Osteosarcoma is the most common primary malignant tumor of bone derived from osteoblasts, which is a noteworthy threat to the health of children and adolescents. In this study, we found that MCM8 has significantly higher expression level in osteosarcoma tissues in comparison with normal tissues, which was also correlated with more advanced tumor grade and pathological stage. In agreement with the role of MCM proteins as indicators of cell proliferation, knockdown/overexpression of MCM8 inhibited/promoted osteosarcoma cell proliferation in vitro and tumor growth in vivo. Also, MCM8 knockdown/overexpression was also significantly associated with the promotion/inhibition of cell apoptosis and suppression/promotion of cell migration. More importantly, mechanistic study identified CTGF as a potential downstream target of MCM8, silencing of which could enhance the regulatory effects of MCM8 knockdown and alleviate the effects of MCM8 overexpression on osteosarcoma development. In summary, MCM8/CTGF axis was revealed as critical participant in the development and progression of osteosarcoma and MCM8 may be a promising therapeutic target for osteosarcoma treatment.

Background and Aims Natural killer (NK) cells play an important role in biliary atresia (BA) pathogenesis; human poliovirus receptor (PVR) is an important NK‐cell modulator. Here, we explored the role of PVR in BA pathogenesis. Methods Poliovirus receptor expression and NK cell‐associated genes were detected in human BA samples and a rotavirus‐induced BA mouse model using quantitative PCR and immunofluorescence staining. Chemically modified small interfering RNA silenced PVR expression in the BA model, and its effects on the population and function of intrahepatic NK cells were investigated using flow cytometry (FCM). The effects of PVR overexpression and knockdown on proliferation, apoptosis and NK‐cell‐mediated lysis of cultured human cholangiocytes were analysed using FCM and cell viability assays. Serum PVR, high‐mobility group box 1 (HMGB1), and interleukin‐1beta (IL‐1beta) levels were measured in a cohort of 50 patients using ELISA. Results Poliovirus receptor expression was upregulated in the biliary epithelium of BA patients and BA model and was positively correlated with the population and activation of intrahepatic NK cells. Silencing of PVR expression impaired the cytotoxicity of NK cells, reduced inflammation and protected mice from rotavirus‐induced BA. Activation of the TLR3‐IRF3 signalling pathway induced PVR expression in cultured cholangiocytes. PVR overexpression promoted proliferation and inhibited the apoptosis of cholangiocytes but exacerbated NK cell‐mediated cholangiocyte lysis. Serum PVR levels were elevated in BA patients and were positively correlated with HMGB1 and IL‐1beta levels. Conclusions Poliovirus receptor contributes to BA pathogenesis by regulating NK cell‐mediated bile duct injury; PVR has the value as a biomarker of BA.

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Objectives: To identify factors associated with outcomes of Kasai portoenterostomy (KPE), and predictors of 2- and 5- year native liver survival (NLS) for infants achieved jaundice clearance (JC) within 6 months of KPE. Methods: This retrospective cohort study was conducted on 151 patients with type III biliary atresia (BA) who underwent KPE at our center. Univariate analysis and logistic regression analyses were performed to identify factors associated with NLS in infants achieved JC. Kaplan-Meier curves and log-rank tests were used to estimate the NLS, and the Cox proportional hazards regression model identified variables most associated with 2- and 5- year NLS at 6 months post-KPE. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of these factors. Results: The 2- and 5- year NLS of infants achieved JC at 3 months post-KPE were not different from those achieved JC earlier. Operation age and total bile acid (TBA) were factors associated with JC. For infants who have achieved JC, DB was the only factor associated with 2-year NLS, the AUC was 0.872, the cutoff value was 14 μmol/L; ALB and DB were factors associated with 5-year NLS, the AUCs were 0.894 and 0.95, and the cutoff values were 39 g/L and 14 μmol/L, respectively. Conclusions: NLS should be estimated at 6 months post-KPE. Preoperative factors are not predictive of NLS. For infants cleared jaundice, DB and ALB can predict NLS with good performance.