Inhibition of YAP/TAZ pathway contributes to the cytotoxicity of silibinin in MCF-7 and MDA-MB-231 human breast cancer cells.

Breast cancer is one of the most common cancers threatening women's health. Our previous study found that silibinin induced the death of MCF-7 and MDA-MB-231 human breast cancer cells. We noticed that silibinin-induced cell damage was accompanied by morphological changes, including the increased cell aspect ratio (cell length/width) and decreased cell area. Besides, the cytoskeleton is also destroyed in cells treated with silibinin. YAP/TAZ, a mechanical signal sensor interacted with extracellular pressure, cell adhesion area and cytoskeleton, is also closely associated with cell survival, proliferation and migration. Thus, the involvement of YAP/TAZ in the cytotoxicity of silibinin in breast cancer cells has attracted our interests. Excitingly, we find that silibinin inhibits the nuclear translocation of YAP/TAZ in MCF-7 and MDA-MB-231 cells, and reduces the mRNA expressions of YAP/TAZ target genes, ACVR1, MnSOD and ANKRD. More importantly, expression of YAP1 gene is negatively correlated with the survival of the patients with breast cancers. Molecular docking analysis reveals high probabilities for binding of silibinin to the proteins in the YAP pathways. DARTS and CETSA results confirm the binding abilities of silibinin to YAP and LATS. Inhibiting YAP pathway either by addition of verteporfin, an inhibitor of YAP/TAZ-TEAD, or by transfection of si-RNAs targeting YAP or TAZ further enhances silibinin-induced cell damage. While enhancing YAP activity by silencing LATS1/2 or overexpressing YAPS127/397A, an active form of YAP, attenuates silibinin-induced cell damage. These findings demonstrate that inhibition of the YAP/TAZ pathway contributes to cytotoxicity of silibinin in breast cancers, shedding lights on YAP/TAZ-targeted cancer therapies.

Metagenomic next-generation sequencing for diagnosis of infectious encephalitis and meningitis: a retrospective study of 90 patients.

BACKGROUND: Infections of the central nervous system (CNS) are potentially life-threatening and can cause serious morbidity. We evaluated the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis and explored the factors affecting the results of mNGS. METHODS: Patients with suspected cases of encephalitis or meningitis who presented in Northern Jiangsu People's Hospital from 1 March 2018 to 30 September 2022 were collected. Demographic, historical, and clinical information were obtained, and cerebrospinal fluid (CSF) samples were treated with mNGS. The pathogen was identified using National Center for Biotechnology Information (NCBI) GenBank sequence data. RESULTS: Ninety-six patients were screened and finally 90 subjects enrolled. Of the 90 enrolled cases, 67 (74.4%) were diagnosed with central nervous system infections, which included 48 cases (71.6%) of viral infection, 11 (12.2%) of bacterial infection, 5 (7.5%) of mycobacterium tuberculosis, 2 (3.0%) of fungal infection, and 1 (1.5%) of rickettsia infection. From these cases, mNGS identified 40 (44.4%) true-positive cases, 3 (3.3%) false-positive case, 22 (24.4%) true-negative cases, and 25 (27.8%) false-negative cases. The sensitivity and specificity of mNGS were 61.5% and 88%, respectively. mNGS of CSF could show a higher positive rate in patients with marked CSF abnormalities, including elevated protein concentrations and monocyte counts. CONCLUSION: mNGS of CSF is an effective method for detecting infectious encephalitis and meningitis, and the results should be analyzed combined with conventional microbiological testing results.

Evaluation of standard breast ultrasonography by adding two-dimensional and three-dimensional shear wave elastography: a prospective, multicenter trial.

OBJECTIVE: To reduce the number of biopsies performed on benign breast lesions categorized as BI-RADS 4-5, we investigated the diagnostic performance of combined two-dimensional and three-dimensional shear wave elastography (2D + 3D SWE) with standard breast ultrasonography (US) for the BI-RADS assessment of breast lesions. METHODS: A total of 897 breast lesions, categorized as BI-RADS 3-5, were subjected to standard breast US and supplemented by 2D SWE only and 2D + 3D SWE analysis. Based on the malignancy rate of less than 2% for BI-RADS 3, lesions assessed by standard breast US were reclassified with SWE assessment. RESULTS: After standard breast US evaluation, 268 (46.1%) participants underwent benign biopsies in BI-RADS 4-5 lesions. By using separated cutoffs for upstaging BI-RADS 3 at 120 kPa and downstaging BI-RADS 4a at 90 kPa in 2D + 3D SWE reclassification, 123 (21.2%) participants underwent benign biopsy, resulting in a 54.1% reduction (123 versus 268). CONCLUSION: Combining 2D + 3D SWE with standard breast US for reclassification of BI-RADS lesions may achieve a reduction in benign biopsies in BI-RADS 4-5 lesions without sacrificing sensitivity unacceptably. CLINICAL RELEVANCE STATEMENT: Combining 2D + 3D SWE with US effectively reduces benign biopsies in breast lesions with categories 4-5, potentially improving diagnostic accuracy of BI-RADS assessment for patients with breast lesions. TRIAL REGISTRATION: ChiCTR1900026556 KEY POINTS: • Reduce benign biopsy is necessary in breast lesions with BI-RADS 4-5 category. • A reduction of 54.1% on benign biopsies in BI-RADS 4-5 lesions was achieved using 2D + 3D SWE reclassification. • Adding 2D + 3D SWE to standard breast US improved the diagnostic performance of BI-RADS assessment on breast lesions: specificity increased from 54 to 79%, and PPV increased from 54 to 71%, with slight loss in sensitivity (97.2% versus 98.7%) and NPV (98.1% versus 98.7%).

Sintilimab-induced inflammatory myopathy in a patient with esophageal cancer: a case report.

The use of immune checkpoint inhibitors (ICIs) has shown remarkable efficacy in the treatment of various malignancies, significantly reshaping cancer treatment. However, as a result of the widespread use of ICIs, several immune-related adverse events (iRAEs) have emerged, some of which can be rare and potentially fatal. In this paper, we reported the earliest case of Sintilimab used in the treatment of esophageal cancer with severe inflammatory myopathy (involving the cardiac, respiratory, and skeletal muscles)in China. This patient was an elderly female who presented to our institution with progressive limb weakness and ptosis. Prior to the onset of symptoms, the patient had undergone a radical esophagectomy for esophageal cancer, experienced several cycles of of radiotherapy and chemotherapy, as well as two doses of Sintilimab treatment. Shortly after initiating immunotherapy, the patient developed symptoms including bilateral ptosis, limb weakness, and difficulty swallowing and breathing. The levels of creatine kinase and troponin I in the patient's blood were significantly elevated, and positive results were observed for anti-skeletal and anti-cardiac muscle antibodies, indicating that the patient might be developing ICIs-related inflammatory myopathy. Fortunately, the patient responded well to treatment including corticosteroids, plasmapheresis, intravenous immunoglobulin, and other supportive therapies. Here, we discuss the incidence, mechanisms, and management strategies of fatal iRAEs. Early detection and timely intervention may be critical in reducing the incidence and mortality rates of iRAEs and improving patient outcomes.

Prediction of clinical response to neoadjuvant therapy in advanced breast cancer by baseline B-mode ultrasound, shear-wave elastography, and pathological information.

Background: Neoadjuvant therapy (NAT) is the preferred treatment for advanced breast cancer nowadays. The early prediction of its responses is important for personalized treatment. This study aimed at using baseline shear wave elastography (SWE) ultrasound combined with clinical and pathological information to predict the clinical response to therapy in advanced breast cancer. Methods: This retrospective study included 217 patients with advanced breast cancer who were treated in West China Hospital of Sichuan University from April 2020 to June 2022. The features of ultrasonic images were collected according to the Breast imaging reporting and data system (BI-RADS), and the stiffness value was measured at the same time. The changes were measured according to the Response evaluation criteria in solid tumors (RECIST1.1) by MRI and clinical situation. The relevant indicators of clinical response were obtained through univariate analysis and incorporated into a logistic regression analysis to establish the prediction model. The receiver operating characteristic (ROC) curve was used to evaluate the performance of the prediction models. Results: All patients were divided into a test set and a validation set in a 7:3 ratio. A total of 152 patients in the test set, with 41 patients (27.00%) in the non-responders group and 111 patients (73.00%) in the responders group, were finally included in this study. Among all unitary and combined mode models, the Pathology + B-mode + SWE model performed best, with the highest AUC of 0.808 (accuracy 72.37%, sensitivity 68.47%, specificity 82.93%, P<0.001). HER2+, Skin invasion, Post mammary space invasion, Myometrial invasion and Emax were the factors with a significant predictive value (P<0.05). 65 patients were used as an external validation set. There was no statistical difference in ROC between the test set and the validation set (P>0.05). Conclusion: As the non-invasive imaging biomarkers, baseline SWE ultrasound combined with clinical and pathological information can be used to predict the clinical response to therapy in advanced breast cancer.

Unexpected breast cancer mimicking benign lesions on ultrasound-guided vacuum-assisted excision biopsy: A retrospective cross-sectional study over a 20-year period.

Objectives: This study investigated the occurrence rate of unexpected breast cancer (UEBC) mimicking benign lesions [Breast Imaging Reporting and Data System (BI-RADS) category 3 or 4a] using ultrasound-guided vacuum-assisted excision biopsy (US-VAEB), and explored the factors responsible for late diagnosis of T2 stage UEBC. Materials and methods: We collected clinicopathologic data and preoperative US imaging features within 3 months before US-VAEB of patients who were diagnosed with UEBC from January 2002 to September 2022. The UEBC were divided into T1 and T2 stageUEBC. The US imaging features as well as clinical and pathological information of T1 and T2 stage UEBC were compared to explore the factors responsible for late diagnosis of T2 stage UEBC. Results: Breast cancer was diagnosed in 91 of 19 306 patients who underwent US-VAEB. We excluded eight patients with breast cancer assigned to BI-RADS 4b category by preoperative US, and two for whom US imaging records were unavailable. Finally, we enrolled 81 patients. The occurrence rate of UEBC after US-VAEB was 0.42%(81/19296). Of the 81 cases of UEBC, 22 were at T2 stage. The ratio of T2 stage UEBC was 27.2%. The differences in risk factor of breast cancer and routine breast US screening between T1 and T2 stage UEBC were significant[96.6% (57/59) vs 81.8% (18/22), 44.1% (26/59) vs 13.6% (3/22), respectively, P<0.05). Conclusion: UEBC was rarely detected by US-VAEB. Most cases of T2 stage UEBC were diagnosed late because of the absence of routine US screening and risk factors for breast cancer. Stricter clinical management regulations for breast lesions and performing regular US screening may be helpful to reduce T2 stage UEBC.

Diagnostic value and mechanism of plasma S100A1 protein in acute ischemic stroke: a prospective and observational study.

Background: Plasma S100A1 protein is a novel inflammatory biomarker associated with acute myocardial infarction and neurodegenerative disease's pathophysiological mechanisms. This study aimed to determine the levels of this protein in patients with acute ischemic stroke early in the disease progression and to investigate its role in the pathogenesis of acute ischemic stroke. Methods: A total of 192 participants from hospital stroke centers were collected for the study. Clinically pertinent data were recorded. The volume of the cerebral infarction was calculated according to the Pullicino formula. Multivariate logistic regression analysis was used to select independent influences. ROC curve was used to analyze the diagnostic value of AIS and TIA. The correlation between S100A1, NF-κB p65, and IL-6 levels and cerebral infarction volume was detected by Pearson correlation analysis. Results: There were statistically significant differences in S100A1, NF-κB p65, and IL-6 among the AIS,TIA, and PE groups (S100A1, [230.96 ± 39.37] vs [185.85 ± 43.24] vs [181.47 ± 27.39], P < 0.001; NF-κB p65, [3.99 ± 0.65] vs [3.58 ± 0.74] vs [3.51 ± 0.99], P = 0.001; IL-6, [13.32 ± 1.57] vs [11.61 ± 1.67] vs [11.42 ± 2.34], P < 0.001). Multivariate logistic regression analysis showed that S100A1 might be an independent predictive factor for the diagnosis of disease (P < 0.001). The AUC of S100A1 for diagnosis of AIS was 0.818 (P < 0.001, 95% CI [0.749-0.887], cut off 181.03, Jmax 0.578, Se 95.0%, Sp 62.7%). The AUC of S100A1 for diagnosis of TIA was 0.720 (P = 0.001, 95% CI [0.592-0.848], cut off 150.14, Jmax 0.442, Se 50.0%, Sp 94.2%). There were statistically significant differences in S100A1, NF-κB p65, and IL-6 among the SCI,MCI, and LCI groups (S100A1, [223.98 ± 40.21] vs [225.42 ± 30.92] vs [254.25 ± 37.07], P = 0.001; NF-κB p65, [3.88 ± 0.66] vs [3.85 ± 0.64] vs [4.41 ± 0.45], P < 0.001; IL-6, [13.27 ± 1.65] vs [12.77 ± 1.31] vs [14.00 ± 1.40], P = 0.007). Plasma S100A1, NF-κB p65, and IL-6 were significantly different from cerebral infarction volume (S100A1, r = 0.259, P = 0.002; NF-κB p65, r = 0.316, P < 0.001; IL-6, r = 0.177, P = 0.036). There was a positive correlation between plasma S100A1 and IL-6 with statistical significance (R = 0.353, P < 0.001). There was no significant positive correlation between plasma S100A1 and NF-κB p65 (R < 0.3), but there was statistical significance (R = 0.290, P < 0.001). There was a positive correlation between IL-6 and NF-κB p65 with statistical significance (R = 0.313, P < 0.001). Conclusion: S100A1 might have a better diagnostic efficacy for AIS and TIA. S100A1 was associated with infarct volume in AIS, and its level reflected the severity of acute cerebral infarction to a certain extent. There was a correlation between S100A1 and IL-6 and NF-κB p65, and it was reasonable to speculate that this protein might mediate the inflammatory response through the NF-κB pathway during the pathophysiology of AIS.

Ultrasonographic Features, Nodule Size, Capsular Invasion, and Lymph Node Metastasis of Solitary Papillary Carcinoma of Thyroid Isthmus.

Objective: This retrospective study aimed to analyze the ultrasound (US) imaging features of solitary papillary thyroid carcinoma (PTC) located in the isthmus and to assess the risk factors for lymph node metastasis (LNM) and tumor capsular invasion. Methods: We included a total of 135 patients with solitary PTC located in the isthmus. All the cases underwent US, total thyroidectomy, and prophylactic central lymph node dissection. Patients' demographic and thyroid isthmus nodules' US characteristics, as well as risk factors associated with LNM and tumor capsular invasion, were analyzed. Results: It was revealed that the occurrence of LNM was higher in male patients than in female patients (P < 0.001). As risk factors, the size of PTC in the isthmus was found to be associated with LNM and tumor capsular invasion (P = 0.005 and 0.000, respectively). The area under the receiver operating characteristic curve (AUC) of the size of the isthmus PTC was 0.64 [95% confidence interval (CI) = 0.55-0.72], indicating a probability for LNM. The AUC value for tumor capsular invasion was 0.77 (95% CI: 0.68-0.83). When the threshold was set to 1.1 cm, the larger size indicated that there was a probability of occurrence of LNM with sensitivity and specificity of 47.4 and 73.7%, respectively. When the threshold was set to 0.7 cm, the larger size indicated that there was potentially a tumor capsular invasion, with sensitivity and specificity of 80.6 and 56.3%, respectively. Wider-than-tall nodules were found to be significantly different from those in LNM and tumor capsular invasion (P = 0.038 and 0.030, respectively). There were significant differences in tumor capsular invasion in extrathyroidal extension (ETE) compared with smooth or ill-defined and lobulated or irregular nodules (P = 0.017). Conclusions: This study showed that the incidence of LNM in male patients was higher than that in female ones. When a US image shows a thyroid isthmus nodule with a wider-than-tall shape, LNM and tumor capsular invasion were likely to occur. When a US image shows a thyroid isthmus nodule with an ETE, tumor capsular invasion was likely to occur. ETE and wider-than-tall may be indicators of FNA under US guidance, even though the size of thyroid isthmus nodule may be <1 cm.

Clinical features of aseptic meningitis with varicella zoster virus infection diagnosed by next-generation sequencing: case reports.

BACKGROUND: The aseptic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, most of which were detected by means of polymerase chain reaction. The authors presented 4 adult immunocompetent patients with acute aseptic meningitis with VZV infection diagnosed by next-generation sequencing (NGS). CASE PRESENTATION: Four patients were admitted to the hospital with headache and fever between March 2018 and August 2019. The median ages were 37 years (range 22-52 years). The median symptoms onset to clinic time was 3.5 days (range 3-6 days). Two patients had signs of meningeal irritation. Rash occurred after the meningitis symptoms in 1 patient (time from meningitis symptoms to rash, 2 days). No other sign or symptom was reported. The brain Magnetic resonance imaging and electroencephalography were normal in all patients. Cerebrospinal fluid (CSF) samples were obtained at a median of 4 days (range 3-7 days) from the meningitis symptoms onset. Opening pressure of lumbar puncture after admission were high in these cases (median 256 mm H2O; range 165-400 mm H2O). White blood cell counts and protein levels were significantly elevated in CSF samples (median 317 × 10^6/L, range 147-478 × 10^6/L; median 1.41 g/L, range 0.57-1.79 g/L). The cytology of CSF demonstrated a lymphocytic pleocytosis, and most multinuclear cells. The culture of CSF was negative for all 4 cases, while T-cell spot test was positive for 2 cases, who were administrated with anti-tuberculosis treatment for suspicious tuberculous meningitis. NGS of CSF (the Vision Medical Research Institute) detected specific sequences of VZV in the 4 cases within 72 h after admission. The inappropriate treatment were stopped while acyclovir were continued intravenously for 10-14 days. All patients recovered completely. CONCLUSIONS: VZV is an infectious agent that causes aseptic meningitis in immunocompetent adults and could not be accompanied by skin manifestations. The NGS of CSF is a rapid detection for the identification and differentiation of meningitis in patients, which is of great importance for providing the rapid and accurate diagnosis and the targeted antimicrobial therapy for central nervous system infection.

Partially cystic thyroid cancer on conventional and elastographic ultrasound: a retrospective study and a machine learning-assisted system.

BACKGROUND: Thyroid carcinoma constitutes the vast majority of all thyroid cancer, most of which is the solid nodule type. No previous studies have examined combining both conventional and elastic sonography to evaluate the diagnostic performance of partially cystic thyroid cancer (PCTC). This retrospective study was designed to evaluate differentiation of PCTC from benign partially cystic nodules with a machine learning-assisted system based on ultrasound (US) and elastography. METHODS: Patients with suspicious partially cystic nodules and finally confirmed were included in the study. We performed conventional US and real-time elastography (RTE). The US features of nodules were recorded. The data set was entered into 6 machine-learning algorithms. Sensitivity, specificity, accuracy, and area under the curve (AUC) were calculated. RESULTS: A total of 177 nodules were included in this study. Among these nodules, 81 were malignant and 96 were benign. Wreath-shaped feature, micro-calcification, and strain ratio (SR) value were the most important imaging features in differential diagnosis. The random forest classifier was the best diagnostic model. CONCLUSIONS: US features of PCTC exhibited unique characteristics. Wreath-shaped partially cystic nodules, especially with the appearance of micro-calcifications and larger SR value, are more likely to be malignant. The random forest classifier might be useful to diagnose PCTC.

[The Characteristics of Ultrasonography and Thermal Tomography in Various Molecular Subtypes of Breast Cancer].

OBJECTIVE: To explore the relationship between the imaging features of ultrasonography and thermal tomography and molecular subtypes of breast cancer. METHODS: 404 female breast cancer patients with complete imaging data and pathological findings from January 2014 to June 2017 were reviewed in the West China Hospital of Sichuan University. Breast cancer pathological molecules were classified into Luminal A like type, Luminal B like type, human epidermal growth receptor-2 (HER-2) overexpression type and Basal like type according to the expression of various immune markers. The correlation of ultrasonographic BI-RADS signs, thermal tomography characteristics and immunohistochemical results of breast cancer was analyzed. RESULTS: Breast cancer lesions with regular morphology, sharp margins, and enhanced posterior echo were more common in Basal like type; Microcalcification was more likely tend to appear in HER-2 expression breast cancer than other subtypes; The q-r curve of Luminal A like breast cancer was nearly 30°, and that was more common between 30°and 45° of HER-2 expression and Basal like breast cancer；The ratio of vertical and horizontal ≥1 of tumors and limited lymph node metastasis could not be used for distinguishing between different subtypes. CONCLUSION: Different molecular subtypes of breast cancer may behave routine ultrasound and thermal tomography imaging features.

Contrast-Enhanced Ultrasound in the Differential Diagnosis of Primary Thyroid Lymphoma and Nodular Hashimoto's Thyroiditis in a Background of Heterogeneous Parenchyma.

OBJECTIVE: To investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the differentiation of primary thyroid lymphoma (PTL) and nodular Hashimoto's thyroiditis (NHT) in patients with background of heterogeneous diffuse Hashimoto's thyroiditis (HT). METHODS: Sixty HT patients with 64 thyroid nodules (31 PTL and 33 NHT) who had undergone CEUS examination were included in this study. With histopathological results as the reference, we evaluated the imaging features of each nodule on both conventional ultrasonography (US) and CEUS. Quantitative CEUS parameters including peak intensity (PI), time to peak (TTP), and area under the time-intensity curve (AUC) were gathered in the nodule and background parenchyma. The ratio indexes of theses parameters were calculated by the ratio of the lesion and the corresponding thyroid parenchyma. Logistic regression and receiver operating characteristic (ROC) curves analyses of valuable US indicators were further preformed to evaluate the diagnostic capability of CEUS in discrimination of PTL and NHT. RESULTS: Among all the observed US imaging features and CEUS parameters, 10 indicators showed significant differences between PTL and NHT (all P < 0.05). All the significant indicators were ranked according to the odds ratios (ORs). Eight of them were CEUS associated including imaging features of enhancement pattern, degree, homogeneity, and quantification parameters of PI, AUC, ratios of PI, AUC, and TTP, while indicators on conventional US, including vascularity and size ranked the last two with ORs less than 3. The five single CEUS parameters showed good diagnostic performance in diagnosis of PTL with areas under ROC curves of 0.72-0.83 and accuracies of 70.3-75.0%. The combination of CEUS imaging features and the ratios of PI, AUC, and TTP demonstrated excellent diagnostic efficiency and achieved area under ROC curve of 0.92, which was significantly higher than any of the five single parameters (all P < 0.05), with a sensitivity of 83.9%, specificity of 87.9%, and accuracy of 85.9%. CONCLUSIONS: CEUS is an efficient diagnostic tool in the differential diagnosis of PTL and NHT for patients with diffuse HT. Conjoint analysis of CEUS imaging features and quantification parameters could improve the diagnostic values.

[Breast Thermal Tomography and High Frequency Ultrasound Imaging in Predicting Breast Cancer: a Preliminary Study].

OBJECTIVE: To determine the clinical value of breast thermal tomography and high frequency ultrasound imaging in diagnosing breast cancer. METHODS: Breast thermal tomography and high frequency ultrasound imaging were performed in 298 patients with breast lumps. The results were compared with pathological diagnosis. RESULTS: The ultrasound imaging had a sensitivity, specificity and the area under the curve (AUC) of 99.02%, 62.78% and 0.814, respectively, compared with 83.33%, 83.16% and 0.830 of thermal tomography, for diagnosing breast cancer. The two imaging results showed statistical significance in the test of non-inferiority (P < 0.001). A combination of the two imaging results produced a sensitivity, specificity and AUC of 83.33%, 89.79% and 0.866, respectively. CONCLUSION: Thermal tomography is not inferior to ultrasonography in detecting breast cancer. The two combined can improve specificity and accuracy of the diagnosis of breast cancer.

Can continuous scans in orthogonal planes improve diagnostic performance of shear wave elastography for breast lesions?

BACKGROUND: Static shear wave elastography (SWE) is used to detect breast lesions, but slice and plane selections result in discrepancies. OBJECTIVE: To evaluate the intraobserver reproducibility of continuous SWE, and whether quantitative elasticities in orthogonal planes perform better in the differential diagnosis of breast lesions. METHOD: One hundred and twenty-two breast lesions scheduled for ultrasound-guided biopsy were recruited. Continuous SWE scans were conducted in orthogonal planes separately. Quantitative elasticities and histopathology results were collected. Reproducibility in the same plane and diagnostic performance in different planes were evaluated. RESULTS: The maximum and mean elasticities of the hardest portion, and standard deviation of whole lesion, had high inter-class correlation coefficients (0.87 to 0.95) and large areas under receiver operation characteristic curve (0.887 to 0.899). Without loss of accuracy, sensitivities had increased in orthogonal planes compared with single plane (from 73.17% up to 82.93% at most). Mean elasticity of whole lesion and lesion-to-parenchyma ratio were significantly less reproducible and less accurate. CONCLUSION: Continuous SWE is highly reproducible for the same observer. The maximum and mean elasticities of the hardest portion and standard deviation of whole lesion are most reliable. Furthermore, the sensitivities of the three parameters are improved in orthogonal planes without loss of accuracies.

Value of contrast-enhanced ultrasonography in the differential diagnosis of enlarged lymph nodes: a meta-analysis of diagnostic accuracy studies.

OBJECTIVE: To evaluate the diagnostic accuracy of contrast-enhanced ultrasonography (CEUS) in differentiating between benign and malignant enlarged lymph nodes using meta-analysis. MATERIALS AND METHODS: Pubmed, Embase, SCI and Cochrane databases were searched for studies (up to September 1, 2014) reporting the diagnostic performance of CEUS in discriminating between benign and malignant lymph nodes. Inclusion criteria were: prospective study; histopathology as the reference standard; and sufficient data to construct 2?2 contingency tables. Methodological quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Patient clinical characteristics, sensitivity and specificity were extracted. The summary receiver operating characteristic curve was used to examine the accuracy of CEUS. A meta-analysis was performed to evaluate the clinical utility in identification of benign and malignant lymph nodes. Sensitivity analysis was performed after omitting outliers identified in a bivariate boxplot and publication bias was assessed with Egger testing. RESULTS: The pooled sensitivity, specificity and AUROC were 0.92 (95%CI, 0.85-0.96), 0.91 (95%CI, 0.82-0.95) and 0.97 (95%CI, 0.95-0.98), respectively. After omitting 3 outlier studies, heterogeneity decreased. Sensitivity analysis demonstrated no disproportionate influences of individual studies. Publication bias was not significant. CONCLUSIONS: CEUS is a promising diagnostic modality in differentiating between benign and malignant lymph nodes and can potentially reduce unnecessary fine-needle aspiration biopsies of benign nodes.

[Sonography of male breast lesions and the pathological diagnosis: a retrospective study of 10 years and literature review].

The sonographic features of male breast lesions, which underwent ultrasound examination in our hospital for the past 10 years, were retrospectively analyzed. Sonographic features of these lesions were standardized as BI RADS image lexicon. The differences in ultrasonic malignant signs were assessed between the benign and the malig nant diseases. Between the two groups, incomplete boundary was statistically different. The specificity was above 95% within the two groups in terms of speculated margin, echogenic halo, calcification, axillary lymphadenopathy, thickening of skin and eccentric of mass to the nipple. High-frequency sonographic examination has a high level of differential diagnosis for male breast lesions.

RSPO2-LGR5 signaling has tumour-suppressive activity in colorectal cancer.

R-spondins are a family of secreted Wnt agonists. One of the family members, R-spondin 2 (RSPO2), has an important role in embryonic development, bone formation and myogenic differentiation; however, its role in human cancers remains largely unknown. Here we show that RSPO2 expression is downregulated in human colorectal cancers (CRCs) due to promoter hypermethylation, and that the RSPO2 reduction correlates with tumour differentiation, size and metastasis. Overexpression of RSPO2 suppresses CRC cell proliferation and tumorigenicity, whereas the depletion of RSPO2 enhances tumour cell growth. RSPO2 has an inhibitory effect on Wnt/ß-catenin signaling in the CRC cells that show suppressed cell proliferation. In human CRC cells, the RSPO2-induced inhibition of Wnt signaling depends on leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5); RSPO2 interacts with LGR5 to stabilize the membrane-associated zinc and ring finger 3 (ZNRF3). Our data suggest that RSPO2 functions as a tumour suppressor in human CRCs, and these data reveal a RSPO2-induced, LGR5-dependent Wnt signaling-negative feedback loop that exerts a net growth-suppressive effect on CRC cells.

[Contrast-enhanced ultrasonography findings for papillary thyroid carcinoma and its pathological bases ].

OBJECTIVE: To investigate the findings of contrast enhanced ultrasound for papillary thyroid carcinoma and its pathological bases. METHODS: Seventy two (72) patients with thyroid nodules underwent routine conventional ultrasound and color Doppler examination, and 86 nodules with TI RADS 3 were examined by contrast-enhanced ultrasound (CEUS . Histopathological examination was kept as standard reference and the findings of CEUS were analyzed. Pathological studies of all nodules were made after post-operative CD34 immunohistochemistry staining examination. RESULTS: Of the total 86 nodules, Adler CDFl classification grades were: grade 0-26. grade I-34. grade II-23 and grade III-3 nodules respectively. Enhancement pattern on CEUS showed that there was low enhancement on 71 nodules, iso enhancement on 12 and high enhancement on 3 nodules. The differences of echo mean intensity. the peak intensity, area under the curve for enhancement intensity and CD34 count between the nodules and surrounding tissue were statistical significant (P < 0. 001). CONCLUSION: Low enhancement pattern on CEUS is the most common finding for papillary thyroid carcinoma, which is related to the difference of microvessel density between the nodules and surrounding tissues in papillary thyroid carcinoma.