Exosomal miR-34s panel as potential novel diagnostic and prognostic biomarker in patients with hepatoblastoma.

PURPOSE: The aim of this study is to identify the diagnostic values of serum exosomal miRNA-34s of patients with HB in a large Asian group and explore the prognostic value of the exosomal miRNA-34s panel compared with other risk factors. METHODS: We retrospectively reviewed 89 children with HB. Among these patients, 63 patients were included as training group to build the diagnostic model for HB. 26 patients were defined as the validation group. The expressions of miRNA-34s were detected by real-time PCR. The comparison of diagnostic and prognostic performance of serum exosomal miRNA-34s was measured using the area under ROC curve (AUC). RESULTS: For patients in the training group, expression of miRNA-34a, miRNA-34b and miRNA-34c was significantly lower in patients with HB compared with control group in serum exosomes. Between HB training group and the control group, exosomal miRNA-34a, miRNA-34b and miRNA-34c had no significant differences compared with the AFP level in diagnosing HB. The performance of the exosomal miRNA-34s panel in differentiating the HB training group from the control group was superior to the AFP level. The value of the exosomal miRNA-34s panel in predicting prognosis of patients with HB was superior to other risk factors in both training group and validation group. CONCLUSIONS: In this study, we found that the expression of exosomal miRNA-34a, miRNA-34b and miRNA-34c was significantly lower in patients with HB compared with the control group, and we confirmed the exosomal miRNA-34s panel could be defined as a diagnostic and prognostic biomarker for patients with HB. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Retrospective Study.

Hedgehog signaling pathway regulates liver regeneration in the Fah-/- knockout mice model xenografted by human hepatocytes.

BACKGROUND: The aim of this study is to evaluates the hypothesis that Hh pathway activation occurs in the Fah-/- Nod/Scid mice model and plays a role in regulating liver regeneration after functional human hepatocytes xenograft. METHODS: Fah-/- Nod/Scid mice were established in Shandong Cancer Hospital affiliated to Shandong University. Xeno-regeneration of Fah-/- Nod/Scid mice livers was then transplanted by human hepatocytes. Hh signaling pathway associated factors were detected by RT-PCR and western blot. All statistical calculations were carried out using the SPSS.16.0 software. RESULTS: Fah-/- mice were healthy and reproduced normally while treated with NTBC. NTBC-OFF Fah-/- mice with HHT gradually gained weight by six weeks after human hepatocyte transplantation. NTBC-OFF Fah-/- mice causes a progressive increase in ALT, AST, GGT and AP, which were used to monitor hepatocyte inflammation. However, liver function in NTBC-OFF Fah Fah-/- mice with HHT returned to normal. Hedgehog pathway activation and Hh-target genes were enhanced follows human hepatocytes transplantation which indicated liver regeneration associated closely with Hh signaling pathway. Moreover, Hh signaling was inhibited by cyclopamine after HHT. CONCLUSIONS: The current study provides novel evidence that Hedgehog signaling pathway regulation is required for optimal regeneration of NTBC OFF Fah-/- mice with HHT.

Combined low miR-34s are associated with unfavorable prognosis in children with hepatoblastoma: A Chinese population-based study.

PURPOSE: The aim of this study is to identify the association between miR-34's family and the prognosis of HB in a large Asian cohort and to explore the interaction of miR-34 with other independent risk factors in the process of affecting prognosis of HB. METHODS: We retrospectively reviewed 78 children with HB (36 female, 42 male) managed in our institutions between 2007 and 2014. The expression of miR-34 was detected by real-time PCR. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: For the entire cohort of 76 patients, The normalized real-time PCR results showed that all three miRNAs were deregulated in tumor tissues as compared with corresponding noncancerous tissue samples. Descriptive survival statistics and Kaplan-Meier curves suggested that AFP levels, metastases, vascular invasion, PRETEXT stage and miR-34 had prognostic significance in this relatively selected cohort. After that we made miR-34 into different combinations. The results demonstrated that combined low miR-34a and miR-34b (HR:2.212, P=0.016), combined low miR-34a and miR-34c (HR:1.984, P=0.025) and combined low miR-34a, miR-34b and miR-34c (HR:3.569, P=0.001) were independent prognostic factors of HB. We further conduct stratified analysis of the impact of other identified risk factors on the combined low of three miR-34. CONCLUSIONS: In this study, we found that miR-34s were deregulated in tumor tissues compared with corresponding noncancerous tissue samples. We also confirmed that combined low miR-34 is an independent prognostic factor related with HB.

[Replantation of fingertip amputation in lack of availability of intravenous anastomosis].

OBJECTIVE: To discuss the replantation of fingertip amputation in lack of availability of intravenous anastomosis. METHODS: From November 2009 to November 2010, 86 patients (104 fingers) with fingertip amputation were treated with replantatioin, including 64 males and 22 females, with an average age of 26 years ranging from 2 to 64 years. The time from injury to therapy was from 30 min to 12 h, time of broken finger ischemia was from 2.5 to 12 h. Preoperative examination showed no obvious abnormalities. Four different replantation methods were selectively applied to these 104 amputated fingertips of 86 cases: (1) replantation with anastomosis of single or bilateral proper digital artery in 37 fingers; (2) replantation with arteriovenous bypass in 27 fingers; (3) replantation with exclusive anastomosis of digital artery in 24 fingers; (4) replantation with removing the palmar pocket method in 16 fingers. RESULTS: One hundred and two of 104 amputated fingertips were survived. Among these survived fingers,75 cases (92 fingers) were followed-up for 6 to 24 months. According to the assessment standard of Chinese Medical Association of Hand Surgery, the results were excellent in 52 cases, good in 19, poor in 4. CONCLUSION: It benefits to expand the indications and improve the survival rate of replantation of fingertip amputation with the correct choice of different replantation methods according to the injury situation of the broken fingertip artery after debridement under the microscope.