A tRNA fragment, 5'-tiRNAVal, suppresses the Wnt/ß-catenin signaling pathway by targeting FZD3 in breast cancer.

tRNA-derived fragments offer a recently identified group of non-coding single-stranded RNAs that are often as abundant as microRNAs in cancer cells and play important roles in carcinogenesis. However, the biological functions of them in breast cancer are still unclear. Hence, we focused on investigating whether tiRNAs could play a key role in the progression of breast cancer. We have identified 5'-tiRNAVal with significantly low expression in breast cancer tissues. The down-regulation of serum 5'-tiRNAVal was positively correlated with stage progression and lymph node metastasis. Overexpression of 5'-tiRNAVal suppressed cells malignant activities. FZD3 was confirmed to be a direct target of 5'-tiRNAVal in breast cancer. In addition, FZD3, ß-Catenin, c-myc and cyclinD1 levels in 5'-tiRNAVal overexpressing cells were downregulated while APC was inversely upregulated. Moreover, 5'-tiRNAVal inhibited the FZD3-mediated Wnt/ß-Catenin signaling pathway in breast cancer cells. Finally, 5'-tiRNAVal levels differentiated breast cancer from healthy controls with a sensitivity of 90.0% and specificity of 62.7%. This is the first study to show that 5'-tiRNAVal as a new tumor-suppressor through inhibition of FZD3/Wnt/ß-Catenin signaling pathway, which could be as a potential diagnostic biomarker for breast cancer.

Coronary sinus flow is reduced in methamphetamine abusers: a transthoracic echocardiographic study.

To compare the coronary sinus flow among healthy participants, methamphetamine abusers without chest pain and those with chest pain. One hundred and eight methamphetamine abusers: 53 ones without chest pain, 55 ones with chest pain, free of ascertained coronary artery disease, were enrolled in this study. A control group of 50 age-matched male healthy participants was studied for comparison. Standard 2D, flow and tissue Doppler echo with measurements of cardiac morphologic and functional indicators, coronary sinus flow, and inferior vena cava (IVC) ultrasound with measurements of the IVC dimensions and their collapsibility index were performed, respectively. Compared to healthy participants, methamphetamine abusers had higher blood pressure, greater left ventricular mass index and more impaired diastolic function, with preserved cardiac sizes, systolic function and right atrial pressure. Methamphetamine abusers with chest pain had faster heart rate than those without chest pain and healthy participants. Coronary sinus flow was significantly less in methamphetamine abusers than in healthy participants (P < 0.05), and was extremely lower in those with chest pain than in healthy participants (about one-fourth) (P < 0.01). The area under the curve (AUC) of coronary sinus flow was 0.913 (0.864-0.962), and the cutoff value with 221.65 mL/min had sensitivity of 83.4%, specificity of 87.2% and accuracy of 85.2% for differentiating methamphetamine abusers from healthy participants. While the AUC of coronary sinus flow was 0.996 (0.989-1.003), and the cutoff value with 172.59 mL/min had sensitivity of 100%, specificity of 93.3% and accuracy of 96.5% for predicting methamphetamine abusers with chest pain. Coronary sinus flow is significant reduced in methamphetamine abusers, which is maybe a good indicator for indentifying methamphetamine abusers from normal population, and for predicting methamphetamine abusers with chest pain.

Oral Contrast-Enhanced Gastric Ultrasonography in the Assessment of Gastric Lesions: A Large-Scale Multicenter Study.

OBJECTIVE: To determine the diagnostic efficiency of oral contrast-enhanced gastric ultrasonography in the evaluation of gastric lesions, based on large-scale multicenter study. METHODS: The study enrolled 383,945 patients with suspect gastric lesions who underwent complete oral contrast-enhanced gastric ultrasonography and endoscopic evaluation. Two operators, unaware of the results of other diagnostic procedures, performed each examination independently. The accuracies of conventional ultrasonography, oral contrast-enhanced gastric ultrasonography, and upper gastrointestinal endoscopy were determined. RESULTS: After oral contrast, the anatomy of the stomach and morphologic features of gastric lesions were clearly visualized. The sensitivities, specificities, positive predictive values, negative predictive values and accuracies of oral contrast-enhanced ultrasonography in detecting the sites, sizes, numbers, and the extent of gastric lesions,were similar to those of upper gastrointestinal endoscopy (P > .05) and far greater than those of conventional ultrasonography (P < .01). Moreover, oral contrast-enhanced ultrasonography was far better than upper gastrointestinal endoscopy (P < .01) and was better than conventional ultrasonography (P < .05) in detecting the submucosal abnormalities (<5mm) and the adjacent structures abnormalities identified in surgical pathology. However, oral contrast-enhanced ultrasonography was a bit poorer than upper gastrointestinal endoscopy (P < .05) and far better than conventional ultrasonography (P < .01) in detecting the minor mucosal abnormalities (<5mm). CONCLUSION: Oral contrast-enhanced gastric ultrasonography is superior to conventional gastric ultrasonography in defining the anatomic location and extension of gastric lesions. Its diagnostic performance is not worse than upper gastrointestinal endoscopy and it can be used as a useful supplement to upper gastrointestinal endoscopy.

A novel approach to assess pulmonary function in patients with chronic obstructive pulmonary disease using tissue velocity imaging.

AIMS: To explore the feasibility of quantitative evaluation of pulmonary function in patients with chronic obstructive pulmonary disease (COPD) using tissue velocity imaging (TVI) and strain rate imaging (SRI) via transthoracic lung ultrasonography. MATERIAL AND METHODS: Eighty inpatients with clinically diagnosed COPD underwent pulmonary function test and transthoracic lung ultrasound on the same day. Lung ultrasound variables and pulmonary function parameters were analyzed. RESULTS: All patients with COPD had faster breathing and significant reduced lung function compared with healthy participants (p<0.05). The lung ultrasound parameters, velocity (max-min, cm/s), displacement (max-min, mm), strain (max-min, %) and strain rate (max-min, 1/s) were significantly higher in patients with COPD (p<0.05). A good negative correlation was found between lung ultrasound variables and pulmonary function parameters in patients with COPD. Stepwise multiple regression analysis indicated that the velocity (max-min, cm/s) was the only independent determinant of FEV1/FVC (%). With the use of FEV1/FVC<70% as the criteria of irreversible pulmonary function impairment to distinguish an abnormal pulmonary function, the area under the ROC was 0.99 for the velocity (max-min, cm/s) of the lung tissue in the process of breathing. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the cut off value (1.19 cm/s) was 97.63%, 100%, 100%, 80%, and 98%, respectively (p<0.001). CONCLUSIONS: Tissue velocity imaging via transthoracic lung ultrasound is a useful modality in the assessment of pulmonary function in patients with COPD.

A novel approach to assessing fetal tissue stiffness using virtual touch tissue quantification.

AIMS: Virtual touch tissue quantification (VTTQ) has been widely used in adults, but its application in fetuses has not been reported. The purposes of this study were to describe the normal shear wave velocity (SWV) values of fetal brain, lung, and liver by VTTQ and to examine the clinical usefulness of this procedure in THE evaluation of gestational age-related SWV changes in the fetal brain, lung and liver. MATERIAL AND METHODS: One hundred fetuses were enrolled in this study and were evaluated at 18 weeks (second trimester) and 35 weeks (third trimester) during pregnancy. The SWV was measured at the cerebral parenchyma, thalamus, cerebellum, choroid plexus, left lung, right lung, right and left lobe of the liver in each participant. RESULTS: The SWV at the cerebral parenchyma were all significantly greater in the third trimesters than in the second trimesters (3.29+/-1.05 vs. 2.22+/-0.97 m/s, p<0.001), while the velocities at thalamus, cerebellum, choroid plexus, left lung, right lung, right lobe of the liver and left lobe of the liver did not differ between the second and the third trimesters (p>0.05). Moreover, the SWV at the cerebral parenchyma correlated significantly with gestational age (r=0.47, p<0.001). CONCLUSIONS: VTTQ can provide numerical measurements of fetal brain, lung and liver stiffness and can effectively and objectively indicate gestational age-related changes in cerebral parenchyma stiffness by measuring SWV values.

Inhibition effect of siRNA-downregulated UHRF1 on breast cancer growth.

The UHRF1 gene plays important roles in both cell proliferation through its NIRF_N domains, a PHD domain, an SRA domain, and a RING domain, and multidrug resistance in breast cancer treatment. In this work, a short-hairpin RNA (shRNA) lentiviral system was introduced in two human breast cancer cell lines (MDA-MB-231 and MCF-7) to downregulate the expression of UHRF1 and study the specific inhibition of UHRF1 in breast cancer growth. The effect of UHRF1-shRNA on breast cancer cell proliferation was examined using methylthiazoletetrazolium, bromodeoxyuridine, and colony formation assays. The proliferative potential of the UHRF1-shRNA-treated cells showed a remarkable decrease. Moreover, the downregulation of UHRF1 in both breast cancer cell lines significantly inhibited the colony formation capacity. Results suggested that the inhibition of UHRF1 via an RNA interference lentiviral system may provide an effective way for breast cancer therapy.

Clinical value of contrast-enhanced ultrasonography in the characterization of focal liver lesions: a prospective multicenter trial.

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is increasingly accepted in clinical settings for diagnostic imaging of focal liver lesions (FLLs). This study aimed to assess the efficacy of CEUS in the characterization of FLLs in comparison with final diagnosis based on gold standard assessment. METHODS: The study was approved by the local ethics committee and participating patients provided written informed consent. A total of 148 patients with 164 FLLs were studied. Unenhanced ultrasonography (US) and CEUS were performed using fundamental and harmonic imaging, respectively. Contrast enhancement was assessed during the arterial, portal and late vascular phases after intravenous administration of contrast (SonoVue, Bracco, Italy). Sensitivity, specificity and diagnostic accuracy of US and CEUS were compared in identifying the lesion as benign, malignant or indeterminate and its actual tumor type. Final diagnosis was established by biopsy (129/164), MR imaging (11/164) or medical history (24/164). RESULTS: When compared to the gold standard, the number of indeterminate diagnoses was reduced from 56.7% (93/164) as assessed by fundamental imaging to 6.1% (10/164) after SonoVue enhanced US examination. Sensitivity and specificity improved from 49% and 25% at baseline US to 93% and 75% with CEUS, respectively (P<0.01). Diagnostic accuracy of CEUS was 88% in contrast to 41% of baseline US. CONCLUSION: SonoVue enhanced US improves the characterization of FLLs and may limit the need for further investigations.