Objective To establish a model of multiple organ dysfunction syndrome in the elderly (MODSE) by intraperitoneal injection of different doses of zymosan, and to compare the multiple organ dysfunction syndrome (MODS) in...Objective To establish a model of multiple organ dysfunction syndrome in the elderly (MODSE) by intraperitoneal injection of different doses of zymosan, and to compare the multiple organ dysfunction syndrome (MODS) in adult and in the elderly rats. Methods Adult and senile rats, injected with different doses of zymosan intraperitoneally were examined for the changes in the function and morphology of the vital organs, including heart, liver, brain, lungs, and kidneys using blood gas and biochemistry analysis and histopathological examination methods. Results Compared with the normal controls of the adult and the elderly rats, the blood gas and blood biochemistry changed in different degrees in the different dosed zymosan groups. Pathological changes were also found in the vital organs including lungs, heart, liver, brain, kidneys, erc in the experimental groups. Under the same concentrations of zymosan, the reductions in respiratory, cardiac and renal functions in the senile groups were much more severe than those in the corresponding adult group. In the similar degree of model duplication, the senile rats had the tendency to die later than the adult rats. Conclusions Zymosan can be used in both elderly and adult rats to induce MODS model, and the best dosage for MODSE was 0.Sg/kg injected peritoneally. The model would hopefully be used in the study of mechanisms and the therapeutics on MODSE.展开更多
Fifty-seven severely burned patients were divided into 2 groups:16 withmultiple organ failure（MOF）,and 41 without MOF.It was found that the levelof thromboxane B<sub>2</sub>（TXB<sub>2</sub>...Fifty-seven severely burned patients were divided into 2 groups:16 withmultiple organ failure（MOF）,and 41 without MOF.It was found that the levelof thromboxane B<sub>2</sub>（TXB<sub>2</sub>）and the ratio between TXB<sub>2</sub> and 6-keto-prostaglandinF<sub>1α</sub>(TBX<sub>2</sub>/6-keto-PGF<sub>1α</sub>)in plasma and in visceral tissues were increased and re-mained significantly high in the first 5～7 d postburn in patients with MOF but notso in those without MOF.The circulatory platelet aggregate ratio（CPAR）wasmarkedly decreased in the same period in MOF group.Myocardial enzymes（CPK,LDH,and GOT）were markedly increased in the first 3d and remainedsignificantly high within 7 d postburn.Degeneration,structural destruction,edema,hemorrhage and thrombosis were revealed in cardiac,pulmonary,renal andhepatic tissues succumbing to functional failure.Thirteen out of the 16 cases de-veloped MOF during the 3rd to 7th day posthurn and 11 died in that period.These findings substantiate that persistent increase of thromboxane andthromboxane/prostacyclin ratio is closely related to the origin and development ofMOF after burn injury.展开更多
Background: Acute lung injury(ALI) is a major component of multiple organ dysfunction syndrome(MODS) following pulmonary and systemic infection. Alveolar macrophages(AMφ) are at the center of ALI pathogenesis. Emergi...Background: Acute lung injury(ALI) is a major component of multiple organ dysfunction syndrome(MODS) following pulmonary and systemic infection. Alveolar macrophages(AMφ) are at the center of ALI pathogenesis. Emerging evidence has shown that cell-cell interactions in the lungs play an important regulatory role in the development of acute lung inflammation. However, the underneath mechanisms remain poorly addressed. In this study, we explore a novel function of lung epithelial cells(LEPCs) in regulating the release of exosomes from AMφ following LPS stimulation.Methods: For the in vivo experiments, C57 BL/6 wildtype(WT) mice were treated with lipopolysaccharide(LPS)(2 mg/kg) in 0.2 ml of saline via intratracheal aerosol administration. Bronchoalveolar lavage fluid was collected at 0–24 h after LPS treatment, and exosomes derived from AMφ were measured. For the in vitro studies, LEPCs and bone marrowderived Mφ(BMDM) were isolated from WT or TLR4-/-mice and were then cocultured in the Transwell? system. After coculture for 0–24 h, the BMDM and supernatant were harvested for the measurement of exosomes and cytokines.Results: We demonstrate that LPS induces macrophages(Mφ) to release exosomes, which are then internalized by neighboring Mφ to promote TNF-α expression. The secreted interleukin(IL)-25 from LEPCs downregulates Rab27 a and Rab27 b expression in Mφ, resulting in suppressed exosome release and thereby attenuating exosome-induced TNF-α expression and secretion.Conclusion: These findings reveal a previously unidentified crosstalk pathway between LEPCs and Mφ that negatively regulates the inflammatory responses of Mφ to LPS. Modulating IL-25 signaling and targeting exosome release may present a new therapeutic strategy for the treatment of ALI.展开更多
Objective To evaluate the sensitivity of arterial ketone body ratio as an indicator for multiple organ failure.Materials and methods The experimental model of multiple organ failure was made in adult and old rats by h...Objective To evaluate the sensitivity of arterial ketone body ratio as an indicator for multiple organ failure.Materials and methods The experimental model of multiple organ failure was made in adult and old rats by hypoperfusion-induced hemorrhagic shock. After blood sampling, the arterial acetoacetate, β-hydroxybutyrate, total ketone body, ALT, AST, BUN, creatinine at 2, 4, 8 hr in hypoperfusion were examined to compare the differences of ketone body ratio and organ failure between adult and old rats. Hepatic and mitochondrial metabolism were assessed by comparing ketone body ratios (AcAc/β-OHB) and free NAD+/NADH ratios. Results Ketone body ratio in old rats at 2, 4, 8 hr after the induction of hemorrhagic shock decreased from 0.68 to 0.31, 0.27 and 0.22, respectively. In adult rats, it decreased from 1.12 to 0.17, 0.12 and 0.09, respectively. Changes of ketone body ratio in the adult group were larger than in the elderly group ( P ＜ 0.001). The development of multiple organ failure is associated with the time of hemorrhagic shock development. Conclusions There was a different ketone body ratio between multiple organ failure in the elderly (MOFE) and multiple organ failure (MOF) in general adults. Ketone body ratio is a better indicator than ALT and AST in reflecting hepatic function in the early status of MOF. (J Geriatr Cardiol 2004;1(2) :125-128. )展开更多
目的探讨老年重症脑卒中患者发生多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)的危险因素。方法前瞻性选择2020年1月至2022年12月广东医科大学附属医院收治的老年重症脑卒中患者112例。根据入院后14 d内多器官功能...目的探讨老年重症脑卒中患者发生多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)的危险因素。方法前瞻性选择2020年1月至2022年12月广东医科大学附属医院收治的老年重症脑卒中患者112例。根据入院后14 d内多器官功能评分系统分为MODS组38例,非MODS组74例。根据最终预后又分为生存组33例和死亡组79例。收集患者一般临床资料、急性生理学与慢性健康状况评估Ⅱ(acute physiology and chronic health evaluation,APACHEⅡ)评分、格拉斯哥昏迷评分(Glasgow coma scale,GCS)和头颅影像学参数。采用logistic回归分析MODS发生的危险因素。结果MODS组脑卒中/脑出血、慢性阻塞性肺疾病、冠心病、吸烟、美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、APACHEⅡ评分、多支血管病变、尿路感染、静脉血栓、出血、癫痫、心肌梗死、急性期机械通气、渗透疗法和住院病死率明显高于非MODS组,GCS明显低于非MODS组,差异有统计学意义(P<0.05,P<0.01)。二元logistic回归分析显示,NIHSS评分、APACHEⅡ评分及多支血管病变是MODS发生的独立危险因素(OR=1.124,95%CI:1.121~1.163,P=0.015;OR=1.265,95%CI:1.296~1.426,P=0.001;OR=2.532,95%CI:1.126~5.013,P=0.026)。死亡组MODS评分、APACHEⅡ评分明显高于生存组,差异有统计学意义(P<0.05)。结论老年重症脑卒中患者急性期易发生MODS。展开更多
文摘Objective To establish a model of multiple organ dysfunction syndrome in the elderly (MODSE) by intraperitoneal injection of different doses of zymosan, and to compare the multiple organ dysfunction syndrome (MODS) in adult and in the elderly rats. Methods Adult and senile rats, injected with different doses of zymosan intraperitoneally were examined for the changes in the function and morphology of the vital organs, including heart, liver, brain, lungs, and kidneys using blood gas and biochemistry analysis and histopathological examination methods. Results Compared with the normal controls of the adult and the elderly rats, the blood gas and blood biochemistry changed in different degrees in the different dosed zymosan groups. Pathological changes were also found in the vital organs including lungs, heart, liver, brain, kidneys, erc in the experimental groups. Under the same concentrations of zymosan, the reductions in respiratory, cardiac and renal functions in the senile groups were much more severe than those in the corresponding adult group. In the similar degree of model duplication, the senile rats had the tendency to die later than the adult rats. Conclusions Zymosan can be used in both elderly and adult rats to induce MODS model, and the best dosage for MODSE was 0.Sg/kg injected peritoneally. The model would hopefully be used in the study of mechanisms and the therapeutics on MODSE.
文摘Fifty-seven severely burned patients were divided into 2 groups:16 withmultiple organ failure（MOF）,and 41 without MOF.It was found that the levelof thromboxane B<sub>2</sub>（TXB<sub>2</sub>）and the ratio between TXB<sub>2</sub> and 6-keto-prostaglandinF<sub>1α</sub>(TBX<sub>2</sub>/6-keto-PGF<sub>1α</sub>)in plasma and in visceral tissues were increased and re-mained significantly high in the first 5～7 d postburn in patients with MOF but notso in those without MOF.The circulatory platelet aggregate ratio（CPAR）wasmarkedly decreased in the same period in MOF group.Myocardial enzymes（CPK,LDH,and GOT）were markedly increased in the first 3d and remainedsignificantly high within 7 d postburn.Degeneration,structural destruction,edema,hemorrhage and thrombosis were revealed in cardiac,pulmonary,renal andhepatic tissues succumbing to functional failure.Thirteen out of the 16 cases de-veloped MOF during the 3rd to 7th day posthurn and 11 died in that period.These findings substantiate that persistent increase of thromboxane andthromboxane/prostacyclin ratio is closely related to the origin and development ofMOF after burn injury.
基金supported by the National Institute of Health Grant(R01-HL-079669 by JF and MAW)the National Institute of Health Grant(R56-HL-123882 by JF)+3 种基金the National Institute of Health Grant(R01HL076179–09 by PW and JF)the VA Merit Award(1I01BX002729 by JF)the National Natural Science Foundation of China(81470262 by JF)the National Institute of Health Grant(R01GM102146 by MJS)
文摘Background: Acute lung injury(ALI) is a major component of multiple organ dysfunction syndrome(MODS) following pulmonary and systemic infection. Alveolar macrophages(AMφ) are at the center of ALI pathogenesis. Emerging evidence has shown that cell-cell interactions in the lungs play an important regulatory role in the development of acute lung inflammation. However, the underneath mechanisms remain poorly addressed. In this study, we explore a novel function of lung epithelial cells(LEPCs) in regulating the release of exosomes from AMφ following LPS stimulation.Methods: For the in vivo experiments, C57 BL/6 wildtype(WT) mice were treated with lipopolysaccharide(LPS)(2 mg/kg) in 0.2 ml of saline via intratracheal aerosol administration. Bronchoalveolar lavage fluid was collected at 0–24 h after LPS treatment, and exosomes derived from AMφ were measured. For the in vitro studies, LEPCs and bone marrowderived Mφ(BMDM) were isolated from WT or TLR4-/-mice and were then cocultured in the Transwell? system. After coculture for 0–24 h, the BMDM and supernatant were harvested for the measurement of exosomes and cytokines.Results: We demonstrate that LPS induces macrophages(Mφ) to release exosomes, which are then internalized by neighboring Mφ to promote TNF-α expression. The secreted interleukin(IL)-25 from LEPCs downregulates Rab27 a and Rab27 b expression in Mφ, resulting in suppressed exosome release and thereby attenuating exosome-induced TNF-α expression and secretion.Conclusion: These findings reveal a previously unidentified crosstalk pathway between LEPCs and Mφ that negatively regulates the inflammatory responses of Mφ to LPS. Modulating IL-25 signaling and targeting exosome release may present a new therapeutic strategy for the treatment of ALI.
文摘Objective To evaluate the sensitivity of arterial ketone body ratio as an indicator for multiple organ failure.Materials and methods The experimental model of multiple organ failure was made in adult and old rats by hypoperfusion-induced hemorrhagic shock. After blood sampling, the arterial acetoacetate, β-hydroxybutyrate, total ketone body, ALT, AST, BUN, creatinine at 2, 4, 8 hr in hypoperfusion were examined to compare the differences of ketone body ratio and organ failure between adult and old rats. Hepatic and mitochondrial metabolism were assessed by comparing ketone body ratios (AcAc/β-OHB) and free NAD+/NADH ratios. Results Ketone body ratio in old rats at 2, 4, 8 hr after the induction of hemorrhagic shock decreased from 0.68 to 0.31, 0.27 and 0.22, respectively. In adult rats, it decreased from 1.12 to 0.17, 0.12 and 0.09, respectively. Changes of ketone body ratio in the adult group were larger than in the elderly group ( P ＜ 0.001). The development of multiple organ failure is associated with the time of hemorrhagic shock development. Conclusions There was a different ketone body ratio between multiple organ failure in the elderly (MOFE) and multiple organ failure (MOF) in general adults. Ketone body ratio is a better indicator than ALT and AST in reflecting hepatic function in the early status of MOF. (J Geriatr Cardiol 2004;1(2) :125-128. )
文摘目的探讨老年重症脑卒中患者发生多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)的危险因素。方法前瞻性选择2020年1月至2022年12月广东医科大学附属医院收治的老年重症脑卒中患者112例。根据入院后14 d内多器官功能评分系统分为MODS组38例,非MODS组74例。根据最终预后又分为生存组33例和死亡组79例。收集患者一般临床资料、急性生理学与慢性健康状况评估Ⅱ(acute physiology and chronic health evaluation,APACHEⅡ)评分、格拉斯哥昏迷评分(Glasgow coma scale,GCS)和头颅影像学参数。采用logistic回归分析MODS发生的危险因素。结果MODS组脑卒中/脑出血、慢性阻塞性肺疾病、冠心病、吸烟、美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、APACHEⅡ评分、多支血管病变、尿路感染、静脉血栓、出血、癫痫、心肌梗死、急性期机械通气、渗透疗法和住院病死率明显高于非MODS组,GCS明显低于非MODS组,差异有统计学意义(P<0.05,P<0.01)。二元logistic回归分析显示,NIHSS评分、APACHEⅡ评分及多支血管病变是MODS发生的独立危险因素(OR=1.124,95%CI:1.121~1.163,P=0.015;OR=1.265,95%CI:1.296~1.426,P=0.001;OR=2.532,95%CI:1.126~5.013,P=0.026)。死亡组MODS评分、APACHEⅡ评分明显高于生存组,差异有统计学意义(P<0.05)。结论老年重症脑卒中患者急性期易发生MODS。
