Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive ...Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.展开更多
乘波体在高空高超声速飞行时,流场温度急剧升高,气体热力学性质发生改变,其气动特性与采用完全气体模型得到的结果存在差异,因此在飞行器设计中开展真实气体效应影响研究具有重要的工程价值。本文针对锥导乘波体设计提出了一种考虑平衡...乘波体在高空高超声速飞行时,流场温度急剧升高,气体热力学性质发生改变,其气动特性与采用完全气体模型得到的结果存在差异,因此在飞行器设计中开展真实气体效应影响研究具有重要的工程价值。本文针对锥导乘波体设计提出了一种考虑平衡气体效应的特征线方法(Method of characteristic, MOC),基于不同半锥角和不同流动捕获曲线生成了不同外形的乘波体,并使用快速估算方法估算平衡气体条件和完全气体条件下各乘波体的气动特性和几何特征参数,研究了不同气体模型对乘波体设计结果的影响。研究结果表明,高马赫数下基于平衡气体模型设计得到的乘波体升阻比、容积率和俯仰力矩系数等特性参数相比完全气体结果存在差异,并且平衡气体效应对不同外形乘波体的影响程度和影响规律不同。展开更多
Photodynamic therapy(PDT)is a promising cancer treatment.This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-tr...Photodynamic therapy(PDT)is a promising cancer treatment.This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-triphenyl-porphyrin(DTP)mediated PDT(DTP-PDT).Cell viability,reactive oxygen species(ROS),and apoptosis were measured with a Cell Counting Kit-8 assay,DCFH-DA fluorescent probe,and Hoechst staining,respectively.Cell apoptosis-and autophagy-related proteins were examined using western blotting.RNA sequencing was used to screen differentially expressed mRNAs(DERs),and bioinformatic analysis was performed to identify the major biological events after DTP-PDT.Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells.The ROS scavenger N-acetyl-L-cysteine(NAC)and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity.DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2,which could also be inhibited by NAC or SB203580.The level of LC3B-Ⅱ,a marker of autophagy,was increased by DTP-PDT.A total of 3496 DERs were obtained after DTP-PDT.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes,the nuclear lumen,protein binding,cell cycle,protein targeting to the endoplasmic reticulum,and ribosomal DNA replication.Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints.Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes.Therefore,DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy,partly through ROS and the P38 MAPK signaling pathway.Genes associated with the cell cycle,ribosomes,DNA replication,and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.展开更多
This editorial provides commentary on an article titled"Potential and limitationsof ChatGPT and generative artificial intelligence(AI)in medical safety education"recently published in the World Journal of Cl...This editorial provides commentary on an article titled"Potential and limitationsof ChatGPT and generative artificial intelligence(AI)in medical safety education"recently published in the World Journal of Clinical Cases.AI has enormous potentialfor various applications in the field of Kawasaki disease(KD).One is machinelearning(ML)to assist in the diagnosis of KD,and clinical prediction models havebeen constructed worldwide using ML;the second is using a gene signalcalculation toolbox to identify KD,which can be used to monitor key clinicalfeatures and laboratory parameters of disease severity;and the third is using deeplearning(DL)to assist in cardiac ultrasound detection.The performance of the DLalgorithm is similar to that of experienced cardiac experts in detecting coronaryartery lesions to promoting the diagnosis of KD.To effectively utilize AI in thediagnosis and treatment process of KD,it is crucial to improve the accuracy of AIdecision-making using more medical data,while addressing issues related topatient personal information protection and AI decision-making responsibility.AIprogress is expected to provide patients with accurate and effective medicalservices that will positively impact the diagnosis and treatment of KD in thefuture.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837)the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100)。
文摘Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.
文摘乘波体在高空高超声速飞行时,流场温度急剧升高,气体热力学性质发生改变,其气动特性与采用完全气体模型得到的结果存在差异,因此在飞行器设计中开展真实气体效应影响研究具有重要的工程价值。本文针对锥导乘波体设计提出了一种考虑平衡气体效应的特征线方法(Method of characteristic, MOC),基于不同半锥角和不同流动捕获曲线生成了不同外形的乘波体,并使用快速估算方法估算平衡气体条件和完全气体条件下各乘波体的气动特性和几何特征参数,研究了不同气体模型对乘波体设计结果的影响。研究结果表明,高马赫数下基于平衡气体模型设计得到的乘波体升阻比、容积率和俯仰力矩系数等特性参数相比完全气体结果存在差异,并且平衡气体效应对不同外形乘波体的影响程度和影响规律不同。
基金supported by the Applied Basic Research Project of Shanxi Province(201901D211470)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi Province(201802093)The National Natural Science Foundation of China(No.81773765).
文摘Photodynamic therapy(PDT)is a promising cancer treatment.This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-triphenyl-porphyrin(DTP)mediated PDT(DTP-PDT).Cell viability,reactive oxygen species(ROS),and apoptosis were measured with a Cell Counting Kit-8 assay,DCFH-DA fluorescent probe,and Hoechst staining,respectively.Cell apoptosis-and autophagy-related proteins were examined using western blotting.RNA sequencing was used to screen differentially expressed mRNAs(DERs),and bioinformatic analysis was performed to identify the major biological events after DTP-PDT.Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells.The ROS scavenger N-acetyl-L-cysteine(NAC)and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity.DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2,which could also be inhibited by NAC or SB203580.The level of LC3B-Ⅱ,a marker of autophagy,was increased by DTP-PDT.A total of 3496 DERs were obtained after DTP-PDT.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes,the nuclear lumen,protein binding,cell cycle,protein targeting to the endoplasmic reticulum,and ribosomal DNA replication.Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints.Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes.Therefore,DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy,partly through ROS and the P38 MAPK signaling pathway.Genes associated with the cell cycle,ribosomes,DNA replication,and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.
文摘This editorial provides commentary on an article titled"Potential and limitationsof ChatGPT and generative artificial intelligence(AI)in medical safety education"recently published in the World Journal of Clinical Cases.AI has enormous potentialfor various applications in the field of Kawasaki disease(KD).One is machinelearning(ML)to assist in the diagnosis of KD,and clinical prediction models havebeen constructed worldwide using ML;the second is using a gene signalcalculation toolbox to identify KD,which can be used to monitor key clinicalfeatures and laboratory parameters of disease severity;and the third is using deeplearning(DL)to assist in cardiac ultrasound detection.The performance of the DLalgorithm is similar to that of experienced cardiac experts in detecting coronaryartery lesions to promoting the diagnosis of KD.To effectively utilize AI in thediagnosis and treatment process of KD,it is crucial to improve the accuracy of AIdecision-making using more medical data,while addressing issues related topatient personal information protection and AI decision-making responsibility.AIprogress is expected to provide patients with accurate and effective medicalservices that will positively impact the diagnosis and treatment of KD in thefuture.
