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      Difference in Leukocyte Composition between Women before and after Menopausal Age, and Distinct Sexual Dimorphism

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          Abstract

          There are sex differences in many inflammatory and immune diseases, and the differences tend to diminish after menopause. The underlying reasons are unclear, but sex hormone levels are likely to be an important factor. Blood leukocyte count and composition provide an indicator of the inflammatory and immune status of an individual. We performed a cross-sectional analysis of blood leukocyte data from 46,879 individuals (26,212 men and 20,667 women, aged 18 to 93 years) who underwent a routine health checkup. In women aged around 50 years, neutrophil percentage (NE%) dropped whilst lymphocyte percentage (LY%) rose. Accordingly, women before age 50 had significantly higher NE%, lower LY%, and higher neutrophil-to-lymphocyte ratio (NLR) than women of 51–70 years of age ( p = 1.35×10 −82, p = 5.32×10 −100, and p = 1.25×10 −26, respectively). In age groups of <50 years, women had higher NE%, lower LY% and higher NLR than men ( p = 1.82×10 −206, p = 1.46×10 −69, and p = 2.30×10 −118, respectively), whereas in age groups of >51 years, it was the reverse ( p = 1.92×10 −15, p = 1.43×10 −84, and p = 1.51×10 −48, respectively). These results show that blood leukocyte composition differs between women before and after menopausal age, with distinct sexual dimorphism.

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          Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age.

          In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. Though the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have been incompletely characterized. To elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated immunophenotypic HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged immunophenotypic human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared with young HSC. Gene expression profiling revealed that aged immunophenotypic human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, developmental potential, and gene expression profile of human HSC are similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.
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            Sex differences in autoimmune disease.

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              Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome.

              The neutrophil/lymphocyte ratio (NLR) has recently been described as a predictor of mortality in patients who undergo percutaneous coronary intervention. The aim of this study was to investigate the utility of admission NLRs in predicting outcomes in patients with acute coronary syndromes (ACS). A total of 2,833 patients admitted to the University of Michigan Health System with diagnoses of ACS from December 1998 to October 2004 were followed. Patients were divided into tertiles according to NLR. The primary end point was all-cause in-hospital and 6-month mortality. The ACS cohort comprised 564 patients with ST-segment elevation myocardial infarctions and 2,269 patients with non-ST-segment elevation ACS. Patients in tertile 3 had higher in-hospital (8.5% vs 1.8%) and 6-month (11.5% vs 2.5%) mortality compared with those in tertile 1 (p <0.001). After adjusting for Global Registry of Acute Coronary Events risk profile, patients in the highest tertile were at an exaggerated risk for in-hospital (odds ratio 2.04, p = 0.013) and 6-month (odds ratio 3.88, p <0.001) mortality. Admission NLR is an independent predictor of in-hospital and 6-month mortality in patients with ACS. This relatively inexpensive marker of inflammation can aid in the risk stratification and prognosis of patients diagnosed with ACS.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 September 2016
                2016
                : 11
                : 9
                : e0162953
                Affiliations
                [1 ]First Affiliated Hospital of Shantou University Medical College, Shantou, China
                [2 ]Shantou University Medical College, Shantou, China
                [3 ]Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
                [4 ]NIHR Biomedical Research Centre in Cardiovascular Disease, Leicester, United Kingdom
                Stellenbosch University Faculty of Medicine and Health Sciences, SOUTH AFRICA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: YC SY XT.

                • Data curation: YC YZ.

                • Formal analysis: YC YZ.

                • Investigation: YC GZ CC PY.

                • Resources: YC GZ CC PY XT.

                • Visualization: YZ SY.

                • Writing – original draft: SY.

                • Writing – review & editing: YC YZ GZ CC PY SY XT.

                ‡ These authors also contributed equally to this work.

                Article
                PONE-D-16-13859
                10.1371/journal.pone.0162953
                5033487
                27657912
                15a59871-9deb-47e7-a418-320586907c8b
                © 2016 Chen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 April 2016
                : 31 August 2016
                Page count
                Figures: 3, Tables: 0, Pages: 10
                Funding
                The author(s) received no specific funding for this work.
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                Data are available from the Ethics Committee of the First Affiliated Hospital of Shantou University Medical College for researchers who meet the criteria for access to confidential data at: Yingmu Cai, Ethics Committee, First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou, 515041, China.

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