BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ...BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.展开更多
BACKGROUND Postoperative acute kidney injury(AKI) is a complex pathological process involved intrarenal and systemic inflammation caused by renal hypoperfusion, nephrotoxic drugs and urinary obstruction. Neutrophil-to...BACKGROUND Postoperative acute kidney injury(AKI) is a complex pathological process involved intrarenal and systemic inflammation caused by renal hypoperfusion, nephrotoxic drugs and urinary obstruction. Neutrophil-to-lymphocyte ratio(NLR) is a marker of inflammation reflecting the progress of many diseases. However, whether NLR at admission can predict the occurrence of AKI after surgery in the intensive care unit(ICU) remains unknown.AIM To clarify the relationship between NLR and the occurrence of AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU.METHODS A retrospective analysis of 282 patients receiving surgical ICU care after gastrointestinal and hepatobiliary surgery in our hospital from December 2014 to December 2018 was performed.RESULTS Postoperative AKI occurred in 84 patients(29.79%) in this cohort. NLR by the multivariate analysis was an independent risk factor for occurrence of postoperative AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU. In this cohort, receiver operating characteristic curves of AKI occurrence showed that the optimal cut-off value of NLR was 8.380. NLR was found to be significantly correlated with the white blood cell count, neutrophil count, lymphocyte count, arterial lactate and dialysis(P < 0.05). Additionally, NLR value at admission was higher in AKI patients compared with the non-AKI patients and increased with the severity of AKI. Patients with NLR ≥ 8.380 exhibited significantly higher incidences of postoperative AKI and severe AKI than patients with NLR < 8.380(AKI: 38.12% vs 14.85%, P < 0.001;severe AKI: 14.36% vs 1.98%, P = 0.001).CONCLUSION NLR at admission is a predictor of AKI occurrence in patients with gastrointestinal and hepatobiliary surgery in ICU. NLR should be included in the routine assessment of AKI occurrence.展开更多
BACKGROUND Acute pancreatitis(AP)is often associated with intestinal injury,which in turn exaggerates the progression of AP.Our recent study has shown that a low level of serum irisin,a novel exercise-induced hormone,...BACKGROUND Acute pancreatitis(AP)is often associated with intestinal injury,which in turn exaggerates the progression of AP.Our recent study has shown that a low level of serum irisin,a novel exercise-induced hormone,is associated with poor outcomes in patients with AP and irisin administration protects against experimental AP.However,the role of irisin in intestinal injury in AP has not been evaluated.AIM To investigate the effect of irisin administration on intestinal injury in experimental AP.METHODS AP was induced in male adult mice by two hourly intraperitoneal injections of Larginine.At 2 h after the last injection of L-arginine,irisin(50 or 250μg/kg body weight)or 1 mL normal saline(vehicle)was administered through intraperitoneal injection.The animals were sacrificed at 72 h after the induction of AP.Intestinal injury,apoptosis,oxidative and endoplasmic reticulum(ER)stress were evaluated.RESULTS Administration of irisin significantly mitigated intestinal damage,reduced apoptosis,and attenuated oxidative and ER stress in AP mice.In addition,irisin treatment also effectively downregulated serum tumor necrosis factor-alpha and interleukin-6 levels and alleviated injury in the pancreas,liver and lung of AP mice.CONCLUSION Irisin-mediated multiple physiological events attenuate intestinal injury following an episode of AP.Irisin has a great potential to be further developed as an effective treatment for patients with AP.展开更多
BACKGROUND Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral antic...BACKGROUND Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral anticoagulants including aspirin. However, the long-term impact of postoperative aspirin on cirrhotic patients after splenectomy remains unknown. AIM The main purpose of this study was to investigate the effect of postoperative long-term low-dose aspirin administration on the development of HCC and longterm survival of cirrhotic patients after splenectomy. METHODS The clinical data of 264 adult patients with viral hepatitis-related cirrhosis who underwent splenectomy at the First Affiliated Hospital of Xi’an Jiaotong University from January 2000 to December 2014 were analyzed retrospectively. Among these patients, 59 who started taking 100 mg/d aspirin within seven days were enrolled in the aspirin group. The incidence of HCC and overall survival were analyzed.RESULTS During follow-up, 41 (15.53%) patients developed HCC and 37 (14.02%) died due to end-stage liver diseases or other serious complications. Postoperative longterm low-dose aspirin therapy reduced the incidence of HCC from 19.02% to 3.40% after splenectomy (log-rank test, P=0.028). Univariate and multivariate analyses showed that not undertaking postoperative long-term low-dose aspirin therapy [odds ratio (OR)=6.211, 95% confidence interval (CI): 1.142-27.324, P=0.016] was the only independent risk factor for the development of HCC. Similarly, patients in the aspirin group survived longer than those in the control group (log-rank test, P=0.041). Univariate and multivariate analyses showed that the only factor that independently associated with improved overall survival was postoperative long-term low-dose aspirin therapy [OR = 0.218, 95%CI: 0.049- 0.960, P=0.044]. CONCLUSION In patients with viral hepatitis-related cirrhosis, long-term post-splenectomy administration of low-dose aspirin reduces the incidence of HCC and improves the long-term overall survival.展开更多
基金Supported by the National Natural Science Foundation of China,No.82100685the Scientific Research Fund of Xi’an Health Commission,No.2021yb08+1 种基金Scientific Research Fund of Xi’an Central Hospital,No.2022QN07Innovation Capability Support Plan of Xi’an Science and Technology Bureau,No.23YXYJ0097.
文摘BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.
基金the National Natura Science Foundation of ChinaNo. 81770491。
文摘BACKGROUND Postoperative acute kidney injury(AKI) is a complex pathological process involved intrarenal and systemic inflammation caused by renal hypoperfusion, nephrotoxic drugs and urinary obstruction. Neutrophil-to-lymphocyte ratio(NLR) is a marker of inflammation reflecting the progress of many diseases. However, whether NLR at admission can predict the occurrence of AKI after surgery in the intensive care unit(ICU) remains unknown.AIM To clarify the relationship between NLR and the occurrence of AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU.METHODS A retrospective analysis of 282 patients receiving surgical ICU care after gastrointestinal and hepatobiliary surgery in our hospital from December 2014 to December 2018 was performed.RESULTS Postoperative AKI occurred in 84 patients(29.79%) in this cohort. NLR by the multivariate analysis was an independent risk factor for occurrence of postoperative AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU. In this cohort, receiver operating characteristic curves of AKI occurrence showed that the optimal cut-off value of NLR was 8.380. NLR was found to be significantly correlated with the white blood cell count, neutrophil count, lymphocyte count, arterial lactate and dialysis(P < 0.05). Additionally, NLR value at admission was higher in AKI patients compared with the non-AKI patients and increased with the severity of AKI. Patients with NLR ≥ 8.380 exhibited significantly higher incidences of postoperative AKI and severe AKI than patients with NLR < 8.380(AKI: 38.12% vs 14.85%, P < 0.001;severe AKI: 14.36% vs 1.98%, P = 0.001).CONCLUSION NLR at admission is a predictor of AKI occurrence in patients with gastrointestinal and hepatobiliary surgery in ICU. NLR should be included in the routine assessment of AKI occurrence.
基金Supported by the National Natural Science Foundation of China,No.81770491
文摘BACKGROUND Acute pancreatitis(AP)is often associated with intestinal injury,which in turn exaggerates the progression of AP.Our recent study has shown that a low level of serum irisin,a novel exercise-induced hormone,is associated with poor outcomes in patients with AP and irisin administration protects against experimental AP.However,the role of irisin in intestinal injury in AP has not been evaluated.AIM To investigate the effect of irisin administration on intestinal injury in experimental AP.METHODS AP was induced in male adult mice by two hourly intraperitoneal injections of Larginine.At 2 h after the last injection of L-arginine,irisin(50 or 250μg/kg body weight)or 1 mL normal saline(vehicle)was administered through intraperitoneal injection.The animals were sacrificed at 72 h after the induction of AP.Intestinal injury,apoptosis,oxidative and endoplasmic reticulum(ER)stress were evaluated.RESULTS Administration of irisin significantly mitigated intestinal damage,reduced apoptosis,and attenuated oxidative and ER stress in AP mice.In addition,irisin treatment also effectively downregulated serum tumor necrosis factor-alpha and interleukin-6 levels and alleviated injury in the pancreas,liver and lung of AP mice.CONCLUSION Irisin-mediated multiple physiological events attenuate intestinal injury following an episode of AP.Irisin has a great potential to be further developed as an effective treatment for patients with AP.
基金Supported by the Ministry of Education Innovation Team Development Program of China,No.IRT16R57
文摘BACKGROUND Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral anticoagulants including aspirin. However, the long-term impact of postoperative aspirin on cirrhotic patients after splenectomy remains unknown. AIM The main purpose of this study was to investigate the effect of postoperative long-term low-dose aspirin administration on the development of HCC and longterm survival of cirrhotic patients after splenectomy. METHODS The clinical data of 264 adult patients with viral hepatitis-related cirrhosis who underwent splenectomy at the First Affiliated Hospital of Xi’an Jiaotong University from January 2000 to December 2014 were analyzed retrospectively. Among these patients, 59 who started taking 100 mg/d aspirin within seven days were enrolled in the aspirin group. The incidence of HCC and overall survival were analyzed.RESULTS During follow-up, 41 (15.53%) patients developed HCC and 37 (14.02%) died due to end-stage liver diseases or other serious complications. Postoperative longterm low-dose aspirin therapy reduced the incidence of HCC from 19.02% to 3.40% after splenectomy (log-rank test, P=0.028). Univariate and multivariate analyses showed that not undertaking postoperative long-term low-dose aspirin therapy [odds ratio (OR)=6.211, 95% confidence interval (CI): 1.142-27.324, P=0.016] was the only independent risk factor for the development of HCC. Similarly, patients in the aspirin group survived longer than those in the control group (log-rank test, P=0.041). Univariate and multivariate analyses showed that the only factor that independently associated with improved overall survival was postoperative long-term low-dose aspirin therapy [OR = 0.218, 95%CI: 0.049- 0.960, P=0.044]. CONCLUSION In patients with viral hepatitis-related cirrhosis, long-term post-splenectomy administration of low-dose aspirin reduces the incidence of HCC and improves the long-term overall survival.
