IRF4 suppresses osteogenic differentiation of BM-MSCs by transcriptionally activating miR-636/DOCK9 axis

Abstract Objectives Osteoblasts are derived from Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs), which play an indispensable role in bone formation. In this study, the authors aim to investigate the role of IRF4 in the osteogenic differentiation of BM-MSCs and its potential molecular mechanism. Methods The authors used lentivirus infection to overexpress IRF4 in BM-MSCs. The expression of IRF4 and osteogenesis-related genes were detected by qRT-PCR and western blot analysis. The osteogenic differentiation of BM-MSCs was evaluated by Alkaline Phosphatase (ALP) activity, Alizarin red staining, and Alkaline Phosphatase (ALP) staining. Chromatin Immunoprecipitation (ChIP), Dual-Luciferase reporter assay and RNA Immunoprecipitation Assay were applied to confirm the regulatory mechanism between IRF4, miR-636 and DOCK9. Results The authors found IRF4 was down-regulated during the osteogenic differentiation of BM-MSCs, and IRF4 overexpression could decrease the osteogenic differentiation of BM-MSCs by specifically promoting the reduction of Alkaline Phosphatase (ALP) activity and down-regulating osteogenic indicators, including OCN, OPN, Runx2 and CollA1. Mechanistically, IRF4 activated microRNA-636 (miR-636) expression via binding to its promoter region, and Dedicator of Cytokinesis 9 (DOCK9) was identified as the target of miR-636 in BM-MSCs. Moreover, the damage in the capacity of osteogenic differentiation of BM-MSCs induced by IRF4 overexpression could be rescued by miR-636 inhibition. Conclusions In summary, this paper proposed that IRF4/miR-636/DOCK9 may be considered as targets for the treatment of osteoporosis (OP).

Predictive effects of a combined indicator in patients with hepatocellular carcinoma after thermal ablation

Aim: This study aimed to investigate the predictive power of the combination of Systemic Immune-Inflammation Index (SII) and albumin-bilirubin (ALBI) grade in prognosis outcomes of early-stage hepatocellular carcinoma (HCC) after thermal ablation. Materials and Methods: This retrospective study was reviewed and approved by our institutional review board, and written informed consent was obtained from each patient. According to the Milan criteria, a total of 405 treatment-naïve patients with clinicopathologically confirmed HCC were enrolled who subsequently underwent thermal ablation from 2011 to 2016. The outcomes of overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were statistically analyzed. Results: The median follow-up time of this study was 45.1 months (range, 1.3–83.2 months). After thermal ablation in patients with SII-ALBI Grades 1, 2, and 3, the cumulative 5-year OS rates were 81.7%, 63.2%, and 26.9%; the 5-year CSS rates were 82.4%, 67.5%, and 26.9%; and the 5-year RFS rates were 49.3%, 44.6%, and 25.3%, respectively (all P < 0.001). On multivariate Cox regression analyses, SII-ALBI was independently associated with the three outcomes after adjustment for various confounders (all P < 0.05). In addition, SII-ALBI played a predictive role in OS, CSS, and RFS for patients with negative alpha-fetoprotein (AFP) (P < 0.05). Compared with SII and ALBI, the AUCs for the prediction of OS and CSS using SII-ALBI were superior to single indicator (bothP < 0.05). Conclusion: Elevated preablation SII-ALBI is associated with shorter OS, CSS, and RFS in patients with early-stage HCC. Our indicator showed the potential to be a supplement tool for patients with negative AFP during follow-up

Efficacy and safety of argon plasma coagulation in the treatment of obstructive tracheobronchial stenosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of argon plasma coagulation (APC) in the treatment of large airway obstruction.</p><p><b>METHODS</b>Totally 389 patients with treacheobronchial stenosis were treated with APC (ARCO3000 type) by bronchoscopy. The stenoses were caused by carcinomas (203 cases, 52.2%), metastatic tumors (67 cases, 17.2%), benign tumors (18 cases, 4.6%), granulomas (93 cases, 23.9%) and other lesions (8 cases, 2.1%). The rate of recanalization, relief of the symptoms, and complications were analyzed.</p><p><b>RESULTS</b>1121 times of APC treatment were performed in the 389 patients. Complete recanalization was achieved in 138 cases (35.5%), partial in 143 (36.8%), mild in 55 (14.1%) and none in 53 (13.6%). The major complications included: super-ventricular tachycardia in 136 cases (34.9%), bleeding in 51 (13.1%), decrease in blood oxygen saturation in 48 (12.3%), asphyxia in 33 (8.5%), ventricular or super-ventricular arrhythmia in 24 (6.2%), short-term aggravation of airway obstruction in 18 (4.6%), and tracheal perforation in 3 (0.78%). All those complications were treated with various measures and no patient died of the complications during the procedure.</p><p><b>CONCLUSION</b>Argon plasma coagulation is effective and relatively safe in relieving the obstruction and dyspnea in patients with large airway obstruction caused by various reasons. However, for the patients with severe airway obstruction, argon plasma coagulation sometimes may cause severe or even lethal complications. Critical consideration of the indication, operators' skill and taking more precautions during the procedure are required to ensure the safety of argon plasma coagulation treatment.</p>