Increased miR-3074-5p expression promotes M1 polarization and pyroptosis of macrophages via ERα/NLRP3 pathway and induces adverse pregnancy outcomes in mice.

Decidual macrophages (dMϕs) play critical roles in regulation of immune-microhomeostasis at maternal-fetal interface during pregnancy, but the underlying molecular mechanisms are still unclear. In this study, it was found that litter size and fetal weight were significantly reduced, whereas the rate of embryo resorption was increased in miR-3074-5p knock-in (3074-KI) pregnant mice, compared to that of wild-type (WT) pregnant mice. Plasma levels of pro-inflammatory cytokines in 3074-KI pregnant mice were also significantly elevated compared to WT pregnant mice at GD7.5. The quantity of M1-Mϕs in uterine tissues of 3074-KI pregnant mice was significantly increased compared to WT pregnant mice at GD13.5. Estrogen receptor-α (ERα) was validated to be a target of miR-3074-5p. Either miR-3074-5p overexpression or ERα knockdown promoted transcriptional activity of NF-κB/p65, induced M1-polarization and pyroptosis of THP1-derived Mϕs, accompanied with increased intracellular levels of cleaved Caspase-1, cleaved IL-1ß, NLRP3, cleaved GSDMD and ASC aggregation. Furthermore, ERα could not only bind to NLRP3 or ASC directly, but also inhibit the interaction between NLRP3 and ASC. The endometrial miR-3074-5p expression level at the middle secretory stage of repeated implantation failure (RIF) patients was significantly decreased compared to that of control fertile women. These data indicated that miR-3074-5p could promote M1 polarization and pyroptosis of Mϕs via activation of NLRP3 inflammasome by targeting ERα, and the dysregulation of miR-3074-5p expression in dMϕs might damage the embryo implantation and placentation by interfering with inflammatory microenvironment at the maternal-fetal interface during early pregnancy.

Epitope delimitation: A new method for defining epitopes of human IgG-reactive antigenic peptides based on rabbit-recognized epitope motifs.

The use of precise epitope peptides as antigens is essential for accurate serological diagnosis of viral-infected individuals, but now it remains an unsolvable problem for mapping precise B cell epitopes (BCEs) recognized by human serum. To address this challenge, we propose a novel epitope delimitation (ED) method to uncover BCEs in the delineated human IgG-reactive (HR) antigenic peptides (APs). Specifically, the method based on the rationale of similarities in humoral immune responses between mammalian species consists of a pair of elements: experimentally delineated HR-AP and rabbit-recognized (RR) BCE motif and corresponding pair of sequence alignment analysis. As a result of using the ED approach, after decoding four RR-epitomes of human papillomavirus types 16/18-E6 and E7 proteins utilizing rabbit serum against each recombinant protein and sequence alignment analysis of HR-APs and RR-BCEs, 19 fine BCEs in 17 of 22 known HR-APs were defined based on each corresponding RR-BCE motifs, including the type-specificity of each delimited BCE in homologous proteins. The test with 22 known 16/20mer HR-APs demonstrated that the ED method is effective and efficient, indicating that it can be used as an alternative method to the conventional identification of fine BCEs using overlapping 8mer peptides.

PD-1 monoclonal antibodies enhance the cryoablation-induced antitumor immune response: a breast cancer murine model research.

BACKGROUND: It has been demonstrated that cryoablation (Cryo) causes specific T-cell immune responses in the body; however, it is not sufficient to prevent tumor recurrence and metastasis. In this report, we evaluated changes in the tumor immune microenvironment (TIME) in distant tumor tissues after Cryo and investigated the immunosuppressive mechanisms that limit the efficacy of Cryo. METHODS: Bilateral mammary tumor models were established in mice, and we first observed the dynamic changes in immune cells and cytokines at different time points after Cryo. Then, we confirmed that the upregulation of PD-1 and PD-L1 signaling in the contralateral tumor tissue was closely related to the immunosuppressive state in the TIME at the later stage after Cryo. Finally, we also evaluated the synergistic antitumor effects of Cryo combined with PD-1 monoclonal antibody (mAb) in the treatment of breast cancer (BC) mouse. RESULTS: We found that Cryo can stimulate the body's immune response, but it also induces immunosuppression. The elevated PD-1/PD-L1 expression in distant tumor tissues at the later stage after Cryo was closely related to the immunosuppressive state in the TIME but also created the conditions for Cryo combined with PD-1 mAb for BC mouse treatment. Cryo + PD-1 mAb could improve the immunosuppressive state of tumors and enhance the Cryo-induced immune response, thus exerting a synergistic antitumor effect. CONCLUSIONS: The PD-1/PD-L1 axis plays an important role in suppressing Cryo-induced antitumor immune responses. This study provides a theoretical basis for Cryo combined with PD-1 mAb therapy in clinical BC patients.

Awareness of tobacco control policies and anti-tobacco attitudes and behaviors among school personnel.

INTRODUCTION: Adolescent smoking is a serious public health concern, and the role of personnel in reducing students'tobacco use has been proven. Anti-tobacco policies are strong factors for tobacco control but most are newly implemented in China. This study aimed to examine the awareness of anti-tobacco policies among school personnel in a southern city of China, and assess its influence on personnel's anti-tobacco attitudes and behaviors towards students. METHODS: An online cross-sectional study was conducted between September 2017 and January 2018 in schools of Shanghai, China. A total of 3194 subjects from 33 schools were selected by a two-stage stratified cluster randomized sampling design. Prevalence of anti-tobacco policy awareness is presented. Crude (ORs) and adjusted odds ratios (AORs) and their 95% confidence intervals (CIs) were estimated to assess the association between policy awareness and anti-tobacco attitudes or behaviors. RESULTS: In all, 22.4% of surveyed participants knew four or five polices presented in the survey and 13.0% of personnel knew none of these policies. Most of the participants fully support prohibiting indoor (94.6%) and outdoor (86.3%) smoking in public places, bans on tobacco advertising (90.9%), and printing warning pictures on cigarette boxes (89.5%). Less than half of the personnel had taken action to stop students from smoking (45.7%), encourage students to quit smoking (42.4%) or participated in relevant educational activities held by schools (37.4%) in the previous year. The school personnel's anti-tobacco attitudes (AOR=1.28; 95% CI: 1.21-1.36) and behaviors (AOR=1.10; 95% CI: 1.03-1.17) were strengthened with increasing level of policy awareness. CONCLUSIONS: The involvement of school personnel can be an important part of intervention to improve anti-tobacco campaigns on campus. The study calls for the implementation of projects or activities to improve anti-tobacco policy awareness in the school environment as part of school tobacco control strategy.

MNSFß Regulates TNFα Production by Interacting with RC3H1 in Human Macrophages, and Dysfunction of MNSFß in Decidual Macrophages Is Associated With Recurrent Pregnancy Loss.

Decidual macrophages (dMϕ) are the second largest population of leukocytes at the maternal-fetal interface and play critical roles in maintaining pregnancy. Our previous studies demonstrated the active involvement of monoclonal nonspecific suppressor factor-ß (MNSFß) in embryonic implantation and pregnancy success. MNSFß is a ubiquitously expressed ubiquitin-like protein that also exhibits immune regulatory potential, but its function in human dMϕ remains unknown. Here, we observed that the proportion of CD11chigh (CD11cHI) dMϕ was significantly increased in dMϕ derived from patients with recurrent pregnancy loss (RPL dMϕ) compared to those derived from normal pregnant women (Control dMϕ). The production of MNSFß and TNFα by RPL dMϕ was also significantly increased compared to that by Control dMϕ. Conditioned medium from RPL dMϕ exerted an inhibitory effect on the invasiveness of human trophoblastic HTR8/SVneo cells, and this effect could be partially reversed by a neutralizing antibody against TNFα. Bioinformatics analysis indicated a potential interaction between MNSFß and RC3H1, a suppressor of TNFα transcription. Immunoprecipitation experiments with human Mϕ differentiated from the human monocyte cell line Thp1 (Thp1-derived Mϕ) proved the binding of MNSFß to RC3H1. Specific knockdown of MNSFß in Thp1-derived Mϕ led to a marked decrease in TNFα production, which could be reversed by inhibiting RC3H1 expression. Interestingly, a significant decrease in the protein level of RC3H1 was observed in RPL dMϕ. Together, our findings indicate that aberrantly increased MNSFß expression in dMϕ may promote TNFα production via its interaction with RC3H1, and these phenomena could result in the disruption of the immune balance at the maternal-fetal interface and thus pregnancy loss.

Three-dimensional shear wave elastography for differentiation of breast lesions: An initial study with quantitative analysis using three orthogonal planes.

OBJECTIVES: To prospectively evaluate the diagnostic performance of three-dimensional (3D) shear wave elastography (SWE) for breast lesions with quantitative stiffness information from transverse, sagittal and coronal planes. METHODS: Conventional ultrasound (US), two-dimensional (2D)-SWE and 3D-SWE were performed for 122 consecutive patients with 122 breast lesions before biopsy or surgical excision. Maximum elasticity values of Young's modulus (Emax) were recorded on 2D-SWE and three planes of 3D-SWE. Area under the receiver operating characteristic curve (AUC), sensitivity and specificity of US, 2D-SWE and 3D-SWE were evaluated. Two combined sets (i.e., BI-RADS and 2D-SWE; BI-RADS and 3D-SWE) were compared in AUC. Observer consistency was also evaluated. RESULTS: On 3D-SWE, the AUC and sensitivity of sagittal plane were significantly higher than those of transverse and coronal planes (both P < 0.05). Compared with BI-RADS alone, both combined sets had significantly (P < 0.05) higher AUCs and specificities, whereas, the two combined sets showed no significant difference in AUC (P > 0.05). However, the combined set of BI-RADS and sagittal plane of 3D-SWE had significantly higher sensitivity than the combined set of BI-RADS and 2D-SWE. CONCLUSIONS: The sagittal plane shows the best diagnostic performance among 3D-SWE. The combination of BI-RADS and 3D-SWE is a useful tool for predicting breast malignant lesions in comparison with BI-RADS alone.

Correction to: MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy.

Following publication of the article, the authors reported that Huixiong Xu had left the department, and requested that the author list be amended accordingly.

MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy.

EVA1A (also known as transmembrane protein 166) is a transmembrane protein involved in the regulation of autophagy that acts as an adaptor protein to recruit or bind proteins in the lysosome or endoplasmic reticulum. In the present study, we identified EVA1A as a target of microRNA-125b (miR-125b), a member of a highly conserved family of miRNAs that has been proposed as a biomarker for hepatocellular carcinoma (HCC). Analysis of oxaliplatin-sensitive and oxaliplatin-resistant HCC cell lines showed that miR-125b is downregulated in resistant cells and its overexpression in sensitive cells decreased resistance to oxaliplatin by inhibiting cell proliferation, migration and epithelial-mesenchymal transition (EMT). EVA1A expression was shown to be upregulated in tissue samples from oxaliplatin-resistant HCC patients, and its ectopic expression partially induced autophagy and reversed the effect of miR-125b on inhibiting the growth of oxaliplatin-resistant cell lines and xenograft tumors. Taken together, our results suggest that miR-125b plays a role in the resistance of HCC cells to chemotherapy via a mechanism involving the downregulation of EVA1A-mediated autophagy.

[Establishment and characterization of A549 tumor monoclonal cell line with UCHL1 gene deletion].

The purpose of this study was to investigate the effects of ubiquitin C-terminal hydrolase-L1 (UCHL1) on non-small cell lung cancer cell line A549. UCHL1 gene knockout A549 cell line was constructed by CRISPR-CAS9 gene editing technique. The mRNA and protein levels of UCHL1 were examined by RT-PCR and Western blot, respectively. Cell proliferation and cycles were analyzed by CCK-8 method and flow cytometry, respectively. The sensitivity of A549 cells to cisplatin was detected by CCK-8 method. Migration ability of A549 cells was detected by scratch assay and Transwell test, and p-Erk expression level was assessed by Western blot. The results showed that UCHL1 gene knockout A549 cells were successfully constructed by CRISPR-CAS9 gene editing technique. After UCHL1 gene knockout, there was no significant change in cell proliferation and cell cycle ratios in A549 cells. UCHL1 gene knockout A549 cells exhibited decreased sensitivity to cisplatin and migration activity, as well as increased p-Erk expression level. These results suggest that the loss of UCHL1 gene function may reduce the sensitivity and migration ability of A549 cells, and this effect may be related to the activation of Erk1/2 signaling pathway.

Complex cystic and solid breast lesions: Diagnostic performance of conventional ultrasound, strain imaging and point shear wave speed measurement.

OBJECTIVE: To assess the performance of conventional high frequency ultrasound (US) and US elastography in diagnosis of complex cystic and solid breast lesions. METHODS: Ninety three lesions in 93 patients underwent conventional US and US elastography, including strain elastography, acoustic radiation force impulse (ARFI) imaging, and point shear wave speed (SWS) measurement. RESULTS: Pathological examination revealed 31 (33.3%) of the 93 lesions were malignant and the remaining 62 (66.7%) were benign. Multivariate analysis showed that elder patient (OR: 25.301), internal vascularity (OR: 4.518), and not circumscribed margin (OR: 3.813) were independent predictors for malignancy, while predominately cystic lesions (OR: 0.178) was a predictor for benign lesions (all p < 0.05). Invalid SWS measurement was occurred in 19 of 31 (61.3%) malignant lesions and 16 of 62 (25.8%) benign lesions, respectively (p < 0.05). The mean SWS value for malignant lesions was significantly lower than that for benign ones, being 1.60±0.63 m/s (range, 0.68-2.70 m/s) versus 2.33±0.77 m/s (range, 0.67-3.97 m/s) (p < 0.05). Areas under the ROC curve (Azs) for Breast Imaging Reporting and Data System (BI-RADS) assessment, strain elasticity score, ARFI imaging and valid point SWS measurement were 0.844, 0.734, 0.763 and 0.778,respectively. CONCLUSIONS: US BI-RADS category, strain elastography score, ARFI imaging patterns and point SWS measurement are useful for malignancy prediction of complex cystic and solid breast lesions. The result that SWS for malignant lesions is lower than benign one should be carefully interpreted since invalid SWS measurement is excluded for analysis. The true stiffness of malignant cystic and solid lesions should be further evaluated with a new generation of two-dimensional SWS imaging.

Three-Dimensional Shear Wave Elastography for Differentiating Benign From Malignant Thyroid Nodules.

OBJECTIVES: To prospectively evaluate the diagnostic performance of 3-dimensional (3D) shear wave elastography (SWE) for assessing thyroid nodules. METHODS: A total of 176 surgically or cytologically confirmed thyroid nodules (63 malignant and 113 benign) in 176 patients who had undergone conventional ultrasound (US), 2-dimensional (2D) SWE, and 3D SWE examinations were included in this study. Quantitative elasticity values (mean elasticity, maximum elasticity, and standard deviation of elasticity of a large region of interest and mean elasticity of a 2-mm region of interest) were measured on 2D and 3D SWE. Diagnostic performances of conventional US, 2D SWE, and 3D SWE were assessed. The role of 2D and 3D SWE in reducing unnecessary fine-needle aspiration (FNA) for nodules with low suspicion was also evaluated. RESULTS: The diagnostic performances in terms of the area under the receiver operating characteristic curve were 0.612 for conventional US, 0.836 for 2D SWE (P < .001 in comparison with conventional US), and 0.839 for 3D SWE (P < .001 in comparison with conventional US). The mean elasticity achieved the highest diagnostic performance in 2D SWE, whereas the standard deviation of elasticity achieved the highest performance in 3D SWE, although no significant difference was found between them (P > .05). Three-dimensional SWE increased the specificity in comparison with 2D SWE (88.5% versus 82.3%; P = .039). For the 37 nodules with low suspicion on conventional US imaging, 2D SWE was able to avoid unnecessary FNA in 77.1% (27 of 35) of benign nodules, and 3D SWE further increased the number to 88.6% (31 of 35). CONCLUSIONS: Three-dimensional SWE is a useful tool for predicting thyroid nodule malignancy and reducing unnecessary FNA procedures in thyroid nodules with low suspicion of malignancy.

miR-3074-5p Promotes the Apoptosis but Inhibits the Invasiveness of Human Extravillous Trophoblast-Derived HTR8/SVneo Cells In Vitro.

OBJECTIVE: The objective of this study was to observe the effects of the overexpression of miR-3074-5p in human trophoblast cells in vitro. DESIGN: Experimental in vitro study in HTR8/SVneo cells. METHODS: HTR8/SVneo cells were transfected with miR-3074-5p mimic. The cell apoptosis and invasion were measured via flow cytometry and transwell assay, respectively. The expression levels of P53, Cyclin Dependent Kinase Inhibitor 1B (P27), BCL-2, BCL2 associated X (BAX), and BCL2 like 14 (BCL-G) in HTR8/SVneo cells were determined by Western blot. The alterations in gene expression profile of HTR8/SVneo cells were evaluated by complementary DNA microarray assay, and the differential expressions of dihydrolipoamide S-succinyltransferase (DLST), growth-associated protein 43 (GAP43), runt-related transcription factor 2 (RUNX2), and C-C type chemokine receptor 3 (CCR3) were validated by Western blot. Biofunctions of these differentially expressed genes were enriched by Gene Ontology analysis. RESULTS: The overexpression of miR-3074-5p in HTR8/SVneo cells promoted cell apoptosis but inhibited cell invasion, being accompanied by the significantly elevated expressions of P27, BCL-2, and BCL-G. Meanwhile, an increased expression of P27 and P57 was also detected in a small sample size of placental villi of recurrent miscarriage (RM) patients. Totally, 411 genes and 397 genes were screened out, respectively, to be downregulated or upregulated at least by 2-folds in miR-3074-5p overexpressed HTR8/SVneo cells. These differentially expressed genes were involved in several important functions related to pregnancy. Subsequently, the reduced expressions of DLST and GAP43 proteins, as well as the increased expressions of CCR3 and RUNX2 proteins, were validated in miR-3074-5p overexpressed HTR8/SVneo cells. CONCLUSION: These data suggested a potential contribution of miR-3074-5p in the pathogenesis of RM by disturbing the normal activities of trophoblast cells.

Increased Expression of NDRG3 in Mouse Uterus During Embryo Implantation and in Mouse Endometrial Stromal Cells During In Vitro Decidualization.

Decidualization is an indispensable event in the embryo implantation process, but its underlying molecular mechanisms remain elusive. In this study, we showed that in mice, the uterine expression of N-myc downstream-regulated gene 3 (NDRG3), a member of the α/ß hydrolase superfamily, was induced by estradiol and progesterone. During the embryo implantation process, uterine Ndrg3 expression was remarkably upregulated, and its expression level at implantation sites (IS) was significantly higher than that at inter-IS. Increased uterine expression of Ndrg3 was associated with artificial decidualization and the activation of delayed implantation. The in vitro decidualization of mouse endometrial stromal cells (ESCs) induced by estradiol and progesterone was also accompanied by increased Ndrg3 expression, and downregulated Ndrg3 expression in ESCs effectively inhibited decidualization. miR-290b-5p was identified as an upstream regulator of Ndrg3, and the uterine expression level of miR-290b-5p was decreased during the implantation process. Furthermore, overexpression of miR-290b-5p in mouse ESCs inhibited their in vitro decidualization. Taken together, these data suggested that Ndrg3 might play an important role in embryo implantation by regulating decidualization potentially via the estrogen/progesterone/miR-290b-5p pathway.

A Proposal to Stratify the Intermediate-Risk Thyroid Nodules According to the AACE/ACE/AME Guidelines with Ultrasound Features.

To propose a risk stratification system for intermediate-risk thyroid nodules (TNs) according to American Association of Clinical Endocrinologists, American College of Endocrinology and Associazione Medici Endocrinologi Medical (AACE/ACE/AME) Guideline with ultrasound (US) features. 1000 patients with 1000 nodules (902 benign nodules and 98 malignant nodules) were included. All the nodules were confirmed with either fine needle aspiration (FNA) cytology and follow-up or histology results after surgery. Univariate analysis and binary multivariate logic regression analysis were applied to analyze the possible risk US features associated with malignancy. Receiver operating characteristic curves (ROC) were drew and compared. Univariate analysis and binary multivariate logistic regression analysis showed that indeterminate hyper-echoic spot (OR = 4.544), slightly ill-defined margin (OR = 2.559), slight hyper-echogenicity (OR = 1.992) and no macro-calcification (OR = 1.921) were risk factors for the intermediate-risk thyroid nodules (TNs). A predicting model was established based on the 4 risk factors. The risk rates of malignancy were 5.7% (26/455) in Stage I, 11.0% (49/445) in Stage II, 23.1% (21/91) in Stage III, 33.3% (3/9) in Stage IV. In conclusion, for the intermediate-risk TNs, special attention should be paid to the TNs with indeterminate hyper-echoic spot, slightly ill-defined margin, slight hyper-echogenicity, or no macro-calcification. The probability of malignancy increased with the number of risk factors increasing.

Malignancy risk stratification of thyroid nodules: comparisons of four ultrasound Thyroid Imaging Reporting and Data Systems in surgically resected nodules.

To compare the efficiency of four different ultrasound (US) Thyroid Imaging Reporting and Data Systems (TI-RADS) in malignancy risk stratification in surgically resected thyroid nodules (TNs). The study included 547 benign TNs and 464 malignant TNs. US images of the TNs were retrospectively reviewed and categorized according to the TI-RADSs published by Horvath E et al. (TI-RADS H), Park et al. (TI-RADS P), Kwak et al. (TI-RADS K) and Russ et al. (TI-RADS R). The diagnostic performances for the four TI-RADSs were then compared. At multivariate analysis, among the suspicious US features, marked hypoechogenicity was the most significant independent predictor for malignancy (OR: 15.344, 95% CI: 5.313-44.313) (P < 0.05). Higher sensitivity was seen in TI-RADS H, TI-RADS K, TI-RADS R comparing with TI-RADS P (P < 0.05 for all), whereas the specificity, accuracy and area under the ROC curve (Az) of TI-RADS P were the highest (all P < 0.05). Higher specificity, accuracy and Az were seen in TI-RADS K compared with TI-RADS R (P = 0.003). With its higher sensitivity, TI-RADS K, a simple predictive model, is practical and convenient for the management of TNs in clinical practice. The study indicates that there is a good concordance between TI-RADS categories and histopathology.

Insulin upregulates GRIM-19 and protects cardiac mitochondrial morphology in type 1 diabetic rats partly through PI3K/AKT signaling pathway.

Insulin is involved in the development of diabetic heart disease and is important in the activities of mitochondrial complex I. However, the effect of insulin on cardiac mitochondrial nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 subunit of retinoic-interferon-induced mortality 19 (GRIM-19) has not been characterized. The aim of this study was to investigate the effect of insulin on the mitochondrial GRIM-19 in the hearts of rats with streptozotocin (STZ)-induced type 1 diabetes. Protein changes of GRIM-19 were evaluated by western blotting and reverse transcription-quantitative polymerase chain reaction. Furthermore, the effects of insulin on mitochondrial complex I were detected in HeLa cells and H9C2 cardiac myocytes. During the development of diabetic heart disease, the cardiac function did not change within the 8 weeks, but the mitochondrial morphology was altered. The hearts from the rats with STZ-induced diabetes exhibited reduced expression of GRIM-19. Prior to the overt cardiac dilatation, mitochondrial alterations were already present. Following subcutaneous insulin injection, it was demonstrated that GRIM-19 protein was altered, as well as the mitochondrial morphology. The phosphoinositide 3-kinase inhibitor LY294002 had an effect on insulin signaling in H9C2 cardiacmyocytes, and decreased the level of GRIM-19 by half compared with that in the insulin group. The results indicate that insulin is essential for the control of cardiac mitochondrial morphology and the GRIM-19 expression partly via PI3K/AKT signaling pathways.

Virtual touch tissue imaging and quantification: value in malignancy prediction for complex cystic and solid breast lesions.

This study was aimed to evaluatethe usefulness of conventional ultrasound (US) and US elastography, including the latest virtual touch tissue imaging and quantification (VTIQ), in malignancy prediction for complex cystic and solid breast lesions. Eighty-nine complex cystic and solid breast lesions were subject to conventional US and US elastography, including strain elastography (SE), virtual touch tissue imaging (VTI) and VTIQ. Among the 89 lesions, thirty-four (38.2%) lesions were malignant and 55 (61.8%) lesions were benign. Sixteen variables were subject to multivariate logistic regression analysis. Pattern 4b in VTI (odds ratio, OR:15.278), not circumscribed margin of lesion (OR:12.346), SWS mean >4.6 m/s in VTIQ (OR:11.896), and age elder than 50 years (OR:6.303) were identified to be independent predictors for malignancy. In receiver operating characteristic (ROC) curve analyses, associated areas under the ROC curve (Az) for conventional US could be significantly elevated, from 0.649 to 0.918, by combining with US elastography (p < 0.0001). The combined diagnostic method was able to improve the specificity (32.7% vs. 87.3%, p < 0.0001) without sacrificing the sensitivity (97.1% vs. 85.3%, p = 0.075). Both conventional US and US elastography contribute substantially to malignancy prediction in complex cystic and solid lesions. The diagnostic efficacy of conventional US in terms of Az and specificity could be significantly improved by combining with US elastography.

Cytologically indeterminate thyroid nodules: increased diagnostic performance with combination of US TI-RADS and a new scoring system.

To investigate the diagnostic performance of combination of ultrasound (US) thyroid imaging reporting and data system (TI-RADS) and a new US scoring system for diagnosing thyroid nodules (TNs) with indeterminate results (Bethesda categories III, IV and V) on fine-needle aspiration (FNA) cytology. 453 patients with 453 cytologically indeterminate TNs were included in this study. Multivariate analyses were performed to construct the scoring system. The diagnostic performances of TI-RADS and the combined method were evaluated and compared. Multivariate analyses revealed that marked hypoechogenicity, taller than wide shape and absence of halo sign were independent predictors for malignancy in cytologically indeterminate TNs. Scoring system was thereafter defined as follows: risk score (RS) = 3.2 x (if marked hypoechogenicity) + 2.8 x (if taller than wide shape) + 1.3 x (if absence of halo sign). Compared with TI-RADS alone, the areas under the receiver operating characteristic curves (AUC), specificity, accuracy and positive predictive value (PPV) of the combined method increased significantly with 0.731 versus 0.569, 48.5% versus 14.1%, 76.2% versus 62.3%, and 70.9% versus 59.9%, respectively (all P < 0.05). The combination of TI-RADS and new US scoring system showed superior diagnostic performances in predicting malignant TNs with indeterminate FNA cytology results in comparison with TI-RADS alone.

Value of shear wave arrival time contour display in shear wave elastography for breast masses diagnosis.

To evaluate the diagnostic performance of shear wave arrival time contour (SWATC) display for the diagnosis of breast lesions and to identify factors associated with the quality of shear wave propagation (QSWP) in breast lesions. This study included 277 pathologically confirmed breast lesions. Conventional B-mode ultrasound characteristics and shear wave elastography parameters were computed. Using the SWATC display, the QSWP of each lesion was assigned to a two-point scale: score 1 (low quality) and score 2 (high quality). Binary logistic regression analysis was performed to identify factors associated with QSWP. The area under the receiver operating characteristic curve (AUROC) for QSWP to differentiate benign from malignant lesions was 0.913, with a sensitivity of 91.9%, a specificity of 90.7%, a positive predictive value (PPV) of 74.0%, and a negative predictive value (NPV) of 97.5%. Compared with using the standard deviation of shear wave speed (SWSSD) alone, SWSSD combined with QSWP increased the sensitivity from 75.8% to 93.5%, but decreased the specificity from 95.8% to 89.3% (P < 0.05). SWSSD was identified to be the strongest factor associated with the QSWP, followed by tumor malignancy and the depth of the lesion. In conclusion, SWATC display may be useful for characterization of breast lesions.