Search

Kinesin family member 18B (KIF18B) is a new tumor-associated protein that contributes to the carcinogenesis of multiple malignancies. However, the detailed relevance of KIF18B in breast cancer has not been fully elucidated. This work aimed was to evaluate a possible relationship between KIF18B and breast cancer progression. Our findings show KIF18B is increased in breast cancer and demonstrate that high KIF18B level predicts a reduced survival rate. Cellular functional studies revealed that knockdown of KIF18B markedly reduces the proliferation, invasion, and epithelial-mesenchymal transition of breast cancer cells and enhances their chemosensitivity toward doxorubicin. Further studies showed that KIF18B modulates the level of phospho-Akt, phospho-glycogen synthase kinase-3β, and β-catenin. Notably, suppression of Akt abolished KIF18B-overexpression-induced increases in activation of Wnt/β-catenin pathway. In addition, re-expression of β-catenin reversed KIF18B-silencing-induced cancer-promoting effect. In vivo animal experiments elucidated that knockdown of KIF18B significantly weakened the tumorigenicity of breast cancer cells. Taken together, data of this study illustrate that KIF18B exerts a potential cancer-promoting function in breast cancer via enhancement of Wnt/β-catenin pathway through modulation of the Akt/GSK-3β axis.

Deregulation of v-myc avian myelocytomatosis viral oncogene homolog (MYC) occurs in a broad range of human cancers and often predicts poor prognosis and resistance to therapy. However, directly targeting oncogenic MYC remains unsuccessful, and indirectly inhibiting MYC emerges as a promising approach. Checkpoint kinase 1 (CHK1) is a protein kinase that coordinates the G2/M cell cycle checkpoint and protects cancer cells from excessive replicative stress. Using c-MYC-mediated T-cell acute lymphoblastic leukemia (T-acute lymphoblastic leukemia) and N-MYC-driven neuroblastoma as model systems, we reveal that both c-MYC and N-MYC directly bind to the CHK1 locus and activate its transcription. CHIR-124, a selective CHK1 inhibitor, impairs cell viability and induces remarkable synergistic lethality with mTOR inhibitor rapamycin in MYC-overexpressing cells. Mechanistically, rapamycin inactivates carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD), the essential enzyme for the first three steps of de novo pyrimidine synthesis, and deteriorates CHIR-124-induced replicative stress. We further demonstrate that dual treatments impede T-acute lymphoblastic leukemia and neuroblastoma progression in vivo. These results suggest simultaneous targeting of CHK1 and mTOR as a novel and powerful co-treatment modality for MYC-mediated tumors.

Prostate cancer is characterised by significant global disparity; mortality rates in Sub-Saharan Africa are double to quadruple those in Eurasia1. Hypothesising unknown interplay between genetic and non-genetic factors, tumour genome profiling envisages contributing mutational processes2,3. Through whole-genome sequencing of treatment-naïve prostate cancer from 183 ethnically/globally distinct patients (African versus European), we generate the largest cancer genomics resource for Sub-Saharan Africa. Identifying ~2 million somatic variants, Africans carried the greatest burden. We describe a new molecular taxonomy using all mutational types and ethno-geographic identifiers, including Asian. Defined as Global Mutational Subtypes (GMS) A–D, although Africans presented within all subtypes, we found GMS-B to be ‘African-specific’ and GMS-D ‘African-predominant’, including Admixed and European Africans. Conversely, Europeans from Australia, Africa and Brazil predominated within ‘mutationally-quiet’ and ethnically/globally ‘universal’ GMS-A, while European Australians shared a higher mutational burden with Africans in GMS-C. GMS predicts clinical outcomes; reconstructing cancer timelines suggests four evolutionary trajectories with different mutation rates (GMS-A, low 0.968/year versus D, highest 1.315/year). Our data suggest both common genetic factors across extant populations and regional environmental factors contributing to carcinogenesis, analogous to gene-environment interaction defined here as a different effect of an environmental surrounding in persons with different ancestries or vice versa. We anticipate GMS acting as a proxy to intrinsic and extrinsic mutational processes in cancers, promoting global inclusion in landmark studies.

Emerging evidence has indicated that suppression of tumorigenicity 7-like (ST7L) is a tumour suppressor in multiple types of cancers. However, the functional involvement of ST7L has not been studied in breast cancer. In the present study, we aimed to investigate the potential biological function of ST7L in breast cancer. Herein, we found that ST7L expression was frequently downregulated in breast cancer cell lines. Functional assays revealed that ST7L overexpression significantly inhibited the proliferation and invasion of breast cancer cells, while ST7L silencing showed opposite effect. Notably, ST7L was found to decrease glycogen synthase kinase (GSK)-3β phosphorylation and downregulate active β-catenin protein expression, thereby leading to repression of β-catenin transcriptional activity. Activation of Wnt/β-catenin signalling by treatment of GSK-3β inhibitor significantly abrogated ST7L-mediated antitumour effect. Additionally, ST7L overexpression blunted the tumorigenicity of breast cancer cells in vivo in xenograft mice. Taken together, our results demonstrate that ST7L exerts antitumor function in breast cancer associated with the suppression of Wnt/β-catenin signalling, suggesting ST7L as a potential therapeutic target for breast cancer.

BackgroundEndoscopic carpal tunnel release (ECTR) has been gradually adopted for the treatment of severe carpal tunnel syndrome (CTS). However, perioperative assessment of neuroanatomical parameters of median nerve, which are important determinant of median nerve recovery, has rarely been reported. This one-year prospective study aimed to investigate the natural history of the neuroanatomical morphology of the median nerve after ECTR in severe CTS patients by high-frequency ultrasonography and assess the ability of neuroanatomical measures to quantify morphological recovery of the median nerve after ECTR.MethodsThis study recruited 31 patients (44 wrists) with a definitive diagnosis of severe CTS and underwent ECTR operation. The edema length (EL) of median nerve from the inlet of the carpal tunnel to the proximal wrist was detected on long axis imaging plane and the anteroposterior diameter (D) and cross-sectional area (CSA) at the inlet of the carpal tunnel on short axis imaging plane were detected by high frequency ultrasound. All these metrics were detected at 3 days before surgery and at the 2nd week, 4th week, 3rd month, 6th month and 12th month after surgery separately.ResultsThere was no significant difference of each parameter between the 2-week postoperative (1.914 ± 0.598 cm in EL, 0.258 ± 0.039 cm in D and 0.138 ± 0.015 cm2in CSA) and 3-days preoperative time points (P-EL =0.250;P-D = 0.125;P-CSA =0.712). From the fourth week to the third month after surgery, the parameters quickly improved. The EL (0.715 ± 0.209 cm), D (0.225 ± 0.017 cm) and CSA (0.117 ± 0.012 cm2) at the 3- month postoperative time points were more reduced than at the fourth week after surgery (P-EL P-D = 0.038;P-CSA =0.014). Thereafter, the neurological anatomy parameters recovered slowly. By the 12-month postoperative time points, the three parameters were neuroanatomically close to normal. Compared to the control group in D (0.213 ± 0.005 cm), there was no difference at the 12-month time point (0.214 ± 0.009 cm,P = 0.939). However, the difference in EL (0.098 ± 0.030 cm vs. 0.016 ± 0.011 cm) and CSA (0.103 ± 0.008 cm2vs. 0.073 ± 0.005 cm2) between patients and healthy volunteers at the 12-month time point still existed (P-EL P-CSA ConclusionsNeuroanatomical parameters were gradually improved after ECTR surgery. The best time for US follow up is at 3-month postoperative time point for patients who do not show clinical improvement, since at this time the change is the greatest for most CTS patients. This study has been registered in Chinese Clinical Trial Registry: ChiCTR-ROC-17014068 (retrospectively registered 20-12-2017).

The aim of the present study was to investigate the changes in cardiac function and myocardial damage in rats with cirrhosis. In addition, a secondary aim was to explore any potential changes in the expression levels of β1-adrenergic (β1) and muscarinic acetylcholine (M2) receptors . A cirrhotic cardiomyopathy (CCM) rat model was established by CCL4-oil solution for subcutaneous injection into the neck. Pathological changes in the liver and myocardial tissues were detecting by H&E staining and Masson trichrome staining. Furthermore, changes in the levels of myocardial enzymes lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) and troponin in serum were measured by ELISA. The myocardial samples were homogenized and centrifuged. Subsequently, the supernatant was collected for detecting the expression of interleukins in myocardial tissue. Changes in the levels of inflammatory factors, IL-1, IL-2 and IL-6 both in the serum and myocardial tissue were determined by ELISA. Changes in echocardiographic measurements were evaluated using high-frequency ultrasound and the expression levels of β1 and M2 receptors in myocardial tissues were determined by western blotting. The normal lobular structure in liver tissues was found to be disappeared 8 weeks after modeling, which was replaced by pseudolobules in the rats in the CCM group. In addition, the myocardial cells were observed to be swollen and disorderly arranged. Compared with those in the control group, the left ventricular end-systolic and end-diastolic dimensions, interventricular septal dimension and LAD in rats in the CCM8 group were found to be significantly increased. The levels of myocardial enzymes LDH, CK-MB and cardiac troponin in the serum were also revealed to be significantly increased in the CCM8 group. Additionally, the levels of IL-1 and IL-6 in both serum and myocardial tissues were significantly increased in rats in the CCM8 group. However, the levels of IL-2 in both serum and myocardial tissues were decreased, which were observed alongside reductions in myocardial β1 and M2 receptor protein expression in the myocardial tissues. Taken together, these results indicate that inflammatory factors may be involved in mediating damage to the myocardium in rats with cirrhosis. During cirrhosis-induced cardiac dysfunction, there may exist a mechanism for downregulation of autonomic nerve system.

Background and purpose: Magnetic resonance (MR) only radiation therapy for prostate treatment provides superior contrast for defining targets and organs-at-risk (OARs). This study aims to develop a deep learning model to leverage this advantage to automate the contouring process. Materials and methods: Six structures (bladder, rectum, urethra, penile bulb, rectal spacer, prostate and seminal vesicles) were contoured and reviewed by a radiation oncologist on axial T2-weighted MR image sets from 50 patients, which constituted expert delineations. The data was split into a 40/10 training and validation set to train a two-dimensional fully convolutional neural network, DeepLabV3+, using transfer learning. The T2-weighted image sets were pre-processed to 2D false color images to leverage pre-trained (from natural images) convolutional layers’ weights. Independent testing was performed on an additional 50 patient’s MR scans. Performance comparison was done against a U-Net deep learning method. Algorithms were evaluated using volumetric Dice similarity coefficient (VDSC) and surface Dice similarity coefficient (SDSC). Results: When comparing VDSC, DeepLabV3+ significantly outperformed U-Net for all structures except urethra (P

Background B-mode ultrasound is one of the most commonly used imaging techniques for evaluating thyroid nodules due to its noninvasive property and excellent performance in terms of discriminating between benign and malignant nodules. However, the accuracy of differential diagnosis strongly depends on the experience of ultrasonographers. In addition to B-mode ultrasound, the elastic mode and contrast-enhanced mode have shown complimentary value in the diagnosis of thyroid nodules. The combination of multiple modes in ultrasonic techniques may effectively undermine diagnostic subjectiveness and improve accuracy. In this study, we evaluated the diagnostic value of combining the three ultrasonic modes for differentiating thyroid cancers. Methods In this retrospective study, we analyzed a total of 196 thyroid nodules with suspected malignancies from 185 patients who gave informed consent. Xi’an Jiaotong University granted ethical approval (No. 2018200) to carry out the study within its facilities. All the patients received ultrasonic examinations with the B mode, elastic mode and contrast-enhanced mode, followed by histopathological confirmation by fine-need aspiration or surgery. A predictive multivariate logistic regression model was selected to integrate the variety of data obtained from the three modes. Results The combination of three ultrasonic techniques for differentiating malignant from benign thyroid nodules showed the highest diagnostic accuracy of 0.985 compared to the B mode alone (0.841) and the two-mode combination. The accuracy of the B mode combined with the elastic technique was 0.954, and the accuracy of the B mode combined with the contrast-enhanced technique was 0.960. Discussion Multimode ultrasonic techniques should be recommended to patients with suspected malignant thyroid nodules in routine clinical practice.

A major rise in the prevalence and influence of colorectal cancer (CRC) leads to substantially increasing healthcare costs and even death. It is widely accepted that early detection and removal of colonic polyps can prevent CRC. Detection of colonic polyps in colonoscopy videos is problematic because of complex environment of colon and various shapes of polyps. Currently, researchers indicate feasibility of Convolutional Neural Network (CNN)-based detection of polyps but better feature extractors are needed to improve detection performance. In this paper, we investigated the potential of the single shot detector (SSD) framework for detecting polyps in colonoscopy videos. SSD is a one-stage method, which uses a feed-forward CNN to produce a collection of fixed-size bounding boxes for each object from different feature maps. Three different feature extractors, including ResNet50, VGG16, and InceptionV3 were assessed. Multi-scale feature maps integrated into SSD were designed for ResNet50 and InceptionV3, respectively. We validated this method on the 2015 MICCAI polyp detection challenge datasets, compared it with teams attended the challenge, YOLOV3 and two-stage method, Faster-RCNN. Our results demonstrated that the proposed method surpassed all the teams in MICCAI challenge and YOLOV3 and was comparable with two-stage method. Especially in detection speed aspect, our proposed method outperformed all the methods, met real-time application requirement. Meanwhile, we also indicated that among all the feature extractors, InceptionV3 obtained the best result of precision and recall. In conclusion, SSD- based method achieved excellent detection performance in polyp detection and can potentially improve diagnostic accuracy and efficiency.

Volumetric lung tumor segmentation and accurate longitudinal tracking of tumor volume changes from computed tomography images are essential for monitoring tumor response to therapy. Hence, we developed two multiple resolution residually connected network (MRRN) formulations called incremental-MRRN and dense-MRRN. Our networks simultaneously combine features across multiple image resolution and feature levels through residual connections to detect and segment the lung tumors. We evaluated our method on a total of 1210 non-small cell (NSCLC) lung tumors and nodules from three data sets consisting of 377 tumors from the open-source Cancer Imaging Archive (TCIA), 304 advanced stage NSCLC treated with anti- PD-1 checkpoint immunotherapy from internal institution MSKCC data set, and 529 lung nodules from the Lung Image Database Consortium (LIDC). The algorithm was trained using 377 tumors from the TCIA data set and validated on the MSKCC and tested on LIDC data sets. The segmentation accuracy compared to expert delineations was evaluated by computing the dice similarity coefficient, Hausdorff distances, sensitivity, and precision metrics. Our best performing incremental-MRRN method produced the highest DSC of 0.74 ± 0.13 for TCIA, 0.75±0.12 for MSKCC, and 0.68±0.23 for the LIDC data sets. There was no significant difference in the estimations of volumetric tumor changes computed using the incremental-MRRN method compared with the expert segmentation. In summary, we have developed a multi-scale CNN approach for volumetrically segmenting lung tumors which enables accurate, automated identification of and serial measurement of tumor volumes in the lung.

PURPOSE Breast cancer is the most common cancer among women worldwide. Medical ultrasound imaging is one of the widely applied breast imaging methods for breast tumors. Automatic breast ultrasound (BUS) image segmentation can measure the size of tumors objectively. However, various ultrasound artifacts hinder segmentation. We proposed an attention-supervised full-resolution residual network (ASFRRN) to segment tumors from BUS images. METHODS In the proposed method, Global Attention Upsample (GAU) and deep supervision were introduced into a full-resolution residual network (FRRN), where GAU learns to merge features at different levels with attention for deep supervision. Two datasets were employed for evaluation. One (Dataset A) consisted of 163 BUS images with tumors (53 malignant and 110 benign) from UDIAT Centre Diagnostic, and the other (Dataset B) included 980 BUS images with tumors (595 malignant and 385 benign) from the Sun Yat-sen University Cancer Center. The tumors from both datasets were manually segmented by medical doctors. For evaluation, the Dice coefficient (Dice), Jaccard similarity coefficient (JSC), and F1 score were calculated. RESULTS For Dataset A, the proposed method achieved higher Dice (84.3 ± 10.0%), JSC (75.2 ± 10.7%), and F1 score (84.3 ± 10.0%) than the previous best method: FRRN. For Dataset B, the proposed method also achieved higher Dice (90.7 ± 13.0%), JSC (83.7 ± 14.8%), and F1 score (90.7 ± 13.0%) than the previous best methods: DeepLabv3 and dual attention network (DANet). For Dataset A + B, the proposed method achieved higher Dice (90.5 ± 13.1%), JSC (83.3 ± 14.8%), and F1 score (90.5 ± 13.1%) than the previous best method: DeepLabv3. Additionally, the parameter number of ASFRRN was only 10.6 M, which is less than those of DANet (71.4 M) and DeepLabv3 (41.3 M). CONCLUSIONS We proposed ASFRRN, which combined with FRRN, attention mechanism, and deep supervision to segment tumors from BUS images. It achieved high segmentation accuracy with a reduced parameter number.

MicroRNAs (miRNAs) contribute to tumorigenesis and progression via acting as tumor suppressors or oncogenes in human cancer. Aberrant expression of miR-302c has been reported in various types of cancer except colorectal cancer (CRC). Thus, our study was aimed to verify the expression of miR-302c and its functional role in CRC. We found a significant reduced expression of miR-302c in CRC tissues compared to tumor-adjacent tissues. Low miR-302c level was remarkably correlated with deeper tumor invasion, lymph node metastasis and advanced TNM stage. Importantly, low miR-302c expression was identified as an independent indicator for poor prognosis of CRC patients. Overexpression of miR-302c repressed migration and invasion capacities of SW620 and SW480 cells in vitro. Mechanistically, miR-302c inversely regulated transcription factor AP4 (TFAP4) abundance in both SW620 and SW480 cells, and it negatively correlated with TFAP4 mRNA expression in CRC samples. Herein, TFAP4, a regulator of epithelial-mesenchymal transition (EMT), was recognized as a direct target gene of miR-302c in CRC. Otherwise, miR-302c overexpression increased E-cadherin expression and reduced the levels of Vimentin and SNAI1, suggesting an inhibitory effect of miR-302c on EMT of CRC cells. Notably, our findings established that the EMT and metastasis of Caco-2 cells were enhanced by miR-302c knockdown, and subsequently reversed by TFAP4 silencing. Collectively, these data indicate that miR-302c represses EMT and CRC metastasis possibly by targeting TFAP4, and it may serve as a potential prognostic factor and therapeutic target for CRC.

Portal hypertension is a major cause of mortality and morbidity in cirrhotic patients. In this study, we aimed to analyze the clinical characteristics of Alu-mediated p21 transcriptional regulator (APTR) during transjugular intrahepatic portosystemic shunt (TIPS) procedure. Portal and hepatic venous blood was drawn from 84 patients with liver cirrhosis and portal hypertension before and after TIPS treatment. Then, we detected biochemical, hemodynamic parameters and APTR expression before and after TIPS treatment. Indeed, TIPS treatment could markedly ameliorate the serum blood urea nitrogen (BUN) level and portal vein hemodynamics in cirrhotic patients. We found that portal venous levels of APTR was significantly decreased after TIPS treatment and its aberrant expression levels were positively correlated with Model for End Stage Liver Disease (MELD), portal hepatic venous pressure gradient (PHPG) in patients. Higher APTR expression in portal vein was associated with poor prognosis. APTR level in portal vein was an independent predictors of mortality. Our data indicated that APTR may serve as a novel biomarker for cirrhotic patients with portal hypertension before and after receiving TIPS.

The aim of this study was to explore the value of transcutaneous laryngeal ultrasonography in the diagnosis of vocal fold polyps. From December 2016 to June 2019, 87 patients with vocal fold polyps diagnosed pathologically in the Otolaryngology Head and Neck Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University were enrolled and examined by electronic laryngoscopy and percutaneous laryngeal ultrasound on the same day before operation. To observe the effect of calcification length as a percentage of thyroid cartilage at the glottic level on vocal fold display, the characteristics of ultrasound images of vocal fold polyps and the value of transcutaneous laryngeal ultrasonography in the diagnosis of vocal fold polyps were assessed. Among 87 patients, the calcification rate of thyroid cartilage at the glottic level was 33.3%. The differences in calcification rate and percentage of calcification length between males and females were statistically significant. The rate of detection of vocal folds decreased gradually with an increase in calcification length percentage. Imaging features of vocal fold polyps were hypo-echoic with a clear boundary and regular shape. The detection rates for circular and non-circular polyps were 92.0% and 70.6%. Ultrasound was more likely to detect circular than non-circular polyps; however, the difference was not significant. Transcutaneous laryngeal ultrasonography can identify the morphology and location of vocal fold polyps and is non-invasive and highly accurate. Therefore, it has the potential to be an effective supplement to laryngoscopy for initial screening and post-operative review of vocal fold polyps.

Forkhead box protein A1 (FOXA1) is a transcription factor; recent studies have reported that FOXA1 has an oncogenic or tumor suppressive role in human malignancies, and its expression is associated with the prognosis of patients with cancer. However, further studies are required to determine the clinical significance of FOXA1 and its role in colorectal cancer (CRC). In the present study, FOXA1 expression was detected in 90 samples of CRC tissues and matched noncancerous tissues using immunohistochemistry. In these cases, FOXA1 expression was detected in 57.8% (52/90) of the CRC samples, whereas only 37.8% (34/90) of the noncancerous specimens exhibited a positive FOXA1 signal. In addition, the present study demonstrated that the mRNA expression levels of FOXA1 were significantly increased in CRC tissues compared with in matched tumor-adjacent tissues. Furthermore, the positive expression of FOXA1 was associated with poor clinicopathological characteristics of CRC, including poor tumor differentiation, large tumor size, lymph node metastases and advanced tumor-node-metastasis tumor stage. Notably, patients with CRC with positive FOXA1 expression exhibited a significantly reduced 5-year survival rate compared with those with negative FOXA1 expression. Multivariate Cox regression analysis revealed that FOXA1 expression was an independent prognostic indicator for patients with CRC. In addition, FOXA1 knockdown evidently inhibited cell proliferation and induced apoptosis in SW480 and HCT116 CRC cells. Notably, FOXA1 knockdown also prominently reduced the expression of yes-associated protein (YAP) in SW480 and HCT116 cells. In conclusion, the results of the present study indicated that FOXA1 may be considered a potential prognostic marker, and may promote tumor growth of CRC by upregulating YAP expression.

Purpose To predict the spatial and temporal trajectories of lung tumor during radiotherapy monitored under a longitudinal magnetic resonance imaging (MRI) study via a deep learning algorithm for facilitating adaptive radiotherapy (ART). Methods We monitored 10 lung cancer patients by acquiring weekly MRI-T2w scans over a course of radiotherapy. Under an ART workflow, we developed a predictive neural network (P-net) to predict the spatial distributions of tumors in the coming weeks utilizing images acquired earlier in the course. The three-step P-net consisted of a convolutional neural network to extract relevant features of the tumor and its environment, followed by a recurrence neural network constructed with gated recurrent units to analyze trajectories of tumor evolution in response to radiotherapy, and finally an attention model to weight the importance of weekly observations and produce the predictions. The performance of P-net was measured with Dice and root mean square surface distance (RMSSD) between the algorithm-predicted and experts-contoured tumors under a leave-one-out scheme. Results Tumor shrinkage was 60% ± 27% (mean ± standard deviation) by the end of radiotherapy across nine patients. Using images from the first three weeks, P-net predicted tumors on future weeks (4, 5, 6) with a Dice and RMSSD of (0.78 ± 0.22, 0.69 ± 0.24, 0.69 ± 0.26), and (2.1 ± 1.1 mm, 2.3 ± 0.8 mm, 2.6 ± 1.4 mm), respectively. Conclusion The proposed deep learning algorithm can capture and predict spatial and temporal patterns of tumor regression in a longitudinal imaging study. It closely follows the clinical workflow, and could facilitate the decision-making of ART. A prospective study including more patients is warranted.

Hashimoto’s disease (HD) is one of the major clinical subtypes of autoimmune thyroid disease. Both environmental and genetic factors contribute to the pathogenesis of HD. Previous evidence has shown that both IRAK2 and TLR10 are potential candidate susceptibility genes for HD. In this study, a total of 3654 Chinese women, including 973 HD cases and 2681 healthy controls, were recruited. Thirty-three tag single nucleotide polymorphisms (SNPs) in IRAK2 and TLR10 were genotyped. Genetic association analyses at both the single-marker and haplotype levels were performed. Gene-by-gene interaction analyses were also conducted in case-only samples, as well as eQTL analyses for significant SNPs based on data extracted from the GTEx database. We identified that two SNPs, rs165501 (OR = 1.20, P = 0.0008, IRAK2) and rs10004195 (OR = 1.23, P = 0.0001, TLR10), were identified to be significantly associated with HD. Rs10004195 was significantly associated with the gene expression of TLR10 in human pituitary tissues (P = 2.00 × 10−4), while rs165501 was significantly associated with the expression of IRAK2 in human thyroid tissues (P = 3.10 × 10−6). No significant results were obtained in the gene-by-gene interaction analyses. Our findings suggest that both IRAK2 and TLR10 play important roles in the onset and development of HD.

Sperm-associated antigen 5 (SPAG5) has currently emerged as a novel oncogene in various cancers. High expression of SPAG5 has been frequently detected in breast cancer. However, the biological function and regulatory mechanism of SPAG5 in breast cancer remain unclear. In this study, we aimed to investigate the potential biological function of SPAG5 in breast cancer cells. Herein, we found that both the mRNA and protein expression of SPAG5 were significantly up-regulated in breast cancer cell lines. Functional experiments showed that silencing of SPAG5 inhibited the proliferation and invasion of breast cancer cells, while the overexpression of SPAG5 promoted the proliferation and invasion of breast cancer cells. Mechanistic investigation demonstrated that SPAG5 promoted the expression of Wnt3 and β-catenin, and increased the activation of β-catenin/TCF4 transcriptional activity. Notably, the inhibition of Wnt3 partially reversed the promotion effect of SPAG5 on breast cancer cell proliferation and invasion and β-catenin/TCF4 signalling. In addition, the inhibition of β-catenin also significantly abrogated SPAG5-mediated oncogenic effects in breast cancer. Taken together, these findings demonstrate that SPAG5 promotes the proliferation and invasion of breast cancer cells by activating Wnt/β-catenin signalling via up-regulating Wnt3 expression.

Accumulating evidence has suggested that microRNA-449b-5p (miR-449b-5p) plays an important role in the development and progression of multiple cancers. However, little is known about the role of miR-449b-5p in breast cancer. In this study, we aimed to investigate the expression level, biological function and underlying mechanism of miR-449b-5p in breast cancer. Our results showed that miR-449b-5p expression was frequently down-regulated in breast cancer cell lines and tissues. The overexpression of miR-449b-5p significantly inhibited growth and invasion, and induced the cell cycle arrest of breast cancer cells. In contrast, the inhibition of miR-449b-5p showed the opposite effect. Interestingly, bioinformatic analysis predicted that cell cycle-related and expression-elevated protein in tumor (CREPT), an important oncogene in breast cancer, was a potential target gene of miR-449b-5p. The overexpression of miR-449b-5p decreased CREPT expression while miR-449b-5p inhibition promoted CREPT expression in breast cancer cells. Restoration of CREPT expression in miR-449b-5p mimics transfected cells partially reversed the suppressive effect of miR-449b-5p on breast cancer cell growth and invasion. Notably, our results showed that miR-449b-5p overexpression decreased the expression of β-catenin and suppressed the activation of Wnt/β-catenin/TCF-4 signaling via targeting CREPT. In addition, blocking Wnt/β-catenin partially reversed the promotion effect of miR-449b-5p inhibition on breast cancer cell growth and invasion. Overall, these results reveal a tumor suppressive role of miR-449b-5p that restricts the growth and invasion of breast cancer cells through targeting CREPT and inhibiting CREPT-mediated activation of Wnt/β-catenin signaling. Our study suggests that the miR-449b-5p/CREPT/Wnt/β-catenin axis may play an important role in the pathogenesis of breast cancer and miR-449-5p may serve as a potential therapeutic target for breast cancer.

We present an adversarial domain adaptation based deep learning approach for automatic tumor segmentation from T2-weighted MRI. Our approach is composed of two steps: (i) a tumor-aware unsupervised cross-domain adaptation (CT to MRI), followed by (ii) semi-supervised tumor segmentation using Unet trained with synthesized and limited number of original MRIs. We introduced a novel target specific loss, called tumor-aware loss, for unsupervised cross-domain adaptation that helps to preserve tumors on synthesized MRIs produced from CT images. In comparison, state-of-the art adversarial networks trained without our tumor-aware loss produced MRIs with ill-preserved or missing tumors. All networks were trained using labeled CT images from 377 patients with non-small cell lung cancer obtained from the Cancer Imaging Archive and unlabeled T2w MRIs from a completely unrelated cohort of 6 patients with pre-treatment and 36 on-treatment scans. Next, we combined 6 labeled pre-treatment MRI scans with the synthesized MRIs to boost tumor segmentation accuracy through semi-supervised learning. Semi-supervised training of cycle-GAN produced a segmentation accuracy of 0.66 computed using Dice Score Coefficient (DSC). Our method trained with only synthesized MRIs produced an accuracy of 0.74 while the same method trained in semi-supervised setting produced the best accuracy of 0.80 on test. Our results show that tumor-aware adversarial domain adaptation helps to achieve reasonably accurate cancer segmentation from limited MRI data by leveraging large CT datasets.

Colorectal cancer (CRC) is a highly invasive tumor that is frequently associated with distant metastasis, which is the primary cause of poor prognosis. However, the mechanisms of metastasis remain poorly understood. MicroRNAs (miRNAs/miRs) have been considered to be implicated in CRC progression. In particular, miR-517a is proposed as a novel tumor-associated miRNA and has a potential role in tumor metastasis. The expression of miR-517a in CRC specimens was detected by reverse transcription-quantitative polymerase chain reaction. Transwell assays were performed to determine the migration and invasion of CRC cells. The putative target genes of miR-517a were disclosed using publicly available databases and western blot analysis. The present study identified that the expression of miR-517a was significantly higher in CRC tissues as compared with adjacent non-tumor tissues. Clinical analysis indicated that increased expression of miR-517a was correlated with poor prognostic features and poor long-term survival of CRC patients. In vitro evidences demonstrated that downregulation of miR-517a inhibited cell migration and invasion in HCT-116 cells. By contrast, upregulation of miR-517a increased the number of migrated and invaded SW480 cells. Notably, miR-517a expression was inversely regulated by forkhead box J3 (FOXJ3) abundance in CRC cells. Furthermore, an inverse correlation between miR-517a and FOXJ3 expression was observed in CRC tissues. In conclusion, miR-517a appears to be an independent prognostic marker for predicting survival of CRC patients, and may promote cell migration and invasion by inhibiting FOXJ3.

Purpose To evaluate the discriminatory value of carotid artery wall thickness and elasticity for thyroid dysfunction in Hashimoto's thyroiditis (HT) patients. Methods A total of 180 female HT patients were assigned to three groups on the basis of laboratory testing: HT hyperthyroidism group (group A), HT hypothyroidism group (group B), and HT euthyroid group (group C). We used radiofrequency sonographic signal analysis for the measurement of intima-media thickness and arterial stiffness. Results Intima-media thickness was significantly higher in group A than in other groups. After stepwise variable selection, distensibility coefficient (DC), compliance coefficient, stiffness index (β), and pulse wave velocity (PWV) were selected to discriminate different thyroid hormone levels, resulting in the following discriminant function: Z1 = −0.398DC + 0.803PWV. The receiver-operator characteristic curve analysis showed that the critical points were DC = 0.022 kPa−1 and PWV = 5.36 m/s for HT hyperthyroidism, and DC = 0.016 kPa−1 and PWV = 6.875 m/s for HT hypothyroidism. Conclusions DC and PWV may be useful for the evaluation of thyroid function in HT patients. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound, 2016

The incidence of Alzheimer’s disease (AD) in individuals >65 years of age is 13% and ~66 million individuals in this age group undergo surgery annually under anesthesia. It is therefore important to determine whether commonly used inhaled anesthetics induce cytotoxicity, which may lead to neurodegeneration. Findings from several studies suggest that the anesthetics, isoflurane, sevoflurane and desflurane, may activate caspases, increase the synthesis and accumulation of β-amyloid (Aβ) protein, and induce hyperphosphorylation of tau proteins, all of which are cellular responses consistent with the neuropathogenesis of AD. Other studies have arrived at different and occasionally contradictory conclusions. The present review attempts to resolve this discrepancy by reviewing previous studies, which have investigated the effects of commonly used inhaled anesthetics on the synthesis and accumulation of Aβ, tau pathology and cognitive function. The possible underlying mechanism was also reviewed. However, several aspects of this phenomenon remain to be elucidated. Further studies are required to fully examine anesthesia-induced neurotoxicity and elucidate the effect of inhaled anesthetics on the onset and progression of AD.

Aberrant activation of Wnt signaling pathway is crucial for the onset and progression of human colorectal cancer (CRC). Owing to the persistent dependence on Wnt signaling for growth and survival, inhibition of this pathway is an attractive approach for new therapies. 11α, 12α-epoxyleukamenin E (EPLE) is a novel ent-kaurane diterpenoid that we previously isolated from Salvia cavaleriei, exhibiting antitumor activities in a variety of cancer cells. Herein, we found that whereas sparing normal human colon mucosal epithelial cells, EPLE selectively inhibited the proliferation of CRC cell lines as well as primary tumor cells. Mechanistically, we demonstrated EPLE exerted its function through suppressing Wnt signaling pathway, as evidenced by EPLE-mediated downregulation of Wnt target genes such as c-Myc, Axin2 and Survivin. Consistently, luciferase reporter assays showed that the EPLE directly blocked Wnt/β-catenin-mediated transcriptional activation. In combination of co-immunoprecipitation and protein structure-based analyses, we determined that the EPLE entered the interface of β-catenin/TCF4 complexes and blocked their interaction that is required for β-catenin-mediated transcriptional activation. Moreover, overexpression of β-catenin alleviated the cytotoxicity of EPLE in CRC cells, supporting Wnt signaling is a major and specific target of EPLE. Combined treatments of EPLE and 5-fluorouracil, the first-line chemotherapy for CRC patients, achieved a synergistic effect. More importantly, EPLE hampered tumor development in a CRC xenograft model. Our data thus establish EPLE as a novel inhibitor of Wnt signaling that holds great promise as a potential candidate for further preclinical evaluation for CRC treatments.

The aim of this study was to investigate the diagnostic values of conventional ultrasound and contrast-enhanced ultrasound (CEUS) in benign and malignant thyroid nodules with calcification. Conventional ultrasound and CEUS were performed in 122 patients with thyroid nodules with calcification. The thyroid nodules were characterized as benign or malignant by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of the two imaging methods were determined. The area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic values of the two imaging methods. In 122 cases of thyroid nodules with calcification, 73 benign nodules and 49 malignant nodules were verified by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of conventional ultrasound were 50%, 77%, 59%, 69%, and 66%, respectively, and those of CEUS were 90%, 92%, 88%, 93%, and 91%, respectively. There were significant differences between the two imaging methods. AUCs of conventional ultrasound and CEUS were 0.628 ± 0.052 and 0.908 ± 0.031, suggesting low and high diagnostic values, respectively. CEUS has high diagnostic values, being significantly greater than those of conventional ultrasound, in differential diagnosis of benign and malignant thyroid nodules with calcification.

Sevoflurane, an inhalational anesthetic, is extensively used during oral cancer surgery. However, the effect of sevoflurane on head and neck squamous cell carcinoma (HNSCC) remains unclear. The objective of the present study was to investigate the effects of sevoflurane on the proliferation, apoptosis and invasion in HNSCC cell lines and the underlying molecular mechanism. The Cell Counting Kit-8 assay was used to evaluate cell proliferation. Apoptosis was analyzed by flow cytometry. Cell invasion was evaluated using the Transwell invasion assay. The expression levels of Akt, p-Akt (Ser473), hypoxia‑inducible factor-1α (HIF-1α), Fas and Bcl-2 were measured by western blotting. Significant inhibition of cell proliferation and induction of apoptosis were observed in FaDu and CAL-27 cells following sevoflurane treatment. The expression of Akt, p-Akt (Ser473) and Bcl-2 was supressed, while that of Fas was significantly increased, which was partly associated with the activation of the HIF-1α pathway. In addition, the results revealed a statistically significant inhibition of cell invasion in the FaDu cell line following exposure to 2 and 4% sevoflurane for 2, 4, 6 and 8 h. Therefore, the present study demonstrated that sevoflurane decreased the malignant behavior of HNSCC cell lines in vitro, which was associated with activation of the HIF-1α pathway.

Summary Deregulation of MYC plays an essential role in T cell acute lymphoblastic leukemia (T-ALL), yet the mechanisms underlying its deregulation remain elusive. Herein, we identify a molecular mechanism responsible for reciprocal activation between Aurora B kinase (AURKB) and MYC. AURKB directly phosphorylates MYC at serine 67, counteracting GSK3β-directed threonine 58 phosphorylation and subsequent FBXW7-mediated proteasomal degradation. Stabilized MYC, in concert with T cell acute lymphoblastic leukemia 1 (TAL1), directly activates AURKB transcription, constituting a positive feedforward loop that reinforces MYC-regulated oncogenic programs. Therefore, inhibitors of AURKB induce prominent MYC degradation concomitant with robust leukemia cell death. These findings reveal an AURKB-MYC regulatory circuit that underlies T cell leukemogenesis, and provide a rationale for therapeutic targeting of oncogenic MYC via AURKB inhibition.

Sevoflurane is the most widely used anaesthetic administered by inhalation. Exposure to sevoflurane in neonatal mice can induce learning deficits and abnormal social behaviours. MicroRNA (miR)-27a-3p, a short, non-coding RNA that functions as a tumour suppressor, is up-regulated after inhalation of anaesthetic, and peroxisome proliferator-activated receptor γ (PPAR-γ) is one of its target genes. The objective of this study was to investigate how the miR-27a-3p-PPAR-γ interaction affects sevoflurane-induced neurotoxicity. A luciferase reporter assay was employed to identify the interaction between miR-27a-3p and PPAR-γ. Primary hippocampal neuron cultures prepared from embryonic day 0 C57BL/6 mice were treated with miR-27a-3p inhibitor or a PPAR-γ agonist to determine the effect of miR-27a-3p and PPAR-γ on sevoflurane-induced cellular damage. Cellular damage was assessed by a flow cytometry assay to detect apoptotic cells, immunofluorescence to detect reactive oxygen species, western blotting to detect NADPH oxidase 1/4 and ELISA to measure inflammatory cytokine levels. In vivo experiments were performed using a sevoflurane-induced anaesthetic mouse model to analyse the effects of miR-27a-3p on neurotoxicity by measuring the number of apoptotic neurons using the Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) method and learning and memory function by employing the Morris water maze test. Our results revealed that PPAR-γ expression was down-regulated by miR-27a-3p following sevoflurane treatment in hippocampal neurons. Down-regulation of miR-27a-3p expression decreased sevoflurane-induced hippocampal neuron apoptosis by decreasing inflammation and oxidative stress-related protein expression through the up-regulation of PPAR-γ. In vivo tests further confirmed that inhibition of miR-27a-3p expression attenuated sevoflurane-induced neuronal apoptosis and learning and memory impairment. Our findings suggest that down-regulation of miR-27a-3p expression ameliorated sevoflurane-induced neurotoxicity and learning and memory impairment through the PPAR-γ signalling pathway. MicroRNA-27a-3p may, therefore, be a potential therapeutic target for preventing or treating sevoflurane-induced neurotoxicity.

Henoch-Schönlein purpura (HSP) is the most common form of systemic small-vessel vasculitis in children, and HSP nephritis (HSPN) is a major complication of HSP and is the primary cause of morbidity and mortality. Previous studies have suggested that inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of HSP. In this study, we performed a detailed analysis to investigate the potential association between iNOS polymorphisms and the risk of HSP and the tendency for children with HSP to develop HSPN in a Chinese Han population. A promoter pentanucleotide repeat (CCTTT)n and 10 functional single-nucleotide polymorphisms (SNPs) from 532 healthy controls and 513 children with HSP were genotyped using the MassARRAY system and GeneScan. The results suggested that the allelic and genotypic frequencies of the rs3729508 polymorphism were nominally associated with susceptibility to HSP. In addition, there was a significant difference in the allelic distribution of the (CCTTT)12 repeats and rs2297518 between the HSP children with and without nephritis; the HSP children with nephritis exhibited a significantly higher frequency of the (CCTTT)12 repeats and A allele of rs2297518 than the HSP children without nephritis (POur results support that iNOS polymorphisms are associated with the risk of HSP and may strongly contribute to the genetic basis of individual differences in the progression to nephritis among children with HSP in the Chinese Han population. What is Known: • The etiology of HSP is unknown, but the genetic factors may play an important role in the pathogenesis of HSP. • iNOS could contribute to the development and clinical manifestations of HSP, and this has not been studied extensively so far. What is New: • Our results support that iNOS polymorphisms not only are associated with HSP risk but also strongly contribute to the genetic basis of individual differences in the progression of HSP to nephritis among Chinese Han children.

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a potential tumor‑suppressor gene in various cancers. However, its biological role and underlying mechanism has not been well investigated in endometrial cancer yet. The aim of the present study aimed to investigate the role and underlying molecular mechanisms of IGFBP‑rP1 in endometrial cancer cells in vitro. The authors used transfection of IGFBP‑rP1 or small interfering (si)RNA in endometrial cancer HEC‑1A or Ishikawa cells, respectively. Biological functional alterations, such as cell growth and cell cycle were analyzed in endometrial cancer cells, combined with the use of PD98059. A panel of proteins including phospho‑retinoblastoma (p‑RB) and p‑extracellular signal‑regulated kinase (ERK)/ERK were detected by western blot analysis. It was observed that IGFBP‑rP1 transfection inhibited cell growth, and induced G1 phase arrest and cellular senescence in HEC‑1A cells while gene silencing presented the adverse functional changes. Moreover, p‑RB and p‑ERK were significantly downregulated or upregulated in HEC‑1A‑IGFBP‑rP1 cells or Ishikawa‑siRNA (IGFBP‑rP1) compared with control cells, respectively. These observations were reinforced in endometrial cancer cells by PD98059 treatment. The authors conclude that IGFBP‑rP1 acts as a potential tumor suppressor via the suppression of the ERK signaling pathway in endometrial cancer cells. These findings suggested that IGFBP‑rP1 may serve as a potential therapeutic target for cancer intervention in the future.

Aberrant activation of the NOTCH signaling pathway is crucial for the onset and progression of T cell leukemia. Yet recent studies also suggest a tumor suppressive role of NOTCH signaling in acute myeloid leukemia (AML) and reactivation of this pathway offers an attractive opportunity for anti-AML therapies. N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid that we previously isolated from Zephyranthes candida, exhibiting inhibitory activities in a variety of cancer cells, particularly those from AML. Here, we report NMHC not only selectively inhibits AML cell proliferation in vitro but also hampers tumor development in a human AML xenograft model. Genome-wide gene expression profiling reveals that NMHC activates the NOTCH signaling. Combination of NMHC and recombinant human NOTCH ligand DLL4 achieves a remarkable synergistic effect on NOTCH activation. Moreover, pre-inhibition of NOTCH by overexpression of dominant negative MAML alleviates NMHC-mediated cytotoxicity in AML. Further mechanistic analysis using structure-based molecular modeling as well as biochemical assays demonstrates that NMHC docks in the hydrophobic cavity within the NOTCH1 negative regulatory region (NRR), thus promoting NOTCH1 proteolytic cleavage. Our findings thus establish NMHC as a potential NOTCH agonist that holds great promises for future development as a novel agent beneficial to patients with AML.

Signaling pathways of tumor necrosis factor-α (TNF-α) and insulin-like growth factor-I (IGF-I) are found to be functionally interrelated in some experimental studies. IGF-I may be involved in the pathogenesis of postoperative cognitive dysfunction (POCD). In order to investigate the possible interaction of TNF-α and IGF-I in POCD, the plasma levels of IGF-I and TNF-α were determined in 44 patients under general anesthesia. As compared with non-POCD patients, POCD patients showed increased TNF-α and decreased IGF-I levels in plasma, as well as a significant negative correlation between TNF-α and IGF-I values. The present results suggest that interaction of increased TNF-α levels and decreased IGF-1 levels might lead to a vicious circle, which may contribute to POCD.

MYCN amplification in human cancers predicts poor prognosis and resistance to therapy. However, pharmacological strategies that directly target N-Myc, the protein encoded by MYCN, remain elusive. Here, we identify a molecular mechanism responsible for reciprocal activation between Polo-like kinase-1 (PLK1) and N-Myc. PLK1 specifically binds to the SCFFbw7 ubiquitin ligase, phosphorylates it, and promotes its autopolyubiquitination and proteasomal degradation, counteracting Fbw7-mediated degradation of N-Myc and additional substrates, including cyclin E and Mcl1. Stabilized N-Myc in turn directly activates PLK1 transcription, constituting a positive feedforward regulatory loop that reinforces Myc-regulated oncogenic programs. Inhibitors of PLK1 preferentially induce potent apoptosis of MYCN-amplified tumor cells from neuroblastoma and small cell lung cancer and synergistically potentiate the therapeutic efficacies of Bcl2 antagonists. These findings reveal a PLK1-Fbw7-Myc signaling circuit that underlies tumorigenesis and validate PLK1 inhibitors, alone or with Bcl2 antagonists, as potential effective therapeutics for MYC-overexpressing cancers.

Insulin-like growth factor (IGF)-1 is implicated in learning and memory. Experimental studies have suggested that the IGF-1 system is beneficial in cognition, especially in Alzheimer's disease (AD), by opposing Aβ amyloid processing and hyperphosphorylated tau toxicity. Low IGF-I and insulin-like growth factor binding protein (IGFBP)-3 serum levels are significantly associated with AD. To assess the relationship between circulating IGF-I and IGFBP3 levels and change of postoperative cognition. The study was performed in patients scheduled for elective head and neck carcinoma surgery under general anesthesia. On the day before the operation and postoperative days 1, 3 and 7, mini-mental state examination (MMSE) was performed by the same doctor, and blood samples were collected at 08:00 h after overnight fasting. The circulating levels of IGF-1 and IGFBP3 were measured by enzyme-linked immunosorbent assay. One hundred and two patients completed all four MMSE tests and forty-four of them completed all the four blood samples collection. Postoperative circulating IGF-1 level, ratio of IGF-1/IGFBP3 and MMSE score significantly decreased, whereas IGFBP3 level significantly increased compared with preoperative values in total patients. The change trends of circulating IGF-1 level and MMSE score were similar. Preoperative circulating IGF-1 level, ratio and MMSE score were significantly lower in POCD group compared to non-POCD group. There was no significant difference in preoperative level of circulating IGFBP3 between the two groups. Preoperative circulating IGF-1 level was negatively correlated with age and positively with MMSE. Logistic regression analysis revealed that lower preoperative IGF-1 level and elderly patients increased the odds of POCD. Down-regulation of circulating IGF-1 level may be involved in the mechanism of postoperative cognitive dysfunction. Older patients had lower circulating IGF-1 levels and were more susceptible to POCD.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). We previously identified tetranectin (TET) as a potential biomarker for PD whose expression is downregulated in the cerebrospinal fluid of PD patients. In the present study, we investigate the role of TET in neurodegeneration in vitro and in vivo. Our results showed that siRNA knockdown of TET decreased cell viability and the number of tyrosine hydroxylase (TH) positive cells, whereas it increased caspase-3 activity and the Bax/Bcl-2 ratio in cultured primary dopaminergic neurons. Overexpression of TET protected dopaminergic neurons against neuronal apoptosis in 1-methyl-4-phenylpyridinium cell culture model in vitro. In TET knockdown mouse model of PD, TET gene deletion decreased the number of TH positive cells in the SNpc, induced apoptosis via the p53/Bax pathway, and significantly impaired the motor behavior of transgenic mice. The findings suggest that TET plays a neuroprotective role via reducing neuron apoptosis and could be a valuable biomarker or potential therapeutic target for the treatment of patients with PD.

Insulin-like growth factor binding protein (IGFBP) 7 may be a critical regulator of memory consolidation. This study was performed to assess the relationship between circulating IGFBP7 levels and postoperative cognition dysfunction (POCD) in patients scheduled for elective head and neck carcinoma surgery under general anesthesia. Among one hundred and two patients included in this study, forty-four patients completed collection of all four blood samples and thirty-five patients were diagnosed with POCD. The results of Mini-Mental State Examination (MMSE) test and enzyme-linked immunosorbent assay showed that postoperative MMSE score and circulating insulin-like growth factor (IGF)-1 level were lower and circulating IGFBP7 level was higher than preoperative level. Circulating IGF-1 level was significantly lower and D-value of preoperative and postoperative day 1 circulating IGFBP7 levels (ΔIGFBP7 1 ) was significantly higher in the POCD group. Age preoperative MMSE, IGF-1 level and ΔIGFBP7 1 significantly correlated with POCD, but preoperative IGFBP7 level not. Logistic regression analysis revealed that older patients, lower preoperative MMSE score, IGF-1 level and higher IGFBP7 level significantly increased the risk of POCD, but ΔIGFBP7 1 not. Hence, circulating IGF-1 and IGFBP7 levels and their changes during operation under general anesthesia may correlate with POCD, but further investigation in larger samples is needed.

Background: The purpose of this study was to investigate the correlation of contrast-enhanced ultrasonographic (CEUS) features with microvessel density (MVD) in papillary thyroid carcinomas (PTCs). Materials and Methods: Contrast-enhanced ultrasonography (CEUS) was performed in 62 patients (17 men and 45 women) with PTC. Tomtec software was applied to analyze the time intensity curve of CEUS. Immunohistochemistry was performed to evaluate the level of MVD in papillary thyroid carcinoma. Then the relationship between quantitative feature and the level of MVD was analyzed using SPSS 16.0 software. Results: The mean peak intensity of PTC tissues was lower than that of peripheral thyroid parenchyma (61.9±11.8% vs 100%, p

OBJECTIVES The purpose of this study was to retrospectively evaluate contrast-enhanced sonography for differentiation of benign and malignant thyroid nodules by analyzing the correlation between maximum intensity and microvessel density. METHODS From February 2010 to May 2012, 122 patients (85 female and 37 male; mean age ± SD, 45 ± 9.1 years) with thyroid nodules (62 papillary thyroid carcinomas, 30 nodular goiters, and 30 adenomas) that underwent routine thyroid sonography and were diagnosed by surgery were included in this study. Contrast-enhanced sonography was performed, and enhancement patterns were classified into 3 groups: high, equal, and low enhancement. As a time-intensity curve parameter, the correlation of maximum intensity with CD31 and CD34 microvessel density counts was analyzed. RESULTS On contrast-enhanced sonography, most patients with papillary thyroid carcinomas showed a heterogeneous low enhancement pattern, whereas most patients with nodular goiters showed an equal enhancement pattern, and patients with adenomas showed a high enhancement pattern. The detection of papillary thyroid carcinomas with low enhancement had sensitivity of 96.8%, specificity of 95.0%, and accuracy of 95.9%. Compared with the papillary thyroid group, the mean microvessel density counts were significantly higher in the nodular goiter and adenoma groups (P< .05). We also found that the maximum intensity was significantly associated with CD31 and CD34 counts (CD31, r = 0.963; P < .01; CD34, r = 0.968; P < .01). CONCLUSIONS Maximum intensity has a significant relationship with microvessel density. Contrast-enhanced sonography is a practical and convenient means for differentiating benign from malignant thyroid nodules.