Objective:To study the influence of continuous blood purification on inflammation and target organ damage in patients with severe acute pancreatitis accompanied by MODS.Methods: A total of 78 patients with severe acut...Objective:To study the influence of continuous blood purification on inflammation and target organ damage in patients with severe acute pancreatitis accompanied by MODS.Methods: A total of 78 patients with severe acute pancreatitis complicated by MODS who were treated in our hospital between June 2012 and March 2016 were selected and divided into control group (n=39) and observation group (n=39) according to random number table. Control group were treated with routine treatment, observation group were treated with conventional treatment plus continuous blood purification, and serum inflammatory factors, liver function indexes and renal function indexes were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of inflammatory factors, liver function indexes and renal function indexes were not statistically significant between two groups of patients. After treatment, serum inflammatory factors IL-6, IL-8, MCP-1 and HMGB1 levels of observation group were lower than those of control group, liver function indexes ALT, AST, TBIL and ALP levels of observation group were lower than those of control group, and renal function indexes Scr and BUN levels of observation group were lower than those of control group.Conclusion: Continuous blood purification can reduce the systemic inflammatory response as well as liver and kidney injury in patients with severe acute pancreatitis complicated by MODS.展开更多
HMGN2 have functions in inflammatory response.However,the role of HMGN2 in severe acute pancreatitis(SAP)remains unclear.Here,our study was to discuss the role and regulatory mechanism ofHMGN2 in SAP.In this study,the...HMGN2 have functions in inflammatory response.However,the role of HMGN2 in severe acute pancreatitis(SAP)remains unclear.Here,our study was to discuss the role and regulatory mechanism ofHMGN2 in SAP.In this study,the SAP cell model of AR42J was used to study the function and mechanism of HMGN2 in SAP.The protein expression in cells and serums were examined by western blot and ELISA assay.qPCR was used to test the transcriptional RNA level.Cell viability were examined by MTT assay.Luciferase assay was used to evaluate the interaction between gene and gene.Our results showed that HMGN2 was significantly upregulated in SAP patients.The database predicted and luciferase assay data indicated the HMGN2 was directly binding with miR-590-3p.ELISA,MTT and western blot experiments showed that the HMGN2 were promoted the cell proliferation,reduced the inflammation,and repressed the cell autophagy.Mechanism studies showed that the pseudogene HMGN2P46 level was positively correlated with HMGN2 and upregulated HMGN2 expression by competing for miR-590-3p in SAP.Taken together,all over these results showed upregulation of HMGN2 alleviates SAP,this process was regulated by HMGN2P46 competitively binding with miR-590-3p,which may provide a new insight for the treatment and intervention in SAP.Pseudogene HMGN2P46 was a miRNA sponge to regulate HMGN2 level by competing for miR-590-3p to alleviate the process of SAP.It provided a novel strategy for the diagnosis and treatment of severe acute pancreatitis.展开更多
Background:Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis(SAP),and controlling such inflammation is vital for managing this often fatal disease.Dexmedetomidine ha...Background:Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis(SAP),and controlling such inflammation is vital for managing this often fatal disease.Dexmedetomidine has been reported to possess protective properties in inflammatory diseases.Therefore,this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate,and if so,to determine the potential mechanism.Methods:SAP was induced with sodium taurocholate.Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration.α-bungarotoxin,a selective alpha-7 nicotinic acetylcholine receptor(α7nAchR)antagonist,was injected intra-peritoneally 30 min before dexmedetomidine administration.The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine.Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition&Analysis System.Six hours after onset,serum pro-inflammatory cytokine(tumor necrosis factorα[TNF-α]and interleukin 6[IL-6])levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer,respectively.Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria.Results:Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α,IL-6,and amylase,strongly alleviating pathological pancreatic injury in the rat model of SAP(TNF-α:174.2±30.2 vs.256.1±42.4 pg/ml;IL-6:293.3±46.8 vs.421.7±48.3 pg/ml;amylase:2102.3±165.3 vs.3186.4±245.2 U/L).However,the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration ofα-bungarotoxin.Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model(discharge frequency:456.8±50.3 vs.332.4±25.1 Hz;discharge amplitude:33.4±5.3 vs.20.5±2.9μV).Conclusions:Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus-andα7nAChR-dependent mechanisms.展开更多
In severe acute pancreatitis (SAP) inflammatory processes foster necrosis, cellular lysis and liberation of vasoactive substances associated with multiple organ failure. The effects of vacuum-assisted closure and Drot...In severe acute pancreatitis (SAP) inflammatory processes foster necrosis, cellular lysis and liberation of vasoactive substances associated with multiple organ failure. The effects of vacuum-assisted closure and Drotrecogin alpha on inflammatory cytokines were evaluated in SAP patients with infected necrosis. Methods: Forty-six patients were included in three groups: Group 1, necrosectomy and abdominal cavity washing;Group 2, necrosectomy plus vacuum-assisted closure (VAC), and Group 3, necrossectomy plus VAC plus Drotrecogin alpha. Immunoreactive IL-32, TNF-α, IL-6, TGF-β and IL-2 cytokines were quantified with ELISA method. Results: IL-32 was significantly increased in all patients, predominantly the non-survivor of Group 3 (p 0.0001). Group 2 maintained increased IL-32 levels throughout. Peak TNF-α was observed in non-survivors of Groups 1 and 2, with a frank tendency to decrease in Group 3. The IL-6 was increased, sustained throughout the study, peaking at the onset in non-survivors. At the end IL-6 tended to diminish, predominantly in survivors. TNF-α and IL-6 were significantly increased on hospitalization, with a maximum peak in non-survivors of all groups. Initial values of TGF-β were significantly increased in survivors of the three groups, and were significantly diminished in non-survivors;affecting pancreas regeneration and favoring systemic inflammation, with possible multiple-organ repercussions. IL-2 levels were elevated, predominantly in non-survivors of Group 1. There was positive correlation between the increase IL-32 and TNF-α, and negative correlation between the increase in TNF-α and decrease in TGF-β;and, a tendency for negative correlation between the IL-2 increased and TGF-β levels. Conclusion: We found a generalized, sustained inflammatory state that fosters a torpid outcome in SAP patients.展开更多
Severe acute pancreatitis(SAP)is a life-threatening acute abdominal disease with two peaks of death:the first in the early stage,characterized by systemic inflammatory response-associated organ failure;and the second ...Severe acute pancreatitis(SAP)is a life-threatening acute abdominal disease with two peaks of death:the first in the early stage,characterized by systemic inflammatory response-associated organ failure;and the second in the late stage,characterized by infectious complications.Neutrophils are the main immune cells participating in the whole process of SAP.In addition to the traditional recognition of neutrophils as the origination of chemokine and cytokine cascades or phagocytosis and degranulation of pathogens,neutrophil extracellular traps(NETs)also play an important roles in inflammatory reactions.We reviewed the role of NETs in the occurrence and development of SAP and its fatal complications,including multiple organs injury,infected pancreatic necrosis,and thrombosis.This review provides novel insights into the involvement of NETs throughout the entire process of SAP,showing that targeting NETs might be a promising strategy in SAP treatment.However,precision therapeutic options targeting NETs in different situations require further investigation.展开更多
文摘Objective:To study the influence of continuous blood purification on inflammation and target organ damage in patients with severe acute pancreatitis accompanied by MODS.Methods: A total of 78 patients with severe acute pancreatitis complicated by MODS who were treated in our hospital between June 2012 and March 2016 were selected and divided into control group (n=39) and observation group (n=39) according to random number table. Control group were treated with routine treatment, observation group were treated with conventional treatment plus continuous blood purification, and serum inflammatory factors, liver function indexes and renal function indexes were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of inflammatory factors, liver function indexes and renal function indexes were not statistically significant between two groups of patients. After treatment, serum inflammatory factors IL-6, IL-8, MCP-1 and HMGB1 levels of observation group were lower than those of control group, liver function indexes ALT, AST, TBIL and ALP levels of observation group were lower than those of control group, and renal function indexes Scr and BUN levels of observation group were lower than those of control group.Conclusion: Continuous blood purification can reduce the systemic inflammatory response as well as liver and kidney injury in patients with severe acute pancreatitis complicated by MODS.
基金This work was supported by National Natural Science Foundation of China[81901957]China Postdoctoral Science Foundation[2018M633723].
文摘HMGN2 have functions in inflammatory response.However,the role of HMGN2 in severe acute pancreatitis(SAP)remains unclear.Here,our study was to discuss the role and regulatory mechanism ofHMGN2 in SAP.In this study,the SAP cell model of AR42J was used to study the function and mechanism of HMGN2 in SAP.The protein expression in cells and serums were examined by western blot and ELISA assay.qPCR was used to test the transcriptional RNA level.Cell viability were examined by MTT assay.Luciferase assay was used to evaluate the interaction between gene and gene.Our results showed that HMGN2 was significantly upregulated in SAP patients.The database predicted and luciferase assay data indicated the HMGN2 was directly binding with miR-590-3p.ELISA,MTT and western blot experiments showed that the HMGN2 were promoted the cell proliferation,reduced the inflammation,and repressed the cell autophagy.Mechanism studies showed that the pseudogene HMGN2P46 level was positively correlated with HMGN2 and upregulated HMGN2 expression by competing for miR-590-3p in SAP.Taken together,all over these results showed upregulation of HMGN2 alleviates SAP,this process was regulated by HMGN2P46 competitively binding with miR-590-3p,which may provide a new insight for the treatment and intervention in SAP.Pseudogene HMGN2P46 was a miRNA sponge to regulate HMGN2 level by competing for miR-590-3p to alleviate the process of SAP.It provided a novel strategy for the diagnosis and treatment of severe acute pancreatitis.
基金This work was supported by a grant from the National Natural Sciences Foundation of China(No.81672449)。
文摘Background:Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis(SAP),and controlling such inflammation is vital for managing this often fatal disease.Dexmedetomidine has been reported to possess protective properties in inflammatory diseases.Therefore,this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate,and if so,to determine the potential mechanism.Methods:SAP was induced with sodium taurocholate.Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration.α-bungarotoxin,a selective alpha-7 nicotinic acetylcholine receptor(α7nAchR)antagonist,was injected intra-peritoneally 30 min before dexmedetomidine administration.The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine.Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition&Analysis System.Six hours after onset,serum pro-inflammatory cytokine(tumor necrosis factorα[TNF-α]and interleukin 6[IL-6])levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer,respectively.Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria.Results:Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α,IL-6,and amylase,strongly alleviating pathological pancreatic injury in the rat model of SAP(TNF-α:174.2±30.2 vs.256.1±42.4 pg/ml;IL-6:293.3±46.8 vs.421.7±48.3 pg/ml;amylase:2102.3±165.3 vs.3186.4±245.2 U/L).However,the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration ofα-bungarotoxin.Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model(discharge frequency:456.8±50.3 vs.332.4±25.1 Hz;discharge amplitude:33.4±5.3 vs.20.5±2.9μV).Conclusions:Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus-andα7nAChR-dependent mechanisms.
文摘In severe acute pancreatitis (SAP) inflammatory processes foster necrosis, cellular lysis and liberation of vasoactive substances associated with multiple organ failure. The effects of vacuum-assisted closure and Drotrecogin alpha on inflammatory cytokines were evaluated in SAP patients with infected necrosis. Methods: Forty-six patients were included in three groups: Group 1, necrosectomy and abdominal cavity washing;Group 2, necrosectomy plus vacuum-assisted closure (VAC), and Group 3, necrossectomy plus VAC plus Drotrecogin alpha. Immunoreactive IL-32, TNF-α, IL-6, TGF-β and IL-2 cytokines were quantified with ELISA method. Results: IL-32 was significantly increased in all patients, predominantly the non-survivor of Group 3 (p 0.0001). Group 2 maintained increased IL-32 levels throughout. Peak TNF-α was observed in non-survivors of Groups 1 and 2, with a frank tendency to decrease in Group 3. The IL-6 was increased, sustained throughout the study, peaking at the onset in non-survivors. At the end IL-6 tended to diminish, predominantly in survivors. TNF-α and IL-6 were significantly increased on hospitalization, with a maximum peak in non-survivors of all groups. Initial values of TGF-β were significantly increased in survivors of the three groups, and were significantly diminished in non-survivors;affecting pancreas regeneration and favoring systemic inflammation, with possible multiple-organ repercussions. IL-2 levels were elevated, predominantly in non-survivors of Group 1. There was positive correlation between the increase IL-32 and TNF-α, and negative correlation between the increase in TNF-α and decrease in TGF-β;and, a tendency for negative correlation between the IL-2 increased and TGF-β levels. Conclusion: We found a generalized, sustained inflammatory state that fosters a torpid outcome in SAP patients.
基金Natural Science Foundation ofChina(Nos.81974552,81774160)the Scientific Research Foundation of the Science and Technology Department of Sichuan Province(No.2022YFS0417).
文摘Severe acute pancreatitis(SAP)is a life-threatening acute abdominal disease with two peaks of death:the first in the early stage,characterized by systemic inflammatory response-associated organ failure;and the second in the late stage,characterized by infectious complications.Neutrophils are the main immune cells participating in the whole process of SAP.In addition to the traditional recognition of neutrophils as the origination of chemokine and cytokine cascades or phagocytosis and degranulation of pathogens,neutrophil extracellular traps(NETs)also play an important roles in inflammatory reactions.We reviewed the role of NETs in the occurrence and development of SAP and its fatal complications,including multiple organs injury,infected pancreatic necrosis,and thrombosis.This review provides novel insights into the involvement of NETs throughout the entire process of SAP,showing that targeting NETs might be a promising strategy in SAP treatment.However,precision therapeutic options targeting NETs in different situations require further investigation.
