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CKD-516 (Valecobulin), a vascular-disrupting agent, inhibits microtubule elongation. We evaluated the effect of CKD-516 on lung cancer cells and the underlying molecular mechanisms. The effects of S516, an active metabolite of CKD-516, were evaluated in HUVECs and three lung cancer cell lines and by a microtubule polymerization assay. Tubulin cross-linking was used to identify the binding site of S516 on tubulin, and Western blotting was performed to identify the intracellular pathways leading to cell death. Subcutaneous lung cancer xenograft models were used to assess the in vivo effect of CKD-516 on tumor growth. S516 targeted the colchicine binding site on β-tubulin. In lung cancer cells, S516 increased endoplasmic reticulum (ER) stress and induced reactive oxygen species (ROS) generation by mitochondria and the ER. In addition, CKD-516 monotherapy strongly inhibited the growth of lung cancer xenograft tumors and exerted a synergistic effect with carboplatin. The findings suggest that CKD-516 exerts an anticancer effect in company with inducing ER stress and ROS production via microtubule disruption in lung cancer cells. CKD-516 may thus have therapeutic potential for lung cancer.  相似文献   
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European Archives of Oto-Rhino-Laryngology - Inflammatory pseudotumor (IPT) in the sinonasal cavity and skull base region is benign non-neoplastic inflammatory process. However, IPT can mimic...  相似文献   
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Much of the work that has been done to the present in exploring age differences in the assessment of depression has utilized normally aging populations. This research has indicated that present depresion scales may yield many false positives for depression because of the large number of somatic items that these scales contain. An important question is whether this same finding would hold in psychiatric populations, which are the ones most likely to be subject to diagnosis. The present study was designed to supply information in that area. The D-scale responses of the MMPI for 6,964 patients were factor-analyzed. Results indicated significant differences in the expression of depression for three age groups–20-39, 40–59 and 60+ years. A central core of items that accounted for one-half of the variances for all three groups was found. Additional items appeared across the age groups with greater to lesser significance in terms of the variance accounted for producing distinct qualitative differences. Concern over declining physical well-being was not part of the central core of depression for the older group in this psychiatric population.  相似文献   
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BackgroundDepression and sleep–wake disorders are recognized as one of the major problems among emergency physicians. While depression is more common in females than in males, the associated factors linking depression and sleep–wake disorders in emergency physicians, particularly females, remain unknown.ObjectiveTo analyze the prevalence of depression and sleep–wake problems among emergency medicine (EM) residents in South Korea and to identify the gender differences and situations that adversely predispose female residents to mental health problems.MethodsWe conducted a cross-sectional analysis using the data collected from the 2019 National EM Residents Wellness Survey targeting all of 630 EM residents in South Korea. The survey included variables potentially influencing depression and sleep–wake problems, such as personal characteristics, work-related stress, and extrinsic environment. Information regarding medical conditions, depression, job stress, and sleep deprivation was obtained using the self-administered Patient Health Questionnaire (PHQ-9), the Apgar Wellness Score (AWS), and the Epworth Sleepiness Scale (ESS). We analyzed the data using IBM SPSS Statistics version 25 and MedCalc version 17.ResultsA total of 384 residents participated in the survey. Overall, 27.5% of the EM residents met the criteria for at least moderate depression and 36.9% of the EM residents had sleep-related problems. We found that difficulty in trading the shift schedule and frequent night shifts was associated with depression (p = .001, p = .005; respectively). Female residents demonstrated an increased risk of depression and sleepiness compared to their male counterparts (odds ratio [OR] 1.95, OR 1.81; respectively). In addition, logistic regression analysis revealed significant differences by gender in depression with regards to flexibility of trading shifts (p = .005), level of training in the emergency medical centre (p = .035), and frequent night shifts (p = .010).ConclusionsApproximately, one-third of EM residents report depression and sleep–wake problems, with female residents showing a higher risk than male residents. Several risk factors were identified, and future strategies should be aimed to address these issues to improve the training environment and overall wellbeing of EM residents.

KEY MESSAGES

  • The prevalence of depression and sleep-related problems were, respectively, 1.95 and 1.81 times higher in female residents compared to their male colleagues.
  • The associated risk factors for depression were flexibility of shift trade, level of training in the emergency medical centre, and frequency of night shifts.
  • Improving the training environment and facilities, as well as offering more flexible duty trading options can provide potential opportunities to reduce the risk.
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999.
BACKGROUND/OBJECTIVESAdequate nutritional intake is essential for good health and well-being. We aimed to compare the nutrient intake from homemade meals, meals sourced externally (“eating out”), and meals from workplace foodservices, as well as the potential association between foodservices used and nutritional quality among adult Korean workers.SUBJECTS/METHODSWe used data from the Korea National Health and Nutrition Examination Survey, a nationwide cross-sectional survey on the health and nutritional status of the Korean population. Data from 6,845 workers aged 20–64 years were included. A survey on dietary behavior and nutrition was conducted using the 24-h dietary recall method. Nutritional quality was examined using the index of nutritional quality (INQ) score. Higher INQ scores reflected poorer nutritional quality, with insufficient intake of a higher number of nutrients. Multivariate linear regression was used to identify the association between the foodservices used and INQ scores after adjusting for other covariates.RESULTSWe found that foodservice users exhibited a higher 1-day intake of total energy and macronutrients (all P < 0.05) and lower INQ scores (P < 0.01) than non-users. The INQ scores for total daily meals decreased with the frequency of foodservice use (P < 0.01). A significant association was observed between the non-use of foodservices and INQ scores (β = 0.29, P < 0.01) after adjusting for other covariates.CONCLUSIONSThe use of workplace foodservices contributed to higher dietary nutritional quality among workers. This study highlights the importance of expanding the scope of workplace foodservices to promote higher nutritional quality and healthy dietary habits among workers.  相似文献   
1000.
Traditional fatigue fracture theory and practice focus principally on structural design. It is thus too conservative and inappropriate when used to predict the high-cycle fatigue life of dies used for metal forming, especially cold forging. We propose a novel mean stress correction model and diagram to predict the high-cycle fatigue lives of cold forging dies, which focuses on the upper part of the equivalent fatigue strength curve. Considering the features of die materials characterized by high yield strength and low ductility, a straight line is assumed for the tensile yield line. To the contrary, a general curve is used to represent the fatigue strength. They are interpolated, based on the distance ratio, when finding an appropriate equivalent fatigue strength curve at the mean stress and stress amplitude between the line and curve. The approach is applied to a well-defined literature example to verify its validity and shed light on the characteristics of die fatigue life. The approach is also applied to practical forging and useful qualitative results are obtained.  相似文献   
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