Predicting three or more metastatic nodes using contrast-enhanced lymphatic US findings in early breast cancer.

OBJECTIVES: To develop and validate a nomogram for predicting ≥ 3 metastatic axillary lymph nodes (ALNs) in early breast cancer with no palpable axillary adenopathy by clinicopathologic data, contrast-enhanced (CE) lymphatic ultrasound (US), and grayscale findings of sentinel lymph nodes (SLNs). MATERIALS AND METHODS: Women with T1-2N0 invasive breast cancer were consecutively recruited for the CE lymphatic US. Patients from Center 1 were grouped into development and internal validation cohorts at a ratio of 2:1. The external validation cohort was constructed from Center 2. The clinicopathologic data and US findings of SLNs were analyzed. A nomogram was developed to predict women with ≥ 3 metastatic ALNs. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curve analysis. RESULTS: One hundred seventy-nine from Center 1 were considered the development cohorts. The remaining 90 participants from Center 1 were internal cohorts and 197 participants from Center 2 were external validation cohorts. The US findings of no enhancement (odds ratio (OR), 15.3; p = 0.01), diffuse (OR, 19.1; p = 0.01) or focal eccentric (OR, 27.7; p = 0.003) cortical thickening, and absent hilum (OR, 169.7; p < 0.001) were independently associated with ≥ 3 metastatic ALNs. Compared to grayscale US or CE lymphatic US alone, the nomogram showed the highest AUC of 0.88 (0.85, 0.91). The nomogram showed a calibration slope of 1.0 (p = 0.80-0.81; Brier = 0.066-0.067) in validation cohorts in predicting ≥ 3 metastatic ALNs. CONCLUSION: Patients likely to have ≥ 3 metastatic ALNs were identified by combining the lymphatic and grayscale US findings of SLNs. Our nomogram could aid in multidisciplinary treatment decision-making. TRIAL REGISTRATION: This trial is registered on www.chictr.org.cn : ChiCTR2000031231. Registered March 25, 2020. CRITICAL RELEVANCE STATEMENT: A nomogram combining lymphatic CEUS and grayscale US findings of SLNs could identify early breast cancer patients with low or high axillary tumor burden preoperatively, which is more applicable to the Z0011 era. Our nomogram could be useful in aiding multidisciplinary treatment decision-making for patients with early breast cancer. KEY POINTS: • CEUS can help identify and diagnose SLN in early breast cancer preoperatively. • Combining lymphatic and grayscale US findings can predict axillary tumor burden. • The nomogram showed a high diagnostic value in validation cohorts.

Sono-anatomy of the middle cervical sympathetic ganglion verified with pathology.

Objectives: Cervical discomfort and other symptoms may be attributable to the middle cervical sympathetic ganglion. The aim of this study was to explore the sonographic features of this ganglion in anatomical specimens and cadavers and evaluate the feasibility of its visualization using high-resolution ultrasonography. Methods: We examined three cervical sympathetic-ganglion specimens and two fresh cadavers using high-resolution ultrasound to explore the sonographic features of this ganglion. Basic imaging characteristics examined included the shape, echo intensity, and location of the ganglion. Core-needle biopsy was performed to examine the suspected middle cervical sympathetic ganglion in the two fresh cadavers and verify the accuracy of the sonographic identification via pathological examination. Results: The middle cervical sympathetic ganglion appeared on high-resolution ultrasonography as an oval-shaped hypoechoic structure, with at least one continuous hypoechoic line connected to each ending in the anatomical specimens and fresh cadavers, and it was distinctly different from the adjacent lymph nodes. Discussion: Based on an adequate understanding of both its location and sonographic features, the direct visualization of the middle cervical sympathetic ganglion using high-resolution ultrasonography is feasible.

MiR-181c-5p Regulates Lung Adenocarcinoma Progression via Targeting PRKN.

Accumulating evidence indicates that microRNAs (miRNAs) have a vital effect on lung adenocarcinoma. However, the contributions and possible mechanisms of miR-181c-5p to lung adenocarcinoma remain largely unclear. Our objective is to clarify the potential mechanism by which miR-181c-5p regulates lung adenocarcinoma progression. RT-qPCR was performed to determine the levels of miR-181c-5p in lung adenocarcinoma tissues and cells. CCK-8 and Transwell assays were conducted to evaluate the viability, migration, and invasion of H460 cells, respectively. The putative target association between miR-181c-5p and the Parkin gene (PRKN) was predicted using miRDB and confirmed by dual-luciferase reporter assay. MiR-181c-5p expression was found to be up-regulated in both lung adenocarcinoma tissues and cells. Suppression of miR-181c-5p resulted in the inhibition of viability, migration, and invasion in lung adenocarcinoma cells. PRKN level was negatively related to miR-181c-5p expression and mediated with the miR-181c-5p's functions on lung adenocarcinoma progression. MiR-181c-5p regulates lung adenocarcinoma progression via targeting PRKN, indicating miR-181c-5p is expected to be a diagnostic and predictive marker for lung adenocarcinoma, providing new insights into the development of treatment strategies for lung adenocarcinoma.

Comparative study of two contrast agents for intraoperative identification of sentinel lymph nodes in patients with early breast cancer.

BACKGROUND: The use of contrast-enhanced ultrasound (CEUS) to locate sentinel lymph nodes (SLNs) in breast cancer has been studied more and more in recent years. This prospective study aimed to compare periareolar injection of two different contrast agents, SonoVue® (SNV) and Sonazoid® (SNZ), followed by CEUS to identify SLNs in breast cancer patients with clinically negative nodes. METHODS: A total of 205 patients with T1-2N0M0 breast cancer were divided into the SNV group and SNZ group. All were administered a periareolar injection of SNV or SNZ and underwent US to identify contrast-enhanced SLNs. Each contrast-enhanced SLN underwent a biopsy with blue dye and examined again by CEUS in vitro. RESULTS: In all cases, contrast-enhanced lymphatic vessels were clearly visualized using US soon after the periareolar injection of SNZ, and the SLNs were easily identified. The SLN identification rates were 75.27% (210/279) for SNV and 93.58% (102/109) for SNZ. Although the accuracy of detecting SLN metastasis was slightly different between the two groups, there was no statistically significant difference between those groups (P=0.615). Moreover, it was possible to identify SLNs in vitro in the SNZ group, and these could be compared with the lymph nodes (LNs) located using SNZ during the preoperative stage and with blue dye during the procedure. This helped in determining the resection requirements. CONCLUSIONS: When comparing the subdermal use of SNV and SNZ, no significant differences in the number of detected SLNs and the diagnosis of metastatic LNs were observed. Because SLNs can be detected for a longer time in living tissues with SNZ, this contrast agent may provide more intraoperative information for complete resection of all preoperative localization of SLN.

Percutaneous Sonazoid-enhanced ultrasonography combined with in vitro verification for detection and characterization of sentinel lymph nodes in early breast cancer.

OBJECTIVES: To assess the efficacy of percutaneous Sonazoid-enhanced ultrasound and in vitro verification for identification sentinel lymph nodes (SLNs) and diagnosis of metastatic SLNs in patients with early breast cancer (BC). METHODS: Sixty-eight patients with early BC were enrolled finally. After the induction of general anesthesia, 0.4 ml of Sonazoid (SNZ), a new second-generation tissue-specific ultrasound contrast agent (UCA), mixed with 0.6 ml of methylene blue, was injected intradermally. The lymphatic vessels and connected SLNs were immediately observed and marked. After being resected, these SLNs were soaked in saline water and examined still in the mode of contrast-enhanced ultrasound (CEUS) in vitro. This procedure could ensure that all the enhanced nodes had been removed as much as possible. The numbers of SLNs detected by UCA and blue dye were recorded. The enhancement patterns of SLNs were compared with the final pathological results. RESULTS: SLNs detection rate by SNZ-CEUS was 100%, which was higher than that by blue dye (95.59%). CEUS identified a median of 1.5 nodes, while blue dye identified a median of 1.9 nodes per case (p = 0.0012). When homogeneous high perfusion and complete annular high perfusion were regarded as negative nodes, the sensitivity and negative predictive value were 92.31% and 96.79% respectively, while the specificity was 84.21%. CONCLUSIONS: Percutaneous SNZ-enhanced ultrasonography combined with in vitro verification is a feasible and reliable method for SLNs identification intraoperatively. Enhancement patterns can be helpful in determining the status of SLNs. KEY POINTS: • CEUS with percutaneous injection of Sonazoid can successfully identify SLNs with the rate of 100% in early breast cancer patients, higher than 95.59% of blue dye. • Sonazoid, with high affinity with reticuloendothelial cells, increases the imaging time of SLNs and facilitates biopsy intraoperatively better than Sonovue as a lymphatic tracer. • Homogenous high and complete annular high perfusions have a sensitivity of 92.31% and a negative predictive value of 96.79% in the prediction of uninvolved SLNs.

A mass-flowing muscle model with shape restrictive soft tissues: correlation with sonoelastography.

Skeletal muscles are always embedded in sheets of connective tissues, which influences muscle biomechanics by shaping the fascicle geometry and encapsulating muscular mass flow. However, existing Hill-type muscle models typically take surrounding tissues into account as a nonlinear spring, without consideration of the muscle geometry and inertia. In this paper, a new muscle model is proposed to simultaneously account for soft tissue constraints on the muscle's shape together with mass flow during stretch. To accomplish this, a mass-variable cable element of the muscle-tendon unit, with parameterization of its geometrical influence on the force-producing capability, is newly formulated based on an arbitrary Lagrangian-Eulerian description. Also, sliding joints are presented to further constrain possible mass flow of the elements via epimuscular soft tissue connections between adjacent muscle bellies. Available experimental data from cat soleus and rat gastrocnemius medialis muscles validates the proposed method. For further verification, a planar model of the triceps surae is developed by integration of this modeling framework, and subject-specific simulations of the passive ankle dynamometry tests are performed and correlated with sonoelastographic evaluations of two male participants. The results confirm that the flow of the muscle mass can alternate its force-generating behaviors, and the established model provides an accurate prediction of muscle behavior under transverse loading. The proposed muscle element could be integrated with larger musculoskeletal models to better investigate biomechanical functions of muscles during locomotion, such as heel impact or vibration responses of the spine, when dynamic effects are substantial.

Novel 4-arylaminoquinazolines bearing N,N-diethyl(aminoethyl)amino moiety with antitumour activity as EGFRwt-TK inhibitor.

Herein, four novel 4-arylaminoquinazoline derivatives with N,N-diethyl(aminoethyl)amino moiety were designed, synthesised and evaluated on biological activities in vitro. All synthesised compounds have inhibitory effects against tumour cells (SW480, A549, A431 and NCI-H1975). In particular, 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(5-((N,N-diethyl(aminoethyl))aminomethyl)furan-2-yl)quinazoline (6a) and 6-(5-((N,N-diethylethyl)aminomethyl)furan-2-yl)-4-(4-(E)-(propen-1-yl)phenylamino)quinazoline (6d) were potent antitumour agents which showed high antiproliferative activities against tumour cells in vitro. Moreover, compound 6a could induce late apoptosis of A549 cells at high concentrations and arrest cell cycle of A549 cells in the G0/G1 phase at tested concentrations. Also, compound 6a could inhibit the activity of wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) with IC50 value of 15.60 nM. Molecular docking showed that compound 6a formed three hydrogen bonds with EGFRwt-TK, while lapatinib formed only two hydrogen bonds with the receptor protein. It is believed that this work would be giving a reference for developing anti-cancer drugs targeted EGFR-TK.

Vascular Cell Co-Culture on Silk Fibroin Matrix.

Silk fibroin (SF), a natural polymer material possessing excellent biocompatibility and biodegradability, and has been widely used in biomedical applications. In order to explore the behavior of vascular cells by co-culturing on regenerated SF matrix for use as artificial blood vessels, human aorta vascular smooth muscle cells (HAVSMCs) were co-cultured with human arterial fibroblasts (HAFs) or human umbilical vein endothelial cells (HUVECs) on SF films and SF tubular scaffolds (SFTSs). Analysis of cell morphology and deoxyribonucleic acid (DNA) content showed that HUVECs, HAVSMCs and HAFs adhered and spread well, and exhibited high proliferative activity whether cultured alone or in co-culture. Immunofluorescence and scanning electron microscopy (SEM) analysis showed that HUVECs and HAFs co-existed well with HAVSMCs on SF films or SFTSs. Cytokine expression determined by reverse transcription-polymerase chain reaction (RT-PCR) indicated that the expression levels of α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SM-MHC) in HAVSMCs were inhibited on SF films or SFTSs, but expression could be obviously promoted by co-culture with HUVECs or HAFs, especially that of SM-MHC. On SF films, the expression of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (CD31) in HUVECs was promoted, and the expression levels of both increased obviously when co-cultured with HAVSMCs, with the expression levels of VEGF increasing with increasing incubation time. The expression levels of VEGF and CD31 in cells co-cultured on SFTSs improved significantly from day 3 compared with the mono-culture group. These results were beneficial to the mechanism analysis on vascular cell colonization and vascular tissue repair after in vivo transplantation of SFTSs.

Hemocompatibility and cytocompatibility of the hirudin-modified silk fibroin.

Hirudin (Hir), a thrombin direct inhibitor, was used to modify a polyethylene glycol diglycidyl ether (PEG-DE) crosslinked regenerated silk fibroin (SF) material to improve hemocompatibility. Hemolysis characteristics, platelet adhesion, platelet activity, and plasma recalcification time were investigated using absorption spectrometry, scanning electron microscopy, MTT analysis, and the time counting method. Hirudin could be grafted evenly to the silk fibroin, and the modified material was resistant to hemolysis at ratios of less than 0.5%. Scanning electron microscopy and MTT results showed that platelet adhesion and aggregation activity decreased after modificaton with trace amounts of hirudin, compared with PEG-DE crosslinked and ethanol-treated silk fibroin film. Plasma recalcification of PEG-DE crosslinked silk fibroin film was slower than with ethanol-treated material, and this increased slightly after hirudin modification. Furthermore, L929, HAVSMC, and HUVEC cells adhered to the modified material, grew well, and possessed high proliferation activity on SF/Hir blend films. This study suggests that hirudin could improve the anticoagulation properties of regenerated silk fibroin materials.

[Effect of Guanfu Base A in patients with ventricular arrhythmias].

OBJECTIVE: To investigate the effect and safety of intravenous Guanfu Base A hydrochloride (GFA) in the treatment of ventricular arrhythmias. METHODS: Patients without severe structural heart disease presenting with equal or more than 150 premature ventricular contractions per hour and/or non sustained ventricular tachycardia in drug-free holter monitoring were recruited in this double blind randomized active-controlled study. Eligible patients were randomly assigned to receive GFA or propafenone intravenously by a proportion of 1:1 in a double-blind manner. Intravenous bolus of the study medicine was given, followed by maintenance infusion for 6 hours. 24 hours continuous electrocardiographic recordings were performed to evaluate the efficacy. Vital signs, electrocardiograms and adverse events were documented before, during and after drug administration. RESULTS: A total of 201 patients came from eight centres were randomized to GFA or propafenone group. The demographic characteristics, the extent of ventricular arrhythmias and baseline clinical findings were comparable between the two groups. There were no significant differences in the percentage of reducing premature ventricular contractions and the accumulated efficacy between two groups. GFA had tendency to be more effective than propafenone in reducing the number of ventricular ectopy (P = 0.0609). There were no significant differences in the onset of action after drug administration between two drugs. The tolerance of GFA was better than propafenone. The adverse events in GFA group were less severe than those in propafenone group. CONCLUSIONS: Intravenous GFA in controlling the premature ventricular contraction has comparable effect to IV propafenone. Tolerance of GFA was better than propafenone.