Objective To explore the effect and mechanism of chemokine CX3CL1 on mouse liver fibrosis model.Methods C57BL/6 mice were randomly divided into CCl-4 model group and normal control group with 8 animals in each group.The model group was injected with 10%CCl-4 intra peritoneally for 6 weeks.After 6 weeks,the mice were sacrificed,and the pathological changes of the mouse liver were observed by HE staining.The level of CX3CL1 in peripheral blood of the mice was measured,and the expression level of CX3CL1 mRNA in the liver tis-sue of the mice was detected.In addition,in order to explore the mechanism of CX3CL1,the level of IFN-γ in mouse serum was detected as well.Results After the 6-week modeling,the liver pathology microscopy showed a successful modeling of liver fibrosis.The serum CX3CL1 level and liver tissue CX3CL1 expression in the model group were found to be significantly up-regulated,which suggested a potential impact on the pathogenesis of liver fi-brosis.In addition,the level of IFN-γ in the serum of mice in the model group increased significantly.Conclusions CX3CL1 is related to liver fibrosis in mice,and its mechanism might be explained by promoting the production of IFN-γ so to prevent liver fibrosis.

BACKGROUND: Osteoporosis is a systemic bone disease characterized by decreased bone density and deterioration of bone microstructure, leading to an increased probability of fragility fractures. Once segmental bone defect occurs, it is easy to cause delayed union and nonunion. METHODS: The aim of this study is to investigate the efficacy of extracorporeal shock wave (ESW) and teriparatideloaded hydrogel (T-Gel) combined strategy on the cell activity and differentiation of osteoporosis derived bone marrow mesenchymal stem cells (OP-BMSCs) in vitro and bone regeneration in osteoporotic segmental bone defects in vivo. RESULTS: In vitro, the strategy of combining ESW and T-Gel significantly enhanced OP-BMSCs proliferation, survival, migration, and osteogenic differentiation by up-regulating the alkaline phosphatase activity, mineralization, and expression of runt-related transcription factor-2, type I collagen, osteocalcin, and osteopontin. In the segmental bone defect models of osteoporotic rabbits, MicroCT evaluation and histological observation demonstrated this ESW-combined with T-Gel injection significantly induced bone healing by enhancing the osteogenic activity of the local microenvironment in osteoporotic defects. CONCLUSION In conclusion, ESW-combined with T-Gel injection could regulate the poor osteogenic microenvironment in osteoporotic defects and show potential for enhancing fragility fractures healing.

Objective To study interleukin-23 (IL-23) levels in serum and dendritic cells of acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B (CHB) and to explore its relationship with the prognosis.Methods Peripheral blood mononuclear cells and serum were collected from 40 ACLF patients with CHB (including survival group 27 cases and non-survival group 13 cases) and 26 healthy controls.Monocytes were induced to immature dendritic cell in vitro and TNF-α was added to induce dendritic cell maturation.IL-23 mRNA of dendritic cells was detected by real time polymerase chain reaction (PCR), and serum IL-23 level was measured by enzyme-linked immuno sorbent assay (ELISA).Differences among the parameters with normal distribution were compared using t test, those with non-normal distribution were compared using non-parametric Mann-Whitney U-test, and the relationship between two variables was assessed by Spearman′s rank correlation.Results International normalized rate (INR) and model for end-stage liver disense (MELD) scores in non-survival group of ACLF were higher than those in survival group (INR: 2.32 vs 1.64, U=69.00, P=0.002 2;MELD:36 vs 30, U=64.50, P=0.001 4).However, there were no significant differences between two groups at gender, age, alanin aminotransferase (ALT), aspartate aminotrans ferase (AST), bilirubin, creatinine, hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and serum IL-23.IL-23 mRNA level in dendritic cells at baseline in non-survival group of ACLF was significantly higher than that in survival group (76 vs 43, U=71.50, P=0.002 8).After treatment, serum IL-23 was significantly declined in survival group ([160±75] ng/L vs [91±49] ng/L, t=4.012, P=0.000 2), but not in non-survival group.Significant positive correlation was observed between IL-23 mRNA level in dendritic cells and MELD score at baseline (r=0.7198,P<0.01).Conclusions Persistent high serum IL-23 level suggests poor prognosis in ACLF patients with CHB.IL-23 mRNA expression in dendritic cells has good consistency with MELD score and the patients with high IL-23 mRNA expression has poor outcome.

BACKGROUND/AIMS: To investigate the role of selected serum microRNA (miRNA) levels as potential noninvasive biomarkers for differentiating S0–S2 (early fibrosis) from S3–S4 (late fibrosis) in patients with a chronic hepatitis B virus (HBV) infection. METHODS: One hundred twenty-three treatment-naive patients with a chronic HBV infection who underwent a liver biopsy were enrolled in this study. The levels of selected miRNAs were measured using a real-time quantitative polymerase chain reaction assay. A logistic regression analysis was performed to assess factors associated with fibrosis progression. Receiver operating characteristic (ROC) curve and discriminant analyses validated these the ability of these predicted variables to discriminate S0–S2 from S3–S4. RESULTS: Serum miR-29, miR-143, miR-223, miR-21, and miR-374 levels were significantly downregulated as fibrosis progressed from S0–S2 to S3–S4 (p < 0.05), but not miR-16. The multivariate logistic regression analysis identified a panel of three miRNAs and platelets that were associated with a high diagnostic accuracy in discriminating S0–S2 from S3–S4, with an area under the curve of 0.936. CONCLUSIONS: The levels of the studied miRNAs, with the exception of miR-16, varied with fibrosis progression. A panel was identified that was capable of discriminating S0–S2 from S3–S4, indicating that serum miRNA levels could serve as a potential noninvasive biomarker of fibrosis progression.
Biomarkers ; Biopsy ; Early Diagnosis* ; Fibrosis ; Hepatitis B virus ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Liver Cirrhosis* ; Liver* ; Logistic Models ; MicroRNAs* ; Polymerase Chain Reaction ; ROC Curve

Objective To assess the clinical diagnostic performance of liver stiffness measurement (LSM) and aspartate transaminase (AST)-to-platelet (PLT) ratio index (APRI) for liver fibrosis in chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) less than or equal to five times of the upper limit of normal (≤5×upper limit of normal [ULN]).Methods FibroScan,blood routine and liver function test were conducted at the day or one day before liver biopsy in 383 CHB patients with ALT≤5 × ULN.The Scheuer scoring system was used for liver histologic assessment.APRI was calculated.Based on the results of liver pathology,the areas under receiver operating characteristic curve (AUC) of LSM and APRI for diagnosis of liver fibrosis stage were compared.Results The median LSM were 5.10 kPa for S0 fibrosis stage,5.20 kPa for S1,6.60 kPa for S2,10.10 kPa for S3,and 18.80 kPa for S4.The median APRI values were 0.36,0.38,0.63,0.61 and 1.27,respectively.The AUC of LSM were 0.817 for ≥S2,0.891 for ≥S3 and 0.913 for ≥S4.And the AUC of APRI were 0.717 for ≥S2,0.711 for ≥S3 and 0.746 for ≥S4.The cut-offs of LSM values were 6.8 kPa for ≥S2,8.7 kPa for ≥S3,and 10.9 kPa for ≥S4.Conclusion LSM can accurately assess the degree of liver fibrosis in CHB patients with ALT ≤5 × ULN,which is superior to APRI in clinical utility.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

The T helper cell 17 (Th17) has important relationship with liver failure caused by hepatitis B virus (HBV).Some studies found that mature,differentiation and proliferation of Th17 cells have a close relationship with interleukin 23,newly discovered in recent years,which function of immune and regulatory mechanism in chronic hepatitis B patients is still unclear.In our country,the main cause of liver failure is hepatitis viruses (mainly HBV),thus the study of immune pathogenesis that why acute exacerbation or liver failure happens in chronic hepatitis B patients has a realistic meaning for improving the prognosis of chronic hepatitis B.

Objective To investigate the frequencies of circulating dendritic cell (DC) subsets and the function of monocyte-derived dendritic cells in patients with hepatitis B-related acute-on-chronic liver failure.Methods Peripheral blood was collected from hepatitis B-related acute-on-chronic liver failure patients (ACLF,n =40) and chronic hepatitis B (CHB,n =40) as well as normal controls (NCs,n =20).Circulating myeloid dendritic cell (Mdc) and plasmic dendritic cell (pDC) frequencies in peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometric analysis.Purified monocytes were isolated by combination of Histopaque-1.077 and CD14 Microbeads.Monocyte-derived dendritic cells (MoDCs) generated in vitro in the presence of interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor upon activation by poly I:C.Costimulatory molecule expression and allostimulatory mixed lymphocyte reaction (AMLR) of MoDCs were detected in patients with hepatitis B-related ACLF.Results The number of circulating mDC decreased only in patients with hepatitis B-related ACLF compared with that in normal controls.However,pDC numbers decreased in both CHB and ACLF patients.We observed a further decrease the pDC numbers in ACLF compared to CHB patients without statistical significance (P ＞ 0.05).MoDC from ACLF patients showed lower expression of costimulatory molecules CD80,CD86 and the mature marker CD83,as well as MHC Ⅱ molecule (HLA-DR) compared to CHB and NC group.Interestingly,MoDC impaired allostimulatory mixed lymphocyte reaction from ACLF patients compared to those in CHB patients and NCs.Conclusions Patients with hepatitis B-related ACLF have a significantly lower expression of surface markers and impaired AMLR of MoDC,as well as decreased number of circulating mDC and pDC,which may be partially related to HBV disease progression in these patients.

Interleukin 23 (IL-23) is a recently discovered cytokine, and growing evidence suggests that IL-23 plays an important role in the development and progression of autoimmune diseases and inflammatory diseases. In recent years, certain research advances in association between IL-23 and liver diseases have been achieved at home and abroad. General features and biological characteristics of IL-23 are described, and its role in the development and progression of diseases such as hepatitis B, hepatitis C, and hepatocellular carcinoma is reviewed here, so that clinicians will have a deeper understanding of the effect of IL-23 in liver diseases and provide optimized therapies for patients with liver diseases.

Liver failure is a threat to human health. The survival of patients has been increased with the improvement in both diagnosis and treatment. Several major advances in the diagnosis and treatment of liver failure have been made in recent years, as follows: the EASL-defined diagnostic criteria for acute-on-chronic liver failure have been validated in the Eastern population, defining more accurately those who need liver transplantation; the diagnostic criteria for acute kidney injury in patients with liver dysfunction have been updated, and the new criteria are able to discover patients with kidney injury earlier; the neurohumoral regulation mechanism and factors predicting the efficacy of vasoactive agents in hepatorenal syndrome have been gradually determined; the concepts of use of granulocyte-colony stimulating factor and β-receptor blocker in liver failure are undergoing fundamental changes.