicting(DTEP)model to better guide immuno-oncology trial designs.Methods:The DTEP model was developed and validated using data from 147 pub-lished randomized immuno-oncology trials.The eligible trials were divided into a training set(approximately 75%of the trials)and a test set(approximately 25%).We employed linear discriminant analysis(LDA)to develop the DTEP model for pre-dicting the DTE status using baseline characteristics available at the trial design stage.The receiver operating characteristic(ROC)curve was utilized to assess the ability of the model to distinguish between trials with and without DTE.We further re-conducted the JUPITER-02 trial in a simulation setting,employing three design approaches to assess the potential benefits of utilizing the DTEP model.Results:Baseline characteristics available during the trial design stage,including cancer type,line of treatment,and experimental and control arm regimens were incorporated,and high accuracy in predicting the DTE status in both the training set(area under the operating characteristic curve(AUC),0.79;95%confidence interval(CI),0.71-0.88)and test set(AUC,0.78;95%CI,0.66-0.90)was achieved.Notably,the model successfully predicted the DTE status in two randomized trials among the test sets that were conducted by our team(ESCORT-1st(absence of DTE)and JUPITER-02(presence of DTE)).In silico re-conduct of the JUPITER-02 trial further showed that the statistical power would be markedly improved when trial designs were guided by the DTEP model.Conclusions:The DTEP model can significantly enhance the precision and effectiveness of immuno-oncology trial designs,thereby facilitating the discovery of effective im-munotherapeutics in a more streamlined and expedited manner.展开更多
基金Project supported by the National Natural Science Foundation of China(No.11071164)the Innovation Program of Shanghai Municipal Education Commission(No.13ZZ118)+1 种基金the Shanghai Leading Academic Discipline Project(No.XTKX2012)the Innovation Fund Project for Graduate Stu-dent of Shanghai(No.JWCXSL1201)
文摘This paper aims at analyzing the shapes of the bounded traveling wave solu- tions for a class of nonlinear wave equation with a quintic term and obtaining its damped oscillatory solutions. The theory and method of planar dynamical systems are used to make a qualitative analysis to the planar dynamical system which the bounded traveling wave solutions of this equation correspond to. The shapes, existent number, and condi- tions are presented for all bounded traveling wave solutions. The bounded traveling wave solutions are obtained by the undetermined coefficients method according to their shapes, including exact expressions of bell and kink profile solitary wave solutions and approxi- mate expressions of damped oscillatory solutions. For the approximate damped oscillatory solution, using the homogenization principle, its error estimate is given by establishing the integral equation, which reflects the relation between the exact and approximate so- lutions. It can be seen that the error is infinitesimal decreasing in the exponential form.
基金the Natural Science Foundation of Liaoning Province,China,No.20180550769
文摘BACKGROUND Aberrant expression of stanniocalcin 2 (STC2) is implicated in colon adenocarcinoma (COAD). A previous study identified that STC2 functions as a tumor promoter to drive development of some cancers, but the role of its overexpression in the development of COAD remains unclear. AIM To evaluate the regulation mechanism of STC2 overexpression in COAD. METHODS The expression of STC2 in COAD was assessed by TCGA COAD database and GEO (GSE50760). Methylation level of the STC2 promoter was evaluated with beta value in UALCAN platform, and the correlation between STC2 expression and survival rate was investigated with TCGA COAD. Transcription binding site prediction was conducted by TRANSFAC and LASAGNA, and a luciferase reporter system was used to identify STC2 promoter activity in several cell lines, including HEK293T, NCM460, HT29, SW480, and HCT116. Western blotting was performed to evaluate the role of Sp1 on the expression of STC2. RESULTS The central finding of this work is that STC2 is overexpressed in COAD tissues and positively correlated with poor prognosis. Importantly, the binding site of the transcription factor Sp1 is widely located in the promoter region of STC2. A luciferase reporter system was successfully constructed to analyze the transcription activity of STC2, and knocking down the expression of Sp1 significantly inhibited the transcription activity of STC2. Furthermore, inhibition of Sp1 remarkably decreased protein levels of STC2. CONCLUSION Our data provide evidence that the transcription factor Sp1 is essential for the overexpression of STC2 in COAD through activation of promoter activity. Taken together, our finding provides new insights into the mechanism of oncogenic function of COAD by STC2.
基金Guangzhou Science and Technology Program Civic Technology Research Plan(No.201903010037)Guangdong Natural Science Foundation(No.2020A1515011539).
文摘Hepatic arterial infusion chemotherapy(HAIC)using a combination of oxaliplatin,fluorouracil,and leucovorin(FOLFOX)has shown promise for hepatocellular carcinoma(HCC)patients classified under Barcelona Clinic Liver Cancer(BCLC)stage C.In China,the combined therapy of camrelizumab and apatinib is now an approved first-line approach for inoperable HCC.This study(NCT04191889)evaluated the benefit of combining camrelizumab and apatinib with HAIC-FOLFOX for HCC patients in BCLC stage C.Eligible patients were given a maximum of six cycles of HAIC-FOLFOX,along with camrelizumab and apatinib,until either disease progression or intolerable toxicities emerged.The primary outcome measured was the objective response rate(ORR)based on the Response Evaluation Criteria in Solid Tumors(RECIST)v1.1.Thirty-five patients were enrolled.Based on RECIST v1.1 criteria,the confirmed ORR stood at 77.1%(95%CI:59.9%to 89.6%),with a disease control rate of 97.1%(95%CI:85.1%to 99.9%).The median progression-free survival was 10.38 months(95%CI:7.79 to 12.45).Patient quality of life had a transient deterioration within four cycles of treatment,and generally recovered thereafter.The most frequent grade≥3 or above treatment-related adverse events included reduced lymphocyte count(37.1%)and diminished neutrophil count(34.3%).The combination of camrelizumab,apatinib,and HAIC demonstrated encouraging results and manageable safety concerns for HCC at BCLC stage C.
基金Supported by the National Natural Science Foundation of China (No. 10671179)
文摘The exact parametric representations of the traveling wave solutions for a nonlinear elastic rod equation are considered. By using the method of planar dynamical systems, in different parameter regions, the phase portraits of the corresponding traveling wave system are given. Exact explicit kink wave solutions, periodic wave solutions and some unbounded wave solutions are obtained.
基金Supported by the National Natural Science Foundation of China(No.11371373 and 10831003)
文摘For the planar Z2-equivariant cubic systems having two elementary focuses, the characterization of a bi-center problem and shortened expressions of the first six Lyapunov constants are completely solved. The necessary and sufficient conditions for the existence of the bi-center are obtained. On the basis of this work, in this paper, we show that under small Z2-equivariant cubic perturbations, this cubic system has at least 13 limit cycles with the scheme 1 6 ∪ 6.
基金supported by the National Natural Science Foundation of China(82003269,82173128,81803327,81930065,and 81903406)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M-5-036)the Young Faculty Development Project of Sun Yat-sen University(84000-31660002).
文摘Background:The presence of delayed treatment effects(DTE)is common in immuno-oncology trials.However,conventional trial designs often overlook the potential presence of DTE,which can result in an underestimation of the required sample size and loss of statistical power.Conversely,when there is actually no apparent delay in treatment effects,alternative trial designs for addressing DTE may lead to an over-estimation of sample size and unnecessary prolongation of the trial duration.To mitigate this challenge,we propose the use of a DTE predicting(DTEP)model to better guide immuno-oncology trial designs.Methods:The DTEP model was developed and validated using data from 147 pub-lished randomized immuno-oncology trials.The eligible trials were divided into a training set(approximately 75%of the trials)and a test set(approximately 25%).We employed linear discriminant analysis(LDA)to develop the DTEP model for pre-dicting the DTE status using baseline characteristics available at the trial design stage.The receiver operating characteristic(ROC)curve was utilized to assess the ability of the model to distinguish between trials with and without DTE.We further re-conducted the JUPITER-02 trial in a simulation setting,employing three design approaches to assess the potential benefits of utilizing the DTEP model.Results:Baseline characteristics available during the trial design stage,including cancer type,line of treatment,and experimental and control arm regimens were incorporated,and high accuracy in predicting the DTE status in both the training set(area under the operating characteristic curve(AUC),0.79;95%confidence interval(CI),0.71-0.88)and test set(AUC,0.78;95%CI,0.66-0.90)was achieved.Notably,the model successfully predicted the DTE status in two randomized trials among the test sets that were conducted by our team(ESCORT-1st(absence of DTE)and JUPITER-02(presence of DTE)).In silico re-conduct of the JUPITER-02 trial further showed that the statistical power would be markedly improved when trial designs were guided by the DTEP model.Conclusions:The DTEP model can significantly enhance the precision and effectiveness of immuno-oncology trial designs,thereby facilitating the discovery of effective im-munotherapeutics in a more streamlined and expedited manner.