Predicting Malignancy of Thyroid Micronodules: Radiomics Analysis Based on Two Types of Ultrasound Elastography Images.

RATIONALE AND OBJECTIVES: To develop a multimodal ultrasound radiomics nomogram for accurate classification of thyroid micronodules. MATERIALS AND METHODS: A retrospective study including 181 thyroid micronodules within 179 patients was conducted. Radiomics features were extracted from strain elastography (SE), shear wave elastography (SWE) and B-mode ultrasound (BMUS) images. Minimum redundancy maximum relevance and least absolute shrinkage and selection operator algorithms were used to select malignancy-related features. BMUS, SE, and SWE radiomics scores (Rad-scores) were then constructed. Multivariable logistic regression was conducted using radiomics signatures along with clinical data, and a nomogram was ultimately established. The calibration, discriminative, and clinical usefulness were considered to evaluate its performance. A clinical prediction model was also built using independent clinical risk factors for comparison. RESULTS: An aspect ratio ≥ 1, mean elasticity index, BMUS Rad-score, SE Rad-score, and SWE Rad-score were identified as the independent predictors for predicting malignancy of thyroid micronodules by multivariable logistic regression. The radiomics nomogram based on these characteristics showed favorable calibration and discriminative capabilities (AUCs: 0.903 and 0.881 for training and validation cohorts, respectively), all outperforming clinical prediction model (AUCs: 0.791 and 0.626, respectively). The decision curve analysis also confirmed clinical usefulness of the nomogram. The significant improvement of net reclassification index and integrated discriminatory improvement indicated that multimodal ultrasound radiomics signatures might work as new imaging markers for classifying thyroid micronodules. CONCLUSION: The nomogram combining multimodal ultrasound radiomics features and clinical factors has the potential to be used for accurate diagnosis of thyroid micronodules in the clinic.

The basic route of nuclear-targeted transport of IGF-1/IGF-1R and potential biological functions in intestinal epithelial cells.

OBJECTIVES: Insulin-like growth factor (IGF-1) plays an important role in many biological processes in the intestinal tract. However, the cellular behaviour and characteristics of IGF-1/IGF-1R in intestinal cells remain unclear. MATERIALS AND METHODS: A series of techniques (such as indirect immunofluorescence, co-localization and Western blot) have been used to systematically study the cellular behaviour of IGF-1/IGF-1R on intestinal cells. RESULTS: We found that IGF-1 can not only internalize into the cytoplasm, but also transport into the cell nuclei. We systematically studied the detailed molecular pathways of IGF-1/IGF-1R's nuclear translocation. We found that IGF-1R underwent clathrin-mediated endocytosis into cells and then entered into Rab-5-positive endosomes. Dynein/dynactin were used as motors to drive Rab-5-positive endosomes carrying IGF-1R (cargo molecule) to Golgi apparatus (transit station) along the surface of the microtubule. IGF-1 and/or IGF-1R entered the cell nuclei through NPC (nuclear pore complex), a process mediated by NUP358. Further study indicated that nuclear localization of IGF-1 and/or IGF-1R promoted cell proliferation and increased the nuclear residence time of signalling molecules activated by IGF-1. Further experiments showed that IGF-1R may regulate the transcription of genes in the cell nuclei, indicating that nuclear-localized IGF-1R plays an important in cell proliferation. CONCLUSIONS: In short, we revealed the molecular mechanism by which IGF-1/IGF-1R transports into the cell nuclei of intestinal cells. More importantly, the current work showed that the nuclear-localized IGF-1R has important biological functions.

Synthesis of difluoromethylated 2-oxindoles and quinoline-2,4-diones via visible light-induced tandem radical cyclization of N-arylacrylamides.

Visible light-induced difluoromethylation of N-arylacrylamides to afford difluoromethylated 2-oxindoles and quinoline-2,4-diones with difluoromethyl 2-pyridyl sulfones as radical precursors has been disclosed. This method provides convenient access to a variety of 2-oxindoles and quinoline-2,4-diones under mild conditions via a proposed tandem radical addition/cyclization process along with good tolerance to various functional groups. In addition, preliminary experimental studies have revealed that water is a key factor in difluoromethylation and the reaction involves an oxidative quenching cycle of the photocatalyst.

A sensitive LC-MS/MS-based bioanalytical method for quantification of salviaflaside and rosmarinic acid in rat plasma and its application in a pharmacokinetic study.

A selective and sensitive liquid chromatography tandem mass spectrometry method was developed for the simultaneous determination of salviaflaside and rosmarinic acid in rat plasma. Sample preparation was carried out through liquid-liquid extraction with ethyl acetate using curculigoside as internal standard (IS). The analytes were determined by selected reaction monitoring operated in the positive ESI mode. Chromatographic separation was performed on an Agilent Eclipse Plus C18 column (100 × 4.6 mm, 1.8 µm) with a mobile phase consisting of methanol-water-formic acid (50:50:0.1, v/v/v) at a flow rate of 0.3 mL/min. The run time was 1.9 min per sample and the injection volume was 5 µL. The method had an LLOQ of 1.6 ng/mL for salviaflaside and 0.94 ng/mL for rosmarinic acid in plasma. The linear calibration curves were fitted over the range of 1.6-320 ng/mL for salviaflaside and 0.94-188 ng/mL for rosmarinic acid in plasma with correlation coefficients (r2 ) >0.99. Intra- and inter-day precisions (relative standard deviation) were < 13.5%, and accuracies (relative error) were between -8.6% and 14.5% for all quality control samples. The method was validated and applied to the pharmacokinetics of salviaflaside and rosmarinic acid in plasma after oral administration of Prunella vulgaris extract to rats.

Detection of neural stem cells function in rats with traumatic brain injury by manganese-enhanced magnetic resonance imaging / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previously we had successfully tracked adult human neural stem cells (NSCs) labeled with superparamagnetic iron oxide particles (SPIOs) in host human brain after transplantation in vivo non-invasively by magnetic resonance imaging (MRI). However, the function of the transplanted NSCs could not be evaluated by the method. In the study, we applied manganese-enhanced MRI (ME-MRI) to detect NSCs function after implantation in brain of rats with traumatic brain injury (TBI) in vivo.</p><p><b>METHODS</b>Totally 40 TBI rats were randomly divided into 4 groups with 10 rats in each group. In group 1, the TBI rats did not receive NSCs transplantation. MnCl2·4H2O was intravenously injected, hyperosmolar mannitol was delivered to disrupt rightside blood brain barrier, and its contralateral forepaw was electrically stimulated. In group 2, the TBI rats received NSCs (labeled with SPIO) transplantation, and the ME-MRI procedure was same to group 1. In group 3, the TBI rats received NSCs (labeled with SPIO) transplantation, and the ME-MRI procedure was same to group 1, but diltiazem was introduced during the electrical stimulation period. In group 4, the TBI rats received phosphate buffered saline (PBS) injection, and the ME-MRI procedure was same to group 1.</p><p><b>RESULTS</b>Hyperintense signals were detected by ME-MRI in the cortex areas associated with somatosensory in TBI rats of group 2. These signals, which could not be induced in TBI rats of groups 1 and 4, disappeared when diltiazem was introduced in TBI rats of group 3.</p><p><b>CONCLUSION</b>In this initial study, we mapped implanted NSCs activity and its functional participation within local brain area in TBI rats by ME-MRI technique, paving the way for further pre-clinical research.</p>

[Relationship of different types of abdominal obesity to risk of metabolic syndrome].

OBJECTIVE: To explore the relationship of different types of abdominal obesity to risk of metabolic syndrome (MS). METHODS: Visceral fat area (VA) and substantial fat area (SA) were assessed by CT in 846 patients, 470 males and 376 females, aged 55 +/- 12, who suffered from at least one cardiometabolic risk factor and divided into 4 groups according to their VA and waist circumference (WC): non-obesity, masked visceral fat obesity (VFO), pseudo-VFO, and VFO groups. Blood pressure, fasting blood glucose, fasting serum insulin, and lipid profile were also measured. The MS risks of different types of abdominal obesity were compared. RESULTS: The prevalence rate of masked VFO of males was 10.9% (51/470), significantly higher than that of female (4.8%, 18/376). The prevalence rate of MS of the male patients with masked VFO was 43.1%, significantly higher than that of those in non-obesity group (25.0%), and lower than those of the males in the pseudo-VFO group (78.7%) and in the VFO group (88.6%), whereas the MS prevalence rate of the males in the pseudo-VFO group was significantly higher than those in the non-obesity and masked VFO groups. On the other hand, the MS prevalence rate of the female patients with masked VFO was 33.3%, not significantly different from that of the female patients in the non-obesity group (31.2%), but significantly lower than those of the pseudo-VFO and VFO groups (78.7% and 90.9% respectively). The MS prevalence rate of the female pseudo-VFO patients was also significantly higher than those in the non-obesity and masked VFO groups. Logistic regression analysis showed that WC and VA were independent risk factors for MS [OR (95% CI) = 1.13 (1.10-1.17), 1.01 (1.01-1.02), respectively, P < 0.01). CONCLUSION: Different types of abdominal obesity have important impacts on the risk of metabolic syndrome. Masked VFO, even though with normal WC, and pseudo-VFO have considerably higher cardiometabolic risks.

Directed differentiation of ventral spinal progenitors and motor neurons from human embryonic stem cells by small molecules.

Specification of distinct cell types from human embryonic stem cells (hESCs) is key to the potential application of these naïve pluripotent cells in regenerative medicine. Determination of the nontarget differentiated populations, which is lacking in the field, is also crucial. Here, we show an efficient differentiation of motor neurons ( approximately 50%) by a simple sequential application of retinoid acid and sonic hedgehog (SHH) in a chemically defined suspension culture. We also discovered that purmorphamine, a small molecule that activates the SHH pathway, could replace SHH for the generation of motor neurons. Immunocytochemical characterization indicated that cells differentiated from hESCs were nearly completely restricted to the ventral spinal progenitor fate (NKX2.2+, Irx3+, and Pax7-), with the exception of motor neurons (HB9+) and their progenitors (Olig2+). Thus, the directed neural differentiation system with small molecules, even without further purification, will facilitate basic and translational studies using human motoneurons at a minimal cost.

Effect of cytoplast on the development of inter-subspecies nuclear transfer reconstructed goat embryo.

The aim of this study was to investigate effect of cytoplast on the development competence of reconstructed embryos derived from inter-subspecies somatic cell nucleus transfer (SCNT). First, the development potency of reconstructed embryos produced by transferring Boer goat fibroblast cell nucleus of different ages into enucleated Sannen goat ova was evaluated in order to determine which age of nuclear donor is favorable for the reconstructed embryos development. Secondly, the another component of reconstructed embryos, "cytoplast," was evaluated by comparing the effect of ovum cytoplast derived from Sannen male symbol x Boer female symbol descendant on the reconstructed embryos development to that of Sannen goat ovum cytoplast. The results revealed that the development rate of the reconstructed embryos derived from 2 months old Boer goat somatic cells was the highest, their gestation rate was up to 50%, and one viable male offspring was obtained. The cytoplast derived from the crossbreeding goats improves the development competence of reconstructed embryos, which birth rate was 5.5%. The genetic identification of offspring by using PCR-SSCP analysis confirmed that these cloned kids were derived from the donor. The results above reveal that the cytoplast of Sannen goat ovum could induce the dedifferentiation of somatic cell nuclei derived from Boer goat, but the reprogramming process of these reconstructed embryos seems incomplete, probably due to some incorrect processes happened after implantation. Relatedness components of nucleus donor in cytoplast of the crossbreeding goat may be helpful to induce the dedifferentiation of somatic cell nuclei completely and improve the development competence of the reconstructed embryos.