Mechanism of microRNA-223-3p inhibiting hepatic stellate cell activation by targeting microtubule-associated protein 1B / 临床肝胆病杂志

ObjectiveTo investigate the effect of microRNA-223-3p （miR-223-3p） on hepatic stellate cell （HSC） activation and its mechanism. MethodsHuman HSC LX2 cells were selected for the study， and LX2 cells were stimulated by TGF-β to establish a model of HSC activation； quantitative real-time PCR was used to measure the change in the expression level of miR-223-3p during HSC activation. After LX2 cells were transfected with miR-223-3p mimic， quantitative real-time PCR， Western blot， and immunofluorescence assay were used to clarify the regulatory effect of miR-223-3p on HSC activation， and dual-luciferase reporter assay was used to verify the association between miR-223-3p and the target gene MAP1B. After LX2 cells were transfected with MAP1B siRNA， Western blot was used to clarify the influence of inhibiting MAP1B expression on HSC activation； after LX2 cells were transfected with miR-223-3p， quantitative real-time PCR and Western blot were used to verify the regulatory effect of miR-223-3p on MAP1B. The independent-samples t test was used for comparison of continuous data between two groups. ResultsHSC in the activated state had a significant reduction in the expression level of miR-223-3p compared with those in the resting state （t=9.12， P<0.001）. Overexpression of miR-223-3p inhibited the mRNA and protein expression levels of the markers for HSC activation alpha-smooth muscle actin and collagen type Ⅰ （mRNA expression： t=8.35 and 12.23， both P<0.01； protein expression： t=16.24 and 20.90， both P<0.001）. The dual-luciferase reporter assay confirmed that MAP1B was a potential target gene of miR-223-3p. Compared with the control group， LX2 cells with miR-223-3p overexpression had significant reductions in the mRNA and protein expression levels of MAP1B （mRNA expression： t=5.95， P<0.01； protein expression： t=11.12， P<0.001）. ConclusionThis study shows that miR-223-3p can inhibit HSC activation by targeting MAP1B.

Arthroscopic treatment for patients with borderline developmental dysplasia of the hip and cam-type femoroacetabular impingement syndrome / 中华骨科杂志

Objective:To evaluate the clinical outcomes of patients with borderline developmental dysplasia of the hip (BDDH) and cam-type femoroacetabular impingement syndrome (FAIS) after hip arthroscopy.Methods:Data were retrospectively reviewed for patients with BDDH and cam-type FAIS who underwent hip arthroscopy surgery from June 2017 to December 2019. A total of 32 patients were enrolled, with a mean age of 36.13±8.67 years (range, 20-50 years), including 15 males and 17 females. The preoperative lateral center-edge angle was 22.3°±1.6° (range 20.1°-24.7°), while the preoperative α angle was 64.1°±4.6° (range, 56.0°-69.8°). All patients were treated with arthroscopic limited acetabular plasty, labral repair, femoral osteoplasty, and capsular plication after excluding from external hip diseases by ultrasound-guided hip blocking test. The visual analogue scale (VAS), modified Harris Hip Scores (mHHS) and International Hip Outcome Tool-12 (iHOT-12) scores were used to evaluate the clinical effects.Results:All patients were followed up, and the mean follow-up time was 2.5±0.8 years (range, 2.0-4.7 years). The VAS score decreased from 6.07±1.56 to 1.96±0.92 at 1 year and to 1.86±1.01 at 2 years after operation ( F=112.64, P<0.001); the mHHS score increased from 53.87±13.04 to 86.12±8.64 at 1 year and to 88.71±8.15 at 2 years after operation ( F=101.70, P<0.001); the iHOT-12 score was improved from 40.00±7.33 to 76.27±9.50 at 1 year and to 78.67±10.31 at 2 years after operation ( F=134.91, P<0.001). The α angle improved to 40.27°±4.52° (range, 34.8°-49.7°) with significant difference ( t=9.24, P<0.001). Conclusion:Hip arthroscopy can achieve satisfied short-term outcomes in treating BDDH and cam-type FAIS with few complications and less trauma.

Short-term mortality of acute-on-chronic liver failure in patients with chronic hepatitis B following lamivudine versus entecavir antiviral treatment / 中国感染与化疗杂志

Objective To compare the short-term mortality of acute-on-chronic liver failure (ACLF) in patients with chronic hepatitis B following lamivudine versus entecavir antiviral treatment. Methods All chronic hepatitis B patients associated with ACLF were included in this analysis if they were treated with lamivudine or entecavirat the Department of Infectious Diseases, Huashan Hospital, Fudan University, from August 2010 to August 2016. Results A total of 56 patients were included (36 in lamivudine group and 20 in entecavir group). The 7-day, 14-day and 28-day survival rate was 94％, 72％ and 64％ in lamivudine group, and 70％, 65％ and 65％ in entecavir group. Lamivudine group showed significantly lower 7-day mortality than entecavir group, but no significant difference in 14-day and 28-day mortality. Subgroup analysis did not show significant difference in 28-day mortality between the two groups either in model for end-stage liver disease (MELD)≤30 patients or in ACLF grade 0-1 patients. Lamivudine treatment was associated with significantly lower 7-day mortality than entecavir in cirrhosis patients, but no significant difference in 14-day and 28-day mortality. Conclusions Lamivudine treatment is associated with significantly higher 7-day survival rate than entecavir. However, the short-term (within 28 days) mortality of acute on chronic liver failure in chronic hepatitis B patients is similar between lamivudine and entecavir treatment. Lamivudine is also appropriate for the patients with cirrhosis or waiting for liver transplantation.

Serum MicroRNA Levels as a Noninvasive Diagnostic Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Liver Fibrosis

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.

Interleukin-23 levels in serum and dendritic cells and its relationship with prognosis of acute-on-chronic liver failure patients with chronic hepatitis B / 中华传染病杂志

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.