External Validation of Ultrasound Radiomics for Small (≤ 4 cm) Renal Mass Differentiation: A Comparison with Radiologists.

BACKGROUND: Renal cell carcinoma, especially in small renal masses (≤ 4 cm) (SRM), has increased. Pathological analysis revealed a high proportion of benign masses, highlighting the urgent need for precise SRM differentiation. OBJECTIVES: This research aimed to independently validate the performance of machine learning-based ultrasound (US) radiomics analysis in differentiating benign from malignant SRM, and to compare its performance with that of radiologists. METHODS: A total of 499 patients from two hospitals were retrospectively included in this study and divided into two cohorts. US images were used to extract radiomics features. To obtain the most robust features, inter-observer correlation coefficient, Spearman correlation coefficient, and least absolute shrinkage and selection operator methods were applied for feature selection. Three models were developed in the training data using the stochastic gradient boosting algorithm, including a clinical model, a radiomics model, and a combined model that integrated clinical factors and radiomics features. The performance of these models was evaluated in the independent external validation data, including discrimination, calibration, and clinical usefulness, and compared with pooled radiologists' assessments. RESULTS: The AUCs of the clinical, radiomics, and combined models were 0.844, 0.942, and 0.954, respectively. The radiomics and combined models significantly outperformed the clinical model (all p < 0.05), while no significant difference was observed between them (p = 0.32). The radiomics and combined models showed good discrimination and calibration. Decision curve analysis exhibited that the combined model had clinical usefulness. Compared with the pooled radiologists' assessment (AUC, 0.799), the combined model showed superior classification results (p < 0.01) and higher specificity (p < 0.01) with similar sensitivity (p = 0.62). CONCLUSION: The combined model incorporating clinical factors and radiomics features accurately distinguished benign from malignant SRM.

Effects of Chemical Valences of Sulfur on the Performance of CsFAMA Perovskite Solar Cells.

The low electrical conductivity and the high surface defect density of the TiO2 electron transport layer (ETL) limit the quality of the following perovskite (PVK) layers and the power conversion efficiency (PCE) of corresponding perovskite solar cells (PSCs). Sulfur was reported as an effective element to passivate the TiO2 layer and improve the PCE of PSCs. In this work, we further investigate the effect of chemical valences of sulfur on the performance of TiO2/PVK interfaces, CsFAMA PVK layers, and solar cells using TiO2 ETL layers treated with Na2S, Na2S2O3, and Na2SO4, respectively. Experimental results show that the Na2S and Na2S2O3 interfacial layers can enlarge the grain size of PVK layers, reduce the defect density at the TiO2/PVK interface, and improve the device efficiency and stability. Meanwhile, the Na2SO4 interfacial layer leads to a smaller perovskite grain size and a slightly degraded TiO2/PVK interface and device performance. These results indicate that S2- can obviously improve the quality of TiO2 and PVK layers and TiO2/PVK interfaces, while SO42- has little effects, even negative effects, on PSCs. This work can deepen the understanding of the interaction between sulfur and the PVK layer and may inspire further progress in the surface passivation field.

Preoperative prediction of macrotrabecular-massive hepatocellular carcinoma based on B-Mode US and CEUS.

OBJECTIVES: To develop a preoperative prediction model to identify macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) and evaluate the model's diagnostic performance in differentiating MTM-HCC from HCC. METHODS: We conducted a mono-center retrospective study in a grade A tertiary hospital in China. Consecutive patients with suspected HCC from February 2019 to December 2020 were eligible for inclusion. All consenting patients underwent CEUS examination and were histologically diagnosed. Based on the clinical and US features between the two groups, we developed a binary logistic regression model and a nomogram for predicting MTM-HCC. RESULTS: A total of 161 patients (median age, 57 years; interquartile range, 48-64 years; 129 men) were included in the analysis. Twenty-seven of the HCCs (16.8%) were of the MTM subtype. Binary logistic regression analysis indicated that PVP hypoenhancement (OR = 15.497; 95% CI: 1.369, 175.451; p = 0.027), AFP > 454.6 ng/mL (OR = 8.658; 95% CI: 3.030, 24.741; p < 0.001), ALB ≤ 29.9 g/L (OR = 3.937; 95% CI: 1.017, 15.234; p = 0.047), halo sign (OR = 3.868; 95% CI: 1.314, 11.391; p = 0.016), and intratumoral artery (OR = 2.928; 95% CI: 1.039, 8.255; p = 0.042) were predictors for MTM subtype. Combining any two criteria showed a high sensitivity (100.0%); combining all five criteria showed a high specificity (99.2%); and the AUC value of the logistic regression model was 0.88 (95% CI: 0.81, 0.92). CONCLUSIONS: BMUS and CEUS could be used for identifying patients suspected of having MTM-HCC. Combining clinical information, BMUS, and CEUS features could achieve a noninvasive diagnosis of MTM-HCC. KEY POINTS: • Contrast-enhanced ultrasound examination helps clinicians to identify MTM-HCCs preoperatively. • PVP hypoenhancement, high AFP levels, low ALB levels, halo signs, and intratumoral arteries could be used to predict MTM-HCCs. • A logistic regression model and nomogram were built to noninvasively diagnose MTM-HCCs with an AUC value of 0.88 (95% CI: 0.81, 0.92).

A Practical CEUS Thyroid Reporting System for Thyroid Nodules.

Background The role of contrast-enhanced US (CEUS) in reducing unnecessary biopsies of thyroid nodules has received little attention. Purpose To construct and externally validate a thyroid imaging reporting and data system (TI-RADS) based on nonenhanced US and CEUS to stratify the malignancy risk of thyroid nodules. Materials and Methods This retrospective study evaluated 756 patients with 801 thyroid nodules who underwent nonenhanced US, CEUS, and fine-needle aspiration and received a final diagnosis from January 2018 to December 2019. Qualitative US features of the thyroid nodules were analyzed with univariable and multivariable logistic regression to construct a CEUS TI-RADS. The CEUS TI-RADS was validated with use of internal cross-validation and external validation. Results A total of 801 thyroid nodules in 590 female (mean age, 44 years ± 13) and 166 male (mean age, 47 years ± 13 [SD]) patients were included. Independent predictive US features included nodule composition at CEUS, echogenicity, nodule shape, nodule margin, echogenic foci, extrathyroidal extension, enhancement direction, peak intensity, and ring enhancement. The CEUS TI-RADS showed a higher area under the receiver operating characteristic curve of 0.93 (95% CI: 0.92, 0.95; P < .001 in comparison with all other systems), a biopsy yield of malignancy of 66% (157 of 239 nodules), and an unnecessary biopsy rate of 34% (82 of 239 nodules). In the external validation, the area under the receiver operating characteristic curve, biopsy yield of malignancy, and unnecessary biopsy rate of CEUS TI-RADS were 0.89 (95% CI: 0.84, 0.92), 61% (65 of 106 nodules), and 39% (41 of 106 nodules) for the first external validation set and 0.90 (95% CI: 0.85, 0.94), 57% (56 of 99 nodules), and 43% (43 of 99 nodules) for the second external validation set. Conclusion A contrast-enhanced US (CEUS) thyroid imaging reporting and data system was created with thyroid nodule malignancy risk stratification according to the simplified regression coefficients of nonenhanced US and qualitative features of CEUS. Clinical trials registration no. ChiCTR2000028712 Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Young's Modulus of Bilateral Infraspinatus Tendon Measured in Different Postures by Shear Wave Elastography Before and After Exercise.

OBJECTIVE: To investigate the Young's modulus value of infraspinatus tendons using shear wave elastography (SWE) technique in normal adults, and to analyze the influence of gender, postures, exercise, and dominant side on Young's modulus of infraspinatus tendons. METHODS: This is a prospective cross-sectional study. From January 2019 to July 2020, 14 healthy subjects were identified, including seven males and seven females aged between 24 to 34, with a mean age of 27.67 ± 3.08 years. The Young's modulus of their infraspinatus tendons was measured by two operators using SWE in neutral and maximum external rotation positions of both sides before exercise and the dominant side after exercise. The Young's modulus values in different sexes, different postures, before vs after exercise, and dominant vs non-dominant side were statistically analyzed. RESULTS: All 14 subjects completed the data collection process. The mean Young's modulus values of infraspinatus tendon for dominant sides in neutral position were 33.04 ± 3.01 kPa for males and 28.76 ± 3.09 kPa for females. And for non-dominant sides in the neutral position, the values were 33.02 ± 2.38 kPa for males and 28.86 ± 2.47 kPa for females. In the maximum external rotation position, the values for dominant sides were 50.19 ± 4.86 kPa for males and 42.79 ± 4.44 kPa for females, and for non-dominant sides were 50.95 ± 3.24 kPa for males and 42.42 ± 3.66 kPa for females. After exercise, the mean Young's modulus values of infraspinatus tendon for dominant sides in neutral position were 54.56 ± 3.76 kPa for males and 46.66 ± 5.99 kPa for females. And for the maximum external rotation position, the values were 59.13 ± 3.78 kPa for males and 54.49 ± 5.67 kPa for females. The Young's modulus of infraspinatus tendon in the neutral and maximum external rotation positions showed statistically significant differences in males and females, as well as before and after exercise (P < 0.05). However, the difference in Young's modulus between the dominant and non-dominant sides was not statistically significant (P > 0.05). Intergroup reliability between both operators was excellent (ICC > 0.85). CONCLUSION: There are gender-related differences and post-exercise increase in Young's modulus, yet such a difference cannot be witnessed between the dominant and non-dominant sides.

Anti-oncogene PTPN13 inactivation by hepatitis B virus X protein counteracts IGF2BP1 to promote hepatocellular carcinoma progression.

Hepatitis B x protein (HBx) affects cellular protein expression and participates in the tumorigenesis and progression of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Metabolic reprogramming contributed to the HCC development, but its role in HBV-related HCC remains largely unclear. Tyrosine-protein phosphatase nonreceptor type 13 (PTPN13) is a significant regulator in tumor development, however, its specific role in hepatocarcinogenesis remains to be explored. Here, we found that decreased PTPN13 expression was associated with HBV/HBx. Patients with low PTPN13 expression showed a poor prognosis. Functional assays revealed that PTPN13 inhibited proliferation and tumorigenesis in vitro and in vivo. Further mechanistic studies indicated that HBx inhibited PTPN13 expression by upregulating the expression of DNMT3A and interacting with DNMT3A. Furthermore, we found that DNMT3A bound to the PTPN13 promoter (-343 to -313 bp) in an epigenetically controlled manner associated with elevated DNA methylation and then inhibited PTPN13 transcription. In addition, we identified IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. We verified the significant negative correlations between PTPN13 expression and c-Myc, PSPH, and SLC7A1 expression in clinical HCC tissue samples. In summary, our findings demonstrate that PTPN13 is a novel regulator of HBV-related hepatocarcinogenesis and may play an important role in HCC. PTPN13 may serve as a prognostic marker and therapeutic target in HBV-related HCC patients.

Deep Learning-Based Radiomics of B-Mode Ultrasonography and Shear-Wave Elastography: Improved Performance in Breast Mass Classification.

OBJECTIVE: Shear-wave elastography (SWE) can improve the diagnostic specificity of the B-model ultrasonography (US) in breast cancer. However, whether deep learning-based radiomics signatures based on the B-mode US (B-US-RS) or SWE (SWE-RS) could further improve the diagnostic performance remains to be investigated. We aimed to develop the B-US-RS and SWE-RS and determine their performances in classifying breast masses. MATERIALS AND METHODS: This retrospective study included 291 women (mean age ± standard deviation, 40.9 ± 12.3 years) from two centers who had US-visible solid breast masses and underwent biopsy and/or surgical resection between June 2015 and July 2017. B-mode US and SWE images of the 198 masses in 198 patients (training cohort) from center 1 were segmented, respectively, to construct B-US-RS and SWE-RS using the least absolute shrinkage and selection operator regression and tested in an independent validation cohort of 65 masses in 65 patients from center 1 and in an external validation cohort of 28 masses in 28 patients from center 2. The performances of B-US-RS and SWE-RS were assessed using receiver operating characteristic (ROC) analysis and compared with that of radiologist assessment [Breast Imaging Reporting and Data System (BI-RADS)] and quantitative SWE parameters [maximum elasticity (E max), mean elasticity (E mean), elasticity ratio (E ratio), and elastic modulus standard deviation (E SD)] by using the McNemar test. RESULTS: The single best-performing quantitative SWE parameter, E max, had a higher specificity than BI-RADS assessment in the training and independent validation cohorts (P < 0.001 for both). The areas under the ROC curves (AUCs) of B-US-RS and SWE-RS both were 0.99 (95% CI = 0.99-1.00) in the training cohort, 1.00 (95% CI = 1.00-1.00) in the independent validation cohort, and 1.00 (95% CI = 1.00-1.00) in the external validation cohort. The specificities of B-US-RS and SWE-RS were higher than that of E max in the training (P < 0.001 for both) and independent validation cohorts (P = 0.02 for both). CONCLUSION: The B-US-RS and SWE-RS outperformed the quantitative SWE parameters and BI-RADS assessment for classifying breast masses. The integration of the deep learning-based radiomics approach would help improve the classification ability of B-mode US and SWE for breast masses.

HBx/ERα complex-mediated LINC01352 downregulation promotes HBV-related hepatocellular carcinoma via the miR-135b-APC axis.

Hepatitis B virus (HBV) infection plays an important role in hepatocarcinogenesis, especially in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers. Novel lncRNAs involved in the initiation and progression of HBV-related hepatocellular carcinoma (HCC) need to be investigated. Here, we report that the long non-coding RNA LINC01352 is markedly downregulated by HBV/HBx (HBV X protein) in HCC cells and clinical samples. The LINC01352 expression level in HCC is an independent prognostic factor for survival. We found that HBx suppresses LINC01352 promoter activity by forming a complex with the estrogen receptor (ERα). Furthermore, using a combination of in vitro and in vivo studies, we confirmed that HBx promotes HCC cell growth and metastasis by inhibiting LINC01352 expression. Further investigation revealed that the downregulation of LINC01352, which acts as an endogenous sponge, increases the expression of miR-135b, leading to the reduced production of adenomatous polyposis coli (APC), consequently activating Wnt/ß-catenin signalling to facilitate tumour progression. These findings strongly suggest that the LINC01352-miR-135b-APC axis regulated by the HBx/ERα complex acts as an important pathogenic factor for tumour progression, which may help provide a theoretical basis for the identification of new therapeutic targets for HBV-related HCC.

Intraoperative radiotherapy (IORT) versus whole-breast external beam radiotherapy (EBRT) in early stage breast cancer: results from SEER database.

PURPOSE: Intraoperative radiotherapy (IORT) has emerged as an alternative to whole-breast external beam radiotherapy (EBRT) for early breast cancer. This study aimed to investigate the risk factors for survival after IORT or whole-breast EBRT in breast cancer patients. MATERIALS AND METHODS: Breast cancer patients undergoing IORT or whole-breast EBRT were included from the surveillance, epidemiology, and end results database. Risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified by Cox proportional hazards regression analysis. RESULTS: The IORT and EBRT groups did not differ significantly in OS and CSS. T2 stage (tumor size > 2 cm) was associated with poorer OS (aHR 3.49, 95% CI 1.05-11.62, P = 0.042), whereas ER-positive tumors were associated with better OS (aHR 0.26, 95% CI 0.09-0.76, P = 0.014). CONCLUSION: IORT was not inferior than EBRT considering the OS and CSS in the short-term follow-up of early breast cancer. It may be a reasonable alternative to EBRT for early breast cancer in select patients with favorable tumor size and receptor status, given the need for long-term monitoring of local control and radiation toxicity.

Combined use of strain elastography and superb microvascular imaging with grayscale ultrasound according to the BI-RADS classification for differentiating benign from malignant solid breast masses.

OBJECTIVE: To evaluate the combined use of strain elastography (SE) and superb microvascular imaging (SMI) with grayscale ultrasound (US) according to the Breast Imaging Reporting and Data System (BI-RADS) classification for differentiating benign from malignant breast masses. METHODS: In total, 166 patients with 177 breast masses categorized as BI-RADS 3-5 were included in the study between April 2016 to September 2017. US, SMI and SE were performed to evaluate each mass. The following outcome measures were compared between US and the combinations of US, SMI, and SE: area under the receiver operating characteristic curve (AUC), sensitivity, specificity. RESULTS: The addition of SMI and SE to US increased the AUC from 0.816 to 0.948 (P < .001); and the specificity from 43.7% to 80.8% (P < .001), without a significant decrease in the sensitivity. Meanwhile, 66.1% (37 of 56) of the benign masses that were indicated for unnecessary biopsy were correctly changed to follow-up. CONCLUSIONS: The addition SMI and SE to US could improve the diagnostic performance in differentiating benign from malignant breast masses compared to US alone. When US was combined with SMI and SE, the specificity were increased, thus significantly reducing unnecessary biopsies.

Impact of body characteristics on ultrasound-measured inferior vena cava parameters in Chinese children.

Ultrasound-measured inferior vena cava (IVC) and abdominal aorta (Ao)-associated parameters have been used to predict volume status for decades, yet research focusing on the impact of individual physical characteristics, including gender, height/weight, body surface area (BSA), and age, assessed simultaneously on those parameters in Chinese children is lacking. The aim of the present study was to explore the impact of individual characteristics on maximum IVC diameter (IVCmax), Ao, and IVCmax/Ao in healthy Chinese children. From September to December 2015, 200 healthy children from 1 to 13 years of age were enrolled. IVCmax and Ao diameters were measured by 2D ultrasound. We found that age (years), height (cm), weight (kg), waist circumference (cm), and BSA (m2) were positively correlated with IVCmax and Ao. Multivariate linear regression showed that age was the only independent variable for IVCmax (mm) in female children, height was the only independent variable for IVCmax in male children, and age was the only independent variable for Ao in both females and males. IVCmax/Ao was not significantly influenced by the subjects' characteristics. In conclusion, IVCmax and Ao were more susceptible to subjects' characteristics than IVCmax/Ao. IVCmax/Ao could be a reliable and practical parameter in Chinese children as it was independent of age, height, and weight.

Computer-Aided Diagnosis of Solid Breast Lesions With Ultrasound: Factors Associated With False-negative and False-positive Results.

OBJECTIVES: To investigate factors that may lead to false-positive or false-negative results in a computer-aided diagnostic system (S-Detect; Samsung Medison Co, Ltd, Seoul, Korea) for ultrasound (US) examinations of solid breast lesions. METHODS: This prospective study was approved by the Institutional Review Board of Sun Yat-sen Memorial Hospital. All patients signed and provided written informed consent before biopsy or surgery. From September 2017 to May 2018, 269 consecutive women with 338 solid breast lesions were included. All lesions were examined with US and S-Detect before biopsy or surgical excision. The final US assessments made by radiologists and S-Detect were matched to the pathologic results. Patient and lesion factors in the "true" and "false" S-Detect groups were compared, and multivariate logistic regression analyses were used to identify the factors associated with false S-Detect results. RESULTS: The mean age of the patients ± SD was 42.6 ± 12.9 years (range, 18-77 years). Of the 338 lesions, 209 (61.8%) were benign, and 129 (38.2%) were malignant. Larger lesions, the presence of lesion calcifications detected by B-mode US, and grades of 2 and 3 according to Adler et al (Ultrasound Med Biol 1990; 16:553-559) were significantly associated with false-positive S-Detect results (odds ratio [OR], 1.071; P = .006; OR, 5.851; P = .001; OR, 1.726; P = .009, respectively). Smaller lesions and the absence of calcifications detected by B-mode US in malignant solid breast lesions were significantly associated with false-negative S-Detect results (OR, 1.141; P = .015; OR, 7.434; P = .016). CONCLUSIONS: Larger benign lesions, the presence of lesion calcifications, and high degrees of vascularity are likely to show false-positive S-Detect results. Smaller malignant lesions and the absence of calcifications are likely to show false-negative S-Detect results.

Sinomenine mitigates collagen-induced arthritis mice by inhibiting angiogenesis.

OBJECTIVE: The objective of the present study is to investigate the inhibitory effects of sinomenine (SIN) on angiogenesis in a collagen-induced arthritis (CIA) mouse model. METHODS: Arthritis assessments for all mice were recorded. The histopathological assessments were performed following haematoxylin and eosin (HE) staining. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) analyses were used to detect the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and angiopoietin 1 (ANG-1) in the serum and in the membrane. Immunohistochemistry was employed to detect the synovium microvessel density (MVD). RESULTS: Compared with the CIA model group, SIN significantly ameliorated swelling and erythema extension, decreased the arthritis index, reduced inflammation, cartilage damage and bone erosion, and lessened the number of CD31 positive cells on the synovium. Moreover, the levels of HIF-1α, VEGF and ANG-1 in the synovium and in the peripheral serum were increased in the untreated CIA model group but were significantly reduced in the 30 mg/kg, 100 mg/kg and 300 mg/kg SIN treatment groups. CONCLUSION: SIN could mitigate CIA by inhibiting angiogenesis, and the mechanism may associate with the HIF-1α-VEGF-ANG-1 axis. Additionally, our study provides a referable experimental basis for the use of SIN for the treatment of rheumatoid arthritis.

Impact of body characteristics on ultrasound-measured inferior vena cava parameters in Chinese children

Ultrasound-measured inferior vena cava (IVC) and abdominal aorta (Ao)-associated parameters have been used to predict volume status for decades, yet research focusing on the impact of individual physical characteristics, including gender, height/weight, body surface area (BSA), and age, assessed simultaneously on those parameters in Chinese children is lacking. The aim of the present study was to explore the impact of individual characteristics on maximum IVC diameter (IVCmax), Ao, and IVCmax/Ao in healthy Chinese children. From September to December 2015, 200 healthy children from 1 to 13 years of age were enrolled. IVCmax and Ao diameters were measured by 2D ultrasound. We found that age (years), height (cm), weight (kg), waist circumference (cm), and BSA (m2) were positively correlated with IVCmax and Ao. Multivariate linear regression showed that age was the only independent variable for IVCmax (mm) in female children, height was the only independent variable for IVCmax in male children, and age was the only independent variable for Ao in both females and males. IVCmax/Ao was not significantly influenced by the subjects' characteristics. In conclusion, IVCmax and Ao were more susceptible to subjects' characteristics than IVCmax/Ao. IVCmax/Ao could be a reliable and practical parameter in Chinese children as it was independent of age, height, and weight.

Is the Collapsibility Index of the Inferior Vena Cava an Accurate Predictor for the Early Detection of Intravascular Volume Change?

The ultrasonographic evaluation of inferior vena cava (IVC) parameters, particularly the collapsibility index (CI), has been widely used in the assessment of the fluid responsiveness of critically ill patients, but the results are conflicting. In this study, we aimed to investigate the early change in CI after increased intravascular volume (IVV) induced by passive leg raising (PLR). A total of 145 healthy volunteers over 18 years old were enrolled between September and December in 2015. Before and 2 min after PLR, the maximum and minimum IVC diameters (maxIVC and minIVC) were measured by color Doppler ultrasonography, and the difference in CI (ΔCI) was calculated. The heart rate (HR) and noninvasive mean arterial pressure (MAP) were also monitored. We found that there was a significant increase in the mean maxIVC and minIVC values and a reduction in CI. Nevertheless, no significant differences in HR or MAP were observed before or 2 min after PLR. The baseline CI had no relationship with individual characteristics and a multiple linear regression analysis of the ΔCI and individual characteristics showed that age, baseline CI, and BMI were independent variables for ΔCI. In conclusion, IVC-CI measured by ultrasound is useful for the detection of early IVV change induced by 2 min PLR. However, its ability to detect the increased IVV value is influenced by age, BMI, and baseline CI. Moreover, only 50.3% of the subjects had an IVC-CI reduction of more than 10%, making IVC-CI of little value for clinical applications, due to its poor sensitivity.

Remote Ischemic Postconditioning Improves Myocardial Dysfunction Via the Risk and Safe Pathways in a Rat Model of Severe Hemorrhagic Shock.

INTRODUCTION: Patients who have been resuscitated after severe hemorrhagic shock still have a high mortality rate. Previously published literature has suggested that remote ischemic postconditioning (RIPostC) has a cardioprotective effect, but few studies have focused on RIPostC performed after severe hemorrhagic shock. In this study, we aim to explore the effects and mechanism of RIPostC on myocardial ischemia and reperfusion injuries after hemorrhagic shock. METHODS: Fifty male rats were randomized into four groups: sham, control, remote ischemic per-conditioning (RIPerC), and RIPostC. Hemorrhagic shock was induced by removing 45% of the estimated total blood volume. Remote ischemic conditioning (RIC) was induced by four cycles of limb ischemia for 5 min followed by 5 min of reperfusion, during and after resuscitation for the RIPerC and RIPostC groups, respectively. Myocardial function, survival rate, IL-6, IL-10, and SOD were detected. Myocardial damage was histopathologically analyzed, and proteins related to the reperfusion injury salvage kinase (RISK) pathway (Akt, MEK, ERK1/2) and the survival activating factor enhancement (SAFE) pathway (STAT-3 and STAT5) were measured. RESULTS: Compared with the control group, the ejection fraction and myocardial performance indexes were significantly better in both RIC groups 2 h after resuscitation. Myocardial damage was attenuated and survival time increased significantly in the RIC groups. IL-6 and cardiac troponin I (cTnI) levels were notably reduced in both RIC groups. Only RIPostC had significantly increased levels of SOD and IL-10. The SAFE and RISK pathways were activated by RIPostC, whereas the effect of RIPerC was not significant. CONCLUSIONS: RIPostC attenuated myocardial dysfunction and survival outcomes via the activation of the SAFE and RISK pathways in this rat model of hemorrhagic shock. RIPerC improves myocardial dysfunction, but might not do so via the SAFE and RISK pathways.

What Help Could Ultrasound Elastography Give to the Diagnosis of Breast Papillary Lesions?

On the basis of results of our previous studies and the findings of other scholars, the most common histologic type of false-positive diagnosis with strain elastography (SE) was papilloma. The objectives of our study were to evaluate whether SE could contribute to conventional ultrasound differentiation between benign and malignant papillary lesions and between papillary lesions and other common benign breast lesions. Data on 89 papillary lesions at our hospital, including 74 benign and 15 malignant papillary lesions, were included in our study. In addition, 198 non-papillary benign tumors were selected as the control group, including 126 fibroadenomas and 72 cases of fibrocystic mastopathy. All patients gave written informed consent. All patients with breast lesions underwent conventional ultrasound and SE examination. Breast Imaging Recording and Data System (BI-RADS) category and SE score were compared with respect to sensitivity, specificity and accuracy in differentiating between benign and malignant papillary lesions. We then explored the possibility of using BI-RADS combined with SE to differentiate papillary lesions from non-papillary benign tumors. For differentiating between benign and malignant papillary lesions, the area under the receiver operating characteristic curve (AUC) of BI-RADS was 0.568, whereas the AUC values of SE score, strain ratio and BI-RADS combined with SE were 0.517, 0.584 and 0.509, respectively (p > 0.05). For differentiating between papillary lesions and non-papillary benign lesions, the AUC of BI-RADS combined with SE was 0.835, which was higher than the values for BI-RADS (0.775) and SE (SE score: 0.648, strain ratio: 0.661) (p < 0.001). The specificity and accuracy of BI-RADS combined with SE were significantly higher than those for BI-RADS alone without a decrease in sensitivity (p < 0.05). SE could not improve the diagnostic efficiency of BI-RADS in differentiating between benign and malignant papillary lesions. However, BI-RADS combined with SE could improve the specificity of BI-RADS without decrease in sensitivity for differentiating breast papillary lesions from non-papillary benign lesions.

Production and characterization of a novel long-acting Herceptin-targeted nanobubble contrast agent specific for Her-2-positive breast cancers.

BACKGROUND: There is an unmet need for specific and sensitive imaging techniques to assess the efficacy of breast cancer therapy, particularly Her-2-expressing cancers. Ultrasonic microbubbles are being developed for use as diagnostic and therapeutic tools. However, nanobubbles circulate longer, are smaller, and diffuse into extravascular tissue to specifically bind target molecules. Here, we characterize a novel Herceptin-conjugated nanobubble for use against Her-2-expressing tumors. METHODS: Phospholipid-shelled nanobubbles conjugated with Herceptin (NBs-Her) were fabricated using a thin-film hydration method and characterized in vitro in breast cancer cell lines and in vivo in a mouse model. RESULTS: The average size of the unconjugated nanobubbles (NBs-Blank) and NBs-Her was 447.1 ± 18.4 and 613.0 ± 25.4 nm, respectively. In cell culture, the NBs-Her adhered to Her-2-positive cells significantly better than to Her-2-negative cells (p < 0.05). In vivo, the peak intensity and the half-time to washout of the NBs-Her were significantly greater than those of the NBs-Blank (p < 0.05). In addition, contrast-enhanced ultrasound imaging quality was improved through the use of the NBs-Her. The nanobubbles were able to penetrate into tumor tissue to allow extravascular imaging, but did not penetrate normal skeletal muscle. CONCLUSIONS: The Herceptin-conjugated nanobubble had many properties that made it useful for in vivo imaging, including longer circulation time and better tumor selectivity. This platform may be able to provide targeted delivery of therapeutic drugs or genes.

Ultrasound Elastography Combined With BI-RADS-US Classification System: Is It Helpful for the Diagnostic Performance of Conventional Ultrasonography?

PURPOSE: To evaluate the additive diagnostic performance of ultrasound elastography (UE) to ultrasound (US) with the 2003 or 2013 Breast Imaging Reporting and Data System (BI-RADS)-US classification systems for the differentiation of benign and malignant breast lesions. METHODS: From June 2010 to December 2012, 738 women with 770 breast lesions were recruited into this retrospective study. Breast lesions were evaluated separately by US, UE, and both. US assessment was based on the 2003 or 2013 BI-RADS-US, and UE assessment was based on a previously reported 5-point scale. Diagnostic performance of US, UE, and both was compared. RESULTS: Before category 4 lesions were subdivided, the area under the receiver operating characteristic curve (AUC) for US, UE, and both were, respectively, 0.735, 0.877, 0.878 (P < .01). When subcategories of 4 lesions were considered, the AUC for US, UE, and both were, respectively, 0.865, 0.877, and 0.883 (P > .05). Adding UE to analysis of 4A lesions can decrease the percentages of malignancy to 2.56%. CONCLUSION: When the 2003 BI-RADS was considered, UE could give US some help in differentiating breast lesions. However, when the 2013 BI-RADS was considered, UE gave little help to US, although it reduced unnecessary biopsies of benign category 4A lesions.