Multimodal imaging findings of sarcomatoid carcinoma of the urinary bladder.

Sarcomatoid carcinoma, a rare and aggressive subtype of bladder cancer, accounting for 0.3% of cases, is more aggressive than urothelial carcinomas. Accurate diagnosis, crucial for treatment, can be challenging. We present a characterized case of sarcomatoid carcinoma of the urinary bladder using multimodal imaging and pathology.

An ultrasound-based nomogram model in the assessment of pathological complete response of neoadjuvant chemotherapy in breast cancer.

Introduction: We aim to predict the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) in breast cancer patients by constructing a Nomogram based on radiomics models, clinicopathological features, and ultrasound features. Methods: Ultrasound images of 464 breast cancer patients undergoing NAC were retrospectively analyzed. The patients were further divided into the training cohort and the validation cohort. The radiomics signatures (RS) before NAC treatment (RS1), after 2 cycles of NAC (RS2), and the different signatures between RS2 and RS1 (Delta-RS/RS1) were obtained. LASSO regression and random forest analysis were used for feature screening and model development, respectively. The independent predictors of pCR were screened from clinicopathological features, ultrasound features, and radiomics models by using univariate and multivariate analysis. The Nomogram model was constructed based on the optimal radiomics model and clinicopathological and ultrasound features. The predictive performance was evaluated with the receiver operating characteristic (ROC) curve. Results: We found that RS2 had better predictive performance for pCR. In the validation cohort, the area under the ROC curve was 0.817 (95%CI: 0.734-0.900), which was higher than RS1 and Delta-RS/RS1. The Nomogram based on clinicopathological features, ultrasound features, and RS2 could accurately predict the pCR value, and had the area under the ROC curve of 0.897 (95%CI: 0.866-0.929) in the validation cohort. The decision curve analysis showed that the Nomogram model had certain clinical practical value. Discussion: The Nomogram based on radiomics signatures after two cycles of NAC, and clinicopathological and ultrasound features have good performance in predicting the NAC efficacy of breast cancer.

Sarcomatoid hepatocellular carcinoma mimics hepatic abscess on contrast-enhanced ultrasound.

Sarcomatoid hepatocellular carcinoma (SHCC) is a rare subtype of hepatocellular carcinoma characterized by abdominal pain or persistent fever with an inflammatory reaction. Here, we report a case of SHCC mimicking hepatic abscess described by not only ultrasonography but also computer tomography. SHCC is a rare subtype of hepatocellular carcinoma characterized by epithelial and mesenchymal tumor features with sarcomatoid morphology. Here, we report a case of SHCC described by ultrasonography and computer tomography as well as confirmed by pathological examination.

Ultrasonographic and pathological findings of syringocystadenoma papilliferum in the skin.

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Two gates mediate NMDA receptor activity and are under subunit-specific regulation.

Kinetics of NMDA receptor (NMDAR) ion channel opening and closing contribute to their unique role in synaptic signaling. Agonist binding generates free energy to open a canonical gate at the M3 helix bundle crossing. Single channel activity is characterized by clusters, or periods of rapid opening and closing, that are separated by long silent periods. A conserved glycine in the outer most transmembrane helices, the M4 helices, regulates NMDAR function. Here we find that the GluN1 glycine mainly regulates single channel events within a cluster, whereas the GluN2 glycine mainly regulates entry and exit from clusters. Molecular dynamics simulations suggest that, whereas the GluN2 M4 (along with GluN2 pre-M1) regulates the gate at the M3 helix bundle crossing, the GluN1 glycine regulates a 'gate' at the M2 loop. Subsequent functional experiments support this interpretation. Thus, the distinct kinetics of NMDARs are mediated by two gates that are under subunit-specific regulation.

Correlation of breast cancer microcirculation construction with tumor stem cells (CSCs) and epithelial-mesenchymal transition (EMT) based on contrast-enhanced ultrasound (CEUS).

OBJECTIVE: This study is to explore the correlation between the contrast-enhanced ultrasound (CEUS) characteristics of breast cancer and the epithelial-mesenchyme transformation (EMT). METHODS: Totally 119 patients of breast cancer underwent CEUS. Tissues in the active area were collected and subjected to the immunohistochemical detection, PT-PCR and Western blot. Correlation analysis was conducted between the clinical pathological parameters and the CEUS indicators. RESULTS: The expression levels of CD44, N-cadherin, and ß-catenin in breast cancer tissues were higher than those in adjacent tissues (P<0.05). However, the expression levels of CD24 and E-cadherin in breast cancer tissues were lower than those in adjacent tissues (P<0.05). There was no significant difference in E-cadherin mRNA and Vimentin levels between cancer and adjacent tissues (P>0.05). The expressions were up-regulated in the CSCs, with higher histological grade, lymph node metastasis, and negative estrogen receptor (ER) expression. Smaller breast tumors, with no lymph node metastasis, lower clinical stage, and positive ER expression, tended to exhibit the up-regulated epithelial phenotype. Breast tumors, with high histological grade, lymph node metastasis, high clinical staging grade, and negative ER expression, tended to exhibit the up-regulated interstitial phenotype. The peak intensity of the time-intensity curve (TIC) for the CEUS was positively correlated with the CSC marker CD44 and the interstitial phenotype marker N-cadherin. The starting time of enhancement was negatively correlated with the N-cadherin. Area under the curve was positively correlated with the expression of CD44 and N-cadherin, while negatively correlated with the epithelial phenotype marker ß-catenin. The time to peak was negatively correlated with the interstitial phenotypes Vimentin and N-cadherin, with no correlation with the E-cadherin or ß-catenin. CONCLUSION: Breast cancers show the enlarged lesions after enlargement and perfusion defect for the CEUS. The fast-in pattern, high enhancement, and high perfusion in the TIC are correlated with the CSCs and EMT expressions, suggesting poor disease prognosis.

Relationship of shear wave elastography anisotropy with tumor stem cells and epithelial-mesenchymal transition in breast cancer.

BACKGROUND: This study is to examine the feasibility of shear wave elastography (SWE) anisotropy in assessing the prognosis of breast cancer. METHODS: We enrolled 119 breast cancer patients from January 2017 to October 2019. SWE was performed before operation. Emax (maximum elasticity value), Emean (average elasticity value), Esd (standard deviation of the lesion elasticity value), Eratio (elasticity value of adipose tissue), anisotropy coefficient and difference were recorded. After operation, we collected clinical pathological data, and performed immunohistochemistry and real-time PCR tests on CD44, CD24, E-cadherin, ß-catenin, vimentin and N-cadherin. Finally, we analyzed the correlation among parameters of SWE, anisotropy and clinicopathology, and markers of CSCs (cancer stem cells) and EMT (epithelial-mesenchymal transition). RESULTS: Emax, Emean and Esd of the cross section were higher than those of the longitudinal section. Breast cancer with a higher elastic modulus was often accompanied by a hyperechoic halo, which was manifested as mixed echo and post-echo attenuation, and was accompanied by a higher BI-RADS (breast imaging reporting and data system) classification. When breast cancer had hyperechoic halo and weakened posterior echo, SWE of the lesion showed more obvious anisotropy. In addition, larger diameter of the longitudinal section indicated higher stiffness of the cross section. Correlation analysis showed that E-cadherin was negatively correlated with SWE in longitudinal section. CD44, N-cadherin, ß-catenin were positively correlated with SWE in longitudinal and cross sections. Vimentin and CD24 had no correlation with SWE parameters. CONCLUSION: SWE of breast cancer is anisotropic. The cross-sectional SWE is better than the longitudinal SWE, Emax is better than Emean, the anisotropy of SWE is better than SWE, and the anisotropy factor is better than the anisotropy difference.

Artificial Intelligence Algorithm-Based Ultrasound Image Segmentation Technology in the Diagnosis of Breast Cancer Axillary Lymph Node Metastasis.

This paper aimed to investigate the application of ultrasound image segmentation technology based on the back propagation neural network (BPNN) artificial intelligence algorithm in the diagnosis of breast cancer axillary lymph node metastasis, thereby providing a theoretical basis for clinical diagnosis. In this study, 90 breast cancer patients with axillary lymph node metastasis were selected as the research objects and rolled randomly into an experimental group and a control group. Besides, all of them were examined by ultrasound. The BPNN algorithm for the ultrasound image segmentation diagnosis method was applied to the patiens from the experimental group, while the control group was given routine ultrasound diagnosis. Thus, the value of this algorithm in ultrasonic diagnosis was compared and explored. The results showed that when the number of hidden layer nodes based on the BPNN artificial intelligence algorithm was 2, 3, 4, 5, 6, 7, and 8, the corresponding segmentation accuracy was 97.3%, 96.5%, 94.8%, 94.8%, and 94.1% in turn. Among them, the segmentation accuracy was the highest when the number of hidden layer nodes was 2. The correlation of independent variable bubble plot analysis showed that the presence or absence of capsules, the presence of crab feet or burrs in breast cancer lesions was critical influencing factors for the occurrence of axillary lymph node metastasis, and the standardized importance was 99.7% and 70.8%, respectively. Besides, the area under the two-dimensional receiver operating characteristic (ROC) curve of the BPNN artificial intelligence algorithm model classification was always greater than the area under the curve of manual segmentation, and the segmentation accuracy was 90.31%, 94.88%, 95.48%, 95.44%, and 97.65% in sequence. In addition, the segmentation specificity of different running times was higher than that of manual segmentation. In conclusion, the BPNN artificial intelligence algorithm had high accuracy, sensitivity, and specificity for ultrasound image segmentation, with a better segmentation effect. Therefore, it had a better diagnostic effect for breast cancer axillary lymph node metastasis.

Circ_0000043 promotes the proliferation, migration, invasiveness, and epithelial-mesenchymal transition in breast cancer cells via the miR-136-Smad3 axis.

Circular RNAs (circRNAs) are tissue-specific RNAs with a more stable structure than linear RNAs, and their association with breast cancer (BC) is poorly understood. This study examined the biological effects of circ_0000043 in the progression of BC. In this study, expression of circ_0000043 in BC tissue samples was measured using quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blot were used to detect the expression of Smad family member 3 (Smad3). CCK-8, wound healing, and Transwell assays were used to assess the effect of circ_0000043 on the proliferation, migration, and invasiveness of BC cells. Moreover, the binding relationships between circ_0000043 and miR-136, and miR-136 and Smad3 were detected by dual-luciferase reporter assay. Additionally, Western blot was used to detect the expressions of markers related to epithelial-mesenchymal transition, including E-cadherin, N-cadherin, and vimentin. Our results show that the expression of circ_0000043 is up-regulated in BC tissues and cell lines. The proliferation, migration, invasiveness, and epithelial-mesenchymal transition of BC cells were significantly inhibited by knockdown of circ_0000043, and overexpression of circ_0000043 had the opposite effects. Additionally, circ_0000043 up-regulate the expression of Smad3 by sponging miR-136. In conclusion, our study demonstrates that circ_0000043 promote the progression of BC via regulating the miR-136-Smad3 axis.

Changes in Tumor Stem Cell Markers and Epithelial-Mesenchymal Transition Markers in Nonluminal Breast Cancer after Neoadjuvant Chemotherapy and Their Correlation with Contrast-Enhanced Ultrasound.

Nonluminal breast cancer has high early metastasis and treatment resistance, and neoadjuvant chemotherapy (NAC) is needed. The presence of cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT) leads to poor prognosis. This study investigated the changes in CSC markers and EMT markers after NAC in nonluminal breast cancer and their correlation with contrast-enhanced ultrasound (CEUS) features and chemotherapy efficacy. Before NAC, the range of nonluminal breast cancer on CEUS was larger than that of two-dimensional ultrasound, but after NAC, it was significantly smaller than that of two-dimensional ultrasound and closer to the postoperative pathological size. After NAC, the enlarged lesions and perfusion defects were significantly less than those before NAC. The time-intensity curve showed the characteristics of slow-in, low enhancement, and low perfusion. Nonluminal breast cancer downregulated the expression of CSC markers and EMT markers after NAC, but the epithelial phenotype of nonluminal breast cancer with good response to chemotherapy was upregulated. In nonluminal breast cancer with poor response to chemotherapy, markers of CSC and EMT were highly expressed before chemotherapy. In conclusion, CEUS is better than conventional ultrasound in estimating NAC efficacy in this mode. CEUS can also predict the prognosis of nonluminal breast cancer before NAC with the characteristics of enhanced enlargement and perfusion defects. The contrast-enhanced time-intensity curve of lesions with relatively poor blood supply may have more CSC and EMT characteristics.

A conserved glycine harboring disease-associated mutations permits NMDA receptor slow deactivation and high Ca2+ permeability.

A variety of de novo and inherited missense mutations associated with neurological disorders are found in the NMDA receptor M4 transmembrane helices, which are peripheral to the pore domain in eukaryotic ionotropic glutamate receptors. Subsets of these mutations affect receptor gating with dramatic effects, including in one instance halting it, occurring at a conserved glycine near the extracellular end of M4. Functional experiments and molecular dynamic simulations of constructs with and without substitutions at this glycine indicate that it acts as a hinge, permitting the intracellular portion of the ion channel to laterally expand. This expansion stabilizes long-lived open states leading to slow deactivation and high Ca2+ permeability. Our studies provide a functional and structural framework for the effect of missense mutations on NMDARs at central synapses and highlight how the M4 segment may represent a pathway for intracellular modulation of NMDA receptor function.

Vitamin E Has Reduced Affinity for a Polyunsaturated Phospholipid: An Umbrella Sampling Molecular Dynamics Simulations Study.

Vitamin E is an essential micronutrient. The primary function of this lipid-soluble antioxidant is to protect membrane phospholipids from oxidation. Whether vitamin E preferentially interacts with polyunsaturated phospholipids to optimize protection of the lipid species most vulnerable to oxidative attack has been an unanswered question for a long time. In this work, we compared the binding of α-tocopherol (αtoc), the form of vitamin E retained by the human body, in bilayers composed of polyunsaturated 1-stearoyl-2-docosahexaenoylphosphatidylcholine (SDPC, 18:0-22:6PC) and, as a control, monounsaturated 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) by umbrella sampling molecular dynamics simulations. From the potential of mean force as a function depth within the bilayer, we find that the binding energy of αtoc is less in SDPC (Δ Gbind = 16.7 ± 0.3 kcal/mol) than that in SOPC (Δ Gbind = 18.3 ± 0.4 kcal/mol). The lower value in SDPC is ascribed to the high disorder of polyunsaturated fatty acids that produces a less tightly packed arrangement. Deformation of the bilayer is observed during desorption, indicating that phosphatidylcholine (PC)-PC and αtoc-PC interactions contribute to the binding energy. Our results do not support the proposal that vitamin E interacts more favorably with polyunsaturated phospholipids.

Docosahexaenoic acid regulates the formation of lipid rafts: A unified view from experiment and simulation.

Docosahexaenoic acid (DHA, 22:6) is an n-3 polyunsaturated fatty acid (n-3 PUFA) that influences immunological, metabolic, and neurological responses through complex mechanisms. One structural mechanism by which DHA exerts its biological effects is through its ability to modify the physical organization of plasma membrane signaling assemblies known as sphingomyelin/cholesterol (SM/chol)-enriched lipid rafts. Here we studied how DHA acyl chains esterified in the sn-2 position of phosphatidylcholine (PC) regulate the formation of raft and non-raft domains in mixtures with SM and chol on differing size scales. Coarse grained molecular dynamics simulations showed that 1-palmitoyl-2-docosahexaenoylphosphatylcholine (PDPC) enhances segregation into domains more than the monounsaturated control, 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC). Solid state 2H NMR and neutron scattering experiments provided direct experimental evidence that substituting PDPC for POPC increases the size of raft-like domains on the nanoscale. Confocal imaging of giant unilamellar vesicles with a non-raft fluorescent probe revealed that POPC had no influence on phase separation in the presence of SM/chol whereas PDPC drove strong domain segregation. Finally, monolayer compression studies suggest that PDPC increases lipid-lipid immiscibility in the presence of SM/chol compared to POPC. Collectively, the data across model systems provide compelling support for the emerging model that DHA acyl chains of PC lipids tune the size of lipid rafts, which has potential implications for signaling networks that rely on the compartmentalization of proteins within and outside of rafts.

All n-3 PUFA are not the same: MD simulations reveal differences in membrane organization for EPA, DHA and DPA.

Eicosapentaenoic (EPA, 20:5), docosahexaenoic (DHA, 22:6) and docosapentaenoic (DPA, 22:5) acids are omega-3 polyunsaturated fatty acids (n-3 PUFA) obtained from dietary consumption of fish oils that potentially alleviate the symptoms of a range of chronic diseases. We focus here on the plasma membrane as a site of action and investigate how they affect molecular organization when taken up into a phospholipid. All atom MD simulations were performed to compare 1-stearoyl-2-eicosapentaenoylphosphatylcholine (EPA-PC, 18:0-20:5PC), 1-stearoyl-2-docosahexaenoylphosphatylcholine (DHA-PC, 18:0-22:6PC), 1-stearoyl-2-docosapentaenoylphosphatylcholine (DPA-PC, 18:0-22:5PC) and, as a monounsaturated control, 1-stearoyl-2-oleoylphosphatidylcholine (OA-PC, 18:0-18:1PC) bilayers. They were run in the absence and presence of 20mol% cholesterol. Multiple double bonds confer high disorder on all three n-3 PUFA. The different number of double bonds and chain length for each n-3 PUFA moderates the reduction in membrane order exerted (compared to OA-PC, S¯CD=0.152). EPA-PC (S¯CD=0.131) is most disordered, while DPA-PC (S¯CD=0.140) is least disordered. DHA-PC (S¯CD=0.139) is, within uncertainty, the same as DPA-PC. Following the addition of cholesterol, order in EPA-PC (S¯CD=0.169), DHA-PC (S¯CD=0.178) and DPA-PC (S¯CD=0.182) is increased less than in OA-PC (S¯CD=0.214). The high disorder of n-3 PUFA is responsible, preventing the n-3 PUFA-containing phospholipids from packing as close to the rigid sterol as the monounsaturated control. Our findings establish that EPA, DHA and DPA are not equivalent in their interactions within membranes, which possibly contributes to differences in clinical efficacy.

Regional Contrast-Enhanced Ultrasonography (CEUS) Characteristics of Breast Cancer and Correlation with Microvessel Density (MVD).

BACKGROUND The aim of this study was to investigate the perfusion characteristics of different breast lesion regions in contrast-enhanced ultrasonography (CEUS). MATERIAL AND METHODS A total of 161 malignant and benign breast lesion cases were subjected to CEUS. Perfusion parameters were analyzed and compared between the central and peripheral lesion regions, and surrounding tissue. Mass section was marked with methylene blue. Samples were subjected to immunohistochemistry, and microvessel density (MVD) was calculated. RESULTS There were significant differences in perfusion performance between the central and peripheral lesion regions, and surrounding tissue. In the malignant tumors, the fast-in and fast-out pattern was the most common type in the peripheral region (57.98%), while the slow-in and slow-out patterns were the major types in the central region and surrounding tissue (49.58% and 57.98%, respectively). Compared with the surrounding tissue, the peripheral region in the cancers exhibited hyperechoic enhancement and fast-in and slow-out pattern, with large area under the curve (AUC), while the central region showed isoechoic enhancement and equally-in and slow-out pattern, with large AUC. In the benign lesions, the peripheral region exhibited hyperechoic enhancement and fast-in and fast-out pattern, with small AUC, while the central region showed isoechoic enhancement and equally-in and -out pattern, with the same AUC value. Moreover, the perfusion parameters in the central and peripheral regions were significantly associated with MVD. CONCLUSIONS It is more objective to evaluate the perfusion performance of breast lesions with the reference of surrounding tissue. Compared with the central region, the peripheral region could better reflect the perfusion characteristics of malignant lesions.

Membrane Disordering by Eicosapentaenoic Acid in B Lymphomas Is Reduced by Elongation to Docosapentaenoic Acid as Revealed with Solid-State Nuclear Magnetic Resonance Spectroscopy of Model Membranes.

BACKGROUND: Plasma membrane organization is a mechanistic target of n-3 (ω-3) polyunsaturated fatty acids. Previous studies show that eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) differentially disrupt plasma membrane molecular order to enhance the frequency and function of B lymphocytes. However, it is not known whether EPA and DHA affect the plasma membrane organization of B lymphomas differently to influence their function. OBJECTIVE: We tested whether EPA and DHA had different effects on membrane order in B lymphomas and liposomes and studied their effects on B-lymphoma growth. METHODS: B lymphomas were treated with 25 µmol EPA, DHA, or serum albumin control/L for 24 h. Membrane order was measured with fluorescence polarization, and cellular fatty acids (FAs) were analyzed with GC. Growth was quantified with a viability assay. (2)H nuclear magnetic resonance (NMR) studies were conducted on deuterated phospholipid bilayers. RESULTS: Treating Raji, Ramos, and RPMI lymphomas for 24 h with 25 µmol EPA or DHA/L lowered plasma membrane order by 10-40% relative to the control. There were no differences between EPA and DHA on membrane order for the 3 cell lines. FA analyses revealed complex changes in response to EPA or DHA treatment and a large fraction of EPA was converted to docosapentaenoic acid (DPA; 22:5n-3). NMR studies, which were used to understand why EPA and DHA had similiar membrane effects, showed that phospholipids containing DPA, similar to DHA, were more ordered than those containing EPA. Finally, treating B lymphomas with 25 µmol EPA or DHA/L did not increase the frequency of B lymphomas compared with controls. CONCLUSIONS: The results establish that 25 µmol EPA and DHA/L equally disrupt membrane order and do not promote B lymphoma growth. The data open a new area of investigation, which is how EPA's conversion to DPA substantially moderates its influence on membrane properties.

Role of multi-mode ultrasound in the diagnosis of level 4 BI-RADS breast lesions and Logistic regression model.

OBJECTIVE: This study is to investigate the diagnostic role of multi-mode ultrasound in level 4 BI-RADS breast lesions and to establish a Logistic regression model. METHODS: Totally 179 patients with 182 sites of breast lesions were enrolled in this study. Preoperatively, the examinations of routine ultrasonography, elastography, contrast-enhanced ultrasonography and three-dimensional color Doppler were performed. Postoperatively, the breast lesions were diagnosed as benign and malignant lesions according to pathological results. Diagnostic indicators of each ultrasound analysis were determined and compared. The relationship between these diagnostic indicators and the benign and malignant features of breast lesions was analyzed by single factor analysis. Logistic regression model was established. RESULTS: The diagnostic indicators with high sensitivity and specificity were tumor edge, enhanced range and score of elastography. Four factors of tumor edge, enhanced order, contrast mode and score of elastography were related with the benign and malignant features of breast lesions. The prediction model was Logit (P) = 0.636 + 4.471X1 + 4.337X2 + 3.753X3 + 3.014X4 + 2.525X5 + 2.105X6. Likelihood ratio test showed that the model was statistically significant (χ(2) = 161.876, P < 0.0001). This model could effectively distinguish between benign and malignant tumors (R(2) = 0.813, prediction accuracy 92.3%). The differences in sensitivity and specificity between multi-mode ultrasound diagnosis and routine ultrasound diagnosis were statistically significant (P < 0.001). However, there was no significant difference between Logistic regression model and multi-mode ultrasound diagnosis. CONCLUSION: Multi-mode ultrasound and Logistic regression model are more effective in diagnosing level 4 BI-RADS breast lesions.