Sepsis不同于感染,是机体对感染的反应失控而导致的危及生命的器官功能障碍。Sepsis的重点在于器官功能障碍而非感染,这可能是美国感染病学会(Infectious Disease Society of America,IDSA)与"拯救Sepsis运动(Surviving Sepsis Cam...Sepsis不同于感染,是机体对感染的反应失控而导致的危及生命的器官功能障碍。Sepsis的重点在于器官功能障碍而非感染,这可能是美国感染病学会(Infectious Disease Society of America,IDSA)与"拯救Sepsis运动(Surviving Sepsis Campaign,SSC)"在重症感染认知上的分歧。对于Sepsis而言,筛查至关重要,可更早地启动集束性治疗策略,从而改善患者预后。Sepsis的理念来源于循证医学证据及大数据研究结果,二者奠定了其坚实的理论基础。本文根据IDSA提出的争议话题,从SSC角度,阐述重症医学对Sepsis本质的认知。展开更多
OBJECTIVE To clarify the role of translocator protein 18 ku(TSPO)on cecum liga⁃tion and puncture(CLP)induced sepsis associat⁃ed encephalopathy(SAE)mice,which consis⁃tently demonstrated astrocyte activation and neu⁃roi...OBJECTIVE To clarify the role of translocator protein 18 ku(TSPO)on cecum liga⁃tion and puncture(CLP)induced sepsis associat⁃ed encephalopathy(SAE)mice,which consis⁃tently demonstrated astrocyte activation and neu⁃roinflammation.Background SAE,a brain dys⁃function,caused by systemic infection without clinical or laboratory evidence of direct infection.Most patients have symptoms such as long-term cognitive dysfunction.As the pathogenesis of SAE is very complex,neuroinflammation for SAE is one of the causes of the disease.TSPO as a marker of neuroinflammation that has the poten⁃tial to regulate neuroinflammation and SAE.METHODS The animal model of SAE was in⁃duced by CLP.TSPO ligands and TSPO knock⁃out mice were used for behavioral and molecular biology research.Survival rate of mice within 120 h on CLP mice was observed.The changes of cog⁃nitive function in mice were observed by Morris water maze and open field test.The changes of proinflammatory factors(IL-1β,TNF-α,IL-6)in hippocampus were observed by ELISA;Astro⁃cyte activation,marked by GFAP,in hippocam⁃pal was analyzed by tissue immunofluorescence and Western blotting.RESULTS Pretreatment with the TSPO ligands,XBD173 or PK11195,sig⁃nificantly improved the survival rate of CLP mice.The results of Morris water maze showed that TSPO ligands significantly increased the number of crossing the platform and the target quadrant time on CLP mice,suggesting that TSPO ligands may improve the learning and memory ability of CLP mice.Subsequent experiments revealed that TSPO ligands can reduce the inflammatory factors(IL-1β,TNF-α,IL-6)and astrocyte activa⁃tion in hippocampus of CLP mice.Similar results were also confirmed in TSPO knockout CLP mice,suggesting intervention of TSPO can reduce neuroinflammatory response and play a protec⁃tive role on SAE mice.CONCLUSION TSPO may play a critical role on SAE mice.Targeting TSPO by pharmacological means may improve the survival rate and cognitive function on CLP mice,which may through inhibiting astrocyte acti⁃vation and neuroinflammation in hippocampal.展开更多
Sepsis can cause a series of damages to various organs of the body,so it has always been regarded as a hot research topic in veterinary clinic.Aiming at the present situation of high morbidity and mortality of canine ...Sepsis can cause a series of damages to various organs of the body,so it has always been regarded as a hot research topic in veterinary clinic.Aiming at the present situation of high morbidity and mortality of canine sepsis,in order to further explore the pathogenesis of this disease,it need to establish a stable and repeatable canine sepsis model that is in line with the clinical characteristics of the disease.The study selected 12 local dogs and randomly divided into three groups:rapid bolus injection group(Group A),continuous infusion group within 30 min(Group B)and continuous infusion group(Group C).Then,the lipopolysaccharides(LPS)with 2 mg·kg^-1 were injected through the brachial vein in different modes of administration,thus the model was fully established.During the modeling period,body temperature(T),respiratory rate(RR),heart rate(HR)and mean arterial pressure(MAP)were monitored at 0,10,20,30,40,50 min and 1,2,3,4,5,6,7,8,9,12 and 24 h.Blood was collected from the canine brachial vein at 0,1,2,3,4,5,6,7,8,9,12 and 24 h,respectively,for the detection of white blood cells(WBC).The test showed that the values of T,RR,HR,MAP,WBC of the dogs in group A all changed but did not exceed the normal range,and the clinical symptoms were not significant.There were no significant changes in the values of RR,HR,T,MAP and WBC of the dogs in Group B,and the clinical symptoms were not significant.The value of T of the dogs in Group C were significantly increased at 40 min(p<0.05),which reached the fever standard and lasted for 7 h;the value of RR increased significantly at 20 min(p<0.05),and a downward trend could be observed at 12 h,then it returned to normal at 24 h;the value of HR increased significantly at 50 min(p<0.05)and recovered at 8 h;the value of HR decreased significantly at 20 min(p<0.05),which remained at 12 h(p<0.05),and returned back to normal at 24 h;the value of WBC decreased significantly from 1 h to 4 h(p<0.05),which was lower than the normal value,and increased significantly at 24 h(p<0.01);all of the four dogs in this group had clinical symptoms such as vomiting,diarrhea and depression.Based on the above results,the changes of indexes and clinical symptoms in Groups A and B did not meet the standards of sepsis.After a long-term continuous intravenous infusion of LPS,the experimental dogs in Group C showed varying degrees of clinical symptoms,such as vomiting,diarrhea and depression one after another.The indexes and clinical symptoms reached the sepsis standard about 3 h after infusion.In brief,this model not only had good stability and good regularity of repeatability,but also lasted for a long time and could be suitable for other subsequent studies.展开更多
Critical care medicine focuses on understanding the pathophysiological mechanisms and treatment approaches for life-threatening conditions,including sepsis,severe trauma/burns,hemorrhagic shock,heatstroke,and acute pa...Critical care medicine focuses on understanding the pathophysiological mechanisms and treatment approaches for life-threatening conditions,including sepsis,severe trauma/burns,hemorrhagic shock,heatstroke,and acute pancreatitis,all of which have high incidence rates.These conditions are primarily characterized by acute multi-organ dysfunction,with sudden onset,severe illness,and high mortality rates.Additionally,critical care treatment demands substantial medical resources,imposing significant economic burdens on patients’families and society.In recent years,critical care medicine has achieved notable progress,especially in multidisciplinary integration with immunology-based fields.Collaboration across disciplines has not only accelerated advancements in critical care but also propelled the rapid development of modern immunology.This paper provides an overview and assessment of the cross-disciplinary fusion between critical care medicine and immunology,exploring how these fields related extensions mutually enhance each other.It further analyzes China’s potential to become a global leader in this area within the next 5 to 10 years.展开更多
Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflamm...Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.展开更多
文摘Sepsis和感染性休克是导致重症患者死亡的主要原因之一。随着对Sepsis病理生理机制和临床诊治研究的逐渐深入,"拯救Sepsis运动(Surviving Sepsis Campaign,SSC)"自2004年起每4年对SSC指南更新一次,使临床诊疗逐渐趋于规范。近10余年的数据显示,Sepsis患者的病死率稳定且呈显著下降趋势。2016年更新的SSC指南在抗感染治疗方面遭遇到了美国感染病学会(Infectious Disease Society of America,IDSA)的挑战,其在官方期刊Clin Infect Dis发表公开立场声明,不再支持SSC指南。这一举动给临床医生借鉴和应用2016年版SSC指南带来很大困惑。深入了解两大学会对于SSC指南争议的本质至关重要,只有回归争议本质,理清分歧的基点,才能更好地使用指南,使其真正成为临床诊治Sepsis和感染性休克的重要参考。
文摘Sepsis不同于感染,是机体对感染的反应失控而导致的危及生命的器官功能障碍。Sepsis的重点在于器官功能障碍而非感染,这可能是美国感染病学会(Infectious Disease Society of America,IDSA)与"拯救Sepsis运动(Surviving Sepsis Campaign,SSC)"在重症感染认知上的分歧。对于Sepsis而言,筛查至关重要,可更早地启动集束性治疗策略,从而改善患者预后。Sepsis的理念来源于循证医学证据及大数据研究结果,二者奠定了其坚实的理论基础。本文根据IDSA提出的争议话题,从SSC角度,阐述重症医学对Sepsis本质的认知。
基金Joint Funds for the Innovation of Science and Technology of Fujian Province(2019Y9009)and Natural Science Foundation of Fujian Province(2020J01618)。
文摘OBJECTIVE To clarify the role of translocator protein 18 ku(TSPO)on cecum liga⁃tion and puncture(CLP)induced sepsis associat⁃ed encephalopathy(SAE)mice,which consis⁃tently demonstrated astrocyte activation and neu⁃roinflammation.Background SAE,a brain dys⁃function,caused by systemic infection without clinical or laboratory evidence of direct infection.Most patients have symptoms such as long-term cognitive dysfunction.As the pathogenesis of SAE is very complex,neuroinflammation for SAE is one of the causes of the disease.TSPO as a marker of neuroinflammation that has the poten⁃tial to regulate neuroinflammation and SAE.METHODS The animal model of SAE was in⁃duced by CLP.TSPO ligands and TSPO knock⁃out mice were used for behavioral and molecular biology research.Survival rate of mice within 120 h on CLP mice was observed.The changes of cog⁃nitive function in mice were observed by Morris water maze and open field test.The changes of proinflammatory factors(IL-1β,TNF-α,IL-6)in hippocampus were observed by ELISA;Astro⁃cyte activation,marked by GFAP,in hippocam⁃pal was analyzed by tissue immunofluorescence and Western blotting.RESULTS Pretreatment with the TSPO ligands,XBD173 or PK11195,sig⁃nificantly improved the survival rate of CLP mice.The results of Morris water maze showed that TSPO ligands significantly increased the number of crossing the platform and the target quadrant time on CLP mice,suggesting that TSPO ligands may improve the learning and memory ability of CLP mice.Subsequent experiments revealed that TSPO ligands can reduce the inflammatory factors(IL-1β,TNF-α,IL-6)and astrocyte activa⁃tion in hippocampus of CLP mice.Similar results were also confirmed in TSPO knockout CLP mice,suggesting intervention of TSPO can reduce neuroinflammatory response and play a protec⁃tive role on SAE mice.CONCLUSION TSPO may play a critical role on SAE mice.Targeting TSPO by pharmacological means may improve the survival rate and cognitive function on CLP mice,which may through inhibiting astrocyte acti⁃vation and neuroinflammation in hippocampal.
基金Supported by the National Natural Science Foundation of China(31772806)Undergraduate Innovative Entrepreneurship Program in Heilongjiang Province(201810224054)the National Key Research and Development Program of China(2016YED0501008)
文摘Sepsis can cause a series of damages to various organs of the body,so it has always been regarded as a hot research topic in veterinary clinic.Aiming at the present situation of high morbidity and mortality of canine sepsis,in order to further explore the pathogenesis of this disease,it need to establish a stable and repeatable canine sepsis model that is in line with the clinical characteristics of the disease.The study selected 12 local dogs and randomly divided into three groups:rapid bolus injection group(Group A),continuous infusion group within 30 min(Group B)and continuous infusion group(Group C).Then,the lipopolysaccharides(LPS)with 2 mg·kg^-1 were injected through the brachial vein in different modes of administration,thus the model was fully established.During the modeling period,body temperature(T),respiratory rate(RR),heart rate(HR)and mean arterial pressure(MAP)were monitored at 0,10,20,30,40,50 min and 1,2,3,4,5,6,7,8,9,12 and 24 h.Blood was collected from the canine brachial vein at 0,1,2,3,4,5,6,7,8,9,12 and 24 h,respectively,for the detection of white blood cells(WBC).The test showed that the values of T,RR,HR,MAP,WBC of the dogs in group A all changed but did not exceed the normal range,and the clinical symptoms were not significant.There were no significant changes in the values of RR,HR,T,MAP and WBC of the dogs in Group B,and the clinical symptoms were not significant.The value of T of the dogs in Group C were significantly increased at 40 min(p<0.05),which reached the fever standard and lasted for 7 h;the value of RR increased significantly at 20 min(p<0.05),and a downward trend could be observed at 12 h,then it returned to normal at 24 h;the value of HR increased significantly at 50 min(p<0.05)and recovered at 8 h;the value of HR decreased significantly at 20 min(p<0.05),which remained at 12 h(p<0.05),and returned back to normal at 24 h;the value of WBC decreased significantly from 1 h to 4 h(p<0.05),which was lower than the normal value,and increased significantly at 24 h(p<0.01);all of the four dogs in this group had clinical symptoms such as vomiting,diarrhea and depression.Based on the above results,the changes of indexes and clinical symptoms in Groups A and B did not meet the standards of sepsis.After a long-term continuous intravenous infusion of LPS,the experimental dogs in Group C showed varying degrees of clinical symptoms,such as vomiting,diarrhea and depression one after another.The indexes and clinical symptoms reached the sepsis standard about 3 h after infusion.In brief,this model not only had good stability and good regularity of repeatability,but also lasted for a long time and could be suitable for other subsequent studies.
基金supported by the National Science Foundation for Distinguished Young Scholars,China(82025021).
文摘Critical care medicine focuses on understanding the pathophysiological mechanisms and treatment approaches for life-threatening conditions,including sepsis,severe trauma/burns,hemorrhagic shock,heatstroke,and acute pancreatitis,all of which have high incidence rates.These conditions are primarily characterized by acute multi-organ dysfunction,with sudden onset,severe illness,and high mortality rates.Additionally,critical care treatment demands substantial medical resources,imposing significant economic burdens on patients’families and society.In recent years,critical care medicine has achieved notable progress,especially in multidisciplinary integration with immunology-based fields.Collaboration across disciplines has not only accelerated advancements in critical care but also propelled the rapid development of modern immunology.This paper provides an overview and assessment of the cross-disciplinary fusion between critical care medicine and immunology,exploring how these fields related extensions mutually enhance each other.It further analyzes China’s potential to become a global leader in this area within the next 5 to 10 years.
基金supported by the National Natural Science Foundation (81601728,31500726)the Natural Science Foundation of Hunan Province (2021JJ41002),China。
文摘Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.
文摘Sepsis是导致重症患者死亡的重要原因。近年来,随着临床和基础研究的不断发展,人们对于Sepsis定义、诊断以及治疗认识不断深入,患者病死率持续下降。每4年颁布一次并更新的"拯救Sepsis运动(Surviving Sepsis Campaign,SSC)"指南受到国际广泛重视。2016年版SSC指南,在对Sepsis和感染性休克重新定义、重新制定诊断标准的基础上,于2017年1月正式发布。然而,2017年11月,美国感染病学会(Infectious Disease Society of America,IDSA)即在其官方期刊Clin Infect Dis发表公开声明,对2016年版SSC指南中关于感染诊疗的推荐意见提出质疑。本文站在IDSA的立场,尝试从Sepsis概念、诊断及治疗3个方面解读IDSA声明,探讨Sepsis中的"感染"问题。
