Paeonol (Pae), a phenolic acid compound isolated from the Moutan Cortex, was previously demonstrated to exert multiple anticancer effects. The rational control of autophagy has been considered a potential treatment strategy for epithelial ovarian cancer. However, whether Pae induces autophagy and the relationship between its antitumour activities and autophagy in epithelial ovarian cancer are still unclear. In this study, we found that Pae induced not only antiproliferation activity and apoptosis but also autophagy, and complete autophagic flux was observed in A2780 and SKOV3 cells. In addition, combination treatment with Pae and an autophagy inhibitor (3-methyladenine and hydroxychloroquine) showed significant synergetic effects on inhibiting cell viability and promoting apoptosis in vitro and in the A2780 xenograft model, without severe side effects, which was often had by cisplatin. These results indicate that autophagy induced by Pae has a cytoprotective role in both A2780 and SKOV3 cells. Mechanistically, we found that Pae inhibited the protein kinase B(Akt)/mammalian target of rapamycin (mTOR) pathway. Furthermore, when combined with the inhibitors MK2206 and rapamycin to inhibit Akt and mTOR kinase activity, Pae-induced autophagy was increased. Taken together, our results demonstrate that Pae induced cytoprotective autophagy by inhibiting the Akt/mTOR pathway in ovarian cancer cells. Thus, the strategy of combining Pae with an autophagy inhibitor to block Akt/mTOR-dependent autophagy could enhance the antitumour activity of Pae and warrants further application for the treatment of ovarian cancer.

Purpose To investigate performance in detectability of small (≤1 cm) low-contrast hypoattenuating focal lesions by using filtered back projection (FBP) and iterative reconstruction (IR) algorithms from two major CT vendors across a range of 11 radiation exposures. Materials and Methods A low-contrast detectability phantom consisting of 21 low-contrast hypoattenuating focal objects (seven sizes between 2.4 and 10.0 mm, three contrast levels) embedded into a liver-equivalent background was scanned at 11 radiation exposures (volume CT dose index range, 0.5-18.0 mGy; size-specific dose estimate [SSDE] range, 0.8-30.6 mGy) with four high-end CT platforms. Data sets were reconstructed by using FBP and varied strengths of image-based, model-based, and hybrid IRs. Sixteen observers evaluated all data sets for lesion detectability by using a two-alternative-forced-choice (2AFC) paradigm. Diagnostic performances were evaluated by calculating area under the receiver operating characteristic curve (AUC) and by performing noninferiority analyses. Results At benchmark exposure, FBP yielded a mean AUC of 0.79 ± 0.09 (standard deviation) across all platforms which, on average, was approximately 2% lower than that observed with the different IR algorithms, which showed an average AUC of 0.81 ± 0.09 (P = .12). Radiation decreases of 30%, 50%, and 80% resulted in similar declines of observer detectability with FBP (mean AUC decrease, -0.02 ± 0.05, -0.03 ± 0.05, and -0.05 ± 0.05, respectively) and all IR methods investigated (mean AUC decrease, -0.00 ± 0.05, -0.04 ± 0.05, and -0.04 ± 0.05, respectively). For each radiation level and CT platform, variance in performance across observers was greater than that across reconstruction algorithms (P = .03). Conclusion Iterative reconstruction algorithms have limited radiation optimization potential in detectability of small low-contrast hypoattenuating focal lesions. This task may be further complicated by a high degree of variation in radiologists' performances, seemingly exceeding real performance differences among reconstruction algorithms. © RSNA, 2018 Online supplemental material is available for this article.

Immunoglobulin D (IgD) myeloma is a rare isotype that comprises 1-2% of multiple myeloma (MM) patients [1-3], which has significantly inferior survival for a median overall survival (OS) between 13 and 21 months [4-6]. Given the lack of large cohort with comprehensive clinical and cytogenetic assessment, knowledge about IgD myeloma is obtained mostly from a limited sample size [7]. Therefore, we carried out a multicenter retrospective study to evaluate the prevalence, clinical features, prognosis, and to develop and validate a prognostic model, including 356 patients with IgD myeloma from 14 centers of Asian Myeloma Network (AMN). Data were collected from China, Korea, and Singapore diagnosed from 2002 to 2019 (Supplementary Table 1). Ethical committee approvals were obtained and study protocol was approved by the Institutional Review Board of each institution. To avoid clinical information leak, and get