Objective:To establish a noninvasive prediction model for liver fibrosis in chronic hepatitis B (CHB) virus infection patients with alanine aminotransferase (ALT) less than upper limit of normal level.Methods:A total of 183 CHB patients with ALT <40 U/L admitted in the First Affiliated of Wenzhou Medical University from January 2014 to September 2017 were enrolled. There were 149 cases of non-marked liver fibrosis (F0-F2) and 34 cases of marked liver fibrosis (F3-F6) according to the Ishak scoring system. The clinical data, liver stiffness measurement (LSM), liver ultrasound imaging, serum biochemical features and hepatitis B virus related indexes of patients were retrospectively analyzed. The independent predictors of liver fibrosis were screened and a prediction model was constructed based on the results of multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was applied to evaluate the established model and other indicators in predicting liver fibrosis.Results:Multivariate logistic regression analysis showed that LSM ( OR=1.327, 95% CI 1.149-1.531), liver ultrasound scores ( OR=6.610, 95% CI 2.704-16.156) were independent predictors of liver fibrosis. The area under ROC curve(AUC)of the established model (LU) in predicting liver fibrosis was 0.873(95% CI 0.799-0.947), which was significantly greater than that of the ultrasound score, LSM, FIB-4, APRI and GPR (AUC=0.790, 0.804, 0.654, 0.673 and 0.770; Z=3.394, 1.982, 2.077, 3.168 and 2.165, all P<0.05 or <0.01). With the cut-off value of -1.787, the sensitivity and specificity of LU model were 85.3% and 77.2%, respectively. Conclusion:The established model (LU) can effectively predict the liver fibrosis in CHB patients with ALT less than upper limit of normal.

Objective To reveal the mechanism of action of AS-Ⅳ on HepG2 cells based on molecular dynamics simulation and experimental evaluation. Methods We constructed a "drug-disease" network pharmacological map, analyzed the core genes of astragaloside Ⅳ (AS-Ⅳ) in HCC, screened key signaling pathways, and established a "drug-target" molecular dynamics model. In vitro assay was used to detect migration, proliferation and invasion abilities. Flow cytometry and qRT-PCR were used to detect the effect of AS-Ⅳ on the cell cycle and apoptosis, and the expression of core gene of HepG2. Results The core target of AS-Ⅳ acting on HCC was VEGFA. Compared with the control group, the high concentration of AS-Ⅳ significantly inhibited the migration, invasion and proliferation of HepG2 cells, blocked the metastasis of HepG2 cells from G₁ to G₂ phase, promoted their apoptosis, down-regulated VEGFA expression and up-regulated TGF-β1 expression. Conclusion AS-Ⅳ may inhibit the proliferation of hepatocellular carcinoma cells through multi-target and multi-pathway.

OBJECTIVETo evaluate the bioequivalence of orally disintegrating tablets of pentoxyverine citrate (tested preparation) in healthy male volunteers.

METHODSA single oral dose of the tested and reference preparations at 25 mg were given to 20 healthy volunteers in a randomized two-period cross-over design. Plasma pentoxyverine citrate concentrations were determined by HPLC-MS/ESI+ method. The pharmacokinetic parameters were calculated and the bioequivalence of the two preparations were evaluated using DAS program.

RESULTSThe Tmax, Cmax, AUC0 15 and AUC0infinity of tested and reference preparations were 1.62-/+0.75 h and 2.52-/+1.21 h, 62.28-/+33.06 microg/L and 59.72-/+33.25 microg/L, 234.44-/+130.01 microg.h.L(-1) and 228.77-/+129.24 microg.h.L(-1), 246.80-/+136.19 microg.h.L(-1) and 244.11-/+140.73 microg.h.L(-1), respectively. The 90% confidence interval of C(max), AUC0 15 and AUC0infinity of tested preparations were 81.4%-138.4%, 86.0%-123.3% and 86.5%-121.2%, respectively.

CONCLUSIONThe tested and reference preparations are bioequivalent.

Adult ; Area Under Curve ; Biological Availability ; Citric Acid ; administration & dosage ; pharmacokinetics ; Cross-Over Studies ; Cyclopentanes ; administration & dosage ; pharmacokinetics ; Humans ; Male ; Tablets ; Therapeutic Equivalency ; Young Adult