BACKGROUND Despite optimal neoadjuvant chemotherapy only 40%of gastric cancer tumours achieve complete or partial treatment response.In the absence of treatment response,neoadjuvant chemotherapy in gastric cancer cont...BACKGROUND Despite optimal neoadjuvant chemotherapy only 40%of gastric cancer tumours achieve complete or partial treatment response.In the absence of treatment response,neoadjuvant chemotherapy in gastric cancer contributes to adverse events without additional survival benefit compared to adjuvant treatment or surgery alone.Additional strategies and methods are required to optimize the allocation of existing treatment regimens such as FLOT chemotherapy(5-Fluorouracil,Leucovorin,Oxaliplatin and Docetaxel).Predictive biomarkers detected using immunohistochemistry(IHC)methods may provide useful data regarding treatment response.AIM To investigate the utility of CD4,CD8,Galectin-3 and E-cadherin in predicting neoadjuvant FLOT chemotherapy tumour response in gastric adenocarcinoma.METHODS Forty-three adult patients with gastric adenocarcinoma,of which 18 underwent neoadjuvant chemotherapy,were included in a prospective clinical cohort.Endoscopic biopsies were obtained from gastric cancer and normal adjacent gastric mucosa.Differences in expression of Galectin-3,Ecadherin,CD4^(+)and CD8^(+)molecules between tumours with and without treatment response to neoadjuvant chemotherapy were assessed with IHC.Treatment response was graded by clinical pathologists using the Tumour Regression Score according to the College of American Pathologists criteria.Treatment response was defined as complete or near complete tumour response,whereas partial or poor/no response was defined as incomplete.Digital IHC images were annotated and quantitatively assessed using QuPath 0.3.1.Biomarker expression between responsive and incomplete response tumours was assessed using a two-sided Wilcoxon test.Biomarker expression was also compared between normal and cancer tissue and between 15 paired tumour samples before and after chemotherapy.We performed a preliminary multivariate analysis and power analysis to guide future study.Statistical analyses were completed using R 4.1.2.RESULTS The ratio between CD4^(+)and CD8^(+)lymphocytes was significantly greater in treatment responsive tumours(Wilcoxon,P=0.03).In univariate models,CD4^(+)/CD8^(+)ratio was the only biomarker that significantly predicted favourable treatment response(Accuracy 86%,P<0.001).Using a glmnet multivariate model,high CD4^(+)/CD8^(+)ratio and low Galectin-3 expression were the most influential variables in predicting a favourable treatment response.Analyses of paired samples found that FLOT chemotherapy also results in increased expression of CD4^(+)and CD8^(+)tumour infiltrating lymphocytes(Paired Wilcoxon,P=0.002 and P=0.008,respectively).Our power analysis suggests future study requires at least 35 patients in each treatment response group for CD8 and Galectin-3 molecules,whereas 80 patients in each treatment response group are required to assess CD4 and E-cadherin biomarkers.CONCLUSION We demonstrate that an elevated CD4^(+)/CD8^(+)Ratio is a promising IHC-based biomarker to predict favourable treatment response to FLOT neoadjuvant chemotherapy in locally advanced gastric cancer.展开更多
Influence of thermomechanical treatments （mill annealing, duplex annealing, solution treatment plus aging and triple annealing） on microstructures and mechanical properties of TC4-DT titanium alloy was investigated....Influence of thermomechanical treatments （mill annealing, duplex annealing, solution treatment plus aging and triple annealing） on microstructures and mechanical properties of TC4-DT titanium alloy was investigated. Results showed that thermomechanical treatments had a significant influence on the microstructure parameters and higher annealing and aging temperature and lower cooling rate led to the decrease of the volume fraction of primaryαand the size of prior-βand the increase of the width of grain boundary αand secondary α. The highest strength was obtained by solution treatment and aging due to a large amount of transformedβand finer grain boundaryαand secondaryαat the expense of slight decrease of elongation and the ultimate strength, yield strength, elongation, reduction of area were 1100 MPa, 1030 MPa, 13%and 53%separately. A good combination of strength and ductility has been obtained by duplex annealing with the above values 940 MPa, 887.5 MPa, 15%and 51%respectively. Analysis between microstructure parameters and tensile properties showed that with the volume fraction of transformedβphase and the prior-βgrain size increasing, the ultimate strength, yield strength and reduction of area increased, but the elongation decreased. While the width of grain boundary α and secondary α showed a contrary effect on the tensile properties. Elimination of grain boundaryαas well as small prior-βgrain size can also improve ductility.展开更多
Influence of heat treatment on the microstructures and mechanical properties of sand-cast Mg-4Y-2Nd-1Gd-0.4Zr magnesium alloy was investigated,and the tensile fracture mechanisms of the studied alloys under different ...Influence of heat treatment on the microstructures and mechanical properties of sand-cast Mg-4Y-2Nd-1Gd-0.4Zr magnesium alloy was investigated,and the tensile fracture mechanisms of the studied alloys under different conditions were also discussed.The results show that the optimum T4 and T6 heat treatment conditions for the as-cast Mg-4Y-2Nd-1Gd-0.4Zr alloy are 525°C,8 h and（525°C,8 h）＋（225°C,16 h）,respectively,with regard to the microstructure observation,DSC heating curve and mechanical properties.The hardness,yield strength,ultimate tensile strength and elongation of the Mg-4Y-2Nd-1Gd-0.4Zr alloy treated by optimum T6 heat treatment are HV91,180 MPa,297 MPa and 7.4%,respectively.Moreover,the Mg-4Y-2Nd-1Gd-0.4Zr alloys under different heat treatment conditions exhibit different tensile fracture modes.展开更多
The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatm...The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].展开更多
Spinel oxide(NiCo_(2)O_(4))has demonstrated great potential to replace noble metal catalysts for the oxidation reaction of air pollutants.To further boost the oxidation ability of such catalysts,in this study,a facile...Spinel oxide(NiCo_(2)O_(4))has demonstrated great potential to replace noble metal catalysts for the oxidation reaction of air pollutants.To further boost the oxidation ability of such catalysts,in this study,a facile surface-engineering strategy wherein NiCo_(2)O_(4) was treated with different alkali solvents was developed.The obtained catalyst(NiCo_(2)O_(4)-OH)showed a higher surface alkalinity and more surface defects compared to the pristine spinel oxide,including enhanced structural distortion as well as promoted oxygen vacancies.The propane oxidation ability of NiCo_(2)O_(4)-OH was greatly enhanced,with a propane conversion rate that was approximately 6.4 times higher than that of pristine NiCo_(2)O_(4) at a reaction temperature 193℃.This work sets a valuable paradigm for the surface modulation of spinel oxide via alkali treatment to ensure a high-performance oxidation catalyst.展开更多
In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid...In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function.Ferroptosis and pyroptosis,cell death forms that can be initiated or blocked concurrently,can play significant roles in developing inflammation and various malignancies.However,their roles in ALF remain unclear.The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF,and revealed that the silent information regulator sirtuin 1(SIRT1)inhibits both pathways through p53,dramatically reducing inflammation and protecting hepatocytes.This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF.Thus,we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms.Additionally,we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways,as well as examples of SIRT1 activators being used as disease treatment strategies,providing new insights into the therapy of ALF.展开更多
文摘BACKGROUND Despite optimal neoadjuvant chemotherapy only 40%of gastric cancer tumours achieve complete or partial treatment response.In the absence of treatment response,neoadjuvant chemotherapy in gastric cancer contributes to adverse events without additional survival benefit compared to adjuvant treatment or surgery alone.Additional strategies and methods are required to optimize the allocation of existing treatment regimens such as FLOT chemotherapy(5-Fluorouracil,Leucovorin,Oxaliplatin and Docetaxel).Predictive biomarkers detected using immunohistochemistry(IHC)methods may provide useful data regarding treatment response.AIM To investigate the utility of CD4,CD8,Galectin-3 and E-cadherin in predicting neoadjuvant FLOT chemotherapy tumour response in gastric adenocarcinoma.METHODS Forty-three adult patients with gastric adenocarcinoma,of which 18 underwent neoadjuvant chemotherapy,were included in a prospective clinical cohort.Endoscopic biopsies were obtained from gastric cancer and normal adjacent gastric mucosa.Differences in expression of Galectin-3,Ecadherin,CD4^(+)and CD8^(+)molecules between tumours with and without treatment response to neoadjuvant chemotherapy were assessed with IHC.Treatment response was graded by clinical pathologists using the Tumour Regression Score according to the College of American Pathologists criteria.Treatment response was defined as complete or near complete tumour response,whereas partial or poor/no response was defined as incomplete.Digital IHC images were annotated and quantitatively assessed using QuPath 0.3.1.Biomarker expression between responsive and incomplete response tumours was assessed using a two-sided Wilcoxon test.Biomarker expression was also compared between normal and cancer tissue and between 15 paired tumour samples before and after chemotherapy.We performed a preliminary multivariate analysis and power analysis to guide future study.Statistical analyses were completed using R 4.1.2.RESULTS The ratio between CD4^(+)and CD8^(+)lymphocytes was significantly greater in treatment responsive tumours(Wilcoxon,P=0.03).In univariate models,CD4^(+)/CD8^(+)ratio was the only biomarker that significantly predicted favourable treatment response(Accuracy 86%,P<0.001).Using a glmnet multivariate model,high CD4^(+)/CD8^(+)ratio and low Galectin-3 expression were the most influential variables in predicting a favourable treatment response.Analyses of paired samples found that FLOT chemotherapy also results in increased expression of CD4^(+)and CD8^(+)tumour infiltrating lymphocytes(Paired Wilcoxon,P=0.002 and P=0.008,respectively).Our power analysis suggests future study requires at least 35 patients in each treatment response group for CD8 and Galectin-3 molecules,whereas 80 patients in each treatment response group are required to assess CD4 and E-cadherin biomarkers.CONCLUSION We demonstrate that an elevated CD4^(+)/CD8^(+)Ratio is a promising IHC-based biomarker to predict favourable treatment response to FLOT neoadjuvant chemotherapy in locally advanced gastric cancer.
基金Project(51101119)supported by the National Natural Science Foundation of China
文摘Influence of thermomechanical treatments （mill annealing, duplex annealing, solution treatment plus aging and triple annealing） on microstructures and mechanical properties of TC4-DT titanium alloy was investigated. Results showed that thermomechanical treatments had a significant influence on the microstructure parameters and higher annealing and aging temperature and lower cooling rate led to the decrease of the volume fraction of primaryαand the size of prior-βand the increase of the width of grain boundary αand secondary α. The highest strength was obtained by solution treatment and aging due to a large amount of transformedβand finer grain boundaryαand secondaryαat the expense of slight decrease of elongation and the ultimate strength, yield strength, elongation, reduction of area were 1100 MPa, 1030 MPa, 13%and 53%separately. A good combination of strength and ductility has been obtained by duplex annealing with the above values 940 MPa, 887.5 MPa, 15%and 51%respectively. Analysis between microstructure parameters and tensile properties showed that with the volume fraction of transformedβphase and the prior-βgrain size increasing, the ultimate strength, yield strength and reduction of area increased, but the elongation decreased. While the width of grain boundary α and secondary α showed a contrary effect on the tensile properties. Elimination of grain boundaryαas well as small prior-βgrain size can also improve ductility.
基金Project(0502)supported by the Aerospace Science and Technology Innovation Fund of China Aerospace Science and Technology CorporationProject(2007CB613701)supported by the National Basic Research Program of ChinaProject(2009AA033501)supported by the National High-tech Research and Development Program of China
文摘Influence of heat treatment on the microstructures and mechanical properties of sand-cast Mg-4Y-2Nd-1Gd-0.4Zr magnesium alloy was investigated,and the tensile fracture mechanisms of the studied alloys under different conditions were also discussed.The results show that the optimum T4 and T6 heat treatment conditions for the as-cast Mg-4Y-2Nd-1Gd-0.4Zr alloy are 525°C,8 h and（525°C,8 h）＋（225°C,16 h）,respectively,with regard to the microstructure observation,DSC heating curve and mechanical properties.The hardness,yield strength,ultimate tensile strength and elongation of the Mg-4Y-2Nd-1Gd-0.4Zr alloy treated by optimum T6 heat treatment are HV91,180 MPa,297 MPa and 7.4%,respectively.Moreover,the Mg-4Y-2Nd-1Gd-0.4Zr alloys under different heat treatment conditions exhibit different tensile fracture modes.
基金funded by the National Natural Science Foundation of China(Grant Nos.:82004081 and 52073145)the National Natural Science Foundation of Nanjing University of Chinese Medicine,China(Grant No.:NZY82004081).
文摘The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].
基金financially supported by the National Natural Science Foundation of China(No.22072069)the Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials(Wuhan University of Science and Technology No.WKDM202303).
文摘Spinel oxide(NiCo_(2)O_(4))has demonstrated great potential to replace noble metal catalysts for the oxidation reaction of air pollutants.To further boost the oxidation ability of such catalysts,in this study,a facile surface-engineering strategy wherein NiCo_(2)O_(4) was treated with different alkali solvents was developed.The obtained catalyst(NiCo_(2)O_(4)-OH)showed a higher surface alkalinity and more surface defects compared to the pristine spinel oxide,including enhanced structural distortion as well as promoted oxygen vacancies.The propane oxidation ability of NiCo_(2)O_(4)-OH was greatly enhanced,with a propane conversion rate that was approximately 6.4 times higher than that of pristine NiCo_(2)O_(4) at a reaction temperature 193℃.This work sets a valuable paradigm for the surface modulation of spinel oxide via alkali treatment to ensure a high-performance oxidation catalyst.
基金Supported by The Hubei Provincial Natural Science Foundation of China,No.2020CFB656.
文摘In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function.Ferroptosis and pyroptosis,cell death forms that can be initiated or blocked concurrently,can play significant roles in developing inflammation and various malignancies.However,their roles in ALF remain unclear.The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF,and revealed that the silent information regulator sirtuin 1(SIRT1)inhibits both pathways through p53,dramatically reducing inflammation and protecting hepatocytes.This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF.Thus,we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms.Additionally,we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways,as well as examples of SIRT1 activators being used as disease treatment strategies,providing new insights into the therapy of ALF.
