Focused ultrasound combined with miR-1208-equipped exosomes inhibits malignant progression of glioma.

BACKGROUND: Exosomes (Exos) can safely and effectively deliver therapeutic substances to glioma cells; however, their blood-brain barrier (BBB) crossing capacity remains limited. Focused ultrasound (FUS) can transiently, reversibly, and locally open the BBB, while the effects of FUS combined with Exos-miRNA on the treatment of glioma have not been explored to date. METHODS: Exos were extracted by differential centrifugation and the efficacy of miR-1208-loaded Exos combined with FUS in the treatment of glioma was detected by CCK-8, colony formation, flow cytometry, transwell and tumour xenografts assays. The METTL3-mediated regulation of IGF2BP2 on mRNA stability of NUP214 was determined by MeRIP-qPCR, half-life and RIP assays. RESULTS: We used Exos secreted by mesenchymal stem cells as carriers for the tumour suppressor gene miR-1208, and following FUS irradiation, more Exos carrying miR-1208 were allowed to pass through the BBB, and the uptake of miR-1208 in Exos by glioma cells was promoted, thereby achieving high-efficiency tumour-suppressive effects. Furthermore, the molecular mechanism underlying this effect was elucidated that miR-1208 downregulated the m6A methylation level of NUP214 mRNA by negatively regulating the expression of METTL3, thereby NUP214 expression and TGF-ß pathway activity were suppressed. CONCLUSIONS: MiR-1208-loaded Exos combined with FUS is expected to become an effective glioma treatment and deserves further clinical evaluation.

Ultrasound-based deep learning in the establishment of a breast lesion risk stratification system: a multicenter study.

OBJECTIVES: To establish a breast lesion risk stratification system using ultrasound images to predict breast malignancy and assess Breast Imaging Reporting and Data System (BI-RADS) categories simultaneously. METHODS: This multicenter study prospectively collected a dataset of ultrasound images for 5012 patients at thirty-two hospitals from December 2018 to December 2020. A deep learning (DL) model was developed to conduct binary categorization (benign and malignant) and BI-RADS categories (2, 3, 4a, 4b, 4c, and 5) simultaneously. The training set of 4212 patients and the internal test set of 416 patients were from thirty hospitals. The remaining two hospitals with 384 patients were used as an external test set. Three experienced radiologists performed a reader study on 324 patients randomly selected from the test sets. We compared the performance of the DL model with that of three radiologists and the consensus of the three radiologists. RESULTS: In the external test set, the DL model achieved areas under the receiver operating characteristic curve (AUCs) of 0.980 and 0.945 for the binary categorization and six-way categorizations, respectively. In the reader study set, the DL BI-RADS categories achieved a similar AUC (0.901 vs. 0.933, p = 0.0632), sensitivity (90.98% vs. 95.90%, p = 0.1094), and accuracy (83.33% vs. 79.01%, p = 0.0541), but higher specificity (78.71% vs. 68.81%, p = 0.0012) than those of the consensus of the three radiologists. CONCLUSIONS: The DL model performed well in distinguishing benign from malignant breast lesions and yielded outcomes similar to experienced radiologists. This indicates the potential applicability of the DL model in clinical diagnosis. KEY POINTS: • The DL model can achieve binary categorization for benign and malignant breast lesions and six-way BI-RADS categorizations for categories 2, 3, 4a, 4b, 4c, and 5, simultaneously. • The DL model showed acceptable agreement with radiologists for the classification of breast lesions. • The DL model performed well in distinguishing benign from malignant breast lesions and had promise in helping reduce unnecessary biopsies of BI-RADS 4a lesions.

Short-term exposure of HFD depresses intestinal cholinergic anti-inflammatory activity through hypothalamic inflammation in mice.

High-fat diet (HFD) exposure has been proven to impair vagus nerve function. However, it is not yet known whether the HFD challenge impacts vagal efferent-based intestinal cholinergic anti-inflammation activity. This investigation aims to evaluate the effect of HFD on intestinal cholinergic anti-inflammatory activity in mice. Mice with or without intracerebroventricular treatment with an antibody against toll-like receptor 4 (TLR4) were fed with HFD or standard chow for 2 weeks. Vagus nerve-based anti-inflammatory activity was analyzed by heart rate variability. Acetylcholine (ACh) content, nicotinic acetylcholine receptor α7 subtype (α7nAChR), and pro-inflammatory cytokines were analyzed by biochemical kits or qRT-PCR. HFD feeding mice exhibit a significant increase in high frequency (HF) and a decrease in the ratio of low frequency/HF, which were accompanied by lower ACh levels and α7nAChR mRNA expression in the intestinal segments. However, anti-TLR4 antibody-treated HFD mice showed normal ACh levels and α7nAChR mRNA expression in the intestinal segments. Moreover, TNF-α production in small intestine was significantly reduced in HFD + antibody group compared with HFD + vehicle group. Collectively, our present results reveal that HFD challenge depresses intestinal cholinergic anti-inflammatory activity, which is mediated by hypothalamic inflammation. Impairment of intestinal cholinergic anti-inflammatory pathway is the cause of intestinal low-grade inflammation by HFD consumption.

Integrated analysis identified prognostic microRNAs in breast cancer.

BACKGROUND: MicroRNAs (miRNAs) play pivotal roles in the development and progression of breast cancer (BC). In this study, we attempted to identify miRNAs associated with BC prognosis and progression via integrated analysis. METHODS: We first screened 83 differentially expressed miRNAs (DEMs) in 1249 BC samples and 151 normal samples. We then validated their roles in expression and prognosis of BC, identified two survival-related DEMs, and established a risk model. The prediction efficiency was assessed in both the training and validation groups. Tissue and cell experiments were conducted to verify the regulatory effects of miR-127 in BC. RESULTS: The ROC curve indicated good prediction ability with 1-, 3-, and 5-year survival rates of 0.73, 0.72, and 0.72, respectively. Moreover, hsa-miR-127 was found to be an independent prognostic factor of BC. Functional analyses revealed that it is involved in various cancer pathways such as the PI3K-Akt and p53 pathways. miR-127 expression was down-regulated in both BC tissues and cell lines. The knockdown of miR-127 substantially increased, whereas overexpression decreased BC cell proliferation, invasion, and migration. This effect of miR-127 was consistent with its tumorigenic ability and tumor volume in nude mice. CONCLUSIONS: These findings indicate that low expression of miR-127 contributes to BC migration, invasion, and tumorigenesis and that it can be a therapeutic target and prognostic biomarker for BC.

Hyperglycemia remission after Roux-en-Y gastric bypass: Implicated to altered monocyte inflammatory response in type 2 diabetes rats.

Hyperglycemia remission by metabolic surgery is implicated in the resolution of low-grade inflammation in type 2 diabetes mellitus (T2DM). However, whether this beneficial effect of metabolic surgery is related to improving monocyte inflammatory response remains undefined. This investigation is addressed to evaluate this relationship. For this purpose, T2DM rats were subjected to Roux-en-Y gastric bypass (RYGB) and/or monocyte depletion or splenic sympathetic denervation. Fasting blood glucose (FBG), plasma tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) were measured, and monocyte inflammatory response was assessed in vitro. The data showed that RYGB significantly reduced lipopolysaccharide (LPS)-induced release of TNF-α and IL-1ß from peripheral monocytes while alleviating hyperglycemia and reducing plasma TNF-α and IL-1ß levels. Hyperglycemia resulting from monocyte depletion by injection of clodronate liposomes resolved one week earlier than vehicle control after RYGB. Splenic denervation abrogated the glucose-lowering effect and decreased LPS-stimulated TNF-α and IL-1ß release from monocytes following RYGB. Overall, our results reveal that a marked reduction of monocyte inflammatory response after RYGB contributes to hyperglycemia remission in T2DM rats. The beneficial effect of RYGB is mediated through vagal-spleen axis anti-inflammatory activity.

The diagnostic accuracy of contrast echocardiography in patients with suspected cardiac masses: A preliminary multicenter, cross-sectional study.

Background: To evaluate the diagnostic accuracy of contrast echocardiography (CE) in patients with suspected cardiac masses. Methods: A multicenter, prospective study involving 108 consecutive patients with suspected cardiac masses based on transthoracic echocardiography performed between November 2019 and December 2020 was carried out. CE examinations were performed in all patients. The echocardiographic diagnosis was established according to the qualitative (echogenicity, boundary, morphology of the base, mass perfusion, pericardial effusion, and motility) and quantitative (area of the masses and peak intensity ratio of the masses and adjacent myocardium A1/A2) evaluations. Results: Final confirmed diagnoses were as follows: no cardiac mass (n = 3), pseudomass (n = 3), thrombus (n = 36), benign tumor (n = 30), and malignant tumor (n = 36). ROC analysis revealed the optimal A1/A2 with cutoff value of 0.295 for a cardiac tumor from a thrombus, with AUC, sensitivity, specificity, PPV, and NPV of 0.958 (95% confidence interval (CI): 0.899-0.988), 100, 91.7, 95.7, and 100%, respectively. CE was able to distinguish malignant from benign tumors with an AUC of 0.953 (95% CI: 0.870-0.990). Multivariate logistic regression analysis revealed that tumor area, base, and A1/A2 were associated with the risk of malignant tumor (OR = 1.003, 95% CI: 1.00003-1.005; OR = 22.64, 95% CI: 1.30-395.21; OR = 165.39, 95% CI: 4.68-5,850.94, respectively). When using A1/A2 > 1.28 as the only diagnostic criterion to identify the malignant tumor, AUC, sensitivity, specificity, PPV, and NPV were 0.886 (95% CI: 0.784-0.951), 80.6, 96.7, 96.7, and 80.7%, respectively. Conclusion: CE has the potential to accurately differentiate cardiac masses by combining qualitative and quantitative analyses. However, more studies with a large sample size should be conducted to further confirm these findings. Clinical trial registration: http://www.chictr.org.cn/, identifier: ChiCTR1900026809.

Deep learning based on ultrasound images assists breast lesion diagnosis in China: a multicenter diagnostic study.

BACKGROUND: Studies on deep learning (DL)-based models in breast ultrasound (US) remain at the early stage due to a lack of large datasets for training and independent test sets for verification. We aimed to develop a DL model for differentiating benign from malignant breast lesions on US using a large multicenter dataset and explore the model's ability to assist the radiologists. METHODS: A total of 14,043 US images from 5012 women were prospectively collected from 32 hospitals. To develop the DL model, the patients from 30 hospitals were randomly divided into a training cohort (n = 4149) and an internal test cohort (n = 466). The remaining 2 hospitals (n = 397) were used as the external test cohorts (ETC). We compared the model with the prospective Breast Imaging Reporting and Data System assessment and five radiologists. We also explored the model's ability to assist the radiologists using two different methods. RESULTS: The model demonstrated excellent diagnostic performance with the ETC, with a high area under the receiver operating characteristic curve (AUC, 0.913), sensitivity (88.84%), specificity (83.77%), and accuracy (86.40%). In the comparison set, the AUC was similar to that of the expert (p = 0.5629) and one experienced radiologist (p = 0.2112) and significantly higher than that of three inexperienced radiologists (p < 0.01). After model assistance, the accuracies and specificities of the radiologists were substantially improved without loss in sensitivities. CONCLUSIONS: The DL model yielded satisfactory predictions in distinguishing benign from malignant breast lesions. The model showed the potential value in improving the diagnosis of breast lesions by radiologists.

Correlation Between Contrast-Enhanced Ultrasound and Immune Response of Distant Hepatocellular Carcinoma After Radiofrequency Ablation in a Murine Model.

OBJECTIVES: To investigate the relationships between contrast-enhanced ultrasound (CEUS) and the immune status of a distant tumor after radiofrequency ablation (RFA) in a mouse model of hepatocellular carcinoma (HCC). METHODS: Twenty-four mice with two liver tumors were randomized into two groups. RFA was performed on the left tumor in the RFA group. Growth of the right tumors in both groups was monitored after RFA. According to tumor growth, two time points at which tumor growth was halted and restored were selected for study. Then, another 24 mice were randomized into RFA and non-RFA groups. The CEUS parameters, apoptosis, CD8+ T cell, and vasculogenic mimicry (VM) of the right tumors were analyzed on the two aforementioned time points in each group. RESULTS: Days 3 and 6 were selected as the time points of tumor retardation and progressive growth, respectively. The different immune status of the distant tumors at the two time points after RFA was confirmed by CD8+ T cell and apoptosis (both P < 0.001). Peak intensity, time to peak, area wash-in, and area wash-out of the CEUS parameters increased significantly in the day-6 RFA group versus the day-3 RFA group (P < .001, P = .017, P = .005, P = .002, respectively). VM of the day-6 RFA group was higher than that of the day-3 RFA group (P = .003). CONCLUSIONS: CEUS maybe a good method to follow the immune response after RFA in an advanced HCC mouse model.

The Utility of the Fifth Edition of the BI-RADS Ultrasound Lexicon in Category 4 Breast Lesions: A Prospective Multicenter Study in China.

RATIONALE AND OBJECTIVES: The objective of this study was to evaluate the utility of the fifth edition of the Breast Imaging-Reporting and Data System (BI-RADS) in clinical breast radiology by using prospective multicenter real-time analyses of ultrasound (US) images. MATERIALS AND METHODS: We prospectively studied 2049 female patients (age range, 19-86 years; mean age 46.88 years) with BI-RADS category 4 breast masses in 32 tertiary hospitals. All the patients underwent B-mode, color Doppler US, and US elastography examination. US features of the mass and associated features were described and categorized according to the fifth edition of the BI-RADS US lexicon. The pathological results were used as the reference standard. The positive predictive values (PPVs) of subcategories 4a-4c were calculated. RESULTS: A total of 2094 masses were obtained, including 1124 benign masses (54.9%) and 925 malignant masses (45.1%). For BI-RADS US features of mass shape, orientation, margin, posterior features, calcifications, architectural distortion, edema, skin changes, vascularity, and elasticity assessment were significantly different for benign and malignant masses (p< 0.05). Typical signs of malignancy were irregular shape (PPV, 57.2%), spiculated margin (PPV, 83.7%), nonparallel orientation (PPV, 63.9%), and combined pattern of posterior features (PPV, 60.6%). For the changed or newly added US features, the PPVs for intraductal calcifications were 80%, 56.4% for internal vascularity, and 80% for a hard pattern on elastography. The associated features such as architectural distortion (PPV, 89.3%), edema (PPV, 69.2%), and skin changes (PPV, 76.2%) displayed high predictive value for malignancy. The rate of malignant was 7.4% (72/975) in category 4a, 61.4% (283/461) in category 4b, and 93.0% (570/613) in category 4c. The PPV for category 4b was higher than the likelihood ranges specified in BI-RADS and the PPVs for categories 4a and 4c were within the acceptable performance ranges specified in the fifth edition of BI-RADS in our study. CONCLUSION: Not only the US features of the breast mass, but also associated features, including vascularity and elasticity assessment, have become an indispensable part of the fifth edition of BI-RADS US lexicon to distinguish benign and malignant breast lesions. The subdivision of category 4 lesions into categories 4a, 4b, and 4c for US findings is helpful for further assessment of the likelihood of malignancy of breast lesions.

Gail Model Improves the Diagnostic Performance of the Fifth Edition of Ultrasound BI-RADS for Predicting Breast Cancer: A Multicenter Prospective Study.

RATIONALE AND OBJECTIVES: The sonographic appearance of benign and malignant breast nodules overlaps to some extent, and we aimed to assess the performance of the Gail model as an adjunctive tool to ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) for predicting the malignancy of nodules. MATERIALS AND METHODS: From 2018 to 2019, 2607 patients were prospectively enrolled by 35 health care facilities. An individual breast cancer risk was assessed by the Gail model. Based on B-mode US, color Doppler, and elastography, all nodules were evaluated according to the fifth edition of BI-RADS, and these nodules were all confirmed later by pathology. RESULTS: We demonstrated that the Gail model, age, tumor size, tumor shape, growth orientation, margin, contour, acoustic shadowing, microcalcification, presence of duct ectasia, presence of architectural distortion, color Doppler flow, BI-RADS, and elastography score were significantly related to breast cancer (all p < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) for combining the Gail model with the BI-RADS category were 95.6%, 91.3%, 85.0%, 97.6%, 92.8%, and 0.98, respectively. Combining the Gail model with the BI-RADS showed better diagnostic efficiency than the BI-RADS and Gail model alone (AUC 0.98 vs 0.80, p < 0.001; AUC 0.98 vs 0.55, p < 0.001) and demonstrated a higher specificity than the BI-RADS (91.3% vs 59.4%, p < 0.001). CONCLUSION: The Gail model could be used to differentiate malignant and benign breast lesions. Combined with the BI-RADS category, the Gail model was adjunctive to US for predicting breast lesions for malignancy. For the diagnosis of malignancy, more attention should be paid to high-risk patients with breast lesions.

Differentiation of cystic biliary atresia and choledochal cysts using prenatal ultrasonography.

PURPOSE: This study explored the performance of prenatal ultrasonography in the differential diagnosis of cystic biliary atresia (CBA) and choledochal cyst (CC). METHODS: Fetuses diagnosed with hepatic hilar cyst in the second trimester were included in this study. A series of prenatal ultrasound examinations were performed in the second and third trimesters. The diameter of the gallbladder (GB) and hepatic cyst were measured, as well as the wall thickness of the GB. The GB-cyst connection, visibility of the right hepatic artery (RHA), and other concomitant abnormalities were carefully evaluated. A neonatal transabdominal ultrasound examination was performed within 1 week after birth, and clinical data were followed up to 6 months after birth. RESULTS: Between January 1, 2016 and January 31, 2020, 53 fetuses diagnosed with hepatic hilar cyst were recruited. Eight were excluded because they were lost to follow-up. Among the 45 cases included in this study, 10 were diagnosed with CBA and 35 with CC after birth. Statistically significant differences were found in GB width, wall thickness, change in GB width, change in cyst length, GB-cyst connection, and RHA visibility between the CBA and CC groups. GB width showed the best diagnostic performance with an area under the curve (AUC) of 0.899. The combination of GB width, GB wall thickness, and GB-cyst connection yielded a comparable AUC of 0.971. CONCLUSION: The GB should be carefully evaluated in fetuses with hepatic hilar cyst. Prenatal ultrasound findings could provide suggestive parameters for the differential diagnosis of CBA from CC.

Can Ultrasound Elastography Help Better Manage Mammographic BI-RADS Category 4 Breast Lesions?

BACKGROUND: To assess the performance of conventional ultrasound (US) combined with strain elastography (SE) in the Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions on mammography. MATERIALS AND METHODS: Women with breast lesions identified as having mammography BI-RADS 4 lesions and underwent US examination were included in China. US features and US BI-RADS assessment were recorded in real-time and prospectively reported. The pathological result was referred to as the gold standard. The performance of US in the mammographic BI-RADS category 4 lesions was evaluated. Diagnostic performances of US BI-RADS, SE and combined both were compared. RESULTS: A total of 751 women with 751 breast lesions classified as mammographic BI-RADS category 4 were included. For mammographic findings, 530 (70.6%) were true positive and 221 (29.4%) were false positive. Conventional US achieved higher positive predictive value (PPV) than mammography (78.5% vs. 70.6%, P=.001). The specificity increased from 34.4% to 47.1% (P< .001) without any loss in sensitivity and the PPV increased to 81.9% (P = .122) when conventional US was used in combination with SE. For conventional US combined with SE, it led to a correct diagnosis of no breast cancer in 104 of the 221 false-positive findings (47.1%) and achieved higher PPV than mammography regardless of patient age and lesion size. CONCLUSION: Conventional US combined with SE is a helpful tool for the noninvasive examination of breast lesions classified as BI-RADS category 4 on mammography. It helped increase the PPV and had the potential to avoid unnecessary biopsies of BI-RADS category 4 lesions detected on mammography.

Case report: Fatal systemic embolism caused by early prosthetic valve endocarditis after Bentall surgery.

Prosthetic valve endocarditis (PVE) is a rare but dangerous complication of Bentall surgery and Staphylococcus epidermidis PVE involving multiple valves simultaneously during the early postoperative period has not been reported. A 42 year old patient admitted to intensive care unit with fever 1 month after aortic valve replacement (Bentall procedure). Echocardiography was of great diagnosis value and suggested large, mobile vegetations on both the prosthetic aortic valve and native tricuspid valve. The presence of Staphylococcus epidermidis was revealed by multiple blood cultures. Surgery was not performed because of the history of aortic valve replacement 1 month ago. He developed acute right femoral artery thromboembolism, multiple cerebral infarction and splenic infarction during hospitalization and died of cerebral infarction after being discharged. This case underlines that patients with early PVE may have poor prognosis and fatal systemic embolism should be aware of in PVE patients with large vegetations present with dyskinesia, abdominal pain, and limb numbness. The timely echocardiography and vascular ultrasound are primary and reliable diagnostic methods in this scenario.

Surgical Outcomes of Aldosterone-Producing Adenoma on the Basis of the Histopathological Findings.

Introduction: Previous studies on the surgical outcomes of aldosterone-producing adenoma (APA) patients were mainly based on the histopathological diagnosis of HE staining or adrenal venous sampling (AVS) instead of the functional pathology. The aim of the present study was to evaluate the surgical outcomes of APA patients based on the functional pathological diagnosis of APA according to HISTALDO (histopathology of primary aldosteronism) consensus. Methods: Clinical data of 137 patients with suspected APA were analyzed retrospectively. All patients had hypertension and spontaneous hypokalemia. In all patients, CT showed a unilateral solitary hypodense adrenal lesion, and a contralateral adrenal gland of normal morphology. Tumors were removed and immunostained for CYP11B2, and their pathology were identified based on HISTALDO consensus. Patients were followed up 6 to 24 months after operation. Results: Among 137 cases of presumptive APA diagnosed by CT, 130 (95%) cases were pathologically diagnosed with classical pathology, including 123 APA(90%) and 7 aldosterone-producing nodule (APN) (5%). 7 cases (5%) had non-functioning adenoma (NFA) with aldosterone-producing micronodule (APM) or multiple aldosterone-producing micronodule (MAPM) in the surrounding adrenal tissue. In all 137 patients, hypertension was complete or partial clinical success postoperatively. Complete clinical success was achieved in 73 (53%), and partial clinical success was achieved in 64 (47%) cases. Serum potassium level recovered to normal in all. In 123 patients with APA, complete clinical success was reached in 67 (54%), and partial clinical success was reached in 56 (46%) cases. Gender, duration of hypertension and the highest SBP were significant independent predictors for cure of APA after surgery. A multiple logistic regression model integrating the three predictors was constructed to predict the outcome, which achieved a sensitivity of 72.4% and a specificity of 73.1%. Conclusion: The specificity of CT in the diagnosis of APA and APN patients with hypokalemia was 95%. All patients achieved complete or partial clinical success after surgery. Gender, duration of hypertension and the highest SBP were independent predictors for the postoperative cure of APA.

MiR-146a mediates TLR-4 signaling pathway to affect myocardial fibrosis in rat constrictive pericarditis model.

BACKGROUND: Myocardial fibrosis (MF) is thought to be associated with constrictive pericarditis (CP). miR-146a has been reported to be related to the survival of myocardial fibroblasts and related signal transduction pathways. The aim of this study was to investigate the expression of miR-146a in CP with MF and the activation of the Toll-like receptor 4 (TLR-4) signaling pathway, to understand the molecular mechanism of MF involvement in CP. METHODS: Thirty rats with different disease duration were randomly divided into three groups: an 8-week model group (CP-8W group), a 16-week model group (CP-16W group) model, and a normal control group (N group). After the CP model was established in the rats, the myocardial tissues were collected. The expression of miR-146a, the key factors of TLR-4 signaling pathway, including IL-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor-κB (NF-κB) and p-NF-κB, and the MF indicator α-SMA in myocardial tissue were detected. After treatment with lipopolysaccharide (LPS), primary cultured rat cardiac fibroblasts (CFs) were transfected with miR-146a. RT-PCR and western blot were used to detect the expression of downstream effectors to further verify the function of miRNA-146a in regulating MF via the TLR-4 signaling pathway. RESULTS: miR-146a was increased in the CP-8W group but not in the CP-16W group. IRAK1 and TRAF6 in the CP-16W group were found to be higher than in the N group and CP-8W group. α-SMA in the model groups was higher than in the N group. Compared with the CP-8W group, α-SMA in the CP-16W model group was further increased. In the experiments using CFs, the expression of IRAK1, TRAF6, p-NF-κB and α-SMA increased in the LPS-treated group compared with the N group. After transfection of CFs with the miR-146a mimics, the expression of IRAK1, TRAF6, p-NF-κB and α-SMA decreased compared with the LPS-treated group. Following transfection of CFs with miR-146a inhibitors, the expression of IRAK1, TRAF6, p-NF-κB and α-SMA increased compared with the LPS-treated group. CONCLUSIONS: The expression of miR-146a demonstrated a dynamic change in the CP model; it was increased at the early time point (CP-8W) and then decreased at the 16W time point. miR-146a suppressed MF by inhibiting the target genes TRAF6 and IRAK1 via the TLR-4 signaling pathway.

Berry syndrome: a case report and literature review.

BACKGROUND: Berry syndrome, a rare combination of cardiac anomalies, consists of aortopulmonary window (APW); aortic origin of the right pulmonary artery; interrupted aortic arch (IAA) or hypoplastic aortic arch or coarctation of the aorta; and an intact ventricular septum. There is lack of review articles that elucidate the clinical features, diagnosis, treatment, and outcomes of Berry syndrome. This publication systematically reviews the 89 cases published since 1982 on Berry syndrome. CASE PRESENTATION: A 38-year-old woman presented with a loud murmur and cyanosis. Transthoracic echocardiography demonstrated a severely dilated aorta and main pulmonary artery with a large intervening defect. Distal to the APW, the ascending aorta gave rise to the right pulmonary artery. Additionally, a type A IAA, an intact ventricular septum, and a large patent ductus arteriosus were revealed. Computed tomography angiography with 3-dimensional reconstruction confirmed above findings. This is the first report of a patient of this age with Berry syndrome who did not undergo surgery. CONCLUSIONS: Berry syndrome is a rare but well-identified and surgically correctable anomaly. Patients with Berry syndrome should be followed up for longer periods to better characterize long-term outcomes.

Risk-predicted dual nomograms consisting of clinical and ultrasound factors for downgrading BI-RADS category 4a breast lesions - A multiple centre study.

Purpose: To develop and to validate a risk-predicted nomogram for downgrading Breast Imaging Reporting and Data System (BI-RADS) category 4a breast lesions. Patients and Methods: We enrolled 680 patients with breast lesions that were diagnosed as BI-RADS category 4a by conventional ultrasound from December 2018 to June 2019. All 4a lesions were randomly divided into development and validation groups at the ratio of 3:1. In the development group consisting of 499 cases, the multiple clinical and ultrasound predicted factors were extracted, and dual-predicted nomograms were constructed by multivariable logistic regression analysis, named clinical nomogram and ultrasound nomogram, respectively. Patients were twice classified as either "high risk" or "low risk" in the two nomograms. The performance of these dual nomograms was assessed by an independent validation group of 181 cases. Receiver Operating Characteristic (ROC) curve and diagnostic value were calculated to evaluate the applicability of the new model. Results: After multiple logistic regression analysis, the clinical nomogram included 2 predictors: age and the first-degree family members with breast cancer. The area under the curve (AUC) value for the clinical nomogram was 0.661 and 0.712 for the development and validation groups, respectively. The ultrasound nomogram included 3 independent predictors (margins, calcification and strain ratio), and the AUC value in this nomogram was 0.782 and 0.747 in the development and validation groups, respectively. In the development group of 499 patients, approximately 50.90% (254/499) of patients were twice classified "low risk", with a malignancy rate of 1.18%. In the validation group of 181 patients, approximately 47.51% (86/181) of patients had been twice classified as "low risk", with a malignancy rate of 1.16%. Conclusions: A dual-predicted nomogram incorporating clinical factors and imaging characteristics is an applicable model for downgrading the low-risk lesions in BI-RADS category 4a and shows good stability and accuracy, which is useful for decreasing the rate of invasive examinations and surgery.

A Novel Model Incorporating Tumor Stiffness, Blood Flow Characteristics, and Ki-67 Expression to Predict Responses After Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To investigate the ability of tumor stiffness, tumor blood flow, and Ki-67 expression alone or in combination in predicting the pathological response to neoadjuvant chemotherapy (NACT) in breast cancer. PATIENTS AND METHODS: This prospective cohort study included 145 breast cancer patients treated with NACT. Tumor stiffness (maximum stiffness (Emax), mean stiffness (Emean)), blood score (BS), and their relative changes, were evaluated before (t0), during (t1-t5), and at the end of NACT (t6) by shear-wave elastography and optical imaging. Ki-67 expression was quantitatively evaluated by immunohistochemistry using core biopsy specimens obtained before NACT. Pathological responses were evaluated by residual cancer burden. The ability of tumor stiffness, BS, Ki-67, and predRCB-which combined ΔEmean (t2) (the relative changes in Emean after the second NACT cycle), BS2 (BS after the second NACT cycle), and Ki-67-in predicting tumor responses was compared using receiver operating characteristic curves and the Z-test. RESULTS: Tumor stiffness and BS decreased during NACT. ΔEmean (t2), BS2, and Ki-67 had better predictive performance than other indexes in identifying a favorable response (AUC = 0.82, 0.81, and 0.80) and resistance responses (AUC = 0.85, 0.79, and 0.84), with no significant differences between the three (p > 0.05). PredRCB had better predictive performance than any parameter alone for a favorable response (AUC = 0.90) and resistance (AUC = 0.93). CONCLUSION: Tumor stiffness, BS, and Ki-67 expression showed good and similar abilities for predicting the pathological response to NACT, and predRCB was a significantly better predictor than each index alone. These results may help design therapeutic strategies for breast cancer patients undergoing NACT.

Efficacy of shear-wave elastography versus dynamic optical breast imaging for predicting the pathological response to neoadjuvant chemotherapy in breast cancer.

PURPOSE: Explore the value of shear-wave elastography (SWE) parameters and dynamic optical breast imaging features for predicting pathological responses to neoadjuvant chemotherapy (NACT) in breast cancer (BC). METHOD: This prospective cohort study included 91 BC patients receiving NACT. Tumor size, SWE (maximum stiffness [Emax] and mean stiffness [Emean]), blood score (BS), and oxygen score (OS) and their relative changes were collected before (t0), during (t1-t5), and after NACT (t6). The pathological response was classified according to the residual cancer burden. Relationships between tumor size, SWE stiffness, BS, and OS at t0-t6 were analyzed, and their predictive power was compared. RESULTS: During six NACT cycles, tumor size, tumor stiffness, and BS decreased, and tumor OS increased. ΔEmean (t2), E2mean, BS2, and OS2 had a greater power than other indexes for predicting a favorable response (AUC = 0.79, 0.71, 0.77, 0.78) and a resistance response (0.86, 0.74, 0.71, 0.71). For the favorable response, predictive power did not differ significantly between ΔEmean (t2), E2mean, BS2, and OS2, whereas for the resistance response, ΔEmean (t2) showed better prediction than E2mean, BS2, and OS2. CONCLUSIONS: SWE stiffness, BS, and OS exhibited good and similar performances in predicting a NACT favorable response, and SWE stiffness showed better performance than BS and OS in predicting NACT resistance. These results may provide an important reference for individualized treatment in BC patients receiving NACT.