BACKGROUND At present,large-scale studies on the clinical characteristics of sepsis-induced cardiomyopathy(SIC)are lacking.AIM To investigate the clinical characteristics of SIC.METHODS Based on the analysis of the MI...BACKGROUND At present,large-scale studies on the clinical characteristics of sepsis-induced cardiomyopathy(SIC)are lacking.AIM To investigate the clinical characteristics of SIC.METHODS Based on the analysis of the MIMIC-III public database,we performed a largescale retrospective study involving sepsis patients who were admitted to the intensive care unit(ICU)and had no concomitant cardiac disease.We used propensity score matching analysis and multivariate logistic regression to ensure the robustness of the results.The primary outcome was hospital mortality,and the secondary outcomes included the number of patients who received mechanical ventilation or renal replacement therapy during their hospital stay,the number of patients administered with vasopressors,the length of ICU stay,and the length of hospital stay.RESULTS In the present study,after screening 38605 patients,3530 patients with sepsis were included.A total of 997 patients met the SIC diagnostic criteria,and the incidence of SIC was 28.20%(95%confidence interval[CI]:26.80%-29.70%).Compared to patients in the non-SIC group,patients in the SIC group were of older age and had a higher Simplified Acute Physiology Score(SAPS)-Ⅰ score,SAPS-Ⅱ score,and Elixhauser comorbidity index(ECI).A total of 367(36.8%)of 997 patients in the SIC group and 818(32.3%)of 2533 patients in the non-SIC group died in the hospital,which resulted in a significant between-group difference(odds ratios=1.22,95%CI:1.05-1.42;P=0.011).For the secondary outcomes,more patients in the SIC group received mechanical ventilation and vasopressors.Multivariate logistic regression analysis showed that age,male sex,ECI,hemoglobin level,diabetes,and mechanical ventilation use on the first day of ICU admission were risk factors for SIC.CONCLUSION Compared with non-SIC patients,hospital mortality is higher in SIC patients.展开更多
BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-assoc...BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and preDIC status in sepsis patients.METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation.RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7%,22.0%and 31.5%,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P<0.05).On day 1,the SIC score with a cut-off value>3 had a significantly higher sensitivity(72.00%)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00%,SAC status 52.00%;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P<0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95%confidence interval[95%CI]:0.060–0.783,P=0.018)and SAC(adjusted HR=0.146,95%CI:0.041–0.513,P=0.003).CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.展开更多
Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonat...Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonatum sibiricum Delar.ex Redoute,Lonicera japonica Thunb.,Hippophae rhamnoides Linn.,Amygdalus Communis Vas,Platycodon grandiflorus(Jacq.)A.DC.,and Cortex Phelloderdri.Herein,we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota.BWBDS protected mice against SILI,which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity.BWBDS selectively promoted the growth of Lactobacillus johnsonii(L.johnsonii)in cecal ligation and puncture treated mice.Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects.Notably,L.johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity,increasing interleukin-10+M2 macrophage production and enhancing intestinal integrity.Furthermore,heat inactivation L.johnsonii(HI-L.johnsonii)treatment promoted macrophage anti-inflammatory activity and alleviated SILI.Our findings revealed BWBDS and gut microbiota L.johnsonii as novel prebiotic and probiotic that may be used to treat SILI.The potential underlying mechanism was at least in part,via L.johnsonii-dependent immune regulation and interleukin-10+M2 macrophage production.展开更多
Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear...Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear.The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD.In mice,knockdown of the gastrin receptor,cholecystokinin B receptor(Cckbr),aggravated lipopolysaccharide(LPS)-induced cardiac dysfunction and increased inflammation in the heart,whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury.Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes,48 h prior to LPS administration,alleviated LPSinduced cardiac injury in Cckbr-deficient mice.The intravenous injection of bone marrow macrophages(BMMs)overexpressing Cckbr reduced LPS-induced myocardial dysfunction.Furthermore,gastrin treatment inhibited toll-like receptor 4(TLR4)expression through the peroxisome proliferator-activated receptor a(PPAR-a)signaling pathway in BMMs.Thus,our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD,which could be used to develop new treatment modalities for SMD.展开更多
Background:The predictive value of red blood cell distribution width(RDW)for mortality in patients withsepsis-induced acute kidney injury(SI-AKI)remains unclear.The present study aimed to investigate the potentialasso...Background:The predictive value of red blood cell distribution width(RDW)for mortality in patients withsepsis-induced acute kidney injury(SI-AKI)remains unclear.The present study aimed to investigate the potentialassociation between RDW at admission and outcomes in patients with SI-AKI.Methods:The Medical Information Mart for Intensive Care(MIMIC)-IV(version 2.0)database,released in Juneof 2022,provides medical data of SI-AKI patients to conduct our related research.Based on propensity scorematching(PSM)method,the main risk factors associated with mortality in SI-AKI were evaluated using Coxproportional hazards regression analysis to construct a predictive nomogram.The concordance index(C-index)and decision curve analysis were used to validate the predictive ability and clinical utility of this model.Patientswith SI-AKI were classified into the high-and low-RDW groups according to the best cut-off value obtained bycalculating the maximum value of the Youden index.Results:A total of 7574 patients with SI-AKI were identified according to the filter criteria.Compared withthe low-RDW group,the high-RDW group had higher 28-day(9.49%vs.31.40%,respectively,P<0.001)and7-day(3.96%vs.13.93%,respectively,P<0.001)mortality rates.Patients in the high-RDW group were moreprone to AKI progression than those in the low-RDW group(20.80%vs.13.60%,respectively,P<0.001).Basedon matched patients,we developed a nomogram model that included age,white blood cells,RDW,combinedhypertension and presence of a malignant tumor,treatment with vasopressor,dialysis,and invasive ventilation,sequential organ failure assessment,and AKI stages.The C-index for predicting the probability of 28-day survivalwas 0.799.Decision curve analysis revealed that the model with RDW offered greater net benefit than that withoutRDW.Conclusion:The present findings demonstrated the importance of RDW,which improved the predictive ability ofthe nomogram model for the probability of survival in patients with SI-AKI.展开更多
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.The heart is one of the most important oxygen delivery organs,and dysfunction significantly increases the mor...Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.The heart is one of the most important oxygen delivery organs,and dysfunction significantly increases the mortality of the body.Hence,the heart has been studied in sepsis for over half a century.However,the definition of sepsis-induced cardiomyopathy is not unified yet,and the conventional conception seems outdated:left ventricular systolic dysfunction(LVSD)along with enlargement of the left ventricle,recovering in 7 to 10 days.With the application of echocardiography in intensive care units,not only LVSD but also left ventricular diastolic dysfunction,right ventricular dysfunction,and even diffuse ventricular dysfunction have been seen.The recognition of sepsis-induced cardiomyopathy is gradually becoming complete,although our understanding of it is not deep,which has made the diagnosis and treatment stagnate.In this review,we summarize the research on sepsis-induced cardiomyopathy.Women and young people with septic cardiomyopathy are more likely to have LVSD,which may have the same mechanism as stress cardiomyopathy.Elderly people with ischemic cardiomyopathy and hypertension tend to have left ventricular diastolic dysfunction.Patients with mechanical ventilation,acute respiratory distress syndrome or other complications of increased right ventricular afterload mostly have right ventricular dysfunction.Diffuse cardiac dysfunction has also been shown in some studies;patients with mixed or co-existing cardiac dysfunction are more common,theoretically.Thus,understanding the pathophysiology of sepsis-induced cardiomyopathy from the perspective of critical care echocardiography is essential.展开更多
Background:Sepsis-induced cardiomyopathy(SIC)is an identified serious complication of sepsis that is associated with adverse outcomes and high mortality.Heat shock proteins(HSPs)have been implicated in suppressing sep...Background:Sepsis-induced cardiomyopathy(SIC)is an identified serious complication of sepsis that is associated with adverse outcomes and high mortality.Heat shock proteins(HSPs)have been implicated in suppressing septic inflammation.The aim of this study was to investigate whether HSP70 can attenuate cellular mitochondrial dysfunction,exuberated inflammation and inflammasome-mediated pyroptosis for SIC intervention.Methods:Mice with cecal ligation plus perforation(CLP)and lipopolysaccharide(LPS)-treated H9C2 cardiomyocytes were used as models of SIC.The mouse survival rate,gross profile,cardiac function,pathological changes and mitochondrial function were observed by photography,echocardiography,hematoxylin-eosin staining and transmission electron microscopy.In addition,cell proliferation and the levels of cardiac troponin I(cTnI),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were determined by Cell Counting Kit-8,crystal violet staining and enzyme-linked immunosorbent assay.Moreover,mitochondrial membrane potential was assessed by immunofluorescence staining,and dynamin-related protein 1 and pyroptosis-related molecules[nucleotide-binding domain,leucine-rich-repeat containing family pyrin domain-containing 3(NLRP3),caspase-1,gasdermin-D(GSDMD),gasdermin-D N-terminal(GSDMD-N)]were measured by western blotting,immunoprecipitation and immunoblotting.Finally,hsp70.1 knockout mice with CLP were used to verify the effects of HSP70 on SIC and the underlying mechanism.Results:Models of SIC were successfully established,as reduced consciousness and activity with liparotrichia in CLP mice were observed,and the survival rate and cardiac ejection fraction(EF)were decreased;conversely,the levels of cTnI,TNF-αand IL-1βand myocardial tissue damage were increased in CLP mice.In addition,LPS stimulation resulted in a reduction in cell viability,mitochondrial destabilization and activation of NLRP3-mediated pyroptosis molecules in vitro.HSP70 treatment improved myocardial tissue damage,survival rate and cardiac dysfunction caused by CLP.Additionally,HSP70 intervention reversed LPS-induced mitochondrial destabiliza-tion,inhibited activation of the NLRP3 inflammasome,caspase-1,GSDMD and GSDMD-N,and decreased pyroptosis.Finally,knockout of hsp70.1 mice with CLP aggravated cardiac dysfunction and upregulated NLRP3 inflammasome activity,and exogenous HSP70 significantly rescued these changes.It was further confirmed that HSP70 plays a protective role in SIC by attenuating mitochondrial dysfunction and inactivating pyroptotic molecules.Conclusions:Our study demonstrated that mitochondrial destabilization and NLRP3 inflammasome activation-mediated pyroptosis are attributed to SIC.Interestingly,HSP70 ameliorates sepsis-induced myocardial dysfunction by improving mitochondrial dysfunction and inhibiting the acti-vation of NLRP3 inflammasome-mediated pyroptosis,and such a result may provide approaches for novel therapies for SIC.展开更多
Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis,which is associated with high morbidity and mortality.11β-hydroxysteroid dehydrogenase type 1(11β-HSD1),encoded by Hsd11b1,is a reducta...Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis,which is associated with high morbidity and mortality.11β-hydroxysteroid dehydrogenase type 1(11β-HSD1),encoded by Hsd11b1,is a reductase that can convert inactive cortisone into metabolically active cortisol,but the role of 11β-HSD1 in sepsis-induced myocardial dysfunction remains poorly understood.The current study aimed to investigate the effects of 11β-HSD1 on a lipopolysaccharide(LPS)-induced mouse model,in which LPS(10 mg/kg)was administered to wild-type C57BL/6J mice and 11β-HSD1 global knockout mice.We asscessed cardiac function by echocardiography,performed transmission electron microscopy and immunohistochemical staining to analyze myocardial mitochondrial injury and histological changes,and determined the levels of reactive oxygen species and biomarkers of oxidative stress.We also employed polymerase chain reaction analysis,Western blotting,and immunofluorescent staining to determine the expression of related genes and proteins.To investigate the role of 11β-HSD1 in sepsis-induced myocardial dysfunction,we used LPS to induce lentivirus-infected neonatal rat ventricular cardiomyocytes.We found that knockdown of 11β-HSD1 alleviated LPS-induced myocardial mitochondrial injury,oxidative stress,and inflammation,along with an improved myocardial function;furthermore,the depletion of 11β-HSD1 promoted the phosphorylation of adenosine 5′-monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor gamma coactivator 1α(PGC-1α),and silent information regulator 1(SIRT1)protein levels both in vivo and in vitro.Therefore,the suppression of 11β-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.展开更多
BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,th...BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.METHODS:The rat models of sepsis were produced by cecal ligation and perforation(CLP)surgery.Rats were randomly(random number) assigned to one of three groups(n=8 for each group):sham group,CLP group and EPO group(1000 lU/kg erythropoietin).Arterial blood was withdrawn at3,6,12,and 24 hours after CLP.cTnl,BNP,CK-MB,LDH,AST,TNF-a,IL-6,IL-10,and CRP were tested by the ELISA assay.Changes of hemodynamic parameters were recorded at 3,6,12,24 hours after the surgery.Histological diagnosis was made by hematoxylin and eosin.Flow cytometry was performed to examine cell apoptosis,myocardium mitochondrial inner membrane potential,and NF-κB(p65).Survival rate at 7 days after CLP was recorded.RESULTS:In the CLP group,myocardial enzyme index and inflammatory index increased at3,6,12 and 24 hours after CLP compared with the sham group,and EPO significantly blocked the increase.Compared with the CLP group,EPO significantly improved LVSP,LV +dpldt_(max) LV-dp/dt_(min),and decreased LVEDP at different time.EPO blocked the reduction of mitochondrial transmembrane potential,suppressed the cardiomyocyte apoptosis,inhibited the activation of NF-κB,and reduced the production of proinflmmatory cytokines.No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.CONCLUSION:Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.展开更多
Sepsis is a common clinical disease;if there is no early active treatment,it is likely to develop into multiple organ dysfunction syndrome and even cause death.Septic cardiomyopathy is a complication of sepsis-related...Sepsis is a common clinical disease;if there is no early active treatment,it is likely to develop into multiple organ dysfunction syndrome and even cause death.Septic cardiomyopathy is a complication of sepsis-related cardiovascular failure,characterized by reversible left ventricular dilatation and decreased ventricular systolic and/or diastolic function.At present,echocardiography and biomarkers are often used to screen septic cardiomyopathy in clinics.Although there is still a lack of clear diagnostic criteria for septic cardiomyopathy,according to existing studies,the pathogenesis of several septic cardiomyopathy has been clarified,such as immune response caused by infection and mitochondrial dysfunction.This review summarizes the characteristics,pathophysiology,and diagnosis of septic cardiomyopathy and focuses on the mechanisms of infection immunity and mitochondrial dysfunction.展开更多
基金Supported by Science and Technology Program of Guangzhou Science,Technology,and Innovation Commission,No.201904010258.
文摘BACKGROUND At present,large-scale studies on the clinical characteristics of sepsis-induced cardiomyopathy(SIC)are lacking.AIM To investigate the clinical characteristics of SIC.METHODS Based on the analysis of the MIMIC-III public database,we performed a largescale retrospective study involving sepsis patients who were admitted to the intensive care unit(ICU)and had no concomitant cardiac disease.We used propensity score matching analysis and multivariate logistic regression to ensure the robustness of the results.The primary outcome was hospital mortality,and the secondary outcomes included the number of patients who received mechanical ventilation or renal replacement therapy during their hospital stay,the number of patients administered with vasopressors,the length of ICU stay,and the length of hospital stay.RESULTS In the present study,after screening 38605 patients,3530 patients with sepsis were included.A total of 997 patients met the SIC diagnostic criteria,and the incidence of SIC was 28.20%(95%confidence interval[CI]:26.80%-29.70%).Compared to patients in the non-SIC group,patients in the SIC group were of older age and had a higher Simplified Acute Physiology Score(SAPS)-Ⅰ score,SAPS-Ⅱ score,and Elixhauser comorbidity index(ECI).A total of 367(36.8%)of 997 patients in the SIC group and 818(32.3%)of 2533 patients in the non-SIC group died in the hospital,which resulted in a significant between-group difference(odds ratios=1.22,95%CI:1.05-1.42;P=0.011).For the secondary outcomes,more patients in the SIC group received mechanical ventilation and vasopressors.Multivariate logistic regression analysis showed that age,male sex,ECI,hemoglobin level,diabetes,and mechanical ventilation use on the first day of ICU admission were risk factors for SIC.CONCLUSION Compared with non-SIC patients,hospital mortality is higher in SIC patients.
基金supported by the National Key Research and Development Program of China(2021YFC2501800)Shanghai Committee of Science and Technology(20Y11900100,21MC1930400,and 20DZ2261200)Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR4059)。
文摘BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and preDIC status in sepsis patients.METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation.RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7%,22.0%and 31.5%,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P<0.05).On day 1,the SIC score with a cut-off value>3 had a significantly higher sensitivity(72.00%)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00%,SAC status 52.00%;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P<0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95%confidence interval[95%CI]:0.060–0.783,P=0.018)and SAC(adjusted HR=0.146,95%CI:0.041–0.513,P=0.003).CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.
基金funded by regular grants and joint grant(File No.0096/2018/A3,0111/2020/A3 and 0056/2020/AMJ)Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery(File No.001/2020/ALC)+4 种基金supported by the Macao Science and Technology Development Fundsupported by 2020 Young Qihuang Scholar funded by the National Administration of Traditional Chinese Medicinesupported by National Natural Science Foundation of China(82025036)supported by the Start-up Research Grant of University of Macao(SRG2022-00020-FHS,China)the Faculty of Health Science,University of Macao(Macao,China).
文摘Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonatum sibiricum Delar.ex Redoute,Lonicera japonica Thunb.,Hippophae rhamnoides Linn.,Amygdalus Communis Vas,Platycodon grandiflorus(Jacq.)A.DC.,and Cortex Phelloderdri.Herein,we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota.BWBDS protected mice against SILI,which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity.BWBDS selectively promoted the growth of Lactobacillus johnsonii(L.johnsonii)in cecal ligation and puncture treated mice.Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects.Notably,L.johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity,increasing interleukin-10+M2 macrophage production and enhancing intestinal integrity.Furthermore,heat inactivation L.johnsonii(HI-L.johnsonii)treatment promoted macrophage anti-inflammatory activity and alleviated SILI.Our findings revealed BWBDS and gut microbiota L.johnsonii as novel prebiotic and probiotic that may be used to treat SILI.The potential underlying mechanism was at least in part,via L.johnsonii-dependent immune regulation and interleukin-10+M2 macrophage production.
基金supported by grants to Chunyu Zeng from the Program of Innovative Research Team by National Natural Science Foundation(81721001,China)National Natural Science Foundation of China(31430043,31730043)+5 种基金Program for Changjiang Scholars,and Innovative Research Team in University(IRT1216,China)the National Key R&D Program of China(2018YFC1312700)by grant to Jingwen Guo from the National Natural Science Foundation of China(82000476)by grant to Yijie Hu from the Excellent Talents Project of Third Military Medical University(B-3232,China)by grant to Hongyong Wang from the Clinical Technology Innovation and Cultivation Program of AMU(CX2019JS220,China)by grant to Xinyue Li from Chongqing Natural Science Foundation(CSTB2022NSCQ-BHX0025,China)。
文摘Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear.The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD.In mice,knockdown of the gastrin receptor,cholecystokinin B receptor(Cckbr),aggravated lipopolysaccharide(LPS)-induced cardiac dysfunction and increased inflammation in the heart,whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury.Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes,48 h prior to LPS administration,alleviated LPSinduced cardiac injury in Cckbr-deficient mice.The intravenous injection of bone marrow macrophages(BMMs)overexpressing Cckbr reduced LPS-induced myocardial dysfunction.Furthermore,gastrin treatment inhibited toll-like receptor 4(TLR4)expression through the peroxisome proliferator-activated receptor a(PPAR-a)signaling pathway in BMMs.Thus,our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD,which could be used to develop new treatment modalities for SMD.
基金This work was supported by the National Natural Science Foundation of China(grant numbers:81901960 and 81902006)the Foundation of Shanghai Hospital Development Center(grant number:SHDC2020CR4100).
文摘Background:The predictive value of red blood cell distribution width(RDW)for mortality in patients withsepsis-induced acute kidney injury(SI-AKI)remains unclear.The present study aimed to investigate the potentialassociation between RDW at admission and outcomes in patients with SI-AKI.Methods:The Medical Information Mart for Intensive Care(MIMIC)-IV(version 2.0)database,released in Juneof 2022,provides medical data of SI-AKI patients to conduct our related research.Based on propensity scorematching(PSM)method,the main risk factors associated with mortality in SI-AKI were evaluated using Coxproportional hazards regression analysis to construct a predictive nomogram.The concordance index(C-index)and decision curve analysis were used to validate the predictive ability and clinical utility of this model.Patientswith SI-AKI were classified into the high-and low-RDW groups according to the best cut-off value obtained bycalculating the maximum value of the Youden index.Results:A total of 7574 patients with SI-AKI were identified according to the filter criteria.Compared withthe low-RDW group,the high-RDW group had higher 28-day(9.49%vs.31.40%,respectively,P<0.001)and7-day(3.96%vs.13.93%,respectively,P<0.001)mortality rates.Patients in the high-RDW group were moreprone to AKI progression than those in the low-RDW group(20.80%vs.13.60%,respectively,P<0.001).Basedon matched patients,we developed a nomogram model that included age,white blood cells,RDW,combinedhypertension and presence of a malignant tumor,treatment with vasopressor,dialysis,and invasive ventilation,sequential organ failure assessment,and AKI stages.The C-index for predicting the probability of 28-day survivalwas 0.799.Decision curve analysis revealed that the model with RDW offered greater net benefit than that withoutRDW.Conclusion:The present findings demonstrated the importance of RDW,which improved the predictive ability ofthe nomogram model for the probability of survival in patients with SI-AKI.
文摘Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.The heart is one of the most important oxygen delivery organs,and dysfunction significantly increases the mortality of the body.Hence,the heart has been studied in sepsis for over half a century.However,the definition of sepsis-induced cardiomyopathy is not unified yet,and the conventional conception seems outdated:left ventricular systolic dysfunction(LVSD)along with enlargement of the left ventricle,recovering in 7 to 10 days.With the application of echocardiography in intensive care units,not only LVSD but also left ventricular diastolic dysfunction,right ventricular dysfunction,and even diffuse ventricular dysfunction have been seen.The recognition of sepsis-induced cardiomyopathy is gradually becoming complete,although our understanding of it is not deep,which has made the diagnosis and treatment stagnate.In this review,we summarize the research on sepsis-induced cardiomyopathy.Women and young people with septic cardiomyopathy are more likely to have LVSD,which may have the same mechanism as stress cardiomyopathy.Elderly people with ischemic cardiomyopathy and hypertension tend to have left ventricular diastolic dysfunction.Patients with mechanical ventilation,acute respiratory distress syndrome or other complications of increased right ventricular afterload mostly have right ventricular dysfunction.Diffuse cardiac dysfunction has also been shown in some studies;patients with mixed or co-existing cardiac dysfunction are more common,theoretically.Thus,understanding the pathophysiology of sepsis-induced cardiomyopathy from the perspective of critical care echocardiography is essential.
文摘Background:Sepsis-induced cardiomyopathy(SIC)is an identified serious complication of sepsis that is associated with adverse outcomes and high mortality.Heat shock proteins(HSPs)have been implicated in suppressing septic inflammation.The aim of this study was to investigate whether HSP70 can attenuate cellular mitochondrial dysfunction,exuberated inflammation and inflammasome-mediated pyroptosis for SIC intervention.Methods:Mice with cecal ligation plus perforation(CLP)and lipopolysaccharide(LPS)-treated H9C2 cardiomyocytes were used as models of SIC.The mouse survival rate,gross profile,cardiac function,pathological changes and mitochondrial function were observed by photography,echocardiography,hematoxylin-eosin staining and transmission electron microscopy.In addition,cell proliferation and the levels of cardiac troponin I(cTnI),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were determined by Cell Counting Kit-8,crystal violet staining and enzyme-linked immunosorbent assay.Moreover,mitochondrial membrane potential was assessed by immunofluorescence staining,and dynamin-related protein 1 and pyroptosis-related molecules[nucleotide-binding domain,leucine-rich-repeat containing family pyrin domain-containing 3(NLRP3),caspase-1,gasdermin-D(GSDMD),gasdermin-D N-terminal(GSDMD-N)]were measured by western blotting,immunoprecipitation and immunoblotting.Finally,hsp70.1 knockout mice with CLP were used to verify the effects of HSP70 on SIC and the underlying mechanism.Results:Models of SIC were successfully established,as reduced consciousness and activity with liparotrichia in CLP mice were observed,and the survival rate and cardiac ejection fraction(EF)were decreased;conversely,the levels of cTnI,TNF-αand IL-1βand myocardial tissue damage were increased in CLP mice.In addition,LPS stimulation resulted in a reduction in cell viability,mitochondrial destabilization and activation of NLRP3-mediated pyroptosis molecules in vitro.HSP70 treatment improved myocardial tissue damage,survival rate and cardiac dysfunction caused by CLP.Additionally,HSP70 intervention reversed LPS-induced mitochondrial destabiliza-tion,inhibited activation of the NLRP3 inflammasome,caspase-1,GSDMD and GSDMD-N,and decreased pyroptosis.Finally,knockout of hsp70.1 mice with CLP aggravated cardiac dysfunction and upregulated NLRP3 inflammasome activity,and exogenous HSP70 significantly rescued these changes.It was further confirmed that HSP70 plays a protective role in SIC by attenuating mitochondrial dysfunction and inactivating pyroptotic molecules.Conclusions:Our study demonstrated that mitochondrial destabilization and NLRP3 inflammasome activation-mediated pyroptosis are attributed to SIC.Interestingly,HSP70 ameliorates sepsis-induced myocardial dysfunction by improving mitochondrial dysfunction and inhibiting the acti-vation of NLRP3 inflammasome-mediated pyroptosis,and such a result may provide approaches for novel therapies for SIC.
基金supported by grants from the National Natural Science Youth Foundation of China(Grant No.81501201)the National Natural Science Youth Foundation of Jiangsu Province(Grant No.BK20151032)Min Huang,and the project of Critical Care Medicine of the Key Clinical Specialty of Jiangsu Province.
文摘Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis,which is associated with high morbidity and mortality.11β-hydroxysteroid dehydrogenase type 1(11β-HSD1),encoded by Hsd11b1,is a reductase that can convert inactive cortisone into metabolically active cortisol,but the role of 11β-HSD1 in sepsis-induced myocardial dysfunction remains poorly understood.The current study aimed to investigate the effects of 11β-HSD1 on a lipopolysaccharide(LPS)-induced mouse model,in which LPS(10 mg/kg)was administered to wild-type C57BL/6J mice and 11β-HSD1 global knockout mice.We asscessed cardiac function by echocardiography,performed transmission electron microscopy and immunohistochemical staining to analyze myocardial mitochondrial injury and histological changes,and determined the levels of reactive oxygen species and biomarkers of oxidative stress.We also employed polymerase chain reaction analysis,Western blotting,and immunofluorescent staining to determine the expression of related genes and proteins.To investigate the role of 11β-HSD1 in sepsis-induced myocardial dysfunction,we used LPS to induce lentivirus-infected neonatal rat ventricular cardiomyocytes.We found that knockdown of 11β-HSD1 alleviated LPS-induced myocardial mitochondrial injury,oxidative stress,and inflammation,along with an improved myocardial function;furthermore,the depletion of 11β-HSD1 promoted the phosphorylation of adenosine 5′-monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor gamma coactivator 1α(PGC-1α),and silent information regulator 1(SIRT1)protein levels both in vivo and in vitro.Therefore,the suppression of 11β-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.
基金supported by a grant from the National Natural Science Foundation of China(81070122)
文摘BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.METHODS:The rat models of sepsis were produced by cecal ligation and perforation(CLP)surgery.Rats were randomly(random number) assigned to one of three groups(n=8 for each group):sham group,CLP group and EPO group(1000 lU/kg erythropoietin).Arterial blood was withdrawn at3,6,12,and 24 hours after CLP.cTnl,BNP,CK-MB,LDH,AST,TNF-a,IL-6,IL-10,and CRP were tested by the ELISA assay.Changes of hemodynamic parameters were recorded at 3,6,12,24 hours after the surgery.Histological diagnosis was made by hematoxylin and eosin.Flow cytometry was performed to examine cell apoptosis,myocardium mitochondrial inner membrane potential,and NF-κB(p65).Survival rate at 7 days after CLP was recorded.RESULTS:In the CLP group,myocardial enzyme index and inflammatory index increased at3,6,12 and 24 hours after CLP compared with the sham group,and EPO significantly blocked the increase.Compared with the CLP group,EPO significantly improved LVSP,LV +dpldt_(max) LV-dp/dt_(min),and decreased LVEDP at different time.EPO blocked the reduction of mitochondrial transmembrane potential,suppressed the cardiomyocyte apoptosis,inhibited the activation of NF-κB,and reduced the production of proinflmmatory cytokines.No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.CONCLUSION:Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.
基金supported by grants from the National Natural Science Foundation of China(82172165)Taishan Young Scholar Program of Shandong Province(tsqn202103171)+1 种基金Project was funded by China Postdoctoral Science Foundation(2020T130072ZX)Clinical Research Center of Shandong University(2020SDUCRCC007).
文摘Sepsis is a common clinical disease;if there is no early active treatment,it is likely to develop into multiple organ dysfunction syndrome and even cause death.Septic cardiomyopathy is a complication of sepsis-related cardiovascular failure,characterized by reversible left ventricular dilatation and decreased ventricular systolic and/or diastolic function.At present,echocardiography and biomarkers are often used to screen septic cardiomyopathy in clinics.Although there is still a lack of clear diagnostic criteria for septic cardiomyopathy,according to existing studies,the pathogenesis of several septic cardiomyopathy has been clarified,such as immune response caused by infection and mitochondrial dysfunction.This review summarizes the characteristics,pathophysiology,and diagnosis of septic cardiomyopathy and focuses on the mechanisms of infection immunity and mitochondrial dysfunction.
