Objective To investigate the feasibility of VTQ value of spleen in noninvasive assessment of staging of liver fibrosis in patients with hepatitis B.Methods VTQ values of spleen were measured in 56 patients with hepatitis B by using ARFI technique and liver biopsy was performed.The patients were then grouped according to the stages of liver fibrosis stage.The results were analyzed by the intergroup comparison,Pearson Correlation analysis,and receiver operating characteristic curve (ROC curve).Results There was positive association of the VTQ value with the stages of liver fibrosis,whose correlation coefficient was 0.83 (P ＜ 0.05);There was no significant difference between the spleen VTQ value and the liver fibrosis S1 and SO (P ＞ 0.05),whereas there were significant differences among other groups (P ＜ 0.05).The area under the ROC curve was 0.95,the cut-off value was 2.79m/s,and the specificity and sensitivity were 81.8％ and 91.7％ respectively.Conclusions The VTQ value measured by ARFI technique has a better value in noninvasive diagnosis of stages of hepatitis B liver fibrosis.

Objective:To present evidence for the pathogenetic role of allergic factor,histamine,in type I allergy for induction of liver damage.Methods:Three groups of rabbits were fed normally and injected (iv) daily with 0, 0.04 or 0.08 ?g/kg phosphohistamine, respectively, for days. The serum level of ALT and AST in each group rabbits was assayed dynamically during the treatment. After treatment for days, the tested rabbits were sacrificed for pathological examination of the liver tissues.Results:The serum level of both ALT and AST in rabbits treated with phosphohistamine increased significantly during the tested periods, compared to that of the control group. However, both ALT and AST levels showed no significant difference between 0.04 ?g/kg and 0.08 ?g/kg groups. Liver microscopic examination, pathological damage could be observed in the tested groups in a time-and dose-dependent manner under microscopic examination. No evident pathological change appeared in the control group.Conclusion:Liver damage could be induced by histamine dosage-and time-dependently. This pathological action of histamine, a type I allergic factor, presents further evidence for a direct role of type I allergy in the pathogenesis hepatic injury.

Objective:To further explore the relationship between Type Ⅰ hypersensitivity reaction and the mechanism of the viral hepatitis B through the research of soluble intercellular adhesion molecular-1(sICAM-1) and soluble vascular cell adhesion molecular-1(sVCAM-1) levels in serum in patients with viral hepatitis B related to Type Ⅰ hypersensitivity reaction and the damage of liver cells, and therefore, provide new theory for the perfection of the immunological mechanism of hepatitis B, especially acute hepatitis B.Methods:Serum sICAM-1 and sVCAM-1 levels were measured in 45 patients with viral hepatitis B and 15 normal cases using double antibody sandwich ELISA method. ALT and AST levels were studied using omni automatic biochemistry analyzer and its correlation with sICAM-1 and sVCAM-1 were observed.Results:The sICAM-1 and sVCAM-1 levels of 7 acute hepatitis B were significantly higher than that of the normal cases. ②The sICAM-1 and sVCAM-1 levels of 38 chronic hepatitis B were also significantly higher than that of the normal cases. ③The sICAM-1 and sVCAM-1 levels of 13 cases moderate chronic hepatitis B were significantly higher than that of 16 cases mild chronic hepatitis B. ④The sICAM-1 and sVCAM-1 levels of 9 serious chronic hepatitis B were significantly higher than that of the group of mild chronic hepatitis B. ⑤Levels of sICAM-1 were significantly positively correlated with serum ALT and AST. ⑥sVACM-1 levels were significantly positively correlated with serum ALT and AST. In conclusion, sICAM-1 and sVCAM-1 levels in patients with acute hepatitis B were most remarkably increased, and then serious chronic hepatitis B, moderate chronic hepatitis B, light chronic hepatitis B in sequence.Conclusion:Serum sICAM-1 and sVCAM-1 levels in patients with viral hepatitis B may reflect the damage of liver. ②Examination of serum sICAM-1 and sVCAM-1 levels in patients with hepatitis B can be used to judge the patient’s condition and to diagnose. ③As an important indication of the inflammatory in Type Ⅰ hypersensitivity reaction, sICAM-1 and sVCAM-1 may interfere the appearence of hepatitis B and the procedure of immunological damage of liver cells.

Objective:To explore the relationship between type I hypersensitivity reaction and the mechanism of the viral hepatitis B through the research of interleukin(IL-13 ) and prostaglandin(PGE1) levels in serum of patients with viral hepatitis B, and therefore, to provide new theory for the perfection of the immunological mechanism of hepatitis B, especially acute hepatitis B.Methods:Serum IL-13 and PGE1 levels were measured in 50 patients with viral hepatitis B and 35 normal cases using double antibody sandwich ELISA method. AST and ALT levels were studied using omni automatic biochemistry analyzer and those correlation with IL-13 and PGE1 were observed.Results:①The IL-13 and PGE1 levels of 10 acute hepatitis B were significantly higher than those of the normal cases; ②The IL-13 and PGE1 levels of 35 chronic hepatitis B were also significantly higher than those of the normal cases; ③The levels of IL-13 and PGE1 were significantly positively correlated with serum ALT and AST.Conclusion:IL-13 and PGE1 levels in patients with acute hepatitis B are most remarkably increased, and correlate with the damage of liver.

ObjectiveTo investigate the correlation of quality of life (QOL) with aspartate aminotransferase-to-platelet ratio index (APRI), liver stiffness measurement (LSM), and histopathology after entecavir antiviral therapy for patients with chronic hepatitis B liver fibrosis. MethodsA total of 95 patients who were diagnosed with chronic hepatitis B and liver fibrosis in The Affiliated Hospital of Yanbian University from October 2013 to March 2015 were enrolled, and all patients underwent entecavir antiviral therapy. Before treatment and at weeks 26, 52, and 78 of treatment, SF-36 scale was used to assess QOL, transient elastography was used to measure LSM, and serum APRI was measured. Among these patients, 31 underwent liver biopsy before treatment and at week 78 of treatment to observe the degree of inflammation and fibrosis, and QOL, APRI, LSM, and histopathology were analyzed before and after antiviral therapy. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data at different time points, and a Spearman correlation analysis was performed. ResultsThere was a tendency of increase in QOL after antiviral treatment, and there were significant differences in general health, role-physical, role-motional, bodily pain, social functioning, and vitality at different time points (H=25.084, 8.699, 12.293, 22.874, 12.079, and 10.403, all P＜0.05). There was a tendency of reduction in APRI, with a significant change after treatment (H=60.030, P＜0.01), and there was also a significant reduction in LSM after treatment (H=35.744, P＜0.01). APRI and LSM were negatively correlated with QOL (all P＜0.05). Among the patients who underwent liver biopsy, 22 achieved the improvement in histological inflammation after antiviral therapy, 15 achieved the improvement in fibrosis, 14 achieved the improvement in both inflammation and QOL, and 8 achieved the improvement in both fibrosis and QOL. ConclusionEntecavir antiviral therapy can improve the QOL of patients with chronic hepatitis B liver fibrosis, and reductions in APRI and LSM can predict the improvement in QOL in patients with chronic hepatitis B liver fibrosis. Improvement in histological inflammation and fibrosis have a certain effect on the improvement in QOL in patients with chronic hepatitis B liver fibrosis.

Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Objective To investigate the effect of carrimycin on the biological function of pancreatic cancer cells. Methods Pancreatic cancer cell lines MIA PaCa-2, BxPC-3, Panc-1, and PATU 8988 were treated with carrimycin at concentrations of 0 (control group), 2, 4, 8, and 16 μmol/L for 24, 48, and 72 hours. MTT assay was used to measure cell viability; EdU cell proliferation assay was used to observe the effect of carrimycin on DNA replication of pancreatic cancer cells; colony formation assay was used to observe the effect of carrimycin on the proliferation of pancreatic cancer cells; flow cytometry was used to analyze the effect of carrimycin on the cell cycle of pancreatic cancer cells; wound healing assay was used to analyze the effect of carrimycin on the migration of pancreatic cancer cells; Western blot was used to measure the expression levels of the markers such as epithelial-mesenchymal transition (EMT) and cell cycle-dependent protein kinase inhibitor 1A (P21); immunofluorescence assay were used to measure the expression levels of EMT-related markers. An analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the control group, carrimycin significantly inhibited the proliferative activity of MIA PaCa-2, BxPC-3, Panc-1, and PATU 8988 cells in a concentration- and time-dependent manner (all P < 0.01); carrimycin at concentrations of 4, 8, and 16 μmol/L significantly reduced DNA replication in MIA PaCa-2 cells ( t =2.378, 4.984, and 18.970, all P < 0.05) and BxPC-3 cells ( t =4.879, 6.089, and 9.521, all P < 0.01); after treatment with carrimycin at concentrations of 4, 8, and 16 μmol/L, colony formation ability significantly decreased with the increase in drug concentration in MIA PaCa-2 cells ( t =5.889, 11.240, and 15.840, all P < 0.001) and BxPC-3 cells ( t =6.717, 15.800, and 18.850, all P < 0.001). After treatment with carrimycin at concentrations of 4, 8, and 16 μmol/L, there was a significant increase in the proportion of cells in G1 phase in MIA PaCa-2 cells ( t =9.071, 12.280, and 19.360, all P < 0.0001) and BxPC-3 cells ( t =3.061, 4.962, and 8.868, all P < 0.05), and there was a significant reduction in the proportion of cells in S phase in MIA PaCa-2 cells ( t =2.316, 4.165, and 5.562, all P < 0.05) and BxPC-3 cells ( t =2.424, 3.264, and 5.744, all P < 0.05). Western blot further demonstrated that compared with the control group, the expression level of the cell cycle-related protein P21 gradually increased with the increase in the concentration of carrimycin in MIA PaCa-2 cells ( t =5.437, 6.453, and 8.799, all P < 0.001) and BxPC-3 cells ( t =25.130, 44.750, and 52.960, all P < 0.000 1). Wound healing assay showed that after treatment for 12, 24, and 48 hours, carrimycin at concentrations of 0, 4, 8, and 16 μmol/L significantly reduced the lateral migration of MIA PaCa-2 cells (all P < 0.05) and BxPC-3 cells (all P < 0.05). Western blot showed that compared with the control group, carrimycin treatment at concentrations of 4, 8, and 16 μmol/L significantly upregulated the expression of the epithelial marker E-cadherin in MIA PaCa-2 cells ( t =2.388, 4.899, and 5.819, all P < 0.05) and BxPC-3 cells ( t =2.533, 5.836, and 6.774, all P < 0.05) and significantly downregulated the expression of the interstitial marker Snail in MIA PaCa-2 cells ( t =12.440, 14.830, and 16.800, all P < 0.000 1) and BxPC-3 cells ( t=5.039, 5.893, and 7.725, all P < 0.01), and it also significantly downregulated the expression of the interstitial marker Vimentin in MIA PaCa-2 cells ( t =3.105, 7.752, and 11.200, all P < 0.05) and BxPC-3 cells ( t =2.555, 4.883, and 9.153, all P < 0.05). Conclusion Carrimycin can effectively inhibit the proliferation, migration, and EMT process of pancreatic cancer cells, thereby exerting an antitumor biological activity.

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.