The diagnostic value of elastography and ultrasound contrast in papillary thyroid microcarcinoma

目的 评估弹性成像与超声造影（CEUS）两种检查技术对鉴别诊断甲状腺微小乳头状癌（TMC）的价值。方法  对常规超声检测出且定性困难的73例80个甲状腺微小结节进行弹性成像及CEUS检查，所有结节均经手术病理证实。比较两种检查方法的准确性。结果 80个结节中CEUS诊断正确率为85.0%（68/80）,其中6例TMC误诊为良性病变，6例良性结节误诊为TMC；弹性成像5分法诊断正确率为92.5%（74/80）,其中3例TMC误诊为良性结节，3例良性结节误诊为TMC。性成像诊断甲状腺微小癌的敏感性94.0%，特异性90.0%，准确性92.5%；CEUS诊断甲状腺微小癌的敏感性88.0%，特异性80.0%，准确性85.0%。结论 CEUS和弹性成像对于诊断TMC方面均有价值，但弹性评分≥3作为诊断TMC的敏感性、特异性及准确性均高于CEUS。Objective: To assess the value of elastic imaging and CEUS two inspection techniques for differential diagnosis of thyroid papillary carcinoma (TMC). Method: To do elastic imaging and CEUS checks to 73 cases of 80 thyroid nodules which was tested by conventional ultrasonic and difficult to quantify. All nodules were confirmed by surgery and pathologic examination. Comparing the accuracy of both detection methods. Result: Of the 80 nodules, the accuracy of CEUS diagnosis was 85.0%（68/80）,  of which 6 cases were misdiagnosed as benign lesions, and 6cases of benign nodules were misdiagnosed as TMC: the accuracy of 5-point scale criteria of elastography was 92.5%（74/80）, of which 3 TMC were misdiagnosed as benign nodules: and 3 benign nodules were misdiagnosed as TMC. The application of elastography in the diagnosis of thyroid microcarcinoma displayed a sensitivity of 94.0%, a specificity of 90.0% and an accuracy of 92.5%. Elastography detection was more advantagerous than CEUS in the diagnosis of thyroid microcarcinoma, and compared to CEUS , the differences were statistically significant（P <0.05）.Conclusion: Elastography and Ultrasound Contrast have highly practical value to diagnosis of TMC.  The sensitivity specificity and accuracy of using elastic score ≥3 as criteria of diagnosis of TMC was higher than that of CEUS

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Methyl Helicterate Inhibits Hepatic Stellate Cell Activation Through Modulation of Apoptosis and Autophagy

Background/Aims: Activated hepatic stellate cells (HSCs) are the major source of extracellular matrix (ECM). Therefore inhibiting HSC activation is considered as an effective strategy to inhibit the process of liver fibrosis. This study aimed to investigate the underlying mechanism of methyl helicterate (MH) isolated from Helicteres angustifolia on the activation of HSCs. Methods: HSC-T6 cells were treated with various concentration of MH and autophagy was inhibited by 3-Methyl adenine (3-MA) or RNA interference. Cell viability was observed by MTT assay and cell colony assay. Cell cycle and apoptosis were analyzed using flow cytometry. Autophagic vacuoles were observed by transmission electron microscopy and monodansyl cadaverine (MDC) staining. Moreover, autophagy-related genes and proteins were detected using real-time PCR and Western blot assays, respectively. Results: MH significantly inhibited HSC activation, as evidenced by the inhibition of cell viability, colony formation and the expression of α-SMA and collagen I. MH caused cell cycle arrest in G2/M phase. Moreover, MH significantly induced apoptosis through regulating the mitochondria-dependent pathway and the activity of caspases. MH treatment significantly increased lysosomes and autophagosomes, and enhanced the formation of autophagic vacuoles and autophagic flux. Interestingly, inhibiting autophagy by 3-MA or RNA interference abolished the ability of MH in inhibiting HSC activation. On the other hand, induction of autophagy promoted MH-induced HSC apoptosis. Further study showed that MH-induced HSC apoptosis and autophagy was mediated by the JNK and PI3K/Akt/mTOR pathways. Conclusion: Our results demonstrate that MH-induced HSC apoptosis and autophagy may be one of the important mechanisms for its anti-fibrosis effect

Development and Evaluation of Peanut Germplasm with Resistance to Aspergillus flavus from Core Collection

Peanut (Arachis hypogaea L.), one of the main oil and cash crops in the world, is easily susceptible to Aspergillus flavus, resulting huge loss in its quality, so Aspergillus flavus infection greatly limits peanut production and industry in China. Therefore, it is imperative to develop new peanut germplasm with resistance to Aspergillus flavus in breeding program. The core collection is well accepted as a useful way to improve the efficiency of crop germplasm evaluation and utilization, which contains a subset of accessions from the entire collection that covers the most of available genetic information. In the present study, a total of 561 accessions of Chinese peanut core collection and 155 accessions of ICRISAT mini core collection were identified. Eight varieties with resistance to Aspergillus flavus invasion and aflatoxin production each were developed, including one (51002-6) with elite agronomic traits. The peanut germplasm with resistance to Aspergillus flavus invasion and aflatoxin production in ICRISAT mini core were more than those in Chinese peanut core collection. In addition, the percentages of accessions with resistance to Aspergillus flavus invasion in var. hypogaea, and accessions resistant to aflatoxin production in var. hirsuta were relatively high in comparison with others. Genetic diversity in the resistant peanut selections was evaluated based on morphological traits and SSR approach. ICG12625 with resistance to aflatoxin production and ICG4750 with resistance to aflatoxin invasion were evaluated by SSR, the genetic distance of them with high-yielding cultivars such as Zhonghua 5, Zhonghua 6 and Zhonghua 12 and Yuanza 9102 was larger. The primers were designed based on the conserved NBS-LRR domains of the disease resistance genes sequence, one RGA (Resistance gene analog) from genomic DNA of six different peanuts with resistance to Aspergillus flavus was obtained through PCR

Olmutinib (BI1482694/HM61713), a Novel Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Reverses ABCG2-Mediated Multidrug Resistance in Cancer Cells

The main characteristic of tumor cell resistance is multidrug resistance (MDR). MDR is the principle cause of the decline in clinical efficacy of chemotherapeutic drugs. There are several mechanisms that could cause MDR. Among these, one of the most important mechanisms underlying MDR is the overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) super-family of transporters, which effectively pump out cytotoxic agents and targeted anticancer drugs across the cell membrane. In recent years, studies found that ABC transporters and tyrosine kinase inhibitors (TKIs) interact with each other. TKIs may behave as substrates or inhibitors depending on the expression of specific pumps, drug concentration, their affinity for the transporters and types of co-administered agents. Therefore, we performed in vitro experiments to observe whether olmutinib could reverse MDR in cancer cells overexpressing ABCB1, ABCG2, or ABCC1 transporters. The results showed that olmutinib at 3 μM significantly reversed drug resistance mediated by ABCG2, but not by ABCB1 and ABCC1, by antagonizing the drug efflux function in ABCG2-overexpressing cells. In addition, olmutinib at reversal concentration affected neither the protein expression level nor the localization of ABCG2. The results observed from the accumulation/efflux study of olmutinib showed that olmutinib reversed ABCG2-mediated MDR with an increasing intracellular drug accumulation due to inhibited drug efflux. We also had consistent results with the ATPase assay that olmutinib stimulated ATPase activity of ABCG2 up to 3.5-fold. Additionally, the molecular interaction between olmutinib and ABCG2 was identified by docking simulation. Olmutinib not only interacts directly with ABCG2 but also works as a competitive inhibitor of the transport protein. In conclusion, olmutinib could reverse ABCG2-mediated MDR. The reversal effect of olmutinib on ABCG2-mediated MDR cells is not due to ABCG2 expression or intracellular localization, but rather related to its interaction with ABCG2 protein resulting in drug efflux inhibition and ATPase stimulation

Dysregulation of hepatic microRNA expression in C57BL/6 mice affected by excretory-secretory products of Fasciola gigantica

The excretory-secretory products released by the liver fluke Fasciola gigantica (FgESPs) play important roles in regulating the host immune response during the infection. Identification of hepatic miRNAs altered by FgESPs may improve our understanding of the pathogenesis of F. gigantica infection. In this study, we investigated the alterations in the hepatic microRNAs (miRNAs) in mice treated with FgESPs using high-throughput small RNA (sRNA) sequencing and bioinformatics analysis. The expression of seven miRNAs was confirmed by quantitative stem-loop reverse transcription quantitative PCR (qRT-PCR). A total of 1,313 miRNAs were identified in the liver of mice, and the differentially expressed (DE) miRNAs varied across the time lapsed post exposure to FgESPs. We identified 67, 154 and 53 dysregulated miRNAs at 1, 4 and 12 weeks post-exposure, respectively. 5 miRNAs (miR-126a-3p, miR-150-5p, miR-155-5p, miR-181a-5p and miR-362-3p) were commonly dysregulated at the three time points. We also found that most of the DE miRNAs were induced by FgESPs in the mouse liver after 4 weeks of exposure. These were subjected to Gene Ontology (GO) enrichment analysis, which showed that the predicted targets of the hepatic DE miRNAs of mice 4 weeks of FgESPs injection were enriched in GO terms, including cell membrane, ion binding, cellular communication, organelle and DNA damage. KEGG analysis indicated that the predicted targets of the most downregulated miRNAs were involved in 15 neural activity-related pathways, 6 digestion-related pathways, 20 immune response-related pathways and 17 cancer-related pathways. These data provide new insights into how FgESPs can dysregulate hepatic miRNAs, which play important roles in modulating several aspects of F. gigantica pathogenesis

The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies

Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte