Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver...Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver failure is not clear.This study aimed to determine Tβ4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.Methods:The study recruited 115 patients with ACHBLF,80 with acute-on-chronic hepatitis B pre-liver failure(pre-ACHBLF),and 86 with chronic hepatitis B(CHB).In addition,there were 36 healthy controls(HCs)from the Department of Hepatology,Qilu Hospital of Shandong University.The 115 patients with ACHBLF were divided into three subgroups:33 with early stage ACHBLF(E-ACHBLF),42 with mid-stage ACHBLF(M-ACHBLF),and 40 with advanced stage ACHBLF(A-ACHBLF).Tβ4 promoter methylation status in peripheral blood mononuclear cells(PBMCs)was measured by methylation-specific polymerase chain reaction,and mRNA was detected by quantitative real-time polymerase chain reaction.Results:Methylation frequency of Tβ4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF,CHB or HCs.However,expression of Tβ4 mRNA showed the opposite trend.In patients with ACHBLF,Tβ4 promoter methylation status correlated negatively with mRNA levels.The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group.Also,Tβ4 promoter methylation frequency was lower in survivors than in non-survivors.When used to predict the 1-,2-,and 3-month incidence of ACHBLF,Tβ4 methylation status was better than the model for end-stage liver disease(MELD)score.The predictive value of Tβ4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF,but not for A-ACHBLF.Conclusions:Tβ4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.展开更多
To obtain a kind of convenient oral dosage form of protein, which can be fully absorbed and is efficient and safe, the thymosin-loaded PLA（polylactic acid） microspheres are prepared by the emulsification- solvent ev...To obtain a kind of convenient oral dosage form of protein, which can be fully absorbed and is efficient and safe, the thymosin-loaded PLA（polylactic acid） microspheres are prepared by the emulsification- solvent evaporation method and the orthogonal design is used to optimize the technology of preparation. The form of the medicament microspheres of thymosin are proved by differential thermal analysis （DTA）. The drug content is determined by the Lowry method, and the package ratio of medicament microspheres of thymosin and drug release in vitro are calculated. The results show that the average diameter and encapsulation efficiency of the product prepared according to the optimized formulation are 13. 8 μm and 80. 7%, respectively. The in vitro release behavior within 12 h can be described by the Higuchi equation with T1/2 = 295 rain. There are no significant changes in size distribution and residual drug contents after being stored at 25℃ and 40 ℃ for 90 d, respectively. Due to the fact that its thymosin content and package ratio meet the requirement, and its releasing half life is long, the thymosin-loaded PLA microsohere has a favorable application future.展开更多
INTRODUCTIONChronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse sequelae ,such as cirrhosis and hepatocellular carcinoma .The World Health Organiz...INTRODUCTIONChronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse sequelae ,such as cirrhosis and hepatocellular carcinoma .The World Health Organization estimates that HBV has infected mord than 350 million people worldwide ,and up to 20% of them will become chromic carricrs and will be at significant risk for cirrhosis and HCC .The ultimate goal of the therapy for chronic hepatitis B is to prevent progression to cirrhosis and to prevent development of HCC.展开更多
基金supported by grants from the Key Project of the Chinese Ministry of Science and Technology(2017ZX102022022)the National Natural Science Foundation of China(81970522)the Key Research and Development Project of Shandong Province(2019GSF108023).
文摘Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver failure is not clear.This study aimed to determine Tβ4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.Methods:The study recruited 115 patients with ACHBLF,80 with acute-on-chronic hepatitis B pre-liver failure(pre-ACHBLF),and 86 with chronic hepatitis B(CHB).In addition,there were 36 healthy controls(HCs)from the Department of Hepatology,Qilu Hospital of Shandong University.The 115 patients with ACHBLF were divided into three subgroups:33 with early stage ACHBLF(E-ACHBLF),42 with mid-stage ACHBLF(M-ACHBLF),and 40 with advanced stage ACHBLF(A-ACHBLF).Tβ4 promoter methylation status in peripheral blood mononuclear cells(PBMCs)was measured by methylation-specific polymerase chain reaction,and mRNA was detected by quantitative real-time polymerase chain reaction.Results:Methylation frequency of Tβ4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF,CHB or HCs.However,expression of Tβ4 mRNA showed the opposite trend.In patients with ACHBLF,Tβ4 promoter methylation status correlated negatively with mRNA levels.The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group.Also,Tβ4 promoter methylation frequency was lower in survivors than in non-survivors.When used to predict the 1-,2-,and 3-month incidence of ACHBLF,Tβ4 methylation status was better than the model for end-stage liver disease(MELD)score.The predictive value of Tβ4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF,but not for A-ACHBLF.Conclusions:Tβ4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.
文摘To obtain a kind of convenient oral dosage form of protein, which can be fully absorbed and is efficient and safe, the thymosin-loaded PLA（polylactic acid） microspheres are prepared by the emulsification- solvent evaporation method and the orthogonal design is used to optimize the technology of preparation. The form of the medicament microspheres of thymosin are proved by differential thermal analysis （DTA）. The drug content is determined by the Lowry method, and the package ratio of medicament microspheres of thymosin and drug release in vitro are calculated. The results show that the average diameter and encapsulation efficiency of the product prepared according to the optimized formulation are 13. 8 μm and 80. 7%, respectively. The in vitro release behavior within 12 h can be described by the Higuchi equation with T1/2 = 295 rain. There are no significant changes in size distribution and residual drug contents after being stored at 25℃ and 40 ℃ for 90 d, respectively. Due to the fact that its thymosin content and package ratio meet the requirement, and its releasing half life is long, the thymosin-loaded PLA microsohere has a favorable application future.
文摘INTRODUCTIONChronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse sequelae ,such as cirrhosis and hepatocellular carcinoma .The World Health Organization estimates that HBV has infected mord than 350 million people worldwide ,and up to 20% of them will become chromic carricrs and will be at significant risk for cirrhosis and HCC .The ultimate goal of the therapy for chronic hepatitis B is to prevent progression to cirrhosis and to prevent development of HCC.
