【摘要】 目的 探讨丙型肝炎病毒非结构蛋白NS4B对肝细胞内p53表达的影响，以及在肝癌发生中的作用与机制。 方法 设置空白对照组、空白载体组、转染NS4B组、转染p53组、共转染NS4B及p53组。使用脂质体介导转染法，转染丙型肝炎病毒非结构蛋白重组质粒PCXN2-NS4B及突变型p53基因重组质粒pC53-CX22AN3进入Chang肝细胞内，并用G418筛选获得稳定表达细胞。采用免疫细胞化学法检测p53表达率。 结果 空白对照组无p53表达，空白载体组及转染NS4B组呈弱阳性表达，转染p53组及共转染组呈阳性表达；转染p53组、共转染组分别与空白对照组、空白载体组及转染NS4B组比较，差异均有统计学意义 （Plt;0.05）。 结论 NS4B可能抑制p53表达，也可能阻止其进入细胞核，但NS4B与突变型p53关系不明确。NS4B导致肝细胞异常增生，诱导肝癌发生可能不依赖p53的异常表达及突变。【Abstract】 Objective To investigate the effect of hepatitis C Virus on-structural protein 4B(HCV NS4B) on expression of p53 in hepatic cell, and to study the role and mechanism in development of hepatocellular carcinoma. Methods The experiment was divided into negative control, pure vector PCXN2, PCXN2-NS4B, PC53-cx22AN3, and co-transfection group. Recombinant plasmid PCXN2-NS4B and mutant p53 gene--PC53-cx22AN3, PC53-cx22AN3 with PCXN2-NS4B, blank vectors were transfected into Chang liver cell by liposome-mediated transfection respectively. Positive cells were screened by G418. The expression rate of p53 was measured by immunocytochemistry. Result No expression rate of p53 gene in control group was found, lower positive expression in group PCXN2 and PCXN2-NS4B. The expression of p53 gene in group PC53-CX22AN3 and co-transfection was ber than the others (Plt;0.005). Conclusion HCV-NS4B may inhibit the expression of p53 gene, and it may play a crucial role in inhibiting p53 transfered to hepatic cells nuclear. But it isn’t clear that the. HCV-NS4B can enhance the role of mutant p53 gene. It suggested that HCV-NS4B induce proliferation of hepatic cell not through regulating the expression of p53.
Objective To investigate the gastrin level in patients with type 2 diabetes mellitus (T2DM) with gastroesophageal reflux disease (GERD), and analyze the possible mechanism of gastrin in the pathogenesis of T2DM combined with GERD. Methods Thirty-eight patients with T2DM combined with GERD treated between January 2013 and January 2015 were designated as group A; 40 patients with T2DM only were regarded as group B; 36 patients with GERD only were regarded as group C; and another 40 healthy volunteers who underwent physical examination at the same period were regarded as group D. The fasting serum levels of gastrin were measured and compared among the above four groups. Results The fasting serum level of gastrin was significantly higher in group A [(116.53±22.02) pg/mL] than group B [(101.89±20.76) pg/mL], group C [(90.04±21.16) pg/mL], and group D [(92.48±19.69) pg/mL] (P<0.01). The fasting serum level of gastrin in group B was significantly higher than group C and D (P<0.05). There was no significant difference between group C and D in terms of fasting serum level of gastrin (P>0.05). Conclusions There is a high level of gastrin in patients with GERD combined with T2DM. Abnormal secretion of gastrin may be closely related with the occurrence and development of T2DM and GERD.
Objective To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with gastric coronary vein embolization for the treatment of liver cirrhosis with gastroesophageal varices hemorrhage, and evaluate its application value. Methods The data of 50 patients with liver cirrhosis who were treated with TIPS combined with gastric coronary vein embolization between June 2009 and January 2013 were retrospectively analyzed. According to Child-Pugh Liver Grade, the patients were divided into grade A liver function group (n=6), grade B liver function group (n=18), and grade C liver function group (n=26); according to the type of stent implantation, the patients were divided into covered stent group (n=29) and bare stent group (n=21). The 1-week and 1-, 3-, 6-, and 12-month postoperative liver function changes were compared, and the 2-year postoperative rebleeding rate, survival rate, stent restenosis rate, and hepatic encephalopathy incidence were observed. Results The success rate of surgery was 100.0% (50/50), and the success rate of emergency surgery was 100.0% (3/3) in 3 patients with active bleeding. The portal vein pressure decreased from (39.46±2.82) cm H2O (1 cm H2O=0.098 kPa) before the surgery to (25.62±2.13) cm H2O after the surgery, and the difference was statistically significant (P<0.05). In grade A and grade B liver function groups, and covered stent and bare stent groups, the differences between preoperative and postoperative liver function indexes were not statistically significant (P>0.05); in grade C liver function group, the 1-week, 1-month, 3-month postoperative values of alanine aminotransferase, aspartate aminotransferase, total bilirubin and direct bilirubin increased compared with the preoperative values, and the differences were statistically significant (P<0.05). The postoperative 2-year rebleeding rate was 12.0% (6/50), and the postoperative 2-year incidence of hepatic encephalopathy was 16.0% (8/50). The postoperative 2-year stent stenosis rate was 26.0% (13/50) in the 50 cases, which was 13.8% (4/29) in covered stent group and 42.9% (9/21) in bare stent group, respectively. The postoperative 2-year survival rate was 90.0% (45/50). Conclusions TIPS combined with gastric coronary vein embolization in the treatment of liver cirrhosis with gastroesophageal varices bleeding has the exact effect, low rebleeding rate, fewer complications, and can be repeated. The preoperative evaluation of patients’ liver function, the application of stent of diameter 8 mm, paying attention to the perioperative period and regular follow-up treatment are helpful to reduce or prevent the occurrence of hepatic encephalopathy, stent stenosis and other complications.
ObjectiveTo investigate the trend of serum bilirubin in patients with liver cirrhosis before and after transjugular intrahepatic portosystemic shunt (TIPS).MethodsThe data of patients with cirrhotic portal hypertension who underwent TIPS between October 2016 and June 2018 were collected retrospectively, including liver function before and after surgery (1 week, 1 month, 3 months, and 6 months after surgery), preoperative and postoperative portal vein pressure, and the Child-Pugh scores, model for end-stage liver disease (MELD) scores, and albumin-bilirubin (ALBI) scores. Paired t-test was used for the statistical measurement data. The total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) levels at five time points were analyzed by analysis of variance of repeated measurement data with its own before and after comparison, and Wilcoxon signed ranks test was used for the ordered data.ResultsA total of 60 patients were included.The portal vein pressure was (27.86±2.53) mm Hg (1 mm Hg=0.133 kPa) before TIPS and (17.22±2.33) mm Hg after TIPS, and the difference was statistically significant (P<0.05). The common logarithm of the serum TBIL level [lg(TBIL)] before surgery and 1 week, 1 month, 3 months, and 6 months after surgery were (1.27±0.23), (1.44±0.21), (1.51±0.20), (1.56±0.22), (1.48±0.19) lg(μmol/L), respectively, and the difference was statistically significant (P<0.001). The common logarithm of the serum DBIL level [lg(DBIL)] at the five time periods were (0.90±0.26), (1.14±0.24), (1.18±0.25), (1.21±0.28), (1.08±0.21) lg(μmol/L), respectively, and the difference was statistically significant (P<0.001). The common logarithm of the serum IBIL level [lg(IBIL)] at the five time periods were (1.00±0.23), (1.13±0.22), (1.20±0.23), (1.26±0.21), (1.22±0.23) lg(μmol/L), respectively, and the difference was statistically significant (P<0.001). There were no statistically significant differences in the three liver reserve function scores (Child-Pugh, MELD, and ALBI, respectively) before and six months after operation (P>0.05). The differences in the composition of Child-Pugh and ALBI before and after surgery were not statistically significant (P>0.05).ConclusionsTIPS has a significant effect on reducing portal hypertension. Serum bilirubin levels continue to increase during a period after TIPS, but begin to decrease within 6 months.