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Objective To investigate the effect and its molecular mechanism of phosphoglycerate mutase 5 (PGAM5) mediated pyroptosis on liver ischemia-reperfusion injury (IRI). Methods C57 mouse models of liver IRI were established and randomly divided into the 6 h reperfusion (6 h group) and 12 h reperfusion (12 h group), and sham operation group (sham group) was established too, 10 rats in each group. The effect of IRI on the parameters in the liver tissues and serum samples was evaluated. The expression levels of PGAM5 and cysteinyl aspartate specific proteinase (Caspase)-1 in the liver tissues during IRI were quantitatively detected. The IRI models of liver cells were established (IRI group). The IRI models of liver cells were established after pretreatment with Caspase-1 inhibitor Z-YVAD-FMK (inhibitor group). The untreated AML12 cells were allocated into the control group. The effect of inhibiting Caspase-1 activity on pyroptosis was analyzed. AML12 cells were transfected with PGAM5 small interfering ribonucleic acid (siRNA) (siRNA group) and siRNA-negative control (siRNA-NC) (siRNA-NC group) by liposome 3000, and then IRI models of liver cells were established. The untreated AML12 cells were assigned into the control group. The effect of PGAM5 mediated pyroptosis on IRI of liver cells was assessed. Results In the 6 h and 12 h groups, partial liver cell edema, hepatic sinusoid narrowing, central vein congestion and occasional spot necrosis were observed in the mouse liver tissues, and these changes in the 12 h group were more aggravated than those in the 6 h group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 h and 12 h groups were higher than those in the sham group, and the values in the 12 h group were higher than those in the 6 h group. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were increased in the 6 h and 12 h groups, and the values in the 12 h group were lower than those in the 6 h group. The relative expression levels of IL-1β messenger ribonucleic acid (mRNA) in the mouse liver tissues in the 6 h and 12 h groups were up-regulated, and the value in the 12 h group was lower than that in the 6 h group. The cell apoptosis rates in the liver tissues were significantly increased in the 6 h and 12 h groups, and the value in the 12 h group was remarkably lower than that in the 6 h group (P < 0.01-0.05). Compared with the sham group, the relative expression levels of PGAM5 mRNA and protein in the mouse liver tissues in the 6 h and 12 h groups were significantly up-regulated, and the values in the 12 h group were significantly higher than those in the 6 h group (P < 0.01-0.05). The protein expression levels of PGAM5 and Caspase-1 in the liver tissues were up-regulated in the 6 h and 12 h groups. Compared with the control group, the relative expression levels of NOD-like receptor protein 3 (NLRP3), cleaved Caspase-1 and Gasdermin D (GSDMD) proteins were up-regulated and the fluorescence intensity of GSDMD was increased in the IRI group. Compared with the IRI group, the relative expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated and the fluorescence intensity of GSDMD was considerably decreased in the inhibitor group (P < 0.01-0.05). Compared with the control group, the cell survival rate was significantly decreased, and the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly up-regulated in the siRNA-NC group (P < 0.01-0.05). Compared with the siRNA-NC group, the cell survival rate was remarkably increased, whereas the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated in the siRNA group (P < 0.01-0.05). Conclusions PGAM5 may aggravate the liver IRI in mouse models probably by mediating pyroptosis via PGAM5/Caspase-1/GSDMD signaling pathway and aggravating liver cell injury.
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Objective:To evaluate liver quadrate lobectomy combined with large-bore cholangio-jejunostomy for the treatment of benign biliary-enteric anastomotic stricture.Methods:The clinical data of 32 patients undergoing liver quadrate lobectomy combined with large-caliber cholangio-jejunostomy were retrospectively analyzed. The bile drainage effect and postoperative complications were analyzed. And the clinical effects of different size of biliary-enteric anastomosis were compared.Results:The most common short-term complications were cholangitis (9.4%) and bile leakage (9.4%), and the most common long-term complications were reflux cholangitis (15.6%). No anastomotic restenosis, stone formation or canceration were found. During the follow-up period, the total bilirubin ( t=19.455, P=0.000), direct bilirubin ( t=18.479, P=0.000), alkaline phosphatase ( t=3.229, P=0.002) and γ-glutamyltranspeptidase ( t=3.057, P=0.003) level were significantly improved. The effect of bile drainage in patients with 2-3 cm diameter of biliary-enteric anastomosis was similar to that in patients with >3 cm diameter ( t=0.284, P=0.778). The incidences of cholangitis (χ 2=0.121, P=0.728), bile leakage (χ 2=0.121, P=0.728) and reflux cholangitis (χ 2=0.205, P=0.652) were no statistical difference in both groups. Conclusion:Liver quadrate lobectomy combined with large-caliber cholangio-jejunostomy is effective in the treatment of benign biliary-enteric anastomotic stricture. More than 2cm in diameter of the biliary-enteric anastomosis is enough.
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Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare and enhanced CT or MRI can be used for its diagnosis. Surgical procedure is the main treatment for HCC with BDTT. The authors introduce the experiences of recurrent patient with HCC and BDTT who was treated with targeted therapy plus immunotherapy, in order to provide reference for its clinical diagnosis and treatment.
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Objective:To investigate the effect of expanded lymphadenectomy on the survival rate of the patients with hilar cholangiocarcinoma(HC).Methods:The clinical data of 129 patients undergoing radical resection of HC were retrospectively analyzed. According to the range of lymphadenectomy, they were divided into regional group(91 cases) and expanded group(38 cases). The clinical data, survival rate and postoperative complications in two groups were compared and analyzed.Results:The 3-year and 5-year survival rates of metastasis free(M0) patients in the regional group and expanded group were 44.1%, 24.8% and 47.0%, 33.6%, respectively; there were no statistically significant difference in survival rates between the two groups(χ 2=0.662, P=0.416). Compared with patients in the regional group, the average number of harvested lymph nodes in the expanded group was significantly increased and the difference was statistically significant( t=14.678, P=0.000), while the incidence of severe complications and mortality does not increase significantly. Conclusion:Expanded lymphadenectomy did not improve the survival rate of M0 HC patients, which while yielding more lymph nodes does not increase the incidence of postoperative complications and mortality in resectable HC patients.
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Objective:To investigate the effects of ulinastatin on liver function in patients with liver cancer after major hepatectomy.Methods:The clinical data of 232 patients with major liver resection due to liver cancer were retrospectively analyzed. According to whether ulinastatin was applied after operation, patients were divided into treatment group (105 cases) and control group (127 cases). The postoperative inflammatory factors, liver function, postoperative complications and hospital stay were compared.Results:The levels of CRP、IL-6 and TBIL、ALT、AST were significantly lower than the control group 3 days after surgery (CRP: t=4.520, P=0.000; IL-6: t=17.982, P=0.000; TBIL: t=9.843, P=0.000; ALT: t=11.913, P=0.000; AST: t=4.520, P=0.000). The incidence of massive ascites in the treatment group (χ 2=4.212, P=0.040) and the average postoperative hospital stay ( t=9.994, P=0.000) were significantly lower than that in the control group. Conclusion:Early application of ulinastatin effectively inhibits the inflammatory process, protects liver function, reduces the incidence of massive ascites, and shortens the postoperative hospital stay.
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Objective:To study the impact of additional resection of an intraoperative proximal bile duct positive margin on the survival rate of patients with hilar cholangiocarcinoma (HCCA).Methods:The clinical data of 214 patients with HCCA treated at the First Affiliated Hospital of Zhengzhou University from January 2000 to January 2017 were analyzed. There were 126 males and 88 females, aged (62.3±17.1) years. These patients were divided into three groups according to the pathological status of bile duct margins and whether the proximal bile duct was further resected. Group A consisted of patients with negative margins without additional resection (161 cases). Group B consisted of patients with negative margins after additional resection (21 cases). Group C consisted of patients with R 1 resections (32 cases). The Kaplan-Meier method was used for survival analysis and log-rank test was used for inter-group comparison. Univariate and multivariate Cox regression analysis were used to analyze prognostic factors. Results:The 3-year and 5-year survival rates of patients in groups A, B, and C were 37.1%, 28.6%, 0 and 18.5%, 10.7%, 0, respectively. The cumulative survival rates of patients in group A and group B were significantly higher than that in group C (all P<0.05). Multivariate Cox regression analysis showed that R 1 proximal bile duct margin ( HR=3.728, 95% CI: 2.531-4.936), margin width >5 mm ( HR=0.534, 95% CI: 0.224-0.857), and T 3-4 staging ( HR=5.655, 95% CI: 3.174-8.203) were independent influencing factors for overall survival of patients with HCCA after attempted radical surgery. Conclusion:The survival rate of patients with HCCA with a positive proximal bile duct margin was significantly improved by further resecting the bile duct to obtain a negative margin. The R 1 proximal bile duct margin was an independent risk factor for prognosis in patients with HCCA after attempted radical resection.
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Objective:To investigate the effect of local antibiotics irrigation on chronic proliferative cholangitis (CPC).Methods:CPC model of rabbits was established. Rabbits were divided into CPC group (without local antibiotics irrigation, n=20) and experimental group (with local antibiotics irrigation, n=20). Only the gallbladder was removed, and 20 rabbits with free bile duct (sham operation) were used as normal control. The inflammatory conditions, proliferation of cholangiocytes, biliary fibrosis and biliary stones formation ability were analyzed. Results:Compared with CPC group, the relative expression of inflammation index lipopolysaccharide and interleukin-6 [(1.21±0.13) vs. (3.24±0.21), (1.52±0.22) vs. (3.10±0.23)], biliary cell proliferation index cyclooxygenase-2 and vascular endothelial growth factor [(2.15±0.12) vs. (4.07±0.22), (2.44±0.14) vs. (3.22±0.21)], fibrosis index transforming growth factor-β and Collagen-I [(2.44±0.28) vs. (4.36±0.44), (1.54±0.13) vs. (2.22±0.18)] and biliary stones formation index β-glucuronidase and Mucin 5AC [(1.74±0.20) vs. (3.42±0.31), (1.47±0.15) vs. (2.81±0.22)] were significantly decreased in experimental group (all P<0.05). Conclusion:Local antibiotics irrigation could inhibit CPC by inhibiting the chronic inflammation of the biliary tract and excessive proliferation of cholangiocytes and biliary fibrosis, and reducing the probability of biliary stone formation.
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Objective:To investigate the efficacy of two different percutaneous transhepatic biliary drainage (PTBD) procedures for malignant obstructive jaundice.Methods:The clinical data of 132 patients with malignant obstructive jaundice who underwent PTBD were retrospectively analyzed. According to whether the tip of the catheter was placed in the intestine, 132 patients were divided into the external drainage group and the internal-external drainage group. The effect on decrease in jaundice (total bilirubin, direct bilirubin levels), postoperative complications, and hospitalization costs of the two drainage methods were compared.Results:Of the 132 patients who were included in this study, there were 91 males and 41 females, aged 18 to 85 years. The external drainage group included 81 patients, and the internal and external drainage group included 51 patients. The total bilirubin [(190.2±41.8)μmol/L vs. (294.9±38.3) μmol/L] and direct bilirubin [(155.4±30.9)μmol/L vs. (242.1±39.6) μmol/L] levels in the external drainage group and the total bilirubin [(179.3±37.1)μmol/L vs. (288.1±35.4)μmol/L] and direct bilirubin [(147.7±32.5)μmol/L vs. (233.7±36.1)μmol/L] levels in the internal-external drainage group were significantly decreased after surgery (all P<0.05). The incidences of reoperation, re-intubation or bilateral catheterization [15.6%(8/51) vs. 3.7%(3/81)] and biliary tract infection [50.9%(26/51) vs. 27.1%(22/81)] in the internal-external drainage group was significantly higher than that in the external drainage group (all P<0.05). The mortality rate due to biliary tract infection in the internal-external drainage group was significantly higher than that of the external drainage group [7.8%(4/51) vs. 0, P<0.05]. Intestinal-derived bacteria such as Escherichia coli, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the main bacteria in the biliary tract infections of the two groups. The hospitalization cost of patients in the internal-external drainage group was significantly higher than that in the external drainage group [(34 928.0±3 693.0) yuan vs. (29 360.0±3 219.0) yuan, P<0.05]. Conclusion:Both PTBD external drainage and internal and external drainage could alleviate the symptoms of jaundice quickly and effectively.
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Objective To analyze the clinical characteristics,diagnosis,treatment and prognostic factors of primary hepatic neuroendocrine tumor (PHNET).Methods To analyze the clinical data of 21 patients with PHNET who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2012 to January 2019.There were 11 males and 10 females,with ages which ranged from 36 to 75 years.Log-rank test was used for single-factor analysis of the relationship between clinical and pathological indicators and prognosis.Cox proportional risk model was used for multi-factor analysis.Results Among the 21 PHNET patients,10 presented with central and upper abdominal pain,3 abdominal pain accompanied by nausea and vomiting,5 abdominal distension,and 3 were asymptomatic.Carbohydrate antigen (CA) 19-9 was elevated in 6 patients and CA125 in 7 patients.Abdominal enhanced CT showed solid liver space occupying lesions.Four patients had solitary and 17 had multiple lesions.The mean diameter was 58 mm.Fourteen patients had lymph node metastasis.Five patients underwent radical hepatectomy,2 transcatheter hepatic arterial chemoembolization + chemotherapy,12 chemotherapy,and 2 supportive treatment.Factors which were associated with prognosis of PHNET patients were surgery,tumor grading,cytokeratin positivity and lymph node metastasis.Multivariate Cox regression analysis showed that inoperability (HR =8.99,95％ CI:1.13-71.80) was an independent risk factor of prognosis of PHNET patients.The prognosis in patients who underwent surgical resection was better.Conclusion Patients with PHNET had no specific clinical manifestations.Surgical resection gave the best results in treatment.As surgical resection affected prognosis,it should be carried out if technically feasible.
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Objective To investigate effects of complete resection of the cyst or incomplete resection with 3 ～ 5 mm remnant proximal cyst wall in treating adult type Ⅰ choledochal cyst (CC).Methods Medical records of 133 surgical patients with type Ⅰ CC from December 1995 to December 2017 in the First Affiliated Hospital of Zhengzhou University were reviewed retrospectively.According to whether to reserve the 3 ～ 5 mm cyst wall in proximal end of cyst,133 patients were divided into unreserved group (n =85) and reserved group (n=48),and the related indicators of the two groups were compared and analyzed.Results No significant difference was observed in age,sex ratio,clinical performance between the two groups(all P＞0.05).And there was no statistical difference in the operation time,intraoperative blood loss,and biliary-intestinal anastomosis diameter between the two groups(all P＞0.05).The main complications of the two groups were similar,including incision and abdominal infection,bile leakage,cholangitis,reflux cholangitis,bile duct stones and anastomotic stricture,and there was no statistical difference in the incidence of each complication.Biliary-intestinal anatomical site malignancy was observed in one patient with recurrent cholangitis in the reserved group in the 33th months.Conclusions There was no statistical difference in the incidence of early and late complications in two different methods of cyst management for treating adult type Ⅰ CC.Whether reserve the 3～5 mm cyst wall in proximal end of CC increases the risk of cancer still needs further studies.
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Objective To explore the clinical significance of intraoperative frozen sections for the diagnosis of unexpected gallbladder neoplasm during cholecystectomy for acute cholecystitis.Methods We retrospectively analyzed the clinical data of acute cholecystitis patients who underwent cholecystectomy at the First Affiliated Hospital of Zhengzhou University,from Dec 2012 to Dec 2017.Results In the 1 386 acute cholecystitis patients,19 patients were found to have concurrent gallbladder neoplasm.Surgeons accurately recognized 9 gallbladder neoplasms by general observation alone,including 2 T2 and 2 T3 gallbladder neoplasms,but missed 10 gallbladder neoplasms.At the same time,we found that 3 Tis and 1 T1a gallbladder neoplasms were missed by frozen sections from 10 gallbladder neoplasms diagnosed by definitive histopathological examination.The sensitivity of frozen sections diagnosis was 60％ and the specificity was 100％.Conclusions During cholecystectomy for acute cholecystitis,the accuracy of surgeons' diagnosis with general observation in unexpected gallbladder neoplasm is poor.The accuracy of frozen sections to diagnose advanced gallbladder neoplasm is high,so we advocate frozen sections of every cholecystectomy sample in acute cholecystitis patients.
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Objective To study the effect of two different percutaneous transhepatic cholangiography and drainage (PTCD) procedures for malignant obstructive jaundice.Methods According to whether the tip of the catheter was carried across the ampulla and into the duodenum,patients were divided into external drainage group (54 cases) and both internal and external drainage group (57 cases).The effects of two surgical procedures on reducing jaundice,the postoperative complications,hospitalization days,and total hospitalization expenses were evaluated.Results Postoperative TBiL decreased significantly in both the two groups (t =2.338,P ＜ 0.05).The postoperative DBiL values went even lower in both external and internal group (t =2.201,P ＜ 0.05).There were 14 cases of biliary tract infection in the external drainage group,and 27 cases in two ways group (x2 =5.473,P ＜0.05).Total hospitalization expenses were statistically different between the two group (t =-2.200,P ＜ 0.05).Conclusion The internal and external drainage has a better drainage effect than the external drainage group,but more likely to cause infection of biliary tract,increase hospitalization expenses.
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Objective To study the expression and the clinical significance of hypoxia-induced factor-1α (HIF-1α) in gallbladder cancer tissues,and the role and mechanism of HIF-1α in metformin-suppressed metastasis in gallbladder carcinoma GBC-SD cells.Methods 24 specimens of gallbladder cancer tissues and 5 specimens of chronic cholecystitis were collected from the First Affiliated Hospital of Zhengzhou University between June 2016 and February 2017.Immunohistochemistry and qPCR were used to detect the expression of HIF-1α in gallbladder cancer tissues,in adjacent non-cancer tissues and in chronic cholecystitis,and the clinical significance was analyzed.The model of metastasis was induced by hypoxia;the wound healing assay and the Transwell assay were used to detect the ability of cell metastasis;the expressions of HIF-1α and VEGF in gallbladder carcinoma GBC-SD cells were detected by western blotting assay and immunofiuorescence.Results The expression of HIF-1α in gallbladder cancer tissues was higher than the adjacent non-cancer tissues and in chronic cholecystitis.The expression of HIF-1α was correlated with lymph node metastasis and TNM staging in gallbladder cancer tissues (P ＜ 0.05).The wound healing rate after 48 h in the negative control group and in the treatment with hypoxia group (1％ O2) in GBC-SD cells were (46.5 ± 4.8) ％ and (67.3 ± 4.0) ％,respectively.The Transwell data showed that the numbers of metastasis after 24 h in the negative control group and in the treatment with hypoxia group GBC-SD cells were (147.4 ± 11.7) and (234.4 ± 17.7),respectively.When compared with the negative control group,treatment with hypoxia significantly increased the ability of metastasis and up-regulated the expression of HIF-1α and VEGF in GBC-SD cells (P ＜ 0.05).The wound healing rate after 48 h in the negative control group,the metformin group,the hypoxia group and the metformin and hypoxia group in GBC-SD cells were (40.6 ± 7.1) ％,(16.4 ± 9.4) ％,(69.5 ± 4.0) ％ and (22.4 ± 7.4) ％,respectively.The Transwell data showed that the numbers of metastasis after 24 h in the negative control group,the metformin group,the hypoxia group and the metformin and hypoxia group in GBC-SD cells were (148.4 ± 6.9),(90.0 ± 8.4),(185.8 ± 10.2) and (113.4± 8.6),respectively.When comparcd with the hypoxia group,treatment with metformin and hypoxia significantly decreased the ability of metastasis and down-regulated the expression of HIF-1α and VEGF in GBC-SD cells (P ＜ 0.05).The wound healing rate after 48 h in the negative control group,the 2MeoE2 group,the hypoxia group,the 2MeoE2 and hypoxia group in GBC-SD cells were (43.4 ±4.4)％,(25.9 ±9.0)％,(63.3 ±2.2)％,(46.2 ±4.5)％,respectively.The Transwell data showed that the numbers of metastasis after 24 h in the negative control group,the 2MeoE2 group,the hypoxia group,the 2MeoE2 and hypoxia group in GBC-SD cells were (144.2 ± 12.6),(80.2 ±7.7),(203.8 ±7.0),(124.0 ± 5.2),respectively.When compared with the hypoxia group,treatment with HIF-1α inhibitor 2MeoE2 and hypoxia significantly decreased the ability of metastasis and down-regulated the expression of HIF-1α and VEGF in GBC-SD cells (P ＜ 0.05).Conclusions The expression of HIF-1 α was correlated with lymph node metastasis and TNM staging in gallbladder cancer tissues.Treatment with hypoxia significantly increased the expression of HIF-1α and VEGF and promoted metastasis of GBC-SD cells,while treatment with metformin decreased the ability of metastasis induced by hypoxia via inhibiting the HIF-1o/VEGF pathway in GBC-SD cells.
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Pancreatic tuberculosis (PTB) is a rare,chronic,specific and infectious disease which is generally secondary to tuberculosis at the common sites of pancreas,and it has a high misdiagnosis rate due to the hidden onset and nonspecific symptoms of PTB.A patient with PTB was admitted to the First Affiliated Hospital of Zhengzhou University in June 2014.Before operation,the space-occupying lesions of the head of pancreas were detected by preoperative imaging examination,and the patient was regarded as with pancreatic cancer.Intraoperative exploration showed cystic duct involvement,and the granulomatous inflammation was detected by rapid pathological examination using frozen section technique,after that the patient received granuloma resection+cholecystectomy according to suspected PTB.The diagnosis of PTB was confirmed by postoperative pathological examination,and the patient received liver-protective and anti-tuberculosis treatments after discharge.
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12 months in 36 patients),during the follow-up 2 patients died.Conclusions The DST is minimally invasive for the treatment of low rectal carcinoma with high rate of anus conservation,and can improve the life quality of the patients.