Thawing Rate Predicts Acute Pulmonary Vein Isolation after Second-Generation Cryoballoon Ablation

OBJECTIVE: To evaluate whether thawing rate could be a novel predictor of acute pulmonary vein isolation (PVI) and explore the predictive value of thawing rate as a factor ensuring long-term PVI (vagus reflex). METHODS: A total of 151 patients who underwent cryoballoon ablation for atrial fibrillation (AF) were enrolled in this retrospective study between January 2017 and June 2018. The thawing rate was calculated using the thawing phase of the cryoablation curve. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of the thawing rate for acute PVI and vagus reflex. RESULTS: ROC curve analyses revealed that the interval thawing rate at 15o C (ITR15) was the most valuable predictor of PVI, with the highest area under curve (AUC) value of the ROC curve. The best cut-off value of ITR15 for PVI was p2.14o C/S and its sensitivity and specificity were 88.62% and 67.18%, respectively. In addition, the ITR15 of the successful PVI group after cryoballoon ablation was significantly slower than the failed PVI group. ITR15 was a predictor of vagus reflex and the occurrence of vagus reflex group had a slower ITR15 compared to the non-occurrence group. CONCLUSIONS: Thawing rate was a novel predictor of acute PVI and the ITR15 was the most valuable predictor of acute PVI. In addition, ITR15 was a predictive factor ensuring long-term PVI (vagus reflex). Our study showed that thawing rate may serve in the early identification of useless cryoballoon ablation

Meta-analysis of quantitative diffusion-weighted MR imaging in the differential diagnosis of breast lesions

BACKGROUND: To determine, in a meta-analysis, the diagnostic performance of quantitative diffusion-weighted (DW) MR imaging in patients with breast lesions. METHODS: English and Chinese studies published prior to June 2009 to assess the diagnostic performance of quantitative DWI in patients with breast lesions were reviewed and summarized with reference to the inclusion and exclusion criteria. Methodological quality was assessed by using the quality assessment of diagnostic studies (QUADAS) instrument. Publication bias analysis was performed by using Comprehensive Meta-analysis version 2. Meta-Disc version 1.4 was used to describe primary results and explore homogeneity by Chi-square test and inconsistency index; to explore threshold effect by receiver operator characteristic (ROC) space and Spearman correlation coefficient; and to pool weighted sensitivity and specificity by fixed or random effect model. A summary ROC (sROC) curve was constructed to calculate the area under the curve (AUC). RESULTS: Of 65 eligible studies, 13 with 615 malignant and 349 benign lesions were included in the original meta-analysis, among which heterogeneity arising from factors other than threshold effect and publication bias was explored. Methodological quality was moderate. The pooled weighted sensitivity and specificity with corresponding 95% confidence interval (CI) in one homogenous subgroup of studies using maximum b = 1000 s/mm(2 )were 0.84 (0.80, 0.87) and 0.84 (0.79, 0.88) respectively. AUC of sROC was 0.9085. Sensitivity analysis demonstrated that the pooled estimates were stable and reliable. CONCLUSIONS: Quantitative DWI has a higher specificity to differentiate between benign and malignant breast lesions compared to that of contrast-enhanced MRI. However, large scale randomized control trials (RCTs) are necessary to assess its clinical value because of disunified diffusion gradient factor b and diagnosis threshold

Effects of high glucose on expression of OPG and RANKL in rat aortic vascular smooth muscle cells

AbstractObjectiveTo explore effect of high glucose on expression of osteoprotegerin (OPG) and receptor activator of NF– κ B ligand (RANKE) in rat aortic vascular smooth muscle cells.MethodsSD rats were intraperitoneally injected with streptozotocin, OPG and RANKL expression in rat thoracic aortas were detected by immunohistochemical staining. In cultured vascular smooth muscle cells (VSMCs) (A7r5), qRT–PCR and Western blot analysis were used to examine the mRNA and protein levels of OPG and RANKL.ResultsOur results demonstrated that OPG expression was increased in hyperglycemic rat aortic VSMCs, while RANKL expression was decreased. Besides, in vitro experiments high glucose induced OPG expression, but depressed RANKL expression by dose– and time–dependent manner in cultured A7r5.ConclusionsOur findings suggested that high glucose could promote the expression of OPG, and inhibit the expression of RANKL in VSMCs, which may be partly be the molecular mechanism of diabetic vascular calcification

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

<p>Abstract</p> <p>Background</p> <p>The crude extract of the fruit bearing plant, <it>Physalis peruviana </it>(golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.</p> <p>Methods</p> <p>Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.</p> <p>Results</p> <p>It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (<it>p </it>< 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (<it>p </it>< 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC₅₀) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G₁accumulation and slight arrest at the G₂/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G₂/M arrest for H1299 cells treated with 5 μg/mL for 24 h.</p> <p>Conclusions</p> <p>In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region

Inhibition of protein ubiquitination by paraquat and 1-methyl-4-phenylpyridinium impairs ubiquitin-dependent protein degradation pathways

Intracytoplasmic inclusions of protein aggregates in dopaminergic cells (Lewy bodies) are the pathological hallmark of Parkinson’s disease (PD). Ubiquitin (Ub), alpha [α]-synuclein, p62/sequestosome 1 and oxidized proteins are major components of Lewy bodies. However, the mechanisms involved in the impairment of misfolded/oxidized protein degradation pathways in PD are still unclear. PD is linked to mitochondrial dysfunction and environmental pesticide exposure. In this work, we evaluated the effect of the pesticide paraquat (PQ) and the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+) on Ub-dependent protein degradation pathways. No increase in the accumulation of Ub-bound proteins or aggregates was observed in dopaminergic cells (SK-N-SH) treated with PQ or MPP+, or in mice chronically exposed to PQ. PQ decreased Ub protein content, but not its mRNA transcription. Protein synthesis inhibition with cycloheximide depleted Ub levels and potentiated PQ–induced cell death. Inhibition of proteasomal activity by PQ was found to be a late event in cell death progression, and had no effect on either the toxicity of MPP+ or PQ, or the accumulation of oxidized sulfenylated, sulfonylated (DJ-1/PARK7 and peroxiredoxins) and carbonylated proteins induced by PQ. PQ- and MPP+-induced Ub protein depletion prompted the dimerization/inactivation of the Ub-binding protein p62 that regulates the clearance of ubiquitinated proteins by autophagic. We confirmed that PQ and MPP+ impaired autophagy flux, and that the blockage of autophagy by the overexpression of a dominant-negative form of the autophagy protein 5 (dnAtg5) stimulated their toxicity, but there was no additional effect upon inhibition of the proteasome. PQ induced an increase in the accumulation of α-synuclein in dopaminergic cells and membrane associated foci in yeast cells. Our results demonstrate that inhibition of protein ubiquitination by PQ and MPP+ is involved in the dysfunction of Ub-dependent protein degradation pathways