Despite advancements in interventional coronary reperfusion technologies following myocardial infarction,a notable portion of patients continue to experience elevated mortality rates as a result of myocardial ischemia...Despite advancements in interventional coronary reperfusion technologies following myocardial infarction,a notable portion of patients continue to experience elevated mortality rates as a result of myocardial ischemia-reperfusion(MI/R)injury.An in-depth understanding of the mechanisms underlying MI/R injury is crucial for devising strategies to minimize myocardial damage and enhance patient survival.Here,it is discovered that during MI/R,double-stranded DNA(dsDNA)-cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signal accumulates,accompanied by high rates of myocardial ferroptosis.The specific deletion of cgas or Sting in cardiomyocytes,resulting in the inhibition of oxidative stress,has been shown to mitigate ferroptosis and I/R injury.Conversely,activation of STING exacerbates ferroptosis and I/R injury.Mechanistically,STING directly targets glutathione peroxidase 4(GPX4)to facilitate its degradation through autophagy,by promoting the fusion of autophagosomes and lysosomes.This STING-GPX4 axis contributes to cardiomyocyte ferroptosis and forms a positive feedback circuit.Blocking the STING-GPX4 interaction through mutations in T267 of STING or N146 of GPX4 stabilizes GPX4.Therapeutically,AAV-mediated GPX4 administration alleviates ferroptosis induced by STING,resulting in enhanced cardiac functional recovery from MI/R injury.Additionally,the inhibition of STING by H-151 stabilizes GPX4 to reverse GPX4-induced ferroptosis and alleviate MI/R injury.Collectively,a novel autophagy-dependent ferroptosis mechanism is identified in this study.Specifically,STING autophagy induced by anoxia or ischemia-reperfusion leads to GPX4 degradation,thereby presenting a promising therapeutic target for heart diseases associated with I/R.展开更多
Background:Persistent external pancreatic fistula(EPF)in patients with pancreatic duct disruption or disconnection can result from minimal access to retroperitoneal pancreatic necrosectomy(MARPN)in severe acute pancre...Background:Persistent external pancreatic fistula(EPF)in patients with pancreatic duct disruption or disconnection can result from minimal access to retroperitoneal pancreatic necrosectomy(MARPN)in severe acute pancreatitis patients,which is a difficult problem for clinicians and requires a long treatment duration.This study aimed to investigate the effectiveness and safety of trans-sinus gastric stent placement and drainage using interventional technology in the management of persistent EPF after MARPN in severe acute pancreatitis.Methods:From August 2018 to December 2020,the data of 9 patients with persistent EPF treated with trans-sinus gastric stent placement and drainage in our hospital were retrospectively collected.The main outcome measures were technical success rate,recurrence rate,new pancreatic fluid collection,morbidity,and mortality.All patients were followed up after the procedure through clinic visits and imaging modalities.Results:The median age of the patients was 46 years(30-61 years).The median persistent EPF duration was 5 months(2-12 months).The median follow-up time was 41 months(range,20-47 months).The median operation time was 48 minutes(range,40-54 minutes),and the technical success rate was 100%.Seven days after treatment,the percutaneous drainage tubes of all patients were removed.Six months after the procedure,2 patients lost the stents,and one of those patients suffered from a pseudocyst,which gradually increased to a maximum diameter of 7 cm over 9 months.Therefore,a double pigtail drainage tube was placed under the guidance of an endoscope.The second of these 2 patients had no recurrence or pseudocyst.Twelve months after the procedure,another 3 patients lost the stents;18 months after the procedure,another 2 patients lost the stents.These patients had no recurrence as well.No other adverse events or deaths occurred during the study period.Conclusion:Trans-sinus tract gastric stent placement and drainage are safe and effective in the treatment of persistent EPF after MARPN in severe acute pancreatitis patients.However,this study had a small sample size and did not include a comparative group.展开更多
基金supported by grants of the National Natural Science Foundation of China(No.82270487,82241203,82200502,84270277,82200507)the National Key Research and Development Program of China(2024YFA1307002,2021YFF0501403)+4 种基金the Shandong Provincial Natural Science Foundation(ZR2023JQ030,2021ZDSYS05,2024CXPT080,ZR2024ZD09,ZR2002QH089)the Program of Introducing Talents of Discipline to Universities(BP0719033)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT320-06)the Taishan Scholars Program of Shandong Province(Zhang M,Zhang C and Zhang J)the Fundamental Research Funds for the Central Universities(No.2023QNTD003 to M.Z.).
文摘Despite advancements in interventional coronary reperfusion technologies following myocardial infarction,a notable portion of patients continue to experience elevated mortality rates as a result of myocardial ischemia-reperfusion(MI/R)injury.An in-depth understanding of the mechanisms underlying MI/R injury is crucial for devising strategies to minimize myocardial damage and enhance patient survival.Here,it is discovered that during MI/R,double-stranded DNA(dsDNA)-cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signal accumulates,accompanied by high rates of myocardial ferroptosis.The specific deletion of cgas or Sting in cardiomyocytes,resulting in the inhibition of oxidative stress,has been shown to mitigate ferroptosis and I/R injury.Conversely,activation of STING exacerbates ferroptosis and I/R injury.Mechanistically,STING directly targets glutathione peroxidase 4(GPX4)to facilitate its degradation through autophagy,by promoting the fusion of autophagosomes and lysosomes.This STING-GPX4 axis contributes to cardiomyocyte ferroptosis and forms a positive feedback circuit.Blocking the STING-GPX4 interaction through mutations in T267 of STING or N146 of GPX4 stabilizes GPX4.Therapeutically,AAV-mediated GPX4 administration alleviates ferroptosis induced by STING,resulting in enhanced cardiac functional recovery from MI/R injury.Additionally,the inhibition of STING by H-151 stabilizes GPX4 to reverse GPX4-induced ferroptosis and alleviate MI/R injury.Collectively,a novel autophagy-dependent ferroptosis mechanism is identified in this study.Specifically,STING autophagy induced by anoxia or ischemia-reperfusion leads to GPX4 degradation,thereby presenting a promising therapeutic target for heart diseases associated with I/R.
文摘Background:Persistent external pancreatic fistula(EPF)in patients with pancreatic duct disruption or disconnection can result from minimal access to retroperitoneal pancreatic necrosectomy(MARPN)in severe acute pancreatitis patients,which is a difficult problem for clinicians and requires a long treatment duration.This study aimed to investigate the effectiveness and safety of trans-sinus gastric stent placement and drainage using interventional technology in the management of persistent EPF after MARPN in severe acute pancreatitis.Methods:From August 2018 to December 2020,the data of 9 patients with persistent EPF treated with trans-sinus gastric stent placement and drainage in our hospital were retrospectively collected.The main outcome measures were technical success rate,recurrence rate,new pancreatic fluid collection,morbidity,and mortality.All patients were followed up after the procedure through clinic visits and imaging modalities.Results:The median age of the patients was 46 years(30-61 years).The median persistent EPF duration was 5 months(2-12 months).The median follow-up time was 41 months(range,20-47 months).The median operation time was 48 minutes(range,40-54 minutes),and the technical success rate was 100%.Seven days after treatment,the percutaneous drainage tubes of all patients were removed.Six months after the procedure,2 patients lost the stents,and one of those patients suffered from a pseudocyst,which gradually increased to a maximum diameter of 7 cm over 9 months.Therefore,a double pigtail drainage tube was placed under the guidance of an endoscope.The second of these 2 patients had no recurrence or pseudocyst.Twelve months after the procedure,another 3 patients lost the stents;18 months after the procedure,another 2 patients lost the stents.These patients had no recurrence as well.No other adverse events or deaths occurred during the study period.Conclusion:Trans-sinus tract gastric stent placement and drainage are safe and effective in the treatment of persistent EPF after MARPN in severe acute pancreatitis patients.However,this study had a small sample size and did not include a comparative group.
