Forest plots of the risk of adult myeloid disease in ever-smokers.

<p>(A) Forms of disease, (B) geographical region, (C) NOS score (high and medium quality), (D) source of controls.</p

Cigarette Smoking and the Risk of Adult Myeloid Disease: A Meta-Analysis

<div><p>Background</p><p>The adult myeloid diseases, myelodysplastic syndrome and acute myeloid leukemia, have been reported to be associated with cigarette smoking, but the results have been conflicting. Previous studies may have ignored the relationship between myelodysplastic syndrome and acute myeloid leukemia, where approximately one-third of myelodysplastic syndrome cases will progress to acute myeloid leukemia, which could induce a serious bias in independent analyses. For the purposes of researching pathogenesis, we suggest that myelodysplastic syndrome and acute myeloid leukemia should be regarded as a single class of adult myeloid disease, and herein assessed the relationship between cigarette smoking and the risk of adult myeloid disease.</p><p>Methods</p><p>The PubMed, Cochrane Library, EBSCO, and EMBASE databases were systematically searched for reports published from 1990 to 2015. Two authors independently assessed the methodological quality and the extracted data. The odds ratios and adjusted odds ratios (OR), a sensitivity analysis, and the publication bias were analyzed using the CMA v2 (Comprehensive Meta Analysis Version 2) software program.</p><p>Results</p><p>Twenty-five studies were included in this meta-analysis. The publication dates ranged from 1990 to 2014. The pooled OR in current smokers and ever-smokers showed an increased risk of adult myeloid disease, with ORs of 1.45 (95% CI, 1.30–1.62; <i>p</i><0.001) and 1.23 (95% CI 1.15–1.32; <i>p</i><0.001) versus non-smokers, respectively. In the subset analyses, the OR of adult myeloid disease was increased regardless of the form of disease, geographical region, NOS (Newcastle Ottawa Scale) score, and source of controls. The smoking status was divided into <20 and ≥20 cigarettes per day, and these groups had ORs of developing adult myeloid disease of 1.24 (95% CI, 1.09–1.40; <i>p</i> = 0.001) and 1.32 (95% CI, 1.14–1.53; <i>p</i><0.001), respectively. In the groups divided based on the number of years the subjects had smoked (<20 and ≥20 years), the ORs were 1.05 (95% CI, 0.90–1.23; <i>p</i> = 0.25) and 1.30 (95% CI, 1.16–1.45; <i>p</i><0.001), respectively. Similarly, <20 and ≥20 pack-years were associated with ORs of 1.15 (95% CI, 1.03–1.29; <i>p</i> = 0.017) and 1.34 (95% CI, 1.18–1.52; <i>p</i><0.001), respectively.</p><p>Conclusions</p><p>This meta-analysis, for the first time, combined myelodysplastic syndrome with acute myeloid leukemia to assess the overall risk of adult myeloid disease, and it demonstrated that cigarette smoking is associated with a significantly increased risk of adult myeloid disease.</p></div

The results of subgroup analyses performed according to the potential sources of heterogeneity.

<p><b>Abbreviations:</b> No. of datasets, Number of datasets (papers); MDS, Myelodysplastic Syndrome; AML, Acute Myeloid Leukemia; Nor A, North America; NOS, Newcastle-Ottawa Scale; Pub. bias, Publication bias; CBC, cannot be calculated; OR, odds ratio; AOR, Adjusted OR; CI, Confidence interval; PB, Population-based; HB, Hospital-based.</p><p>The results of subgroup analyses performed according to the potential sources of heterogeneity.</p

Forest plots of the association of adult myeloid disease with the smoking status based on cigarettes smoked per day (A-B), the duration of smoking (in years) (C-D), and the pack-years smoked (E-F).

<p>Forest plots of the association of adult myeloid disease with the smoking status based on cigarettes smoked per day (A-B), the duration of smoking (in years) (C-D), and the pack-years smoked (E-F).</p

Forest plots of the risk of adult myeloid disease in current smokers.

<p>(A) Forms of disease, (B) geographical region, (C) NOS score (high and medium quality), (D) source of controls.</p

Characteristics of the included studies.

<p><b>Abbreviations:</b> No. of subjects, Number of subjects; MDS, Myelodysplastic Syndrome; AML, Acute Myeloid Leukemia; ANNL, Acute Nonlymphocytic Leukemia; NOS, Newcastle-Ottawa Scale; PB, Population-Based; HB, Hospital-Based; BMI, Body Mass Index.</p><p>Characteristics of the included studies.</p

Odds ratio estimates of the risk of adult myeloid disease according to the smoking status.

<p><b>Abbreviations:</b> No. of datasets, number of datasets; OR, Odds ratio; AOR, Adjusted OR; CI, Confidence interval; Pub. bias, Publication bias.</p><p>Odds ratio estimates of the risk of adult myeloid disease according to the smoking status.</p

Immunofluorescence Imaging Strategy for Evaluation of the Accessibility of DNA 5‑Hydroxymethylcytosine in Chromatins

DNA 5-hydroxymethylcytosine (5hmC) is an important epigenetic modification found in various mammalian cells. Immunofluorescence imaging analysis essentially provides visual pictures for the abundance and distribution of DNA 5hmC in single cells. However, nuclear DNA is usually wrapped around nucleosomes, packaged into chromatins, and further bound with many functional proteins. These physiologically relevant events would generate barriers to the anti-5hmC antibody to selectively recognize 5hmC in DNA. By taking advantage of these naturally generated barriers, here, we present a strategy to evaluate the accessibility of DNA 5hmC in chromatins in situ. We demonstrate that a few of the 5hmC sites in DNA are exposed or accessible to anti-5hmC antibody under nondenaturing conditions, suggesting that these 5hmC sites are not covered by functional DNA-binding proteins in mouse embryonic stem cells. Consistently, these 5hmC foci were distributed in open euchromatin regions as revealed by the 4′,6-diamidino-2-phenylindole (DAPI) staining. By overexpressing TET1 catalytic domain (responsible for oxidation 5mC to produce 5hmC) in human MCF-7 cells, we observed a significant increase in accessible 5hmC along with an increase in total 5hmC sites. Collectively, by the use of the nondenaturing immunofluorescence imaging approach, we could obtain a visual landscape on the accessibility of DNA 5hmC in chromatins

Engineering High-Potential Photo-oxidants with Panchromatic Absorption

Challenging photochemistry demands high-potential visible-light-absorbing photo-oxidants. We report (i) a highly electron-deficient Ru­(II) complex (<b>eDef-Rutpy</b>) bearing an <i>E</i>_1/2^0/+ potential more than 300 mV more positive than that of any established Ru­(II) bis­(terpyridyl) derivative, and (ii) an ethyne-bridged <b>eDef-Rutpy</b>−(porphinato)­Zn­(II) (<b>eDef-RuPZn</b>) supermolecule that affords both panchromatic UV–vis spectral domain absorptivity and a high <i>E</i>_1/2^0/+ potential, comparable to that of Ce­(NH₄)₂(NO₃)₆ [<i>E</i>_1/2(Ce^3+/4+) = 1.61 V vs NHE], a strong and versatile ground-state oxidant commonly used in organic functional group transformations. <b>eDef-RuPZn</b> exhibits ∼8-fold greater absorptive oscillator strength over the 380–700 nm range relative to conventional Ru­(II) polypyridyl complexes, and impressive excited-state reduction potentials (¹<i>E</i>^–/* = 1.59 V; ³<i>E</i>^–/* = 1.26 V). <b>eDef-RuPZn</b> manifests electronically excited singlet and triplet charge-transfer state lifetimes more than 2 orders of magnitude longer than those typical of conventional Ru­(II) bis­(terpyridyl) chromophores, suggesting new opportunities in light-driven oxidation reactions for energy conversion and photocatalysis

Clinical Nomogram for Predicting Survival Outcomes in Early Mucinous Breast Cancer

<div><p>Background</p><p>The features related to the prognosis of patients with mucinous breast cancer (MBC) remain controversial. We aimed to explore the prognostic factors of MBC and develop a nomogram for predicting survival outcomes.</p><p>Methods</p><p>The Surveillance, Epidemiology, and End Results (SEER) database was searched to identify 139611 women with resectable breast cancer from 1990 to 2007. Survival curves were generated using Kaplan-Meier methods. The 5-year and 10-year cancer-specific survival (CSS) rates were calculated using the Life-Table method. Based on Cox models, a nomogram was constructed to predict the probabilities of CSS for an individual patient. The competing risk regression model was used to analyse the specific survival of patients with MBC.</p><p>Results</p><p>There were 136569 (97.82%) infiltrative ductal cancer (IDC) patients and 3042 (2.18%) MBC patients. Patients with MBC had less lymph node involvement, a higher frequency of well-differentiated lesions, and more estrogen receptor (ER)-positive tumors. Patients with MBC had significantly higher 5 and10-year CSS rates (98.23 and 96.03%, respectively) than patients with IDC (91.44 and 85.48%, respectively). Univariate and multivariate analyses showed that MBC was an independent factor for better prognosis. As for patients with MBC, the event of death caused by another disease exceeded the event of death caused by breast cancer. A competing risk regression model further showed that lymph node involvement, poorly differentiated grade and advanced T-classification were independent factors of poor prognosis in patients with MBC. The Nomogram can accurately predict CSS with a high C-index (0.816). Risk scores developed from the nomogram can more accurately predict the prognosis of patients with MBC (C-index = 0.789) than the traditional TNM system (C-index = 0.704, <i>P</i>< 0.001).</p><p>Conclusions</p><p>Patients with MBC have a better prognosis than patients with IDC. Nomograms could help clinicians make more informed decisions in clinical practice. The competing risk regression model, as a more rational model, is recommended for use in the survival analysis of patients with MBC in the future.</p></div