AIM To investigate the relationship between autophagy and perineural invasion(PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively coll...AIM To investigate the relationship between autophagy and perineural invasion(PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubuleassociated protein 1 A/1 B-light chain 3(LC3) and PNI marker ubiquitin carboxy-terminal hydrolase(UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis. RESULTS In 109 cases of pancreatic cancer, 68.8%(75/109) had evidence of PNI and 61.5%(67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels(P < 0.05). LC3 expression was related to lymph node metastasis(P < 0.05) and was positively correlated with neural invasion(P < 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients(P < 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer(P < 0.05). CONCLUSION PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.展开更多
AIM: To review and evaluate the diagnostic dilemma of xanthogranulomatous cholecystitis(XGC) clinically.METHODS: From July 2008 to June 2014, a total of 142 cases of pathologically diagnosed XGC were reviewed at our h...AIM: To review and evaluate the diagnostic dilemma of xanthogranulomatous cholecystitis(XGC) clinically.METHODS: From July 2008 to June 2014, a total of 142 cases of pathologically diagnosed XGC were reviewed at our hospital, among which 42 were misdiagnosed as gallbladder carcinoma(GBC) based on preoperative radiographs and/or intra-operative findings. The clinical characteristics, preoperative imaging, intra-operative findings, frozen section(FS) analysis and surgical procedure data of these patients were collected and analyzed.RESULTS: The most common clinical syndrome in these 42 patients was chronic cholecystitis, followed by acute cholecystitis. Seven(17%) cases presented with mild jaundice without choledocholithiasis. Thirtyfive(83%) cases presented with heterogeneous enhancement within thickened gallbladder walls on imaging, and 29(69%) cases presented with abnormal enhancement in hepatic parenchyma neighboring the gallbladder, which indicated hepatic infiltration. Intra-operatively, adhesions to adjacent organs were observed in 40(95.2%) cases, including the duodenum, colon and stomach. Thirty cases underwent FS analysis and the remainder did not. The accuracy rate of FS was 93%, and that of surgeon's macroscopic diagnosis was 50%. Six cases were misidentified as GBC by surgeon's macroscopic examination and underwent aggressive surgical treatment. No statistical difference was encountered in the incidence of postoperative complications between total cholecystectomy and subtotal cholecystectomy groups(21% vs 20%, P > 0.05).CONCLUSION: Neither clinical manifestations and laboratory tests nor radiological methods provide apractical and effective standard in the differential diagnosis between XGC and GBC.展开更多
BACKGROUND:The high mortality of patients with severe acute pancreatitis(SAP)is due to multiorgan dysfunction.The mechanisms of SAP are still obscure.The aim of this study was to investigate the role of nuclear factor...BACKGROUND:The high mortality of patients with severe acute pancreatitis(SAP)is due to multiorgan dysfunction.The mechanisms of SAP are still obscure.The aim of this study was to investigate the role of nuclear factor-kappa B(NF-κB)activation in rats with SAP associated with liver injury and the protection effect of triptolide against liver injury in rats with SAP.METHODS:Ninety Wistar rats were randomly divided into three groups(n=30 each group):severe acute pancreatitis(group P),treatment with triptolide(group T),and sham operation(group S).SAP models were induced by retrograde injection of 5%sodium taurocholate to the pancreatic duct.After the model was successfully established,no treatment was given to group P.In group T,triptolide(0.05 mg/ml)was injected intraperitoneally(0.2 mg/kg).In group S,the abdominal walls of rats were opened,sutured,but not treated.The rats-were sacrificed after operation at 2,6,and 12 hours,respectively.The serum levels of amylase(AMY),alanine aminotransferase(ALT),tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)were determined at three time points(10 rats for each time point).Liver tissues were obtained to detect the activity of NF-κB and to observe their pathological changes with light and electron microscopes.RESULTS:The serum levels of AMY and ALT were higher in groups P and T than in group S.The serum AMY levels were significantly lower in group T than in group P at 12 hours after operation.The serum ALT levels were significantly lower in group T than in group P at 6,12 hours after operation.At the three time points,the levels of TNF-αand IL-6 in groups P and T increased more significantly than in group S.In group T they were decreased more significantly than in group P at the three time points.In groups P and T,NF-κB activity in liver tissue increased more significantly than in group S at the three time points.The activity of NF-κB was higher in group P than in groups S and T at the three time points.Liver pathological damages were milder in group T than in group P under light and electron microscopes.CONCLUSIONS:NF-κB plays an important role in the pathogenesis of liver injury in rats with SAP.Triptolide can reduce pathological damage to the liver.Its mechanism is to inhibit the activity of NF-κB and to decrease the release of inflammatory mediators.展开更多
BACKGROUND:Morphological and functional changes commonly occur in livers of brain-death donors.Preven-tion of liver injury from brain-death will benefit the results of transplantation.This study was conducted to evalu...BACKGROUND:Morphological and functional changes commonly occur in livers of brain-death donors.Preven-tion of liver injury from brain-death will benefit the results of transplantation.This study was conducted to evaluate the protection effects of glycine on the liver of brain-death donor.METHODS:Fourty-two male Wistar rats were randomly divided into brain-death donor(BDD)group(B),glycine pretreatment group with BDD(G),and strychnine pre-treatment group with BDD(S).For these groups,brain death model was established in donor rats and liver trans-plantation was performed subsequently utilizing microsur-gical techniques.After the establishment of the model and during cold rinsing of liver donors or liver reperfusion of recipients,glycine was given at a dose of 0.6 mmol,25μmol and 25μmol in the group G,and a same dose of gly-cine and strychnine(1000:1)was prescribed for the group S,but nothing for the group B.Before cold rinsing at 2 and 6 hours after portal vein(PV)reperfusion,blood sam-ples were taken from infrahepatic vena cava(IHVC)to de-termine the levels of alanine aminotransferase(ALT),as-partate aminotransferase(AST),tumor necrosis factor al-pha(TNF-α)and hyaluronic acid(HA).At 6 hours after PV reperfusion,graft samples were fixed for morphological observation and apoptosis of hepatocytes was detected using the TUNEL method.RESULTS:Before liver cold rinsing and at 2 and 6 hours af-ter PV reperfusion,the serum levels of ALT,AST,TNF-α,HA and apoptosis index(AI)in the groups B and S were significantly higher than those in the group G(P<0.05).There was no significant difference between the groups B and S(P>0.05).Electron microscopy showed that Kupffer cells were activated and hepatic cells injured more obvious-ly in the groups B and S than in the group G.CONCLUSION:Glycine pretreatment can improve the via-bility of the liver of the brain-death donor rat.展开更多
Background:Liver injury is one of the most common complications during sepsis.Macrophage migration inhibitory factor(MIF)is an important proinflammatory cytokine.This study explored the role of MIF in the lipopolysacc...Background:Liver injury is one of the most common complications during sepsis.Macrophage migration inhibitory factor(MIF)is an important proinflammatory cytokine.This study explored the role of MIF in the lipopolysaccharide(LPS)-induced liver injury through genetically manipulated mouse strains.Methods:The model of LPS-induced liver injury was established in wild-type and Mif-knockout C57/BL6 mice.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBil)were detected,and the expressions of MIF,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were measured.Liver histopathology was conducted to assess liver injury.Moreover,the inhibitions of MIF with(S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester(ISO-1)and 4-iodo-6-phenylpyrimidine(4-IPP)were used to evaluate their therapeutic potential of liver injury.Results:Compared with wild-type mice,the liver function indices and inflammation factors presented no significant difference in the Mif-/-mice.After 72 h of the LPS-induced liver injury,serum levels of ALT,AST,and TBil as well as TNF-αand IL-1βwere significantly increased,but the knockout of Mif attenuated liver injury and inflammatory response.In liver tissue,m RNA levels of TNF-α,IL-1βand NF-κB p65 were remarkably elevated in LPS-induced liver injury,while the knockout of Mif reduced these levels.Moreover,in LPS-induced liver injury,the inhibitions of MIF with ISO-1 and 4-IPP alleviated liver injury and slightly attenuated inflammatory response.Importantly,compared to mice with LPS-induced liver injury,Mif knockout or MIF inhibitions significantly prolonged the survival of the mice.Conclusions:In LPS-induced liver injury,the knockout of Mif or MIF inhibitions alleviated liver injury and slightly attenuated inflammatory response,thereby prolonged the survival of the mice.Targeting MIF may be an important strategy to protect the liver from injury during sepsis.展开更多
BACKGROUND:Brain-dead donors have been the main sources in organ transplantation.But many studies show that brain-death affects the organ's function after transplantation.This study was undertaken to investigate l...BACKGROUND:Brain-dead donors have been the main sources in organ transplantation.But many studies show that brain-death affects the organ's function after transplantation.This study was undertaken to investigate liver injury after brain-death in rats and the protective effects of N-acetyleysteine(NAC)on liver injury.METHODS:A total of 30 Wistar rats were randomized into 3 groups:normal control group(C),brain-dead group(B),and NAC pretreatment group(N).At 4 hours after the establishment of a brain-dead model,serum was collected to determine the levels of ALT,AST,TNF-αand hyaluronic acid(HA).Hepatic tissue was obtained for electron microscopic examination.RESULTS:At 4 hours,the levels of ALT,AST,TNF-a,and HA in group N were significantly higher than those in group C,but these parameters were significantly lower than those in group B.Electron microscopy showed activated Kupffer cells,denuded sinusoidal endothelial cells(SECs),and widened fenestration in group B,but eliminated activation of Kupffer cells and intact SECs in group N.CONCLUSION:Brain death can cause liver injury,and N-acetyleysteine can protect the liver from the injury.展开更多
Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahe...Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.展开更多
OBJECTIVE: To investigate the protective mechanism of different ischemic preconditioning (IPC) to ischemia/reperfusion (I/R) injury of rat liver graft. METHODS: 192 Wistar rats were randomly divided into 4 groups (48 ...OBJECTIVE: To investigate the protective mechanism of different ischemic preconditioning (IPC) to ischemia/reperfusion (I/R) injury of rat liver graft. METHODS: 192 Wistar rats were randomly divided into 4 groups (48 rats in each group): control group (group C), experimental group 1 (group E_1), experimental group 2 (group E_2), and experimental group 3 (group E_3). IPC was not carried out in group C. In the experimental groups, IPC was carried out by blocking blood flow of the portal vein and hepatic artery and then reperfusion by removal of the clamp before donor liver was resected. Group E_1: 5-minute ischemia and 10-minute reperfusion; Group E_2: 5-minute ischemia and 5-minute reperfusion and one more the same procedure; Group E_3: 10-minute ischemia and 15-minute reperfusion. Four hours after IPC, liver transplantations were performed. Recipient blood and graft samples were obtained to determine the levels of ALT, AST, TNF-α and apoptosis index at 0.5, 2, 6, 24 hours after portal vein reperfusion. RESULTS: At 0.5, 2 hours after portal vein reperfusion, the levels of TNF-α in the experimental groups E_1, E_2, and E_3 were significantly lower than in the control group (P<0.05), and the levels in group E_2 were significantly lower than in groups E_1 and E_3 (P<0.05). At 24 hours, the levels of TNF-α in group E_2 were significantly lower than in groups C, E_1 anti E_3 (P<0.05). At 2 and 6 hours, apoptosis index in the experimental groups E_1, E_2, and E_3 was significantly less than in the control group (P<0.05). Apoptosis index in group E_2 was significantly less than groups E_1 and E_3(P<0.05). At 24 hours apoptosis index in the experimental groups E_1, E_2 , and E_3 was significantly less than in the control group (P<0.05). CONCLUSIONS: Ischemic preconditioning could attenuate liver graft injury by decreasing apoptosis of hepatocytes and production of TNF-α. The method of IPC with 5-minute ischemia, 5-minute reperfusion and one more the same procedure is a better way to protect liver graft from ischemia-reperfusion injury.展开更多
Background:HMex-3A,an RNA-binding protein,was found to be associated with tumorigenesis.However,the roles of h Mex-3A in hepatocellular carcinoma(HCC)progression remained unclear.Methods:The different expression of h ...Background:HMex-3A,an RNA-binding protein,was found to be associated with tumorigenesis.However,the roles of h Mex-3A in hepatocellular carcinoma(HCC)progression remained unclear.Methods:The different expression of h Mex-3A between HCC tissues and non-tumor tissues was evaluated using The Cancer Genome Atlas database.Thereafter,the h Mex-3A expression was evaluated in HCC tissues using Western blotting and q RT-PCR.Immunohistochemistry was performed to investigate the association between h Mex-3 A level and clinicopathological features including prognosis in HCC patients.In addition,we used si-h Mex-3A to knockdown h Mex-3A in HCC cells to test Cell Counting Kit-8,colony formation,cell migration and invasion.Results:The h Mex-3A expression was significantly elevated in HCC tissues.Analysis of the clinicopathological parameters suggested that h Mex-3A expression was significantly associated with pathological grade(P=0.019)and TNM stage(P=0.001)in HCC.Moreover,univariate and multivariate Coxregression analyses revealed that high h Mex-3A expression(HR=1.491,95%CI:1.107–2.007;P=0.009)was an independent risk factor for overall survival in HCC patients.Finally,we confirmed that si-h Mex-3A could significantly inhibit HCC cell proliferation,migration,and invasion in vitro.Conclusions:HMex-3A may contribute to the progression of HCC and might be used as a novel therapeutic target and prognostic marker in HCC.展开更多
Background： Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead （BD） rats. In this study, we observed the effect ofsalubrinal （Sa...Background： Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead （BD） rats. In this study, we observed the effect ofsalubrinal （Sal, Sigma, USA） on liver cells in BD rats and explored its relevant mechanisms. Methods： Thirty Sprague-Dawley rats were equally randomized into three groups： BD group, Sal group, and DMSO group. The BD models were established by increasing intracranial pressure in a modified, slow, and intermittent way. In the drug groups, Sal was administered I h before the induction of BD. After modeling was completed, the blood and liver samples were harvested. CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction. PKR-like ER kinase （PERK）, P-eukaryotic translation initiation factor 2a （elF2a）, elF2a, CHOP and caspase-12 expression was detected using western blotting （WB）. CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry （IHC）. Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer. Hepatic cell apoptosis was detected using TUNEL. The results were analyzed using Quantity-one v4.62 software （Bio-Rad, USA）. Results： CHOP and caspase-12 expression and PERK, elF2a, and P-elF2a protein expression showed no significant difference between BD group and DMSO group. Compared with BD group, Sal group had a significantly higher P-elF2C level and a lower P-PERK level 2 h and 6 h alter BD （P 〈 0.05）. However, eIF2a expression showed no significant difference （P 〉 0.05）. After the Sal treatment, CHOP and caspase- 12 mRNA expression significantly decreased 4 hatter BD （P 〈 0.05）. WB and IHC indicated that CHOP and caspase- 12 expression also significantly decreased after Sal treatment. Sal was associated with improved liver function and decreased hepatic cell apoptosis. Conclusions： Sal can significantly reduce apoptosis in hepatic cells of BD rats. This protective effect may be achieved via the PERK-elF2a signaling pathway.展开更多
Brain-dead donors have become one of the main sources of organs for transplantation in Western countries.The quality of donor organs is closely related to the outcome of the transplantation.Experimental studies have c...Brain-dead donors have become one of the main sources of organs for transplantation in Western countries.The quality of donor organs is closely related to the outcome of the transplantation.Experimental studies have confirmed the inferior graft survival of livers from brain-dead donors compared with those from living donors.Studies conducted in the past 10 years have shown that brain death is associated with effects on the decreased donor organ quality.However,whether the decrease in the viability of donor organs is caused by brain death or by the events before and after brain death remains uncertain.The purpose of this review is to introduce the advances and controversies regarding the influence of brain death on the viability of donor livers and to summarize the mechanisms of the different protective interventions for donor livers.展开更多
基金Supported by the National Natural Science Foundation of China,No.U1504815
文摘AIM To investigate the relationship between autophagy and perineural invasion(PNI), clinical features, and prognosis in patients with pancreatic cancer. METHODS Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubuleassociated protein 1 A/1 B-light chain 3(LC3) and PNI marker ubiquitin carboxy-terminal hydrolase(UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis. RESULTS In 109 cases of pancreatic cancer, 68.8%(75/109) had evidence of PNI and 61.5%(67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels(P < 0.05). LC3 expression was related to lymph node metastasis(P < 0.05) and was positively correlated with neural invasion(P < 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients(P < 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer(P < 0.05). CONCLUSION PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.
基金Supported by The Science and Technology Support Project of Sichuan Province,No.2014SZ0002-10
文摘AIM: To review and evaluate the diagnostic dilemma of xanthogranulomatous cholecystitis(XGC) clinically.METHODS: From July 2008 to June 2014, a total of 142 cases of pathologically diagnosed XGC were reviewed at our hospital, among which 42 were misdiagnosed as gallbladder carcinoma(GBC) based on preoperative radiographs and/or intra-operative findings. The clinical characteristics, preoperative imaging, intra-operative findings, frozen section(FS) analysis and surgical procedure data of these patients were collected and analyzed.RESULTS: The most common clinical syndrome in these 42 patients was chronic cholecystitis, followed by acute cholecystitis. Seven(17%) cases presented with mild jaundice without choledocholithiasis. Thirtyfive(83%) cases presented with heterogeneous enhancement within thickened gallbladder walls on imaging, and 29(69%) cases presented with abnormal enhancement in hepatic parenchyma neighboring the gallbladder, which indicated hepatic infiltration. Intra-operatively, adhesions to adjacent organs were observed in 40(95.2%) cases, including the duodenum, colon and stomach. Thirty cases underwent FS analysis and the remainder did not. The accuracy rate of FS was 93%, and that of surgeon's macroscopic diagnosis was 50%. Six cases were misidentified as GBC by surgeon's macroscopic examination and underwent aggressive surgical treatment. No statistical difference was encountered in the incidence of postoperative complications between total cholecystectomy and subtotal cholecystectomy groups(21% vs 20%, P > 0.05).CONCLUSION: Neither clinical manifestations and laboratory tests nor radiological methods provide apractical and effective standard in the differential diagnosis between XGC and GBC.
文摘BACKGROUND:The high mortality of patients with severe acute pancreatitis(SAP)is due to multiorgan dysfunction.The mechanisms of SAP are still obscure.The aim of this study was to investigate the role of nuclear factor-kappa B(NF-κB)activation in rats with SAP associated with liver injury and the protection effect of triptolide against liver injury in rats with SAP.METHODS:Ninety Wistar rats were randomly divided into three groups(n=30 each group):severe acute pancreatitis(group P),treatment with triptolide(group T),and sham operation(group S).SAP models were induced by retrograde injection of 5%sodium taurocholate to the pancreatic duct.After the model was successfully established,no treatment was given to group P.In group T,triptolide(0.05 mg/ml)was injected intraperitoneally(0.2 mg/kg).In group S,the abdominal walls of rats were opened,sutured,but not treated.The rats-were sacrificed after operation at 2,6,and 12 hours,respectively.The serum levels of amylase(AMY),alanine aminotransferase(ALT),tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)were determined at three time points(10 rats for each time point).Liver tissues were obtained to detect the activity of NF-κB and to observe their pathological changes with light and electron microscopes.RESULTS:The serum levels of AMY and ALT were higher in groups P and T than in group S.The serum AMY levels were significantly lower in group T than in group P at 12 hours after operation.The serum ALT levels were significantly lower in group T than in group P at 6,12 hours after operation.At the three time points,the levels of TNF-αand IL-6 in groups P and T increased more significantly than in group S.In group T they were decreased more significantly than in group P at the three time points.In groups P and T,NF-κB activity in liver tissue increased more significantly than in group S at the three time points.The activity of NF-κB was higher in group P than in groups S and T at the three time points.Liver pathological damages were milder in group T than in group P under light and electron microscopes.CONCLUSIONS:NF-κB plays an important role in the pathogenesis of liver injury in rats with SAP.Triptolide can reduce pathological damage to the liver.Its mechanism is to inhibit the activity of NF-κB and to decrease the release of inflammatory mediators.
文摘BACKGROUND:Morphological and functional changes commonly occur in livers of brain-death donors.Preven-tion of liver injury from brain-death will benefit the results of transplantation.This study was conducted to evaluate the protection effects of glycine on the liver of brain-death donor.METHODS:Fourty-two male Wistar rats were randomly divided into brain-death donor(BDD)group(B),glycine pretreatment group with BDD(G),and strychnine pre-treatment group with BDD(S).For these groups,brain death model was established in donor rats and liver trans-plantation was performed subsequently utilizing microsur-gical techniques.After the establishment of the model and during cold rinsing of liver donors or liver reperfusion of recipients,glycine was given at a dose of 0.6 mmol,25μmol and 25μmol in the group G,and a same dose of gly-cine and strychnine(1000:1)was prescribed for the group S,but nothing for the group B.Before cold rinsing at 2 and 6 hours after portal vein(PV)reperfusion,blood sam-ples were taken from infrahepatic vena cava(IHVC)to de-termine the levels of alanine aminotransferase(ALT),as-partate aminotransferase(AST),tumor necrosis factor al-pha(TNF-α)and hyaluronic acid(HA).At 6 hours after PV reperfusion,graft samples were fixed for morphological observation and apoptosis of hepatocytes was detected using the TUNEL method.RESULTS:Before liver cold rinsing and at 2 and 6 hours af-ter PV reperfusion,the serum levels of ALT,AST,TNF-α,HA and apoptosis index(AI)in the groups B and S were significantly higher than those in the group G(P<0.05).There was no significant difference between the groups B and S(P>0.05).Electron microscopy showed that Kupffer cells were activated and hepatic cells injured more obvious-ly in the groups B and S than in the group G.CONCLUSION:Glycine pretreatment can improve the via-bility of the liver of the brain-death donor rat.
基金supported by grants from the National Natural Science Foundation of China(81971881)Medical Science and Technology Project of Henan Provincial Health Commission(SB201901045)。
文摘Background:Liver injury is one of the most common complications during sepsis.Macrophage migration inhibitory factor(MIF)is an important proinflammatory cytokine.This study explored the role of MIF in the lipopolysaccharide(LPS)-induced liver injury through genetically manipulated mouse strains.Methods:The model of LPS-induced liver injury was established in wild-type and Mif-knockout C57/BL6 mice.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBil)were detected,and the expressions of MIF,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were measured.Liver histopathology was conducted to assess liver injury.Moreover,the inhibitions of MIF with(S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester(ISO-1)and 4-iodo-6-phenylpyrimidine(4-IPP)were used to evaluate their therapeutic potential of liver injury.Results:Compared with wild-type mice,the liver function indices and inflammation factors presented no significant difference in the Mif-/-mice.After 72 h of the LPS-induced liver injury,serum levels of ALT,AST,and TBil as well as TNF-αand IL-1βwere significantly increased,but the knockout of Mif attenuated liver injury and inflammatory response.In liver tissue,m RNA levels of TNF-α,IL-1βand NF-κB p65 were remarkably elevated in LPS-induced liver injury,while the knockout of Mif reduced these levels.Moreover,in LPS-induced liver injury,the inhibitions of MIF with ISO-1 and 4-IPP alleviated liver injury and slightly attenuated inflammatory response.Importantly,compared to mice with LPS-induced liver injury,Mif knockout or MIF inhibitions significantly prolonged the survival of the mice.Conclusions:In LPS-induced liver injury,the knockout of Mif or MIF inhibitions alleviated liver injury and slightly attenuated inflammatory response,thereby prolonged the survival of the mice.Targeting MIF may be an important strategy to protect the liver from injury during sepsis.
文摘BACKGROUND:Brain-dead donors have been the main sources in organ transplantation.But many studies show that brain-death affects the organ's function after transplantation.This study was undertaken to investigate liver injury after brain-death in rats and the protective effects of N-acetyleysteine(NAC)on liver injury.METHODS:A total of 30 Wistar rats were randomized into 3 groups:normal control group(C),brain-dead group(B),and NAC pretreatment group(N).At 4 hours after the establishment of a brain-dead model,serum was collected to determine the levels of ALT,AST,TNF-αand hyaluronic acid(HA).Hepatic tissue was obtained for electron microscopic examination.RESULTS:At 4 hours,the levels of ALT,AST,TNF-a,and HA in group N were significantly higher than those in group C,but these parameters were significantly lower than those in group B.Electron microscopy showed activated Kupffer cells,denuded sinusoidal endothelial cells(SECs),and widened fenestration in group B,but eliminated activation of Kupffer cells and intact SECs in group N.CONCLUSION:Brain death can cause liver injury,and N-acetyleysteine can protect the liver from the injury.
文摘Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.
文摘OBJECTIVE: To investigate the protective mechanism of different ischemic preconditioning (IPC) to ischemia/reperfusion (I/R) injury of rat liver graft. METHODS: 192 Wistar rats were randomly divided into 4 groups (48 rats in each group): control group (group C), experimental group 1 (group E_1), experimental group 2 (group E_2), and experimental group 3 (group E_3). IPC was not carried out in group C. In the experimental groups, IPC was carried out by blocking blood flow of the portal vein and hepatic artery and then reperfusion by removal of the clamp before donor liver was resected. Group E_1: 5-minute ischemia and 10-minute reperfusion; Group E_2: 5-minute ischemia and 5-minute reperfusion and one more the same procedure; Group E_3: 10-minute ischemia and 15-minute reperfusion. Four hours after IPC, liver transplantations were performed. Recipient blood and graft samples were obtained to determine the levels of ALT, AST, TNF-α and apoptosis index at 0.5, 2, 6, 24 hours after portal vein reperfusion. RESULTS: At 0.5, 2 hours after portal vein reperfusion, the levels of TNF-α in the experimental groups E_1, E_2, and E_3 were significantly lower than in the control group (P<0.05), and the levels in group E_2 were significantly lower than in groups E_1 and E_3 (P<0.05). At 24 hours, the levels of TNF-α in group E_2 were significantly lower than in groups C, E_1 anti E_3 (P<0.05). At 2 and 6 hours, apoptosis index in the experimental groups E_1, E_2, and E_3 was significantly less than in the control group (P<0.05). Apoptosis index in group E_2 was significantly less than groups E_1 and E_3(P<0.05). At 24 hours apoptosis index in the experimental groups E_1, E_2 , and E_3 was significantly less than in the control group (P<0.05). CONCLUSIONS: Ischemic preconditioning could attenuate liver graft injury by decreasing apoptosis of hepatocytes and production of TNF-α. The method of IPC with 5-minute ischemia, 5-minute reperfusion and one more the same procedure is a better way to protect liver graft from ischemia-reperfusion injury.
基金supported by grants from the Medical Science and Technology Program of Henan Province(SBGJ2018002)Basic Research Project of Henan Science and Technology Department(142300410221)+1 种基金National S&T Major Project of China(2018ZX10301201-008)National Key Research and Development Program of China(2018YFC2000500)。
文摘Background:HMex-3A,an RNA-binding protein,was found to be associated with tumorigenesis.However,the roles of h Mex-3A in hepatocellular carcinoma(HCC)progression remained unclear.Methods:The different expression of h Mex-3A between HCC tissues and non-tumor tissues was evaluated using The Cancer Genome Atlas database.Thereafter,the h Mex-3A expression was evaluated in HCC tissues using Western blotting and q RT-PCR.Immunohistochemistry was performed to investigate the association between h Mex-3 A level and clinicopathological features including prognosis in HCC patients.In addition,we used si-h Mex-3A to knockdown h Mex-3A in HCC cells to test Cell Counting Kit-8,colony formation,cell migration and invasion.Results:The h Mex-3A expression was significantly elevated in HCC tissues.Analysis of the clinicopathological parameters suggested that h Mex-3A expression was significantly associated with pathological grade(P=0.019)and TNM stage(P=0.001)in HCC.Moreover,univariate and multivariate Coxregression analyses revealed that high h Mex-3A expression(HR=1.491,95%CI:1.107–2.007;P=0.009)was an independent risk factor for overall survival in HCC patients.Finally,we confirmed that si-h Mex-3A could significantly inhibit HCC cell proliferation,migration,and invasion in vitro.Conclusions:HMex-3A may contribute to the progression of HCC and might be used as a novel therapeutic target and prognostic marker in HCC.
基金This study was supported by a grant of National Natural Science Foundation of China （No. 81171849）.
文摘Background： Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead （BD） rats. In this study, we observed the effect ofsalubrinal （Sal, Sigma, USA） on liver cells in BD rats and explored its relevant mechanisms. Methods： Thirty Sprague-Dawley rats were equally randomized into three groups： BD group, Sal group, and DMSO group. The BD models were established by increasing intracranial pressure in a modified, slow, and intermittent way. In the drug groups, Sal was administered I h before the induction of BD. After modeling was completed, the blood and liver samples were harvested. CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction. PKR-like ER kinase （PERK）, P-eukaryotic translation initiation factor 2a （elF2a）, elF2a, CHOP and caspase-12 expression was detected using western blotting （WB）. CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry （IHC）. Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer. Hepatic cell apoptosis was detected using TUNEL. The results were analyzed using Quantity-one v4.62 software （Bio-Rad, USA）. Results： CHOP and caspase-12 expression and PERK, elF2a, and P-elF2a protein expression showed no significant difference between BD group and DMSO group. Compared with BD group, Sal group had a significantly higher P-elF2C level and a lower P-PERK level 2 h and 6 h alter BD （P 〈 0.05）. However, eIF2a expression showed no significant difference （P 〉 0.05）. After the Sal treatment, CHOP and caspase- 12 mRNA expression significantly decreased 4 hatter BD （P 〈 0.05）. WB and IHC indicated that CHOP and caspase- 12 expression also significantly decreased after Sal treatment. Sal was associated with improved liver function and decreased hepatic cell apoptosis. Conclusions： Sal can significantly reduce apoptosis in hepatic cells of BD rats. This protective effect may be achieved via the PERK-elF2a signaling pathway.
文摘Brain-dead donors have become one of the main sources of organs for transplantation in Western countries.The quality of donor organs is closely related to the outcome of the transplantation.Experimental studies have confirmed the inferior graft survival of livers from brain-dead donors compared with those from living donors.Studies conducted in the past 10 years have shown that brain death is associated with effects on the decreased donor organ quality.However,whether the decrease in the viability of donor organs is caused by brain death or by the events before and after brain death remains uncertain.The purpose of this review is to introduce the advances and controversies regarding the influence of brain death on the viability of donor livers and to summarize the mechanisms of the different protective interventions for donor livers.
