Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failu...Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failure(CHF).Methods:In vitro,the H_(9)C_(2) cell model was induced by ANGII,and cell proliferation and related protein expression were detected by Cell Counting Kit-8 and Western blot.In vivo,A rat model of CHF was prepared by ligation of the left anterior descending coronary artery.The effects of QXHLF on cardiac function in CHF rats were evaluated by cardiac index,hemodynamic changes,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,immunohistochemistry,Western blot and RT-PCR.The expression of pro-apoptotic factors and anti-apoptotic factors,as well as TGFβ1,p-p38,TAK 1 mRNA,and protein,were detected.Results:In vitro,QXHLF has a significant inhibitory effect on the proliferation of H_(9)C_(2) cells.QXHLF can reduce the expression levels of TAK 1,TGFβ1,p-p38,Caspase3 and BAX proteins in H_(9)C_(2) cells,and increase the expression level of BCL_(2) protein.In vivo,QXHLF has the potential to increase left ventricular systolic pressure,m aximum rate of change in left ventricular pressure while decreasing left ventricular end diastolic pressure,and inhibiting the serum levels of brain natriuretic peptide.Moreover,QXHLF exhibits significant improvements in the pathological alterations of myocardial cells and fibers in CHF rats,leading to enhanced myocardial tissue morphology and notable advantages in combating myocardial fibrosis.QXHLF can reduce the levels of BAX and Caspase3 and up-regulate the expression of BCL_(2),thereby inhibiting cardiomyocyte apoptosis.Furthermore,QXHLF demonstrates inhibitory effects on the mRNA and protein expression levels of TGFβ_(1),TAK_(1),and p-p38 in the heart tissue of the CHF rat model.Conclusion:These findings indicate that QXHLF has a therapeutic effect on CHF by inhibiting the p38-MAPK signaling pathway,reducing myocardial fibrosis,preventing apoptosis,inhibiting cell proliferation,and restoring myocardial injury.展开更多
BACKGROUND Rectal carcinoma(RC),one of the most common malignancies globally,presents an increasing incidence and mortality year by year,especially among young people,which seriously affects the prognosis and quality ...BACKGROUND Rectal carcinoma(RC),one of the most common malignancies globally,presents an increasing incidence and mortality year by year,especially among young people,which seriously affects the prognosis and quality of life of patients.At present,dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)parameters and serum carbohydrate antigen 19-9(CA19-9)and CA125 Levels have been used in clinical practice to evaluate the T stage and differentiation of RC.However,the accuracy of these evaluation modalities still needs further research.This study explores the application and value of these methods in evaluating the T stage and differentiation degree of RC.AIM To analyze the diagnostic performance of DCE-MRI parameters combined with serum tumor markers(TMs)in assessing pathological processes and prognosis of RC patients.METHODS A retrospective analysis was performed on 104 RC patients treated at Yantai Yuhuangding Hospital from May 2018 to January 2022.Patients were categorized into stages T1,T2,T3,and T4,depending on their T stage and differentiation degree.In addition,they were assigned to low(L group)and moderate-high differentiation(M+H group)groups based on their differentiation degree.The levels of DCE-MRI parameters and serum CA19-9 and CA125 in different groups of patients were compared.In addition,the value of DCE-MRI parameters[volume transfer constant(Ktrans),rate constant(Kep),and extravascular extracellular volume fraction(Ve)in assessing the differentiation and T staging of RC patients was discussed.Furthermore,the usefulness of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels in the evaluation of RC differentiation and T staging was analyzed.RESULTS Ktrans,Ve,CA19-9 and CA125 were higher in the high-stage group and L group than in the low-stage group and M+H Group,respectively(P<0.05).The areas under the curve(AUCs)of the Ktran and Ve parameters were 0.638 and 0.694 in the diagnosis of high and low stages,respectively,and 0.672 and 0.725 in diagnosing moderate-high and low differentiation,respectively.The AUC of DCE-MRI parameters(Ktrans+Ve)in the diagnosis of high and low stages was 0.742,and the AUC in diagnosing moderate-high and low differentiation was 0.769.The AUCs of CA19-9 and CA-125 were 0.773 and 0.802 in the diagnosis of high and low stages,respectively,and 0.834 and 0.796 in diagnosing moderate-high and low differentiation,respectively.Then,we combined DCE-MRI(Ktrans+Ve)parameters with CA19-9 and CA-125 and found that the AUC of DCE-MRI parameters plus serum TMs was 0.836 in the diagnosis of high and low stages and 0.946 in the diagnosis of moderate-high and low differentiation.According to the Delong test,the AUC of DCE-MRI parameters plus serum TMs increased significantly compared with serum TMs alone in the diagnosis of T stage and differentiation degree(P<0.001).CONCLUSION The levels of the DCE-MRI parameters Ktrans and Ve and the serum TMs CA19-9 and CA125 all increase with increasing T stage and decreasing differentiation degree of RC and can be used as indices to evaluate the differentiation degree of RC in clinical practice.Moreover,the combined evaluation of the above indices has a better effect and more obvious clinical value,providing important guiding importance for clinical condition judgment and treatment selection.展开更多
基金the Science and Technology Research Project of the Education Department of Jilin Province(No.JJKH20220862KJ)the Jilin Province higher education teaching reform research topic(No.20224BRFI7U003M)National Natural Science Foundation of China(No.82074324).
文摘Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failure(CHF).Methods:In vitro,the H_(9)C_(2) cell model was induced by ANGII,and cell proliferation and related protein expression were detected by Cell Counting Kit-8 and Western blot.In vivo,A rat model of CHF was prepared by ligation of the left anterior descending coronary artery.The effects of QXHLF on cardiac function in CHF rats were evaluated by cardiac index,hemodynamic changes,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,immunohistochemistry,Western blot and RT-PCR.The expression of pro-apoptotic factors and anti-apoptotic factors,as well as TGFβ1,p-p38,TAK 1 mRNA,and protein,were detected.Results:In vitro,QXHLF has a significant inhibitory effect on the proliferation of H_(9)C_(2) cells.QXHLF can reduce the expression levels of TAK 1,TGFβ1,p-p38,Caspase3 and BAX proteins in H_(9)C_(2) cells,and increase the expression level of BCL_(2) protein.In vivo,QXHLF has the potential to increase left ventricular systolic pressure,m aximum rate of change in left ventricular pressure while decreasing left ventricular end diastolic pressure,and inhibiting the serum levels of brain natriuretic peptide.Moreover,QXHLF exhibits significant improvements in the pathological alterations of myocardial cells and fibers in CHF rats,leading to enhanced myocardial tissue morphology and notable advantages in combating myocardial fibrosis.QXHLF can reduce the levels of BAX and Caspase3 and up-regulate the expression of BCL_(2),thereby inhibiting cardiomyocyte apoptosis.Furthermore,QXHLF demonstrates inhibitory effects on the mRNA and protein expression levels of TGFβ_(1),TAK_(1),and p-p38 in the heart tissue of the CHF rat model.Conclusion:These findings indicate that QXHLF has a therapeutic effect on CHF by inhibiting the p38-MAPK signaling pathway,reducing myocardial fibrosis,preventing apoptosis,inhibiting cell proliferation,and restoring myocardial injury.
文摘BACKGROUND Rectal carcinoma(RC),one of the most common malignancies globally,presents an increasing incidence and mortality year by year,especially among young people,which seriously affects the prognosis and quality of life of patients.At present,dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)parameters and serum carbohydrate antigen 19-9(CA19-9)and CA125 Levels have been used in clinical practice to evaluate the T stage and differentiation of RC.However,the accuracy of these evaluation modalities still needs further research.This study explores the application and value of these methods in evaluating the T stage and differentiation degree of RC.AIM To analyze the diagnostic performance of DCE-MRI parameters combined with serum tumor markers(TMs)in assessing pathological processes and prognosis of RC patients.METHODS A retrospective analysis was performed on 104 RC patients treated at Yantai Yuhuangding Hospital from May 2018 to January 2022.Patients were categorized into stages T1,T2,T3,and T4,depending on their T stage and differentiation degree.In addition,they were assigned to low(L group)and moderate-high differentiation(M+H group)groups based on their differentiation degree.The levels of DCE-MRI parameters and serum CA19-9 and CA125 in different groups of patients were compared.In addition,the value of DCE-MRI parameters[volume transfer constant(Ktrans),rate constant(Kep),and extravascular extracellular volume fraction(Ve)in assessing the differentiation and T staging of RC patients was discussed.Furthermore,the usefulness of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels in the evaluation of RC differentiation and T staging was analyzed.RESULTS Ktrans,Ve,CA19-9 and CA125 were higher in the high-stage group and L group than in the low-stage group and M+H Group,respectively(P<0.05).The areas under the curve(AUCs)of the Ktran and Ve parameters were 0.638 and 0.694 in the diagnosis of high and low stages,respectively,and 0.672 and 0.725 in diagnosing moderate-high and low differentiation,respectively.The AUC of DCE-MRI parameters(Ktrans+Ve)in the diagnosis of high and low stages was 0.742,and the AUC in diagnosing moderate-high and low differentiation was 0.769.The AUCs of CA19-9 and CA-125 were 0.773 and 0.802 in the diagnosis of high and low stages,respectively,and 0.834 and 0.796 in diagnosing moderate-high and low differentiation,respectively.Then,we combined DCE-MRI(Ktrans+Ve)parameters with CA19-9 and CA-125 and found that the AUC of DCE-MRI parameters plus serum TMs was 0.836 in the diagnosis of high and low stages and 0.946 in the diagnosis of moderate-high and low differentiation.According to the Delong test,the AUC of DCE-MRI parameters plus serum TMs increased significantly compared with serum TMs alone in the diagnosis of T stage and differentiation degree(P<0.001).CONCLUSION The levels of the DCE-MRI parameters Ktrans and Ve and the serum TMs CA19-9 and CA125 all increase with increasing T stage and decreasing differentiation degree of RC and can be used as indices to evaluate the differentiation degree of RC in clinical practice.Moreover,the combined evaluation of the above indices has a better effect and more obvious clinical value,providing important guiding importance for clinical condition judgment and treatment selection.
