Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Me...Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Methods:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020.We analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and prognosis.Results:A total of 32 ASTC patients were included in the analysis.The majority of the patients had a history of biliary operations,and clinical manifestations were occult and atypical.The positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance imaging.Treatment with effective antibiotics was provided as soon as diagnosis was established.After treatment,most patients had a good outcome.Elevated levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis.Conclusions:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.展开更多
AIM To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS Sprague-Dawley rats ...AIM To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS Sprague-Dawley rats were divided into three groups (n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting (WB) and quantitative real-time (qRT)-PCR. AML-12 cell lines were then subjected to normal culture, anoxic incubator tank culture (hypoxia) and anoxic incubator tank culture with Mfn2 knockdown (hypoxia + Si), and data of qRT-PCR, WB, mitochondrial membrane potential (Delta psi m), apoptosis, endoplasmic reticulum Ca2+ concentrations and mitochondrial Ca2+ concentrations were collected. RESULTS Both sham and normal culture groups showed no injury during the experiment. The RIC group showed amelioration of liver function compared with the orthotopic liver transplantation group (P < 0.05). qRTPCR and WB confirmed that Mfn2-mitochondrial Ca2+ uptake 1/2 (MICUs) axis was changed (P < 0.005). In AML-12 cell lines, compared with the hypoxia group, the hypoxia + Si group attenuated the collapse of..m and apoptosis (P < 0.005). The endoplasmic reticulum Ca2+ decrease and mitochondrial Ca2+ overloading observed in the hypoxia group were also attenuated in the hypoxia + Si group (P < 0.005). Finally, qRT-PCR and WB confirmed the Mfn2-MICUs axis change in all the groups (P < 0.005). CONCLUSION Mfn2 participates in liver injury in rat RIC models and AML-12 hypoxia cell lines by regulating the MICUs pathway.展开更多
BACKGROUND: Collateralized intraand extra-hepatic routes in patients with Budd-Chiari syndrome (BCS) were important. This study aimed to investigate the feasibility and clinical outcomes of the staged management of BC...BACKGROUND: Collateralized intraand extra-hepatic routes in patients with Budd-Chiari syndrome (BCS) were important. This study aimed to investigate the feasibility and clinical outcomes of the staged management of BCS based on the degree of compensation provided by intraor extra-hepatic collateral circulations. METHODS: A total of 103 adult patients with BCS caused by co-obstruction of the inferior vena cava (IVC) and main hepatic veins (MHVs) between March 2001 and October 2009 were enrolled in this study. Based on the pathological classification and degree of hemodynamic compensation by collateral circulations, treatment priority for IVC hypertension was determined in the first-stage treatment. Patients were deemed eligible for second-stage treatment when the first-stage treatment failed to relieve. RESULTS: Imaging results revealed that most patients had collateral circulations to different extents. Based on the degree of compensation provided by these collateral circulations, 74 patients underwent single-stage treatment for IVC hypertension, i.e., radiologic intervention (RI) for 61 patients and surgical procedures (SPs) for 13. One patient was treated for portal hypertension. Twenty-nine patients underwent second-stage treatment (25 underwent RI and SP, and 4 only SP). The general morbidity and mortality after all procedures were 8.3% and 1.5%, respectively. After a median follow-up of 35 months, 4 patients underwent second-stage treatment and 7 underwent recanalization of the IVC/MHVs. Two patients died of hepatocellular carcinoma and 1 died of graft obstruction. CONCLUSION: Staged management produces excellent outcomes for patients with BCS caused by co-obstruction of the IVC and MHVs.展开更多
Background:Delayed gastric emptying(DGE)is the main complication after pancreaticoduodenectomy(PD),but the mechanism is still unclear.The aim of this study was to elucidate the role of complete resection of the gastri...Background:Delayed gastric emptying(DGE)is the main complication after pancreaticoduodenectomy(PD),but the mechanism is still unclear.The aim of this study was to elucidate the role of complete resection of the gastric antrum in decreasing incidence and severity of DGE after PD.Methods:Sprague-Dawley rats were divided into three groups:expanded resection(ER group),complete resection(CR group),and incomplete resection(IR group)of the gastric antrum.The tension(g)of remnant stomach contraction was observed.We analyzed the histological morphology of the gastric wall by different excisional methods after distal gastrectomy.Moreover,patients underwent PD at our department between January 2012 and May 2016 were included in the study.These cases were divided into IR group and CR group of the gastric antrum,and the clinical data were retrospectively analyzed.Results:The ex vivo remnant stomachs of CR group exhibited much greater contraction tension than others(P<0.05).The contraction tension of the remnant stomach increased with increasing acetylcholine concentration,while remained stable at the concentration of 10×10^(-5 )mol/L.Furthermore,174 consecutive patients were included and retrospectively analyzed in the study.The incidence of DGE was significantly lower(3.5%vs.21.3%,P<0.01)in CR group than in IR group.In addition,hematoxylin-eosin staining analyses of the gastric wall confirmed that the number of transected circular smooth muscle bundles were higher in IR group than in CR group(8.24±0.65 vs.3.76±0.70,P<0.05).Conclusions:The complete resection of the gastric antrum is associated with decreased incidence and severity of DGE after PD.Gastric electrophysiological and physiopathological disorders caused by damage to gastric smooth muscles might be the mechanism underlying DGE.展开更多
BACKGROUND： Postoperative pancreatic fistula （POPF） is a serious complication and results in prolonged hospitalization and high mortality. The present study aimed to evaluate the safety and effectiveness of total c...BACKGROUND： Postoperative pancreatic fistula （POPF） is a serious complication and results in prolonged hospitalization and high mortality. The present study aimed to evaluate the safety and effectiveness of total closure of pancreatic section for end-to-side pancreaticojejunostomy in pancreaticoduodenectomy （PD）. METHODS： This was a prospective randomized clinical trial comparing the outcomes of PD between patients who un- derwent total closure of pancreatic section for end-to-side pancreaticojejunostomy （Group A） vs those who underwent conventional pancreaticojejunostomy （Group B）. The primary endpoint was the incidence of pancreatic fistula. Secondary endpoints were morbidity and mortality rates. RESULTS： One hundred twenty-three patients were included in this study. The POPF rate was significantly lower in Group A than that in Group B （4.8% vs 16.7%, P〈0.05）. About 38.3% patients in Group B developed one or more complications; this rate was 14.3% in Group A （P〈0.01）. The wound/abdomi- nal infection rate was also much higher in Group B than that in Group A （20.0% vs 6.3%, P〈0.05）. Furthermore, the average hospital stays of the two groups were 18 days in Group A, and 24 days in Group B, respectively （P〈0.001）. However, there was no difference in the probability of mortality, biliary leakage,delayed gastric emptying, and pulmonary infection between the two groups. CONCLUSION： Total closure of pancreatic section for end-to- side pancreaticojejunostomy is a safe and effective method for pancreaticojejunostomy in PD.展开更多
BACKGROUND： Immunosuppression reagents have side effects and cause considerable long-term morbidity and mortality in patients after liver transplantation. Sufficient evidences showed that minimization or withdrawal o...BACKGROUND： Immunosuppression reagents have side effects and cause considerable long-term morbidity and mortality in patients after liver transplantation. Sufficient evidences showed that minimization or withdrawal of immunosuppression reagents does not deteriorate the recipient＇s immune response and physiological function and therefore, is feasible in some recipients of liver transplantation. However, the mechanisms are not clear. The present review was to update the current status of immunosuppression in liver transplantation and the mechanism of minimization or withdrawal of immunosuppression in liver recipients.DATA SOURCES： We searched articles in English on minimization or withdrawal of immunosuppression in liver transplantation in Pub Med. We focused on the basic mechanisms of immune tolerance in liver transplantation. Studies on immunosuppression minimization or withdrawal protocols and biomarker in tolerant recipients were also analyzed.RESULTS： Minimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance, which may not be permanent and can be affected by various factors. However, accurately evaluating immune status post-transplant is a prerequisite to achieve individualized immunosuppression. Numerous mechanisms for immune tolerance have been found, including immunophenotypic shift of memory CD8＋ T cells and CD4＋ T cell subsets. Activation of the inflammasome through apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain（ASC） in dendritic cells is associated with rejection after liver transplantation. CONCLUSIONS： Minimization or withdrawal of immunosuppression can be achieved by the induction of immune toler-ance via different mechanisms. This process could be affected by immunophenotypic shift of memory CD8＋ T cells and CD4＋ T cell subsets, which may be correlated with activation of the inflammasome through ASC in dendritic cells.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recogn...BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profiling and subsequent experimental verification revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.CONCLUSION We provide evidence for the expression and function of RFWD3 in HCC.RFWD3 affects the prognosis,proliferation,invasion,and metastasis of HCC by regulating the Wnt/β-catenin signalling pathway.展开更多
基金This study was supported by a grant from the National Natural Science Foundation of China(81870457).
文摘Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Methods:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020.We analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and prognosis.Results:A total of 32 ASTC patients were included in the analysis.The majority of the patients had a history of biliary operations,and clinical manifestations were occult and atypical.The positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance imaging.Treatment with effective antibiotics was provided as soon as diagnosis was established.After treatment,most patients had a good outcome.Elevated levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis.Conclusions:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.
基金Supported by Science and Technology Innovation Talents Support Plan,Department of Education,Henan Province,China,No.17HASTIT044China Postdoctoral Science Foundation,No.2017M610374
文摘AIM To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS Sprague-Dawley rats were divided into three groups (n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting (WB) and quantitative real-time (qRT)-PCR. AML-12 cell lines were then subjected to normal culture, anoxic incubator tank culture (hypoxia) and anoxic incubator tank culture with Mfn2 knockdown (hypoxia + Si), and data of qRT-PCR, WB, mitochondrial membrane potential (Delta psi m), apoptosis, endoplasmic reticulum Ca2+ concentrations and mitochondrial Ca2+ concentrations were collected. RESULTS Both sham and normal culture groups showed no injury during the experiment. The RIC group showed amelioration of liver function compared with the orthotopic liver transplantation group (P < 0.05). qRTPCR and WB confirmed that Mfn2-mitochondrial Ca2+ uptake 1/2 (MICUs) axis was changed (P < 0.005). In AML-12 cell lines, compared with the hypoxia group, the hypoxia + Si group attenuated the collapse of..m and apoptosis (P < 0.005). The endoplasmic reticulum Ca2+ decrease and mitochondrial Ca2+ overloading observed in the hypoxia group were also attenuated in the hypoxia + Si group (P < 0.005). Finally, qRT-PCR and WB confirmed the Mfn2-MICUs axis change in all the groups (P < 0.005). CONCLUSION Mfn2 participates in liver injury in rat RIC models and AML-12 hypoxia cell lines by regulating the MICUs pathway.
基金supported by grants from the National Natural Science Foundation of China (81100304)the Projects of Ministry of Public Health (201002015)
文摘BACKGROUND: Collateralized intraand extra-hepatic routes in patients with Budd-Chiari syndrome (BCS) were important. This study aimed to investigate the feasibility and clinical outcomes of the staged management of BCS based on the degree of compensation provided by intraor extra-hepatic collateral circulations. METHODS: A total of 103 adult patients with BCS caused by co-obstruction of the inferior vena cava (IVC) and main hepatic veins (MHVs) between March 2001 and October 2009 were enrolled in this study. Based on the pathological classification and degree of hemodynamic compensation by collateral circulations, treatment priority for IVC hypertension was determined in the first-stage treatment. Patients were deemed eligible for second-stage treatment when the first-stage treatment failed to relieve. RESULTS: Imaging results revealed that most patients had collateral circulations to different extents. Based on the degree of compensation provided by these collateral circulations, 74 patients underwent single-stage treatment for IVC hypertension, i.e., radiologic intervention (RI) for 61 patients and surgical procedures (SPs) for 13. One patient was treated for portal hypertension. Twenty-nine patients underwent second-stage treatment (25 underwent RI and SP, and 4 only SP). The general morbidity and mortality after all procedures were 8.3% and 1.5%, respectively. After a median follow-up of 35 months, 4 patients underwent second-stage treatment and 7 underwent recanalization of the IVC/MHVs. Two patients died of hepatocellular carcinoma and 1 died of graft obstruction. CONCLUSION: Staged management produces excellent outcomes for patients with BCS caused by co-obstruction of the IVC and MHVs.
基金supported by a grant from the National Natural Science Foundation of China(No.81870457)。
文摘Background:Delayed gastric emptying(DGE)is the main complication after pancreaticoduodenectomy(PD),but the mechanism is still unclear.The aim of this study was to elucidate the role of complete resection of the gastric antrum in decreasing incidence and severity of DGE after PD.Methods:Sprague-Dawley rats were divided into three groups:expanded resection(ER group),complete resection(CR group),and incomplete resection(IR group)of the gastric antrum.The tension(g)of remnant stomach contraction was observed.We analyzed the histological morphology of the gastric wall by different excisional methods after distal gastrectomy.Moreover,patients underwent PD at our department between January 2012 and May 2016 were included in the study.These cases were divided into IR group and CR group of the gastric antrum,and the clinical data were retrospectively analyzed.Results:The ex vivo remnant stomachs of CR group exhibited much greater contraction tension than others(P<0.05).The contraction tension of the remnant stomach increased with increasing acetylcholine concentration,while remained stable at the concentration of 10×10^(-5 )mol/L.Furthermore,174 consecutive patients were included and retrospectively analyzed in the study.The incidence of DGE was significantly lower(3.5%vs.21.3%,P<0.01)in CR group than in IR group.In addition,hematoxylin-eosin staining analyses of the gastric wall confirmed that the number of transected circular smooth muscle bundles were higher in IR group than in CR group(8.24±0.65 vs.3.76±0.70,P<0.05).Conclusions:The complete resection of the gastric antrum is associated with decreased incidence and severity of DGE after PD.Gastric electrophysiological and physiopathological disorders caused by damage to gastric smooth muscles might be the mechanism underlying DGE.
基金supported by grants from the Foundation of Mega Project of National Science and Technology(2016ZX10002020-009)Innovative Talent Project of Science and Technology of Henan Colleges(17HASTIT044)
文摘BACKGROUND： Postoperative pancreatic fistula （POPF） is a serious complication and results in prolonged hospitalization and high mortality. The present study aimed to evaluate the safety and effectiveness of total closure of pancreatic section for end-to-side pancreaticojejunostomy in pancreaticoduodenectomy （PD）. METHODS： This was a prospective randomized clinical trial comparing the outcomes of PD between patients who un- derwent total closure of pancreatic section for end-to-side pancreaticojejunostomy （Group A） vs those who underwent conventional pancreaticojejunostomy （Group B）. The primary endpoint was the incidence of pancreatic fistula. Secondary endpoints were morbidity and mortality rates. RESULTS： One hundred twenty-three patients were included in this study. The POPF rate was significantly lower in Group A than that in Group B （4.8% vs 16.7%, P〈0.05）. About 38.3% patients in Group B developed one or more complications; this rate was 14.3% in Group A （P〈0.01）. The wound/abdomi- nal infection rate was also much higher in Group B than that in Group A （20.0% vs 6.3%, P〈0.05）. Furthermore, the average hospital stays of the two groups were 18 days in Group A, and 24 days in Group B, respectively （P〈0.001）. However, there was no difference in the probability of mortality, biliary leakage,delayed gastric emptying, and pulmonary infection between the two groups. CONCLUSION： Total closure of pancreatic section for end-to- side pancreaticojejunostomy is a safe and effective method for pancreaticojejunostomy in PD.
基金supported by grants from the National Natural Science Foundation of China(81100304)Science and Technology Bureau of Zhengzhou(131PLJRC658)
文摘BACKGROUND： Immunosuppression reagents have side effects and cause considerable long-term morbidity and mortality in patients after liver transplantation. Sufficient evidences showed that minimization or withdrawal of immunosuppression reagents does not deteriorate the recipient＇s immune response and physiological function and therefore, is feasible in some recipients of liver transplantation. However, the mechanisms are not clear. The present review was to update the current status of immunosuppression in liver transplantation and the mechanism of minimization or withdrawal of immunosuppression in liver recipients.DATA SOURCES： We searched articles in English on minimization or withdrawal of immunosuppression in liver transplantation in Pub Med. We focused on the basic mechanisms of immune tolerance in liver transplantation. Studies on immunosuppression minimization or withdrawal protocols and biomarker in tolerant recipients were also analyzed.RESULTS： Minimization or withdrawal of immunosuppression can be achieved by the induction of immune tolerance, which may not be permanent and can be affected by various factors. However, accurately evaluating immune status post-transplant is a prerequisite to achieve individualized immunosuppression. Numerous mechanisms for immune tolerance have been found, including immunophenotypic shift of memory CD8＋ T cells and CD4＋ T cell subsets. Activation of the inflammasome through apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain（ASC） in dendritic cells is associated with rejection after liver transplantation. CONCLUSIONS： Minimization or withdrawal of immunosuppression can be achieved by the induction of immune toler-ance via different mechanisms. This process could be affected by immunophenotypic shift of memory CD8＋ T cells and CD4＋ T cell subsets, which may be correlated with activation of the inflammasome through ASC in dendritic cells.
基金Supported by National Natural Science Foundation of China,No.82172944 and No.81900558Co-operation Research Plan of Medical Science and Technology of Henan Province,No.LHGJ20190149the Key Scientific Research Projects of Universities of Henan Province,No.21A320052。
文摘BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profiling and subsequent experimental verification revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.CONCLUSION We provide evidence for the expression and function of RFWD3 in HCC.RFWD3 affects the prognosis,proliferation,invasion,and metastasis of HCC by regulating the Wnt/β-catenin signalling pathway.
