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Purpose To identify and quantify lung changes associated with coronavirus disease-2019 (COVID-19) with quantitative lung CT during the disease. Methods This retrospective study reviewed COVID-19 patients who underwent multiple chest CT scans during their disease course. Quantitative lung CT was used to determine the nature and volume of lung involvement. A semi-quantitative scoring system was also used to evaluate lung lesions. Results This study included eighteen cases (4 cases in mild type, 10 cases in moderate type, 4 cases in severe type, and without critical type cases) with confirmed COVID-19. Patients had a mean hospitalized period of 24.1 ± 7.1 days (range: 14–38 days) and underwent an average CT scans of 3.9 ± 1.6 (range: 2–8). The total volumes of lung abnormalities reached a peak of 8.8 ± 4.1 days (range: 2–14 days). The ground-glass opacity (GGO) volume percentage was higher than the consolidative opacity (CO) volume percentage on the first CT examination (Z = 2.229, P = 0.026), and there was no significant difference between the GGO volume percentage and that of CO at the peak stage (Z = - 0.628, P = 0.53). The volume percentage of lung involvement identified by AI demonstrated a strong correlation with the total CT scores at each stage (r = 0.873, P = 0.0001). Conclusions Quantitative lung CT can automatically identify the nature of lung involvement and quantify the dynamic changes of lung lesions on CT during COVID-19. For patients who recovered from COVID-19, GGO was the predominant imaging feature on the initial CT scan, while GGO and CO were the main appearances at peak stage. Electronic supplementary material The online version of this article (10.1007/s10140-020-01856-4) contains supplementary material, which is available to authorized users.

MAPK/extracellular signal-regulated kinase kinase (MEK) 1/2 inhibitors (MEKis) have recently achieved surprising success in treating unresectable plexiform neurofibromas (PNFs). However, few studies have investigated the mechanisms of MEKi resistance in patients with PNF. We determined the efficacy of six different MEKis for treating PNFs, explored drug resistance mechanisms, and identified potential combination therapies to overcome resistance. By screening drug efficacy among six MEKis in human NF1-deficient PNF cell lines, TAK-733 was found to reduce PNF cell viability the most. We then cultured the TAK-733‒resistant cells and explored the potential targets for further treatment. Both high-throughput drug screening and RNA sequencing analyses of MEKi-resistant PNF cells identified cyclin-dependent kinase inhibitors as potential agents for PNFs. Dinaciclib, a cyclin-dependent kinase inhibitor, showed synergistic effects on MEKi-resistant cells. Coadministration of dinaciclib and TAK-733 significantly reduced cell viability and inhibited sphere formation and colony formation. Dinaciclib did not affect MEK signaling but decreased the expression of several prosurvival proteins, including survivin and cyclin-dependent kinase 1, to induce apoptosis and inhibit mitosis. TAK-733/dinaciclib combination therapy induced tumor reduction in PNF patient‒derived xenografts mouse models. Therefore, the combination of MEKi and cyclin-dependent kinase inhibitor may be promising for treating inoperable PNFs, especially when drug resistance exists. Our findings provide evidence for future clinical trials with MEKi-resistant patients with PNF.

MicroRNA-26a (miR-26a) has been reported to be involved in the tumorigenesis of several tumors, but its biological function and molecular mechanism in multiple myeloma (MM) are still unknown. In this study, we found that overexpression of miR-26a obviously inhibited MM cell growth, and delayed tumor growth in xenografts. Further studies showed that overexpression of miR-26a induced cell cycle arrest at G0/G1 phase in MM cells. MiR-26a mimic down-regulated the expression levels of CDK6 and E2F1, but up-regulated p53 and p21 expression. In contrast, overexpression of CDK6 decreased the effect of miR-26a mimic on MM cell survival. Moreover, miR-26a targeted CDK6 mRNA and thus suppressed CDK6 protein expression. Overexpression of miR-26a also enhanced the cytotoxic action of doxorubicin against MM. These results demonstrated that miR-26a was involved in the development of MM through regulating CDK6 signaling pathway, and indicated that miR-26a could be as a novel target for anti-tumor therapy in clinic as a single strategy or in combination with other anti-tumor drugs in MM.

To investigate IRF6 gene mutation in a van Der Woude syndrome (VWS) family in Henan province.PCR and DNA sequencing was employed to detect the mutation of IRF6.Secondary construction transformation analysis was performed using PIX-Protein Identification software.A CGCTGC(r.279c--t) transversion of IRF6 was identified in condon 6, showing complete segregation with the disease phenotypes and was resulting in changes of the secondary constructure of IRF6.VWS is caused by mutations in IRF6 gene, and IRF6 is closely related to the development of lip, palate and tooth.