Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-...Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.展开更多
Energy resolution calibration is crucial for gamma-ray spectral analysis,as measured using a scintillation detector.A locally constrained regularization method was proposed to determine the resolution calibration para...Energy resolution calibration is crucial for gamma-ray spectral analysis,as measured using a scintillation detector.A locally constrained regularization method was proposed to determine the resolution calibration parameters.First,a Monte Carlo simulation model consistent with an actual measurement system was constructed to obtain the energy deposition distribution in the scintillation crystal.Subsequently,the regularization objective function is established based on weighted least squares and additional constraints.Additional constraints were designed using a special weighting scheme based on the incident gamma-ray energies.Subsequently,an intelligent algorithm was introduced to search for the optimal resolution calibration parameters by minimizing the objective function.The most appropriate regularization parameter was determined through mathematical experiments.When the regularization parameter was 30,the calibrated results exhibited the minimum RMSE.Simulations and test pit experiments were conducted to verify the performance of the proposed method.The simulation results demonstrate that the proposed algorithm can determine resolution calibration parameters more accurately than the traditional weighted least squares,and the test pit experimental results show that the R-squares between the calibrated and measured spectra are larger than 0.99.The accurate resolution calibration parameters determined by the proposed method lay the foundation for gamma-ray spectral processing and simulation benchmarking.展开更多
This paper summarizes the nursing experience of a 65-year-old elderly patient with fulminant myocarditis complicated by cardiogenic shock who received veno-arterial extracorporeal membrane oxygenation(V-A ECMO)combine...This paper summarizes the nursing experience of a 65-year-old elderly patient with fulminant myocarditis complicated by cardiogenic shock who received veno-arterial extracorporeal membrane oxygenation(V-A ECMO)combined with intra-aortic balloon pump(IABP)support therapy.The core nursing measures included:establishing a multidisciplinary collaboration team to implement daily goal management;standardized anticoagulation monitoring;refined hemodynamic management;stepped respiratory support;and early rehabilitation intervention.After 9 days of ECMO support combined with 5 days of IABP support,the patient’s cardiac and respiratory functions recovered.The patient was discharged on the 42nd day and was fully recovered during the follow-up on the 60th day.This case suggests that refined nursing care for ECMO combined with IABP is the key to the treatment of fulminant myocarditis.展开更多
基金funded by the Natural Science Foundation of Guangdong Province(grant number 2022A1515012315)Guangdong Medical Science and Technology Research Fund Project(grant number A2023185)+2 种基金the Discipline Construction Project of Guangdong Medical University(grant number 4SG22005G)the 2023 Provincial Basic and Applied Basic Research Fund Enterprise Joint Fund Project(grant number 2023A1515220149)Southern Medical University Shunde Hospital 2023 Research Initiation Programme Project(SRSP2023016).
文摘Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.
基金supported by the National Natural Science Foundation of China(No.41804141)。
文摘Energy resolution calibration is crucial for gamma-ray spectral analysis,as measured using a scintillation detector.A locally constrained regularization method was proposed to determine the resolution calibration parameters.First,a Monte Carlo simulation model consistent with an actual measurement system was constructed to obtain the energy deposition distribution in the scintillation crystal.Subsequently,the regularization objective function is established based on weighted least squares and additional constraints.Additional constraints were designed using a special weighting scheme based on the incident gamma-ray energies.Subsequently,an intelligent algorithm was introduced to search for the optimal resolution calibration parameters by minimizing the objective function.The most appropriate regularization parameter was determined through mathematical experiments.When the regularization parameter was 30,the calibrated results exhibited the minimum RMSE.Simulations and test pit experiments were conducted to verify the performance of the proposed method.The simulation results demonstrate that the proposed algorithm can determine resolution calibration parameters more accurately than the traditional weighted least squares,and the test pit experimental results show that the R-squares between the calibrated and measured spectra are larger than 0.99.The accurate resolution calibration parameters determined by the proposed method lay the foundation for gamma-ray spectral processing and simulation benchmarking.
文摘This paper summarizes the nursing experience of a 65-year-old elderly patient with fulminant myocarditis complicated by cardiogenic shock who received veno-arterial extracorporeal membrane oxygenation(V-A ECMO)combined with intra-aortic balloon pump(IABP)support therapy.The core nursing measures included:establishing a multidisciplinary collaboration team to implement daily goal management;standardized anticoagulation monitoring;refined hemodynamic management;stepped respiratory support;and early rehabilitation intervention.After 9 days of ECMO support combined with 5 days of IABP support,the patient’s cardiac and respiratory functions recovered.The patient was discharged on the 42nd day and was fully recovered during the follow-up on the 60th day.This case suggests that refined nursing care for ECMO combined with IABP is the key to the treatment of fulminant myocarditis.
