Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are often present in newly diagnosed acute myeloid leukemia (AML) patients with an incidence rate of approximately 30%. Recently, many FLT3 inhibitors have been developed and exhibit positive preclinical and clinical effects against AML. However, patients develop resistance soon after undergoing FLT3 inhibitor treatment, resulting in short durable responses and poor clinical effects. This review will discuss the main mechanisms of resistance to clinical FLT3 inhibitors and summarize the emerging strategies that are utilized to overcome drug resistance. Basically, medicinal chemistry efforts to develop new small-molecule FLT3 inhibitors offer a direct solution to this problem. Other potential strategies include the combination of FLT3 inhibitors with other therapies and the development of multitarget inhibitors. It is hoped that this review will provide inspiring insights into the discovery of new AML therapies that can eventually overcome the resistance to current FLT3 inhibitors.

Background: It is necessary to examine doctors working with illness from a professional point of view, because it is not only related to their occupational health, but more importantly, will affect the treatment effect of patients and the overall medical level of the hospital. The purpose of this study was to explore the relationship between doctors' presenteeism and job burnout, and to identify other factors that are associated with presenteeism. Methods: A cross-sectional survey involving doctors (except for primary doctors) was conducted in China. Using one item measure about presenteeism and a 15-item Chinese version of the BMI-GS questionnaire, this study investigated prevalence of doctors' presenteeism and job burnout, and determined the relationship between presenteeism and job burnout by logistical model. Results: Relationship between presenteeism and job burnout were explored, and the influence of work factors were evaluated. The survey was completed by 1376/1547 hospital doctors, with a response rate of 88.9%. Presenteeism was reported by 30.7% of participants. Using MBI-GS, 86.8% of all doctors had moderate job burnout and 6.0%(n = 82) were severe job burnout. Logistic regression analysis showed that doctors with medium, high degree of emotional exhaustion and high degree of cynicism were more likely to practice presenteeism (all p < 0.05). In addition, two other work-related factors, including the doctors' department and position, were also likely to relate with presenteeism (all p < 0.05). Conclusions: By examining the relationship between presenteeism and job burnout, this study determined that there is indeed a significant correlation between the two. This result has a certain reference value for the development of work health, especially presenteeism and job burnout theory, and also makes a certain contribution to the relevant research literature.

Background Colorectal adenoma (CA) is an important precancerous lesion and early screening target of colorectal cancer (CRC). Lipids with numerous physiological functions are proved to be involved in the development of CRC. However, there is no lipidomic study with large-scale serum samples on diagnostic biomarkers for CA. Methods The serum lipidomics of CA patients (n = 50) and normal control (NR) (n = 50) was performed by ultra high performance liquid chromatography-high resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). Univariate and multivariate statistical analyses were utilized to screen the differential lipids between groups, and combining the constituent ratio analysis and diagnostic efficiency evaluation by receiver operating characteristic (ROC) curve disclosed the potential mechanism and biomarkers for CA. Results There were obvious differences in serum lipid profiles between CA and NR groups. Totally, 79 differential lipids were selected by criterion of P < 0.05 and fold change > 1.5 or < 0.67. Triacylglycerols (TAGs) and phosphatidylcholines (PCs) were the major differential lipids with ratio > 60%, indicating these two lipid metabolic pathways showed evident disequilibrium, which could contribute to CA formation. Of them, 12 differential lipids had good diagnostic ability as candidate biomarkers for CA (AUC ≥ 0.900) by ROC analysis. Conclusions To our knowledge, this is the first attempt to profile serum lipidomics and explore lipid biomarkers of CA to help early screening of CRC. 12 differential lipids are obtained to act as potential diagnostic markers of CA. PCs and fatty acids were the main dysregulated biomarkers for CA in serum.

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