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BackgroundImmunomodulatory drugs (IMiDs), such as lenalidomide, are therapeutically active compounds that bind and modulate the E3 ubiquitin ligase substrate recruiter cereblon, thereby affect steady-state levels of cereblon and cereblon binding partners, such as ikaros and aiolos, and induce many cellular responses, including cytotoxicity to multiple myeloma (MM) cells. Nevertheless, it takes many days for MM cells to die after IMiD induced depletion of ikaros and aiolos and thus we searched for other cereblon binding partners that participate in IMiD cytotoxicity.MethodsCereblon binding partners were identified from a MM cell line expressing histidine-tagged cereblon by pulling down cereblon and its binding partners and verified by co-immunoprecipitation. IMiD effects were determined by western blot analysis, cell viability assay, microRNA array and apoptosis analysis.ResultsWe identified argonaute 2 (AGO2) as a cereblon binding partner and found that the steady-state levels of AGO2 were regulated by cereblon. Upon treatment of IMiD-sensitive MM cells with lenalidomide, the steady-state levels of cereblon were significantly increased, whereas levels of AGO2 were significantly decreased. It has been reported that AGO2 plays a pivotal role in microRNA maturation and function. Interestingly, upon treatment of MM cells with lenalidomide, the steady-state levels of microRNAs were significantly altered. In addition, silencing of AGO2 in MM cells, regardless of sensitivity to IMiDs, significantly decreased the levels of AGO2 and microRNAs and massively induced cell death.ConclusionThese results support the notion that the cereblon binding partner AGO2 plays an important role in regulating MM cell growth and survival and AGO2 could be considered as a novel drug target for overcoming IMiD resistance in MM cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2331-0) contains supplementary material, which is available to authorized users.

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Mumps presents a serious threat to public health in China. We conducted a descriptive analysis to identify the epidemiological characteristics of mumps in Shandong Province. Spatial autocorrelation and space-time scan analyses were utilized to detect spatial-temporal clusters. From 2005 to 2014, 115745 mumps cases were reported in Shandong, with an average male-to-female ratio of 1.94. Mumps occurred mostly in spring (32.17% of all reported cases) and in children aged 5 to 9 (40.79% of all reported cases). The Moran’s I test was significant and local indicators of spatial autocorrelation (LISA) analysis revealed significant spatial clusters with high incidence. The results showed that the mid-west of Shandong Province and some coastal regions (Qingdao City and Weihai City) were high-risk areas, particularly in the center of the Jining City and the junction of Dongying City, Binzhou City and Zibo City. The results could assist local and national public health agencies in formulating better public health strategic planning and resource allocation.

This study aimed to predict the incidence of mumps using a seasonal autoregressive integrated moving average (SARIMA) model, and provide theoretical evidence for early warning prevention and control in Zibo City, Shandong Province, China. Monthly mumps data from Zibo City gathered between 2005 and 2013 were used as a training set to construct a SARIMA model, and the monthly mumps in 2014 were defined as a test set for the model. From 2005 to 2014, a total of 8722 cases of mumps were reported in Zibo City; the male-to-female ratio of cases was 1.85:1, the age group of 1–20 years old accounted for 94.05% of all reported cases, and students made up the largest proportion (65.89%). The main serious endemic areas of mumps were located in Huantai County, Linzi District, and Boshan District of Zibo City. There were two epidemic peaks from April to July and from October to January in next year. The fitted model SARIMA (0, 1, 1) (0, 1, 1)12 was established (AIC = 157.528), which has high validity and reasonability. The SARIMA model fitted dynamic changes of mumps in Zibo City well. It can be used for short-term forecasting and early warning of mumps.

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