Edited by Zhijie ChangKeywords: microRNA miR-155 IFN-b Osteoclast differentiation SOCS1 MITF a b s t r a c t IFN-b is induced via a c-fos dependent mechanism that is present downstream of the receptor activator of NF-jB ligand (RANKL)-RANK signal transduction cascade during osteoclast differentiation. Increased production of IFN-b in turn inhibits osteoclastogenesis. However, the mechanism by which IFN-b exerts its suppressive function remains unclear. In the present study, we found that miR-155, an IFN-b-induced miRNA, mediated the suppressive effect of IFN-b on osteoclast differentiation by targeting SOCS1 and MITF, two essential regulators of osteoclastogenesis. These findings have not only demonstrated that miR-155 inhibits osteoclast differentiation, but also provided a new therapeutic target for treatment of osteoclast-mediated diseases.

BACKGROUND: The overlapping features of biliary atresia (BA) and other neonatal cholestasis with alternative causes (non-BA) have posed challenges for diagnosis. Matrix metalloproteinase-7 (MMP-7) has been reported to be promising in diagnosing BA. We aimed to validate the diagnostic accuracy of MMP-7 for BA in a large population sample. METHODS: We enrolled 288 patients with neonatal obstructive jaundice from March 2017 to October 2018. Serum MMP-7 levels were measured by using an enzyme-linked immunosorbent assay. Receiver operating characteristic curves were constructed, and decision curve analysis was done. A Pearson correlation coefficient test was conducted to assess the correlation between MMP-7 levels and other characteristics. RESULTS: The median serum MMP-7 levels were 38.89 ng/mL (interquartile range: 22.96-56.46) for the BA group and 4.4 ng/mL (interquartile range: 2.73-6.56) for the non-BA group (P , .001). The area under the receiver operating characteristic curve value was 0.9829 for MMP-7, and the sensitivity, specificity, positive predictive value, and negative predictive value were 95.19%, 93.07%, 97.27%, and 91.43%, respectively, at a cutoff value of 10.37 ng/mL. When MMP-7 was combined with g glutamyl transferase, the diagnostic accuracy was slightly improved without significance when compared with MMP-7 alone and had an area under the curve of 0.9880 (P = .08). Decision curve analysis also showed potential for MMP-7 to be used for clinical applications. A significant correlation was found with fibrosis stage from liver biopsy (R = 0.47; P , .001). CONCLUSIONS: MMP-7 demonstrated good accuracy in diagnosing BA and holds promise for future clinical application. Furthermore, its correlation with liver fibrosis indicated its potential use as a therapeutic target or prognostic biomarker.

Background:A thoracoscopic approach for repair of esophageal atresia (EA) with tracheoesophageal fistula (TEF) has become a standard procedure in many pediatric surgical centers. However, whether thoracotomy or thoracoscopy offer advantages in terms of surgical outcomes is not known.Methods:To evaluate the efficacy and safety of thoracoscopic repair (TR) versus conventional open repair (COR) for EA with TEF.PubMed, Cochrane Library, and EMBASE were searched to identify relevant literature until 2016.Studies comparing surgical outcomes of patients undergoing TR versus COR for EA with TEF were reviewed.The quality of each included study was assessed using the Newcastle–Ottawa scale score. A fixed or random-effect model was applied depending on heterogeneity tests.Results:Eight observational clinical studies involving 452 patients were included in this meta-analysis. The meta-analysis of 2 major postoperative complications (leaks and strictures) did not show significant differences between TR and COR. Overall estimates of the odds ratio (OR) of TR versus COR for leaks and strictures were: 1.57 (95% confidence interval [CI], 0.77–3.20; P = 0.22) and 0.90 (95% CI, 0.27–2.97; P = 0.86), respectively. However, meta-analysis of operation time (OR = 19.59, 95% CI = 0.77–38.40, P = 0.04), timing of extubation (OR = −2.50, 95% CI = −3.39 to −1.62, P < 0.001), time to 1st oral feeding (OR = −2.58, 95% CI = −3.79 to −1.36, P < 0.001), and duration of hospital stay (OR = −10.76, 95% CI = −16.39 to −5.12, P < 0.001) showed significant differences.No randomized controlled trial was included, and most studies had small sample sizes and were based on retrospective analysis.Conclusion:TR and COR show a similar complication rates of leaks and strictures for EA/TEF repair. Although associated with a longer operative time, TR has the advantages of an earlier time to extubation and 1st oral feeding, and shorter hospital stay.

Cancer cells can survive under hypoxia by metabolic reprogramming to achieve a high level of glycolysis, which contributes to the development of chemoresistance. Therefore, inhibition of glycolysis would be a novel strategy for overcoming hypoxia‑induced drug resistance. Baicalein, a flavonoid derived from the root of Scutellaria baicalensis, has been reported to exert strong antitumor activity toward various types of cancer. In the present study, we evaluated the effect of baicalein on hypoxia-induced 5-fluorouracil (5-FU) resistance in gastric cancer AGS cells and investigated the possible molecular mechanisms. We found that baicalein increased the sensitivity of AGS cells to 5-FU treatment under hypoxia. In addition, the hypoxia-enhanced glycolytic flux and expression of several critical glycolysis-associated enzymes (HK2, LDH-A and PDK1) in the AGS cells were suppressed by baicalein. Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-1α (HIF-1α) expression in AGS cells. These results together suggest that inhibition of glycolysis via regulation of the PTEN/Akt/HIF-1α signaling pathway may be one of the mechanisms whereby baicalein reverses 5-FU resistance in cancer cells under hypoxia.