Objective There is a dilemma of ibuprofen treatment with patent ductus arteriosus(PDA)as to how and when to treat.We aimed to clarify this issue in very preterm infants(VPIs;<32 weeks).Methods:This retrospective st...Objective There is a dilemma of ibuprofen treatment with patent ductus arteriosus(PDA)as to how and when to treat.We aimed to clarify this issue in very preterm infants(VPIs;<32 weeks).Methods:This retrospective study included 1659 VPIs who were diagnosed with PDA according to echocardiographic examinations and cardiovascular dysfunction scoring system(the CVD scoring).The VPIs were classified into six groups(A1,A2,A3,B1,B2,and B3)based on CVD scores(A,<3,and B,≥3),and treatment with ibuprofen for PDA(1,conservational management;2,early ibuprofen treatment;and 3,late ibuprofen treatment).Treatment was stopped when PDA was closed,CVD score was zero or PDA needed ligation.Results:VPIs with CVD scores<3 had most PDA closure without surgery,and early ibuprofen treatment did not significantly affect PDA closure.VPIs with CVD scores≥3 had some PDA closure after 2 courses of treatment,but closure rates decreased linearly with ibuprofen course(1^(st)75.2%,2^(nd)62.3%,3^(rd)50.0%,P<0.0001),and early ibuprofen treatment(group B2)did not increase PDA closure compared to late ibuprofen treatment(group B3).In these same infants,the longer they were in CVD scores≥3,the more the complications of preterm were increased(retinopathy of prematurity ROP 1^(st)16.5%,2^(nd)23.8%,3^(rd)29.6%,P=0.016;bronchopulmonary dysplasia BPD 1^(st)15.5%,2^(nd)26.7%,3^(rd)33.8%,P<0.0001;intraventricular hemorrhage IVH 1^(st)20.4%,2^(nd)32.4%,3^(rd)23.8%,P=0.015).Conclusion:Ibuprofen is suggested for PDA closure when the PDA reopens or has developed into the stage when the CVD score≥3.展开更多
Background:Chronic kidney disease(CKD)is associated with common pathophysiological processes,such as inflammation and fibrosis,in both the heart and the kidney.However,the underlying molecular mechanisms that drive th...Background:Chronic kidney disease(CKD)is associated with common pathophysiological processes,such as inflammation and fibrosis,in both the heart and the kidney.However,the underlying molecular mechanisms that drive these processes are not yet fully understood.Therefore,this study focused on the molecular mechanism of heart and kidney injury in CKD.Methods:We generated an microRNA(miR)-26a knockout(KO)mouse model to investigate the role of miR-26a in angiotensin(Ang)-II-induced cardiac and renal injury.We performed Ang-II modeling in wild type(WT)mice and miR-26a KO mice,with six mice in each group.In addition,Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD.Histological staining,immunohistochemistry,quantitative real-time polymerase chain reaction(PCR),and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury.Immunofluorescence reporter assays were used to detect downstream genes of miR-26a,and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1(LIMS1).We also used an adeno-associated virus(AAV)to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury.Dunnett’s multiple comparison and t-test were used to analyze the data.Results:Compared with the control mice,miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion.Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues.Downregulation of miR-26a activated the LIMS1/integrin-linked kinase(ILK)signaling pathway in the heart and kidney,which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD.Furthermore,knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway;on the contrary,supplementation with exogenous miR-26a reversed all these changes.Conclusions:Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD.This is attributed to its ability to regulate the LIMS1/ILK signaling pathway,which represents a common molecular mechanism in both heart and kidney tissues.展开更多
文摘Objective There is a dilemma of ibuprofen treatment with patent ductus arteriosus(PDA)as to how and when to treat.We aimed to clarify this issue in very preterm infants(VPIs;<32 weeks).Methods:This retrospective study included 1659 VPIs who were diagnosed with PDA according to echocardiographic examinations and cardiovascular dysfunction scoring system(the CVD scoring).The VPIs were classified into six groups(A1,A2,A3,B1,B2,and B3)based on CVD scores(A,<3,and B,≥3),and treatment with ibuprofen for PDA(1,conservational management;2,early ibuprofen treatment;and 3,late ibuprofen treatment).Treatment was stopped when PDA was closed,CVD score was zero or PDA needed ligation.Results:VPIs with CVD scores<3 had most PDA closure without surgery,and early ibuprofen treatment did not significantly affect PDA closure.VPIs with CVD scores≥3 had some PDA closure after 2 courses of treatment,but closure rates decreased linearly with ibuprofen course(1^(st)75.2%,2^(nd)62.3%,3^(rd)50.0%,P<0.0001),and early ibuprofen treatment(group B2)did not increase PDA closure compared to late ibuprofen treatment(group B3).In these same infants,the longer they were in CVD scores≥3,the more the complications of preterm were increased(retinopathy of prematurity ROP 1^(st)16.5%,2^(nd)23.8%,3^(rd)29.6%,P=0.016;bronchopulmonary dysplasia BPD 1^(st)15.5%,2^(nd)26.7%,3^(rd)33.8%,P<0.0001;intraventricular hemorrhage IVH 1^(st)20.4%,2^(nd)32.4%,3^(rd)23.8%,P=0.015).Conclusion:Ibuprofen is suggested for PDA closure when the PDA reopens or has developed into the stage when the CVD score≥3.
基金supported by grants from the National Natural Science Foundation of China(Nos.82200749,82241047,82070735,82030024,81720108007 and 81270725)Natural Science Foundation of Jiangsu Province(No.BK20221282)National Key Research Programme of Ministry of Science and Technology(Nos.2018YFC130046,2018YFC1314000).
文摘Background:Chronic kidney disease(CKD)is associated with common pathophysiological processes,such as inflammation and fibrosis,in both the heart and the kidney.However,the underlying molecular mechanisms that drive these processes are not yet fully understood.Therefore,this study focused on the molecular mechanism of heart and kidney injury in CKD.Methods:We generated an microRNA(miR)-26a knockout(KO)mouse model to investigate the role of miR-26a in angiotensin(Ang)-II-induced cardiac and renal injury.We performed Ang-II modeling in wild type(WT)mice and miR-26a KO mice,with six mice in each group.In addition,Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD.Histological staining,immunohistochemistry,quantitative real-time polymerase chain reaction(PCR),and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury.Immunofluorescence reporter assays were used to detect downstream genes of miR-26a,and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1(LIMS1).We also used an adeno-associated virus(AAV)to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury.Dunnett’s multiple comparison and t-test were used to analyze the data.Results:Compared with the control mice,miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion.Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues.Downregulation of miR-26a activated the LIMS1/integrin-linked kinase(ILK)signaling pathway in the heart and kidney,which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD.Furthermore,knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway;on the contrary,supplementation with exogenous miR-26a reversed all these changes.Conclusions:Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD.This is attributed to its ability to regulate the LIMS1/ILK signaling pathway,which represents a common molecular mechanism in both heart and kidney tissues.
