Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Diagnosing Hepatocellular Carcinoma: Diagnostic Performance and Interobserver Agreement.

OBJECTIVES: To determine the diagnostic performance and inter-reader agreement of the contrast-enhanced ultrasound liver imaging reporting and data system (CEUS-LI-RADS) for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. METHODS: In this prospective study, CEUS-LI-RADS categories (LR-5 for predicting HCC) were assigned by six blinded readers and compared to the definitive HCC diagnosis in patients with liver cirrhosis per the 2017 China Liver Cancer Guidelines (CLCG). CEUS features were recorded in 96 patients with 96 histology-proven lesions. The diagnostic performance of LR-5 was described by the sensitivity, specificity and accuracy. Multi-reader agreement was assessed by using intraclass correlation coefficients (ICC). RESULTS: In cirrhotic patients, the specificity of LR-5 (range: 92.7-100.0 %) was statistically higher than that of CLCG for each reader (range: 28.6-64.3 %). However, the sensitivity (range: 38.6-63.6 %) and accuracy (range: 53.4-70.7 %) were statistically lower in CEUS-LIRADS than in CLCG (sensitivity range: 88.6-100.0 %; accuracy range: 77.6-86.2 %). Only fair to moderate inter-reader agreement was achieved for the CEUS-LI-RADS category (ICC = 0.595) and washout appearance (ICC range: 0.338 to 0.555). Neither nodule-in-nodule nor mosaic architecture was observed more often in HCC (all P > 0.05), with poor inter-reader consistency for both (both ICC < 0.20). CONCLUSION: CEUS-LI-RADS category 5 has a high specificity but a low accuracy for identifying HCC in high-risk patients. Inter-reader agreement is not satisfactory concerning CEUS-LIRADS category and washout appearance. Moreover, the clinical value of ancillary features favoring HCC is quite limited.

Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation.

Ultrasound-targeted microbubble destruction (UTMD) mediates gene transfection with high biosafety and thus has been promising toward treatment of type 1 diabetes. However, the potential application of UTMD in type 2 diabetes (T2D) is still limited, due to the lack of systematic design and dynamic monitoring. Herein, an efficient gene delivery system is constructed by plasmid deoxyribonucleic acid (DNA) encoding glucagon-like peptide 1 (GLP-1) in ultrasound-induced microbubbles, toward treatment of T2D in macaque. The as designed UTMD afforded enhancement of cell membrane penetration and GLP-1 expression in macaque, which is characterized by ultrasound-guided biopsy to monitor the dynamic process of islet cells for 6 months. Also, improvement of pancreatic beta cell regeneration, and regulation of plasma glucose in macaque with T2D is achieved. The approach would serve as promising alternatives for the treatment of T2D.

Plaque Elasticity and Intraplaque Neovascularisation on Carotid Artery Ultrasound: A Comparative Histological Study.

OBJECTIVE: Plaque elasticity and intraplaque neovascularisation are strongly suggestive of vulnerable plaque. This study aimed to investigate the relationship between intraplaque neovascularisation and plaque elasticity, and to compare the ultrasound findings with histopathological changes. METHODS: Patients enrolled in this study presented with symptomatic carotid stenosis (> 70%) and later underwent both pre-operative ultrasonography and endarterectomy. Contrast enhanced ultrasound (CEUS) and shear wave elastography (SWE) were used to measure the neovascularisation and elasticity of the plaque, respectively. After removal, plaques were histologically assessed to determine the microvessel density (MVD), matrix metalloproteinase (MMP)-9 expression, and type I/type III collagen ratio using immunohistochemistry staining and morphometry. A correlation analysis was used to establish the relationship among the aforementioned quantitative parameters. Inter- and intra-observer consistency evaluations were performed using the intraclass correlation coefficient and Bland-Altman plots. RESULTS: Ninety-four symptomatic patients with 98 plaques were included. The area under the curve (AUC) of the carotid plaque detected using CEUS correlated with its shear wave velocity (SWV) (r = -.714; p < .001), MVD (r = .842; p < .001), collagen type I/III ratio (r = -.833; p < .001), and MMP-9 (r = .738; p < .001). SWE was positively correlated with the type I/III collagen ratio (r = .805; p < .001). The overall interexaminer consistency of the SWE was acceptable (r = .638; p < .001). The interobserver correlation coefficient of the AUC, time to peak (TP), mean transit time (MTT), and SWV were .719, .756, .733, and .686, respectively. The intra-observer variability values of the AUC, TP, MTT, and SWV were .826, .845, .633, and .748, respectively. CONCLUSION: SWE and CEUS can comprehensively evaluate the vulnerability of the carotid plaque by assessing the elasticity of the plaque and neovascularisation within it. The negative correlation between the intraplaque neovascularisation and elasticity, further validated by histological findings, suggests that the more abundant the neovascularisation, the less elasticity.

Long non-coding RNA SDCBP2-AS1 delays the progression of ovarian cancer via microRNA-100-5p-targeted EPDR1.

BACKGROUND: Dysregulation of long non-coding RNAs has been implied to connect with cancer progression. This research was to decipher the mechanism of long non-coding RNA SDCBP2-AS1 in ovarian cancer (OC) through regulation of microRNA (miR)-100-5p and ependymin-related protein 1 (EPDR1). METHODS: LncRNA SDCBP2-AS1 and EPDR1 levels in OC were assessed by Gene Expression Profiling Interactive Analysis. lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 levels in OC tissues and cells were determined. SKOV3 and A2780 cells were transfected with lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1-related plasmids or sequences, and then their functions in cell viability, apoptosis, migration, and invasion were evaluated. The interplay of lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 was clarified. RESULTS: LncRNA SDCBP2-AS1 and EPDR1 levels were suppressed whilst miR-100-5p level was elevated in OC. After upregulating lncRNA SDCBP2-AS1 or EPDR1, viability, migration, and invasion of OC cells were impaired, and apoptosis rate was increased. Downregulating EPDR1 or upregulating miR-100-5p partially mitigated upregulated lncRNA SDCBP2-AS1-induced impacts on the biological functions of OC cells. LncRNA SDCBP2-AS1 sponged miR-100-5p, and EPDR1 was targeted by miR-100-5p. CONCLUSION: It is illustrated that lncRNA SDCBP2-AS1 regulates EPDR1 by sponge adsorption of miR-100-5p to inhibit the progression of OC.

Active Transportation of Liposome Enhances Tumor Accumulation, Penetration, and Therapeutic Efficacy.

Liposomes are the first and mostly explored nanocarriers for cancer drug delivery, which have shown great promise in clinical applications, but their limited accumulation and penetration into the tumor interstitial space, significantly reduce the therapeutic efficacy. Here, a γ-glutamyltranspeptidase (GGT)-triggered charge-switchable approach is reported that can trigger the fast endocytosis and transcytosis of the liposome in tumor microenvironments to overcome the harsh biological barriers in tumor tissues. The active transporting liposomal nanocarrier (GCSDL) is prepared by surface modification with a glutathione (GSH) moiety and encapsulated with doxorubicin (DOX). When the GCSDL contacts with tumor vascular endothelial cells, the overexpressed GGT enzyme on cytomembrane catalyzes the hydrolysis of GSH to generate cationic primary amines. The cationic GCSDL triggers fast caveolae-mediated endocytosis and vesicle-mediated transcytosis, resulting in sequential transcytosis to augment its tumor accumulation and penetration. Along with continual intercellular transportation, GCSDL can release DOX throughout the tumor to induce cancer cell apoptosis, resulting in complete eradication of hepatocellular carcinoma and cessation of pancreatic ductal adenocarcinoma's progression. This study develops an efficient strategy to realize high tumor accumulation and deep penetration for the liposomal drug delivery system via active transcytosis.

A novel single-chain enzyme complex with chain reaction properties rapidly producing thromboxane A2 and exhibiting powerful anti-bleeding functions.

Uncontrollable bleeding is still a worldwide killer. In this study, we aimed to investigate a novel approach to exhibit effective haemostatic properties, which could possibly save lives in various bleeding emergencies. According to the structure-based enzymatic design, we have engineered a novel single-chain hybrid enzyme complex (SCHEC), COX-1-10aa-TXAS. We linked the C-terminus of cyclooxygenase-1 (COX-1) to the N-terminus of the thromboxane A2 (TXA2 ) synthase (TXAS), through a 10-amino acid residue linker. This recombinant COX-1-10aa-TXAS can effectively pass COX-1-derived intermediate prostaglandin (PG) H2 (PGH2 ) to the active site of TXAS, resulting in an effective chain reaction property to produce the haemostatic prostanoid, TXA2 , rapidly. Advantageously, COX-1-10aa-TXAS constrains the production of other pro-bleeding prostanoids, such as prostacyclin (PGI2 ) and prostaglandin E2 (PGE2 ), through reducing the common substrate, PGH2 being passed to synthases which produce aforementioned prostanoids. Therefore, based on these multiple properties, this novel COX-1-10aa-TXAS indicated a powerful anti-bleeding ability, which could be used to treat a variety of bleeding situations and could even be useful for bleeding prone situations, including nonsteroidal anti-inflammatory drugs (NSAIDs)-resulted TXA2 -deficient and PGI2 -mediated bleeding disorders. This novel SCHEC has a great potential to be developed into a biological haemostatic agent to treat severe haemorrhage emergencies, which will prevent the complications of blood loss and save lives.

MicroRNA-148a promotes apoptosis and suppresses growth of breast cancer cells by targeting B-cell lymphoma 2.

MicroRNAs (miRNAs) contribute toward tumorigenesis through the modulation of tumor-related genes. MiR-148a has been characterized as a tumor-suppressing miRNA and its downregulation has been reported in tumors of a variety of cancers. However, the functional role of miR-148a in breast cancer is not yet fully understood. Using both in-vitro and in-vivo models, we confirmed that miR-148a acts to inhibit the proliferation of breast cancer cells. Through the use of bioinformatic approaches in miRNA target prediction, we determined that B-cell lymphoma 2 (BCL-2) is a likely target of miR-148a. The overexpression and tumorigenic effects of BCL-2 have already been confirmed in cancerous tumors of the breast. A dual-luciferase assay was performed to confirm that miR-148a targets the 3'-untranslated region of BCL-2. In this study, we first characterized the downregulation of miR-148a in breast cancer tissues. We then found that restoring expression of miR-148a suppressed the expression of BCL-2 at the level of both mRNA and protein. Upregulation of miR-148a caused a subsequent reduction of proliferation and an increase in apoptosis. In conclusion, we have confirmed the role of miR-148a as a pivotal regulator in breast cancer through its targeting of BCL-2. This evidence strongly suggests that miR-148a could prove to be a novel therapeutic target in breast cancer.

[Research on child neglect situation and influential factors of left-behind children and living-with-parents children aged 6-17 year-old in rural areas of two provinces, western China].

OBJECTIVE: To investigate the situation and the influential factors of child neglect between left-behind children and living-with-parents children aged 6-17 years in the rural areas in western China. METHODS: Students were randomly selected according to the principle of multi-stage stratified cluster sampling and they were from three cities in Shanxi and four districts in Chongqing. Among the 4,131 children, there were 1,874 students in the 6-11 years group and the left-behind children accounted for 50.21% (941/1,874) in this group. There were 2,257 students in the 12-17 years old group and the left-behind children accounted for 53.35% (1,204/2,257) in this group. The questionnaire named "Evaluation on Neglect for Elementary and Secondary School Students Aged 6-17 Years in Rural Areas in China" was used in the field investigation. The students' neglect frequency was described by neglect rate and the factors affecting students' neglect were analyzed by means of binary logistic regression. RESULTS: In the 6-11 years old group, the neglect rates of left-behind children and living-with-parents children were 63.03% (474/752) and 43.87% (347/791), respectively (χ2=58.86, P<0.001). In the 12-17 years old group, the neglect rates of left-behind children and living-with-parents children were 60.64% (627/1 034) and 53.57% (495/924), respectively (χ2=9.96, P<0.001). For factors influencing left-behind children, compared to the factors about boys, younger mother (≤40 years old), presence of parents' income reduction within the last year and nuclear family, the factors about girls, elder mother (41-49 years), absence of parents' income reduction within the last year and three-generation family or single-parent family were associated with lower neglect risk, and OR values were 0.67, 0.68, 0.70, 0.73, and 0.43 (P<0.05); compared to the factors about Han nationality, only child, with separate room at home, and resident children, the factors about other nationalities, non-only child, no separate room at home, and non-resident children were associated with high neglect risk, and OR values were 1.85, 1.34, 1.46, and 1.32 (P<0.05); compared to the lower father's education background (primary school or uneducated), the higher father's education background (junior middle school, senior middle school, technical secondary school, college and above) was associated with lower neglect risk, and OR values were 0.66, 0.50, and 0.25 (P<0.05); compared to good relationship between children and parents as well as good relationship between parents, fair or poor relationship was associated with high neglect risk, and OR values were 1.57-3.79 (P<0.05). For factors influencing non-left-behind children, compared to the factors about younger mother (≤40 years old), changes of patient's work in the last year, presence of parents' income reduction within the last year and nuclear family, the factors about elder mother (41-49 years), no changes of patients' work in the last year, absence of parents' income reduction within the last year and three-generation family or single-parent family were associated with lower neglect risk, and OR values were 0.69, 0.71, 0.75, 0.82, and 0.56 (P<0.05); compared to the factors about Han nationality, only child and younger father (≤40 years old), other nationalities, the factors about non-only child, and elder father (41-49 years) were associated with high neglect risk, and OR values were 1.45, 1.56, and 1.57 (P<0.05); compared to lower father's education background (primary school or uneducated), higher father's education background (junior middle school, senior middle school, technical secondary school, college and above) was associated with lower neglect risk, and OR values were 0.65 and 0.49 (P<0.05); compared to good relationship between children and parents as well as good relationship between parents, fair or poor relationship was associated with high neglect risk, and OR values were 1.56-7.69 (P<0.05). CONCLUSION: The situation of child neglect among left-behind children aged 6-17 years in rural areas of the two provinces in western China was serious, their neglect rates were higher than those of living-with-parents children, and there were many risk factors affecting the neglect rates of the two group children.

[Analysis on the neglected conditions and influence factors of middle school students aged 12 to 17 years old in rural areas of Shaanxi Province and Chongqing City].

OBJECTIVE: 10 learn about the neglected conditions and intuence factors of middle school students aged 12 to 17 years old in rural areas of Shaanxi Province and Chongqing City. METHODS: The scale and evaluation method formulated in "The Normal Value of Evaluation on the Neglect of Middle School Students from 12 to 17 Years Old in Rural China" was adopted. 2257 respondents among which there were 1157 male students and 1,100 female students in the rural areas of Shaanxi Province and Chongqing City were selected according to the principle of multi-stage stratified cluster sampling. The severe degree of neglect was reflected through the indicator of neglect degree. The method of binary Logistic regression analysis was adopted to analyze the influence factors of neglect. Results The total neglect degree of respondents was (51. 80 ± 9. 06). The neglect degree of middle school students in the rural areas of Chongqing was (53. 21 ± 9. 03). The neglect degree of middle school students in the rural areas of Shaanxi was 50. 50 8. 90. The statistical significance was found in the difference between the two groups (U =6. 17, P <0. 01). The neglect degree of male students was (51. 93 ± 8. 67) while the neglect degree of female students was (51. 66 ± 9. 46). The statistical significance was not found in the difference between the two groups of total neglect degree of different sexes (U = 0. 60, P > 0. 05). The statistical significance was noticed in the differences of neglect degrees of middle school students in different grades at all levels (P <0. 05). The neglect degrees of junior three and senior three students were relatively high. Their total neglect degrees were (53. 54 ± 9. 70) and (53. 36 ± 8. 69) respectively. Except social neglect and safety neglect, there was statistical significance in the differences of neglect degrees of students with different family backgrounds at all levels (P <0. 01). The neglect degree of middle school students in a remarried family was the highest. The total neglect degree was (56. 92 ± 8. 83). The factors influencing the neglect of middle school students were shown in the result of Logistic regression analysis, including the educational level of their fathers, whether they had a separate room, family types, whether the working places of their parents changed in one year, whether the incomes of their parents decreased in one year, their relationship with their parents and the relationship between their parents. CONCLUSION: The neglected conditions of middle school students in the rural areas of Shaanxi Province and Chongqing City are relatively severe and the factors influencing the neglect of children include the educational level of their fathers, whether they have a separate room, family types, whether the working places of their parents changed in one year, whether the incomes of their parents decrease in one year, their relationship with their parents and the relationship between their parents.

[The situation of neglect state among elementary and high school students aged 6-17 years in rural areas of two western provinces of China].

OBJECTIVE: To understand the neglect situation of elementary and high school students aged 6-17 years in western rural areas of China. METHODS: Using multi-stage stratified cluster sampling method, 4 131 students were recruited from 26 rural elementary and high schools of 7 districts in Shanxi province and Chongqing from September 2012 to April 2013. The investigation was conducted based on 'The Development of Neglect Evaluation Norms and Influence Factors for Primary and Middle School Students' in rural areas of China. SAS 9.21 software was used for analyzing neglect rate and neglect degree for groups of age, sex and neglect types (including neglect of physical, emotional, medical, educational, safety and social). RESULTS: The total neglect rate and degree were 55.50% (1 943/3 501) and 49.96 ± 9.67; the neglect rates for males and females were 56.78% (1 018/1 793) and 54.16% (925/1 708) (P = 0.119); the neglect degrees were 50.08 ± 9.31 and 49.83 ± 10.02 (P = 0.479), respectively. The girls' medical neglect rate (18.25%, 348/1 907) was significantly higher than that in boys (14.72%, 294/1 997) (P < 0.01); the boys' neglect degrees of physical, educational and social neglect (50.05 ± 10.46, 49.99 ± 10.81, 57.63 ± 14.63) were significantly higher than that in girls (49.34 ± 10.70, 49.07 ± 11.30, 56.37 ± 14.80) (P < 0.05). The total neglect rates of 6-8, 9-11, 12-14 and 15-17 groups were 44.48% (310/697), 60.40% (511/846), 60.89% (601/987) and 53.66% (521/971) (P < 0.01), and the total neglect degrees among these groups were 46.89 ± 8.57, 51.88 ± 9.25, 51.88 ± 9.25 and 51.72 ± 8.89 (P < 0.01), respectively. Except the neglect rates of medical and social neglect, significant differences were found in other three neglect rates and neglect degrees. The rates of social, emotional and safety neglect in 9-11 group were higher than that in other groups (28.39% (264/930), 26.41% (239/905), 20.35% (187/919)). The 12-14 group has the highest educational neglect rate(29.41%, 317/1 078). While the physical and emotional neglect degrees in 12-14 and 15-17 group were higher than that in other groups(12-14 group: 51.59 ± 10.02, 53.43 ± 12.02, 15-17 group: 51.96 ± 9.80, 52.61 ± 11.59). The social, safety, educational and medical neglect degrees were the highest in 6-8, 9-11, 12-14 and 15-17 group (60.91 ± 13.13, 48.29 ± 11.34, 52.43 ± 10.55, 51.15 ± 17.25), respectively. The neglect rates and neglect degrees were significantly higher in minorities(68.88% (374/543) and 52.91 ± 9.14) than those in Han population (53.04% (1 569/2 958), 49.44 ± 9.67)(P < 0.01 in both indexes); and the neglect rates and neglect degrees were significantly higher in children with siblings group (58.20% (1 504/2 584), 50.58 ± 9.54) than those the in one-child group (47.87% (439/917), 48.27 ± 9.80) (P < 0.01 in both indexes); and the neglect rates and neglect degrees were significantly higher in left-hand students (61.65% (1 101/1 786), 51.41 ± 9.51) than those in living-with-parents students(49.10% (842/1 715), 48.56 ± 9.61) (P < 0.01 in both indexes). CONCLUSION: The children neglect situation is serious in western rural areas, close attention from families, schools and the society is in urgent need.

SLC7A11, a potential immunotherapeutic target in lung adenocarcinoma.

SLC7A11 has significant translational value in cancer treatment. However, there are few studies on whether SLC7A11 affects the immune status of lung adenocarcinoma (LUAD). Information on SLC7A11 expression and its impact on prognosis was obtained from the cancer genome atlas and gene expression omnibus databases. The differentially expressed genes (DEGs) were analysed by GO and KEGG. GSEA enrichment analysis was performed in the SLC7A11-high and SLC7A11-low groups. The relationship between SLC7A11 and tumour immunity, immune checkpoints, and immune cell infiltration was studied using R language. We analysed the correlation between SLC7A11 and chemotactic factors (CFs) and chemokine receptors using the TISIDB database. SLC7A11 is overexpressed in many tumours, including LUAD. The 5-year overall survival of patients in the SLC7A11-high group was lower than in the SLC7A11-low group. KEGG analysis found that the DEGs were enriched in ferroptosis signaling pathways. GSEA analysis found that the survival-related signaling pathways were enriched in the SLC7A11-low group. The SLC7A11-low group had higher immune scores and immune checkpoint expression. SLC7A11 was negatively correlated with many immune cells (CD8+ T cells, immature dendritic cells), CFs, chemokine receptors (such as CCL17/19/22/23, CXCL9/10/11/14, CCR4/6, CX3CR1, CXCR3) and MHCs (major histocompatibility complex). SLC7A11 may regulate tumour immunity and could be a potential therapeutic target for LUAD.

A nomogram based on clinical information, conventional ultrasound and radiomics improves prediction of malignant parotid gland lesions.

Although conventional ultrasound (CUS) allows for clear detection of parotid gland lesions (PGLs), it fails to accurately provide benign-malignant differentiation due to overlapping morphological features. Radiomics is capable of processing large-quantity volume of data hidden in CUS image undiscovered by naked eyes. The aim was to explore the potential of CUS-based radiomics score (Rad-score) in distinguishing benign (BPGLs) and malignant PGLs (MPGLs). A consecutive of 281 PGLs (197 in training set and 84 in test set) with definite pathological confirmation was retrospectively enrolled. 1465 radiomics features were extracted from CUS images and Rad-score was constructed by using Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. Different nomogram models, including clinic-radiomics (Clin + Rad-score), CUS-clinic (CUS + Clin) and combined CUS-clinic-radiomics (CUS + Clin + Rad-score), were built using logistic regression. The diagnostic performance of different models were calculated and compared by area under receiver operating curve (AUC) and corresponding sensitivity and specificity. Finally, 26 radiomics features were independent signatures for predicting MPGLs, with MPGLs having higher Rad-scores in both cohorts (both P < 0.05). In the test population, CUS + Clin + Rad-score obtained an excellent diagnostic result, with significantly higher AUC value (AUC = 0.91) when compared to that of CUS + Clin (AUC = 0.84) and Clin + Rad-score (AUC = 0.74), respectively (both P < 0.05). In addition, the sensitivity of this combined model was higher than that of single Rad-score model (100.00% vs. 71.43%, P = 0.031) without compromising the specificity value (82.86% vs. 88.57%, P = 0.334). The calibration curve and decision curve analysis also indicated the clinical effectiveness of the proposed combined nomogram. The combined CUS-clinic-radiomics model may help improve the discrimination of BPGLs from MPGLs.

SWEmean of Quadriceps, a Potential Index of Complication Evaluation to Patients with Chronic Obstructive Pulmonary Disease.

Purpose: To develop a potential quadriceps' index of complication evaluation for patients with chronic obstructive pulmonary disease (COPD) which is simple, convenient, and quantifiable. Patients and Methods: We conducted a prospective study of 59 patients with COPD and 56 healthy controls recruited by the Chengdu First People's Hospital. Grayscale ultrasound (US) of the rectus femoris was performed to measure thickness (RFthick) and cross-sectional area (RFcsa). Shear wave elastography was used to determine the mean elasticity index (SWEmean) of the rectus femoris (SWERFmean), vastus lateralis (SWEVLmean) and vastus medialis (SWEVMmean). Clinical features included dyspnea index score (modified British Medical Research Council (MMRC) score), COPD Assessment Test (CAT), the Five-Repetition Sit-to-Stand Test (5STS) and the Six-Minute Walk Test (6MWT). We compared the differences between US parameters and SWEmean in healthy controls and COPD patients. We also described the correlation between US parameters, SWEmean and clinical features of patients with COPD. Results: The intra-observer repeatability for the performance of using SWE to measure quadriceps stiffness was excellent (intraclass correlation coefficient (ICC)>0.75, p < 0.001). There was a statistically significant difference in the SWEmean of the quadriceps (p < 0.001), but no significant difference in terms of RFthic and RFcsa (p > 0.05) between healthy controls and COPD patients. The SWERFmean was positively correlated with the 6MWT (r = 0.959, p < 0.001), and negatively related to the mMRC (r=-0.825, p < 0.001), CAT (r=-0.993, p < 0.001) and 5STS (r=-0.936, p < 0.001). However, the RFthic, RFcsa, SWEVLmean and SWEVMmean were not correlated with clinical features (p > 0.05). Conclusion: As a supplement to US, SWE reflects changes of stiffness in the quadriceps of COPD patients, and can expanding the dimension of US for assessing the quadriceps. Furthermore, SWEmean was associated with clinical features, and represents a potential index with which to reflect the clinical features of COPD patients.

Integrative Analysis of the Metabolome and Transcriptome Provides Insights into the Mechanisms of Flavonoid Biosynthesis in Quinoa Seeds at Different Developmental Stages.

Quinoa (Chenopodium quinoa Willd.) is a crop with high nutritional and health benefits. Quinoa seeds are rich in flavonoid compounds; however, the mechanisms behind quinoa flavonoid biosynthesis remain unclear. We independently selected the high-generation quinoa strain 'Dianli-3260', and used its seeds at the filling, milk ripening, wax ripening, and mature stages for extensive targeted metabolome analysis combined with joint transcriptome analysis. The results showed that the molecular mechanism of flavonoid biosynthesis in quinoa seeds was mainly concentrated in two pathways: "flavonoid biosynthesis pathway" and "flavone and flavonol biosynthesis pathway". Totally, 154 flavonoid-related metabolites, mainly flavones and flavonols, were detected in the four development stages. Moreover, 39,738 genes were annotated with KEGG functions, and most structural genes of flavonoid biosynthesis were differentially expressed during grain development. We analyzed the differential flavonoid metabolites and transcriptome changes between the four development stages of quinoa seeds and found that 11 differential flavonoid metabolites and 22 differential genes were the key factors for the difference in flavonoid biosynthesis. This study provides important information on the mechanisms underlying quinoa flavonoid biosynthesis, the screening of potential quinoa flavonoid biosynthesis regulation target genes, and the development of quinoa products.

Mechanosensitive channel Piezo1 induces cell apoptosis in pancreatic cancer by ultrasound with microbubbles.

Ultrasound (US), as a safe and non-invasive tool, has drawn researchers' attention to treat pancreatic ductal adenocarcinoma (PDAC). Piezo1, a mechanosensitive channel, can be activated by various mechanical stimuli. In this study, we tested the expression of Piezo1 in PDAC cell lines and tissues, and cell apoptosis in vitro and in vivo with siRNA, a lentivirus system, and a subcutaneous xenograft tumor-bearing model under the condition of US with microbubbles (MBs). We found that Piezo1 was highly expressed in PDAC cells; it was activated by US with MBs and was closely related to the apoptosis of PDAC cell lines and tumors. This study highlighted the idea of utilizing the high expression of Piezo1 in PDAC and US with MBs to provide a non-invasive strategy for the treatment of PDAC from the aspect of mechanotransduction.

Ultrasound-Based Radiomics Can Classify the Etiology of Cervical Lymphadenopathy: A Multi-Center Retrospective Study.

Medical diagnostic imaging is essential for the differential diagnosis of cervical lymphadenopathy. Here we develop an ultrasound radiomics method for accurately differentiating cervical lymph node tuberculosis (LNTB), cervical lymphoma, reactive lymph node hyperplasia, and metastatic lymph nodes especially in the multi-operator, cross-machine, multicenter context. The inter-observer and intra-observer consistency of radiomics parameters from the region of interest were 0.8245 and 0.9228, respectively. The radiomics model showed good and repeatable diagnostic performance for multiple classification diagnosis of cervical lymphadenopathy, especially in LNTB (area under the curve, AUC: 0.673, 0.662, and 0.626) and cervical lymphoma (AUC: 0.623, 0.644, and 0.602) in the whole set, training set, and test set, respectively. However, the diagnostic performance of lymphadenopathy among skilled radiologists was varied (Kappa coefficient: 0.108, *p < 0.001). The diagnostic performance of radiomics is comparable and more reproducible compared with those of skilled radiologists. Our study offers a more comprehensive method for differentiating LNTB, cervical lymphoma, reactive lymph node hyperplasia, and metastatic LN.

Reproducibility of ultrasound-guided attenuation parameter (UGAP) to the noninvasive evaluation of hepatic steatosis.

The aim of this study was to identify the applicability of an ultrasound-guided attenuation parameter (UGAP) for the noninvasive assessment of hepatic steatosis in clinical practice and to compare its correlation with B-mode ultrasound (US). From May to July 2021, 63 subjects with different body mass index (BMI) grades were included in the prospective study. All of them performed UGAP measurements, under different breathing manipulations, positions, diet statuses, and operators. After that, the UGAP values were compared with the visual grades of hepatic steatosis on B-mode US using a 4-point scale method. The intraclass correlation (ICC) of the UGAP values between the two radiologists was 0.862 (p < 0.001), and the ICCs of the UGAP values on the same day and different days by radiologist A were 0.899 (p < 0.001) and 0.910 (p < 0.001), respectively. There were no significant differences in UGAP values under different breathing manipulations (p > 0.05), positions (p > 0.05), or diet statuses (p = 0.300). The UGAP values in the fasting (supine position, segment V, 1) condition among the lean (BMI < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 28 kg/m2) and obese groups (BMI ≥ 28 kg/m2) were 0.60 ± 0.12, 0.66 ± 0.14, and 0.71 ± 0.11 dB/cm/MHz, respectively, with a significant difference (p = 0.006). The correlation coefficients (Rho) between the UGAP values and the visual grades of hepatic steatosis by the two reviewers were 0.845 (p < 0.001) and 0.850 (p < 0.001), corresponding to a strong relationship. Steatosis grades by reviewer 1 (p = 0.036) and reviewer 2 (p = 0.003) were significant factors determining the UGAP values according to the multivariate linear regression analysis. UGAP demonstrated excellent intraobserver and interobserver reproducibility in the assessment of hepatic steatosis. UGAP may be a promising tool in clinical practice to predict hepatic steatosis.

Metal-Organic Framework (MOF)-Based Ultrasound-Responsive Dual-Sonosensitizer Nanoplatform for Hypoxic Cancer Therapy.

Sonodynamic therapy (SDT), which uses reactive oxygen species to target tumors, has shown promise in the management of unresectable cancers. However, the hypoxic tumor environment limits SDT efficiency, making complete tumor destruction challenging. Here, a dual-sonosensitizer nanoplatform is developed by loading an alkyl radical generator (2,2-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH) onto a zirconium metal-organic framework (Zr-MOF). The Zr-MOF@AIPH nanoparticles (NPs) can produce singlet oxygen, which can kill tumor cells under normoxic conditions, as well as alkyl radicals, which can kill tumor cells under both normoxic and hypoxic conditions. The combination of these free radicals further enhances SDT efficiency. Meanwhile, the nitrogen generated owing to AIPH decomposition can reduce the cavitation threshold and enhance the acoustic cavitation effect, thereby promoting NP penetration at the tumor site. Moreover, Zr-MOF@AIPH NPs exhibit good photoacoustic, fluorescence, and ultrasound imaging abilities due to their porphyrin-based structure and the nitrogen generated, which can remotely control NP delivery and determine the optimal therapeutic time window, ensuring the maximization of SDT efficiency. In vitro and in vivo examinations prove the superior antitumor efficacy, excellent biocompatibility, and favorable imaging ability of Zr-MOF@AIPH. This study spearheads the charge toward improving SDT efficacy in hypoxic environments via a combination of complementary sonosensitizers.

Erythrocyte-Camouflaged Mesoporous Titanium Dioxide Nanoplatform for an Ultrasound-Mediated Sequential Therapies of Breast Cancer.

BACKGROUND: The hypoxic microenvironment promotes tumor resistance to most treatments, especially highly oxygen-dependent sonodynamic therapy (SDT). METHOD AND RESULTS: In view of the aggravation of hypoxia by oxygen consumption during SDT, a biomimetic drug delivery system was tailored to integrate SDT with hypoxia-specific chemotherapy. In this system, mesoporous titanium dioxide nanoparticles (mTNPs) were developed to deliver the hypoxia-activated prodrug AQ4N with high loading efficiency. Subsequently, a red blood cell (RBC) membrane was coated onto the surface of mTNP@AQ4N. RBC-mTNPs@AQ4N inherited the immune escape ability from RBC membranes, thus efficiently reducing the immunological clearance and improving the work concentration. Upon activation by ultrasound (US), mTNPs as sonosensitizers generate reactive oxide species (ROS), which not only induce apoptosis and necrosis but also disrupt RBC membranes to achieve the US-mediated on-demand release of AQ4N. The released AQ4N was activated by hypoxia to convert into toxic products, which effectively supplemented the inefficiency of SDT in hypoxic tissues. Importantly, SDT-aggravated hypoxia further potentiated this hypoxia-specific chemotherapy of AQ4N. CONCLUSION: Based on the sequential strategy, RBC-mTNPs@AQ4N exhibited an excellent synergistic therapeutic effect, thus potentially advancing the development of SDT in cancer treatments.

Non-invasive prediction of lymph node status for patients with early-stage invasive breast cancer based on a morphological feature from ultrasound images.

BACKGROUND: This study aimed to estimate the value of a morphological feature on ultrasound (US) for preoperative diagnosis of axillary lymph node (ALN) status in patients with early-stage invasive breast cancer (ESIBC). METHODS: In this retrospective work, a total of 239 ESIBC patients, were recruited, and their preoperative US images and postoperative pathology results were collected. The relationship between US images based on morphological features and ALN metastasis was investigated. The tumor circularity and US-reported ALN status were developed as a nomogram to predict the ALN status. RESULTS: Among the 239 participants, 82 (34.31%) had ALN metastasis, and 157 (65.69%) did not. There was a statistically significant difference in tumors between participants diagnosed with and without ALN metastasis. The median value was 0.47 vs. 0.62 (P<0.001) in the training group, respectively, and the value was 0.50 vs. 0.60 (P<0.001) in the validation group, respectively. The clinical model nomogram was shown to have high efficiency in predicting ALN status among our research population. The area under the curve (AUC) was 0.89 in the training group and 0.90 in the validation group and the accuracy was 85.79% and 81.63%, respectively. CONCLUSIONS: The clinical model nomogram based on tumor circularity and US-reported ALN status is a non-invasive approach for ALN metastasis prediction in ESIBC patients with high efficacy.