Accurate breast cancer diagnosis using a stable feature ranking algorithm.

BACKGROUND: Breast cancer (BC) is one of the most common cancers among women. Since diverse features can be collected, how to stably select the powerful ones for accurate BC diagnosis remains challenging. METHODS: A hybrid framework is designed for successively investigating both feature ranking (FR) stability and cancer diagnosis effectiveness. Specifically, on 4 BC datasets (BCDR-F03, WDBC, GSE10810 and GSE15852), the stability of 23 FR algorithms is evaluated via an advanced estimator (S), and the predictive power of the stable feature ranks is further tested by using different machine learning classifiers. RESULTS: Experimental results identify 3 algorithms achieving good stability ([Formula: see text]) on the four datasets and generalized Fisher score (GFS) leading to state-of-the-art performance. Moreover, GFS ranks suggest that shape features are crucial in BC image analysis (BCDR-F03 and WDBC) and that using a few genes can well differentiate benign and malignant tumor cases (GSE10810 and GSE15852). CONCLUSIONS: The proposed framework recognizes a stable FR algorithm for accurate BC diagnosis. Stable and effective features could deepen the understanding of BC diagnosis and related decision-making applications.

Early Diagnosis of High-Risk Chronic Obstructive Pulmonary Disease Based on Quantitative High-Resolution Computed Tomography Measurements.

Purpose: Quantitative computed tomography (QCT) techniques, focusing on airway anatomy and emphysema, may help to detect early structural changes of COPD disease. This retrospective study aims to identify high-risk COPD participants by using QCT measurements. Patients and Methods: We enrolled 140 participants from the Second Affiliated Hospital of Shenyang Medical College who completed inspiratory high-resolution CT scans, pulmonary function tests (PFTs), and clinical characteristics recorded. They were diagnosed Non-COPD by PFT value of FEV1/FVC >70% and divided into two groups according percentage predicted FEV1 (FEV1%), low-risk COPD group: FEV1% ≥ 95%, high-risk group: 80% < FEV1% < 95%. The QCT measurements were analyzed by the Student's t-test (or Mann-Whitney U-test) method. Then, feature candidates were identified using the LASSO method. Meanwhile, the correlation between QCT measurements and PFTs was assessed by the Spearman rank correlation test. Furthermore, support vector machine (SVM) was performed to identify high-risk COPD participants. The performance of the models was evaluated in terms of accuracy (ACC), sensitivity (SEN), specificity (SPE), F1-score, and area under the ROC curve (AUC), with p <0.05 considered statistically significant. Results: The SVM based on QCT measurements achieved good performance in identifying high-risk COPD patients with 85.71% of ACC, 88.34% of SEN, 84.00% of SPE, 83.33% of F1-score, and 0.93 of AUC. Further, QCT measurements integration of clinical data improved the performance with an ACC of 90.48%. The emphysema index (%LAA-950) of left lower lung was negatively correlated with PFTs (P < 0.001). The airway anatomy indexes of lumen diameter (LD) were correlated with PFTs. Conclusion: QCT measurements combined with clinical information could provide an effective tool for an early diagnosis of high-risk COPD. The QCT indexes can be used to assess the pulmonary function status of high-risk COPD.

miR-145-5p attenuates inflammatory response and apoptosis in myocardial ischemia-reperfusion injury by inhibiting (NADPH) oxidase homolog 1.

Myocardial ischemia-reperfusion (I/R) injury is a common complication following reperfusion therapy that involves a series of immune or apoptotic reactions. Studies have revealed the potential roles of miRNAs in I/R injury. Herein, we established a myocardial I/R model in rats and a hypoxia/reoxygenation (H/R) model in H9c2 cells and investigated the effect of miR-145-5p on myocardial I/R injury. After 3 h or 24 h of reperfusion, left ventricular end-systolic pressure (LVESP), ejection fraction (EF), and fractional shortening (FS) were obviously decreased, and left ventricular end-diastolic pressure (LVEDP) was increased. Meanwhile, I/R induced an increase in myocardial infarction area. Moreover, a decrease in miR-145-5p and increase in (NADPH) oxidase homolog 1 (NOH-1) were observed following I/R injury. With this in mind, we performed a luciferase reporter assay and demonstrated that miR-145-5p directly bound to NOH-1 3' untranslated region (UTR). Furthermore, miR-145-5p mimics decreased the levels of tumor necrosis factor (TNF)-α, IL-1ß, and IL-6 via oxygen and glucose deprivation/reperfusion (OGD/R) stimulation. Upregulation of miR-145-5p increased cell viability and reduced apoptosis accompanied by downregulation of Bax, cleaved caspase-3, cleaved poly(ADP-ribose) polymerase (PARP) and upregulation of Bcl2. In addition, miR-145-5p overexpression increased superoxide dismutase (SOD) activity and reduced reactive oxygen species (ROS) and malondialdehyde (MDA) content under OGD/R stress. Notably, NOH-1 could significantly abrogate the above effects, suggesting that it is involved in miR-145-5p-regulated I/R injury. In summary, our findings indicated that miR-145-5p/NOH-1 has a protective effect on myocardial I/R injury by inhibiting the inflammatory response and apoptosis.

S100A12 is a promising biomarker in papillary thyroid cancer.

S100A12 belongs to the S100 family and acts as a vital regulator in different types of tumors. However, the function of S100A12 in thyroid carcinoma has not yet been investigated. In this study, we analyzed the expression of S100A12 in human papillary thyroid cancer (PTC) samples and two PTC cell lines. In addition, we explored the effects of S100A12 on PTC cell progression in vitro and in vivo. Our results showed that S100A12 was significantly upregulated in PTC specimens. Moreover, silencing S100A12 markedly inhibited PTC cell proliferation, migration, invasion and cell cycle progression. In addition, knockdown of S100A12 significantly reduced the expression of CyclinD1, CDK4 and p-ERK in PTC cells. An in vivo study also showed that silencing S100A12 dramatically suppressed tumor cell growth and decreased Ki67 expression in a xenograft mouse model. This study provides novel evidence that S100A12 serves as an oncogene in PTC. Knockdown of S100A12 suppressed PTC cell proliferation, migration, and invasion and induced G0/G1 phase arrest via the inhibition of the ERK signaling pathway. Therefore, S100A12 may be a potent therapeutic target for PTC.

IL-34 causes inflammation and beta cell apoptosis and dysfunction in gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is characterized by glucose intolerance during gestation. It is associated with a series of maternal and foetal complications. Interleukin (IL)-34 is a recently discovered pro-inflammatory cytokine that functions as a ligand for colony-stimulating factor-1 receptor (CSF-1R). The contribution of IL-34 in the development of multiple chronic inflammatory diseases and autoimmune diseases has been recently discovered. The aim of this study was to evaluate whether IL-34 participates in the pathogenesis of GDM. METHOD: A total of 120 women were enrolled in this study, which included 60 GDM patients and age- and sex-matched healthy pregnant women. The expression of IL-34 in serum, cord blood and placental tissues was analysed by ELISA and Western blot assays. The association between IL-34 levels and clinical features was also studied. We additionally evaluated the effect of recombinant mouse IL-34 (rmIL-34) on apoptosis and pancreatic ß cell function. RESULTS: We found that IL-34 expression is highly increased in serum, cord blood and placental tissues in patients with GDM. In addition, there was a positive association between serum IL-34 and insulin resistance and glucose concentrations. Our data also revealed that IL-34 contributes to the apoptosis of pancreatic ß cells in GDM caused by CSF-1R. Furthermore, functional studies found that IL-34 inhibited pancreatic ß cell function and cell viability, while CSF-1R inhibitor blocked this effect. CONCLUSION: IL-34 plays a crucial role in the development of GDM by targeting CSF-1R, insulin production and ß cell function.

[The Effect of miR-17-5p on Vascular Lesion and Expression of VLDLR in Atherosclerotic Mice].

OBJECTIVE: To investigate the effect of miR-17-5p on vascular lesion and expression of very low density lipoprotein receptor (VLDLR) in atherosclerotic (AS) mice. METHODS: ApoE-/- mice were fed with high fat diet for 15 weeks to establish atherosclerotic mice models, and these mice were injected with miR-17-5p inhibitor antagomiR-17-5p 20 mg/kg from week 13 to week 15 to interfere the expression of miR-17-5p. AS model group (injection of normal saline) and NC miRNA group (injection of negative control inhibitors) were set and C57BL/6 mice were fed with normal diet for 15 weeks as normal control group (NC group, injection of normal saline during week 13-15). HE staining was used to detect the pathological changes of arterial vessels in each group and the vascular morphological changes were measured as well, so as to investigate the therapeutic effect of interfering miR-17-5p on AS vascular lesions. According to the prediction of Targetscan target gene prediction database, VLDLR as the target gene of miR-17-5p, the distribution of VLDLR in vascular tissues of mice in each group was observed by immunofluorescence. The effect of miR-17-5p on the expression of VLDLR mRNA in the arterial tissues of each group was detected by real-time PCR, and the changes of VLDLR protein expression caused by miR-17-5p in the arterial tissues in each group was detected by Western blot. RESULTS: The results of HE staining showed thatcompared with the NC group, the AS model group had obvious plaques in vascular endothelium, smooth muscle cell disorder and intimal hyperplasia, while the antagomiR-17-5p treated mice had significantly less lesions compared with the NC miRNA group. The intimal area of mice in the AS model group was bigger compared with NC group, but decreased after the inhibition of miR-17-5p. There was no statistically significant difference in the area of the media in each group. Vascular lumen area was smaller and intima/media ratio (I/M) values were lower in the AS model group and the NC miRNA group compared with the NC group, while the antagomiR-17-5p group alleviated this effect (P<0.05). Immunofluorescence showed that the expression of VLDLR in the AS model group was decreased, and that in the antagomiR-17-p group was higher than that in the NC miRNA group. The expression of VLDLR gene in the AS model group was lower than that in the NC group (P<0.01), while the VLDLR gene expression was higher in the antagomiR17-p group than that in the NC miRNA group (P<0.05). The results of VLDLR expression detected by Western blot were similar. CONCLUSION: miR-17-5p inhibitors may effectively alleviate the pathological changes of arterial vessels in AS mice by up-regulating the expression of VLDLR in arterial tissues, and may become a new therapeutic target for AS disease.