Search

Abstract Objective Endometrial cancer (EC) is the ninth most common malignancy among women. While mutations in JAK2 are frequently observed in EC, the specific biological functions of JAK2 in endometrial cancer are poorly understood. Methods The genetic alterations of JAK2 in different cancer types were explored using sequencing dataset deposited at TCGA database. JAK2 mutations were detected in EC formalin-fixed paraffin-embedded (FFPE) samples using Sanger sequencing. The expression levels of JAK2 was accessed using the TCGA database and immunohistochemistry. Furthermore, the relationships between JAK2 expression and staging and prognosis of EC patients were investigated using the TCGA database. Down-regulation of JAK2 were achieved by transient transfection with short hairpin RNAs (shRNAs). Effects of JAK2 on cancer cells proliferation and migration were evaluated by CCK8, colony formation, and transwell assay. The potential biological functions of JAK2 in EC were identified based on bioinformatics analysis. Effects of JAK2 on expression levels of target genes were detected by RT-qPCR and western blotting. Co-immunoprecipitation (co-IP) assays was used to detect the physical association between JAK2 and HIF-1α. Results Frequent mutations and down-regulation of JAK2 were found in EC. Loss-of-function (LOF) assays suggested that JAK2 silencing in endometrial cancer cells promoted cell proliferation and migration, which were partially dependent on HIF-1α signaling pathway. Furthermore, our findings demonstrated that JAK2 interacted with HIF-1α and reduced HIF1α protein expression under hypoxia. Conclusion These findings revealed novel molecular mechanisms underlying JAK2 LOF mutations-driven endometrial tumorigenesis and revealed that the HIF-1α pathway may be a potential therapeutic target in JAK2-mutated endometrial cancer.

Abstract Introduction Community‐acquired pneumonia (CAP) is the major cause of infection‐related mortality worldwide. Patients with CAP frequently present with admission hyperglycemia. Objectives The aim of this study was to evaluate the association between admission blood glucose (ABG) level and clinical outcomes in elderly CAP patients (≥80 years of age) with or without diabetes. Methods In this single center retrospective study, 290 elderly patients diagnosed with CAP were included. Demographic and clinical information were collected and compared. The associations between admission blood glucose level and the 30‐day mortality as well as intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) in elderly CAP patients with or without diabetes were assessed. Results Of the 290 eligible patients with CAP, 159 (66.5%) patients were male, and 64 (22.1%) had a known history of diabetes at hospital admission. After adjusting for age and sex, the logistic regression analysis had identified several risk factors that might be associated with clinical outcomes in elderly patients with CAP. Multivariable logistic regression analysis revealed that admission glucose level > 11.1 mmol/L was significant associated with ICU admission, IMV, and 30‐day mortality both in non‐diabetic and diabetic patients. Furthermore, Kaplan–Meier analysis indicated that patients with higher admission glucose level were correlated statistically significantly with 30‐day mortality in patients with CAP (P 11.1 mmol/L was a significant risk factor for 30‐day hospital mortality.

Abstract The authors aimed to explore the association between visit‐to‐visit blood pressure variability (BPV) in pregnant women and adverse neonatal outcomes. The study included 52 891 pregnant women. BPV was calculated as standard deviation (SD) and coefficient of variation (CV) of systolic blood pressure (SBP) or diastolic blood pressure (DBP). All participants were divided into four groups by the quartiles of BPV. When comparing the highest quartiles to the lowest quartiles of DBP SD in all participants, the fully adjusted ORs were 1.19 (95% CI 1.11–1.27, p for trend