AKT1 Promotes Tumorigenesis and Metastasis by Directly Phosphorylating Hexokinases.

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.

Photoactivated Gas-Generating Nanocontrast Agents for Long-Term Ultrasonic Imaging-Guided Combined Therapy of Tumors.

To date, long-term and continuous ultrasonic imaging for guiding the puncture biopsy remains a challenge. In order to address this issue, a multimodality imaging and therapeutic method was developed in the present study to facilitate long-term ultrasonic and fluorescence imaging-guided precision diagnosis and combined therapy of tumors. In this regard, certain types of photoactivated gas-generating nanocontrast agents (PGNAs), capable of exhibiting both ultrasonic and fluorescence imaging ability along with photothermal and sonodynamic function, were designed and fabricated. The advantages of these fabricated PGNAs were then utilized against tumors in vivo, and high therapeutic efficacy was achieved through long-term ultrasonic imaging-guided treatment. In particular, the as-prepared multifunctional PGNAs were applied successfully for the fluorescence-based determination of patient tumor samples collected through puncture biopsy in clinics, and superior performance was observed compared to the clinically used SonoVue contrast agents that are incapable of specifically distinguishing the tumor in ex vivo tissues.

Value of Contrast-Enhanced Ultrasound Combined with Immune-Inflammatory Markers in Predicting Axillary Lymph Node Metastasis of Breast Cancer.

RATIONALE AND OBJECTIVES: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) combined with immune-inflammatory markers in predicting axillary lymph node metastasis (ALNM) in breast cancer patients. METHODS: From January 2020 to June 2023, the clinicopathological data and ultrasound features of 401 breast cancer patients who underwent biopsy or surgery were recorded. Patients were randomly divided into a training set (321 patients) and a validation set (80 patients). The risk factors for ALNM were determined using univariate, least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis, and prediction models were constructed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess their diagnostic performance. RESULTS: Logistic regression analysis demonstrated that systemic immunoinflammatory index (SII), CA125, Ki67, pathological type, lesion size, enhancement pattern and Breast Imaging Reporting and Data System (BI-RADS) category were significant risk factors for ALNM. Three different models were constructed, and the combined model yielded an AUC of 0.903, which was superior to the clinical model (AUC=0.790) and ultrasound model (AUC=0.781). A nomogram was constructed based on the combined model, calibration curves and DCA demonstrated its satisfactory performance in predicting ALNM. CONCLUSION: The nomogram combining ultrasound features and immune-inflammatory markers could serve as a valuable instrument for predicting ALNM in breast cancer patients. DATA AVAILABILITY STATEMENT: The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.

Defect-Rich Metastable MoS2 Promotes Macrophage Reprogramming in Breast Cancer: A Clinical Perspective.

Tumor-associated macrophages (TAMs) play a crucial function in solid tumor antigen clearance and immune suppression. Notably, 2D transitional metal dichalcogenides (i.e., molybdenum disulfide (MoS2) nanozymes) with enzyme-like activity are demonstrated in animal models for cancer immunotherapy. However, in situ engineering of TAMs polarization through sufficient accumulation of free radical reactive oxygen species for immunotherapy in clinical samples remains a significant challenge. In this study, defect-rich metastable MoS2 nanozymes, i.e., 1T2H-MoS2, are designed via reduction and phase transformation in molten sodium as a guided treatment for human breast cancer. The as-prepared 1T2H-MoS2 exhibited enhanced peroxidase-like activity (≈12-fold enhancement) than that of commercial MoS2, which is attributed to the charge redistribution and electronic state induced by the abundance of S vacancies. The 1T2H-MoS2 nanozyme can function as an extracellular hydroxyl radical generator, efficiently repolarizing TAMs into the M1-like phenotype and directly killing cancer cells. Moreover, the clinical feasibility of 1T2H-MoS2 is demonstrated via ex vivo therapeutic responses in human breast cancer samples. The apoptosis rate of cancer cells is 3.4 times greater than that of cells treated with chemotherapeutic drugs (i.e., doxorubicin).

Exosome-derived circUPF2 enhances resistance to targeted therapy by redeploying ferroptosis sensitivity in hepatocellular carcinoma.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) can be treated with sorafenib, which is the primary choice for targeted therapy. Nevertheless, the effectiveness of sorafenib is greatly restricted due to resistance. Research has shown that exosomes and circular RNAs play a vital role in the cancer's malignant advancement. However, the significance of exosomal circular RNAs in the development of resistance to sorafenib in HCC remains uncertain. METHODS: Ultracentrifugation was utilized to isolate exosomes (Exo-SR) from the sorafenib-resistant HCC cells' culture medium. Transcriptome sequencing and differential expression gene analysis were used to identify the targets of Exo-SR action in HCC cells. To identify the targets of Exo-SR action in HCC cells, transcriptome sequencing and analysis of differential expression genes were employed. To evaluate the impact of exosomal circUPF2 on resistance to sorafenib in HCC, experiments involving gain-of-function and loss-of-function were conducted. RNA pull-down assays and mass spectrometry analysis were performed to identify the RNA-binding proteins interacting with circUPF2. RNA immunoprecipitation (RIP), RNA pull-down, electrophoretic mobility shift assay (EMSA), immunofluorescence (IF) -fluorescence in situ hybridization (FISH), and rescue assays were used to validate the interactions among circUPF2, IGF2BP2 and SLC7A11. Finally, a tumor xenograft assay was used to examine the biological functions and underlying mechanisms of Exo-SR and circUPF2 in vivo. RESULTS: A novel exosomal circRNA, circUPF2, was identified and revealed to be significantly enriched in Exo-SR. Exosomes with enriched circUPF2 enhanced sorafenib resistance by promoting SLC7A11 expression and suppressing ferroptosis in HCC cells. Mechanistically, circUPF2 acts as a framework to enhance the creation of the circUPF2-IGF2BP2-SLC7A11 ternary complex contributing to the stabilization of SLC7A11 mRNA. Consequently, exosomal circUPF2 promotes SLC7A11 expression and enhances the function of system Xc- in HCC cells, leading to decreased sensitivity to ferroptosis and resistance to sorafenib. CONCLUSIONS: The resistance to sorafenib in HCC is facilitated by the exosomal circUPF2, which promotes the formation of the circUPF2-IGF2BP2-SLC7A11 ternary complex and increases the stability of SLC7A11 mRNA. Focusing on exosomal circUPF2 could potentially be an innovative approach for HCC treatment.

Expression and clinical significance of ECHS1 in gastric cancer.

Background: Gastric cancer (GC), as one of the most common malignant tumors and the 3rd primary cause of death by cancer globally, poses a great threat to public health. Despite many advancements have been achieved in current treatment avenues for GC, the 5-year survival rates of GC patients remain substandard. Short-chain enoyl-CoA hydratase (ECHS1) exerts pro- or anti-cancer activities in different cancer backgrounds. However, its clinical significance and biological role in GC remain vague and need further investigation. Methods: The expression of ECHS1 in GC tumors and adjacent normal tissues was examined using the GEPIA platform and clinical samples. The effects of ECHS1 on GC cell proliferation and migration were evaluated using colony formation and transwell migration assays. Results: ECHS1 was upregulated in GC tumor tissues in both mRNA and protein levels and increased ECHS1 was markedly linked with tumor location, depth of tumor invasion, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stage of GC patients. High ECHS1 expression was also linked with a shorter overal survival (OS), first progression (FP) and post progression survival (PPS). Further subgroup analysis showed that OS was significantly shorter in GC patients with high ECHS1 expression compared to those with low ECHS1 expression belonging to tumors with T3 stage, N2 stage or in instestinal Lauren subgroup. In addition, cytological experiments showed that there was higher ECHS1 expression in GC cell lines compared to the normal gastric epithelium (GES-1) cells, and ECHS1 can promote GC cell proliferation and migration in vitro. Conclusion: ECHS1 plays an oncogenic role in GC and might be a promising therapeutic target for GC.

Evaluation of standard breast ultrasonography by adding two-dimensional and three-dimensional shear wave elastography: a prospective, multicenter trial.

OBJECTIVE: To reduce the number of biopsies performed on benign breast lesions categorized as BI-RADS 4-5, we investigated the diagnostic performance of combined two-dimensional and three-dimensional shear wave elastography (2D + 3D SWE) with standard breast ultrasonography (US) for the BI-RADS assessment of breast lesions. METHODS: A total of 897 breast lesions, categorized as BI-RADS 3-5, were subjected to standard breast US and supplemented by 2D SWE only and 2D + 3D SWE analysis. Based on the malignancy rate of less than 2% for BI-RADS 3, lesions assessed by standard breast US were reclassified with SWE assessment. RESULTS: After standard breast US evaluation, 268 (46.1%) participants underwent benign biopsies in BI-RADS 4-5 lesions. By using separated cutoffs for upstaging BI-RADS 3 at 120 kPa and downstaging BI-RADS 4a at 90 kPa in 2D + 3D SWE reclassification, 123 (21.2%) participants underwent benign biopsy, resulting in a 54.1% reduction (123 versus 268). CONCLUSION: Combining 2D + 3D SWE with standard breast US for reclassification of BI-RADS lesions may achieve a reduction in benign biopsies in BI-RADS 4-5 lesions without sacrificing sensitivity unacceptably. CLINICAL RELEVANCE STATEMENT: Combining 2D + 3D SWE with US effectively reduces benign biopsies in breast lesions with categories 4-5, potentially improving diagnostic accuracy of BI-RADS assessment for patients with breast lesions. TRIAL REGISTRATION: ChiCTR1900026556 KEY POINTS: • Reduce benign biopsy is necessary in breast lesions with BI-RADS 4-5 category. • A reduction of 54.1% on benign biopsies in BI-RADS 4-5 lesions was achieved using 2D + 3D SWE reclassification. • Adding 2D + 3D SWE to standard breast US improved the diagnostic performance of BI-RADS assessment on breast lesions: specificity increased from 54 to 79%, and PPV increased from 54 to 71%, with slight loss in sensitivity (97.2% versus 98.7%) and NPV (98.1% versus 98.7%).

Ultrasound-based radiomics combined with immune status to predict sentinel lymph node metastasis in primary breast cancer.

In the past few years, the axillary lymph node dissection technique has been steadily replaced by sentinel lymph node biopsy for treating and diagnosing breast cancer, thereby minimizing the complications and sequelae of the patients. Nevertheless, sentinel lymph node biopsy still presents limitations, such as high operation requirements, prolonged surgical duration, and adverse reactions to tracer agents. This study developed a novel non-invasive method to predict sentinel lymph node metastasis in breast cancer by analyzing the ultrasound imaging characteristics of the primary tumor, combined with the analysis of peripheral blood T-cell subsets that reflect the immune status of the body. The radiomic features analyzed in this study were extracted from preoperative ultrasound images of 199 solitary breast cancer patients, who were undergoing surgery and were pathologically diagnosed at the Yancheng First People's Hospital. All cases were randomly categorized in a 4:1 ratio to the training (n = 159) and validation (n = 40) cohorts. The extracted radiomics features were subjected to dimensional reduction with the help of the least absolute shrinkage and selection operator technique, resulting in the inclusion of 19 radiomics features. Four classifiers, including naïve Bayesian, logistic regression, classification decision tree, and support vector machine, were utilized to model the radiomics features, conventional ultrasound features, and peripheral blood T cell subsets in the training dataset, and validated using the validation dataset. The best-performing model was chosen for constructing the combined model. The radiomics model constructed using the logistic regression showed the best performance, with the training and validation cohorts showing areas under the curve (AUCs) of 0.77 and 0.68, respectively. The conventional ultrasound and peripheral blood T cell models constructed using the classification decision tree showed the best performance, wherein the training cohort presented AUCs of 0.71 and 0.81, respectively, while the validation cohort presented AUCs of 0.68 and 0.69, respectively. The combined model constructed by logistic regression showed AUCs of 0.91 and 0.79 in the training and validation datasets, respectively. The resulting combined model can be considered a simple, non-invasive method with strong reproducibility and clinical significance. Thus, it can be utilized to predict sentinel lymph node metastasis in breast cancer. Furthermore, the combined model can be effectively used to guide clinical decisions related to the selection of surgical procedures in breast surgery.

circFAM134B is a key factor regulating reticulophagy-mediated ferroptosis in hepatocellular carcinoma.

Ferroptosis is an important mode of regulated cell death (RCD). Its inhibition is closely related to therapeutic resistance and poor prognosis in hepatocellular carcinoma (HCC). Previous reports have demonstrated ferroptosis as a biological process highly dependent on selective autophagy, such as ferritinophagy, lipophagy, and clockophagy. Our study also revealed a role for ER-phagy-mediated ferroptosis in HCC cells treated with multi-targeted tyrosine kinase inhibitors (TKIs). In the current study, we found that the homologous circular RNA (circRNA) of the family with sequence similarity 134, member B (FAM134B), hsa_circ_0128505 (was abbreviated as circFAM134B in the present study), was identified to specifically target ER-phagy to promote lenvatinib (LV)-induced ferroptosis using reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), and western blot (WB) assays in HCC cells. RNA pull-down and mass spectrometry analyses suggested that circFAM134B and FAM134B mRNA were enriched with several common interacting proteins. Among them, poly (A) binding protein cytoplasmic 4 (PABPC4) was identified as the most enriched binding partner. It was proven to be a novel antagonist against the nonsense-mediated mRNA decay (NMD) mechanism. We then applied RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter, and NMD reporter gene assays to further explore the exact role and underlying mechanism of circFAM134B-PABPC4-FAM134B axis in HCC cells. circFAM134B was confirmed as a sponge that competitively interacted with PABPC4, thereby influencing FAM134B mRNA nonsense decay. Our results provide novel evidences and strategies for the comprehensive treatment of HCC.

Exosomal circTGFBR2 promotes hepatocellular carcinoma progression via enhancing ATG5 mediated protective autophagy.

Exosomes contribute substantially to the communication between tumor cells and normal cells. Benefiting from the stable structure, circular RNAs (circRNAs) are believed to serve an important function in exosome-mediated intercellular communication. Here, we focused on circRNAs enriched in starvation-stressed hepatocytic exosomes and further investigated their function and mechanism in hepatocellular carcinoma (HCC) progression. Differentially expressed circRNAs in exosomes were identified by RNA sequencing, and circTGFBR2 was identified and chosen for further study. The molecular mechanism of circTGFBR2 in HCC was demonstrated by RNA pulldown, RIP, dual-luciferase reporter assays, rescue experiments and tumor xenograft assay both in vitro and vivo. We confirmed exosomes with enriched circTGFBR2 led to an upregulated resistance of HCC cells to starvation stress. Mechanistically, circTGFBR2 delivered into HCC cells via exosomes serves as a competing endogenous RNA by binding miR-205-5p to facilitate ATG5 expression and enhance autophagy in HCC cells, resulting in resistance to starvation. Thus, we revealed that circTGFBR2 is a novel tumor promoter circRNA in hepatocytic exosomes and promotes HCC progression by enhancing ATG5-mediated protective autophagy via the circTGFBR2/miR-205-5p/ATG5 axis, which may be a potential therapeutic target for HCC.

Diagnosing sentinel lymph node metastasis of T1/T2 breast cancer with conventional ultrasound combined with double contrast-enhanced ultrasound: a preliminary study.

Background: In patients with T1/T2 breast cancer (BC), sentinel lymph node (SLN) status is essential for prognosis and treatment. This study investigated the value of conventional ultrasound combined with double contrast-enhanced ultrasound in diagnosing the metastasis of SLNs in patients with T1/T2 BC. Methods: This study employed a prospective design (this diagnostic study was not registered on a clinical trial platform), and the participants formed a convenience series. Based on the inclusion and exclusion criteria, 163 patients with BC who received treatment in the First Affiliated Hospital of Soochow University from July 2017 to December 2021 were included in this study. A total of 165 SLNs from 163 patients with T1/T2 BC were analyzed. All patients underwent percutaneous contrast-enhanced ultrasound (PCEUS) to trace SLNs before the operation. Subsequently, all patients underwent conventional ultrasound and intravenous contrast-enhanced ultrasound (ICEUS) examinations to observe the SLNs. The results of the conventional ultrasound, ICEUS, and PCEUS of the SLNs were analyzed. The associations between the risk of SLN metastasis and imaging features were evaluated via a nomogram based on the pathological results. Results: Overall, 54 metastatic SLNs and 111 nonmetastatic SLNs were evaluated. Metastatic SLNs displayed a greater cortical thickness, area ratio, eccentric fatty hilum, and hybrid blood flow on conventional ultrasound compared with nonmetastatic SLNs (P<0.001). According to PCEUS, 75.93% of metastatic SLNs showed heterogeneous enhancement (type II and III), and 73.88% of nonmetastatic SLNs showed homogeneous enhancement (type I; P<0.001). According to ICEUS, heterogeneous enhancement (type B/C, 20.37% vs. 11.71%) and overall enhancement (55.56% vs. 23.42%) were more common in metastatic SLNs than in nonmetastatic SLNs (P<0.001). Logistic regression analysis showed that the cortical thickness and enhancement type of PCEUS were independent predictors of SLN metastasis. Moreover, a nomogram combining these factors showed a high diagnostic ability for SLN metastasis (unadjusted concordance index 0.860, 95% CI: 0.730-0.990; bootstrap-corrected concordance index 0.853). Conclusions: The nomogram of cortical thickness and enhancement type of PCEUS could effectively diagnose SLN metastasis in patients with T1/T2 BC.

Prediction of Renal Function 1 Year After Transplantation Using Machine Learning Methods Based on Ultrasound Radiomics Combined With Clinical and Imaging Features.

Kidney transplantation is the most effective treatment for advanced chronic kidney disease (CKD). If the prognosis of transplantation can be predicted early after transplantation, it might improve the long-term survival of patients with transplanted kidneys. Currently, studies on the assessment and prediction of renal function by radiomics are limited. Therefore, the present study aimed to explore the value of ultrasound (US)-based imaging and radiomics features, combined with clinical features to develop and validate the models for predicting transplanted kidney function after 1 year (TKF-1Y) using different machine learning algorithms. A total of 189 patients were included and classified into the abnormal TKF-1Y group, and the normal TKF-1Y group based on their estimated glomerular filtration rate (eGFR) levels 1 year after transplantation. The radiomics features were derived from the US images of each case. Three machine learning methods were employed to establish different models for predicting TKF-1Y using selected clinical and US imaging as well as radiomics features from the training set. Two US imaging, four clinical, and six radiomics features were selected. Then, the clinical (including clinical and US image features), radiomics, and combined models were developed. The area under the curves (AUCs) of the models was 0.62 to 0.82 within the test set. Combined models showed statistically higher AUCs than the radiomics models (all p-values <.05). The prediction performance of different models was not significantly affected by the different machine learning algorithms (all p-values >.05). In conclusion, US imaging features combined with clinical features could predict TKF-1Y and yield an incremental value over radiomics features. A model integrating all available features may further improve the predictive efficacy. Different machine learning algorithms may not have a significant impact on the predictive performance of the model.

Fluorescence, ultrasonic and photoacoustic imaging for analysis and diagnosis of diseases.

Biomedical imaging technology, which allows us to peer deeply within living subjects and visually explore the delivery and distribution of agents in living things, is producing tremendous opportunities for the early diagnosis and precise therapy of diseases. In this feature article, based on reviewing the latest representative examples of progress together with our recent efforts in the bioimaging field, we intend to introduce three typical kinds of non-invasive imaging technologies, i.e., fluorescence, ultrasonic and photoacoustic imaging, in which optical and/or acoustic signals are employed for analyzing various diseases. In particular, fluorescence imaging possesses a series of outstanding advantages, such as high temporal resolution, as well as rapid and sensitive feedback. Hence, in the first section, we will introduce the latest studies on developing novel fluorescence imaging methods for imaging bacterial infections, cancer and lymph node metastasis in a long-term and real-time manner. However, the issues of imaging penetration depth induced by photon scattering and light attenuation of biological tissue limit their widespread in vivo imaging applications. Taking advantage of the excellect penetration depth of acoustic signals, ultrasonic imaging has been widely applied for determining the location, size and shape of organs, identifying normal and abnormal tissues, as well as confirming the edges of lesions in hospitals. Thus, in the second section, we will briefly summarize recent advances in ultrasonic imaging techniques for diagnosing diseases in deep tissues. Nevertheless, the absence of lesion targeting and dependency on a professional technician may lead to the possibility of false-positive diagnosis. By combining the merits of both optical and acoustic signals, newly-developed photoacoustic imaging, simultaneously featuring higher temporal and spatial resolution with good sensitivity, as well as deeper penetration depth, is discussed in the third secretion. In the final part, we further discuss the major challenges and prospects for developing imaging technology for accurate disease diagnosis. We believe that these non-invasive imaging technologies will introduce a new perspective for the precise diagnosis of various diseases in the future.

Diagnostic value of radiomics model based on gray-scale and contrast-enhanced ultrasound for inflammatory mass stage periductal mastitis/duct ectasia.

Objective: The present study aimed to investigate the clinical application value of the radiomics model based on gray-scale ultrasound (GSUS) and contrast-enhanced ultrasound (CEUS) images in the differentiation of inflammatory mass stage periductal mastitis/duct ectasia (IMSPDM/DE) and invasive ductal carcinoma (IDC). Methods: In this retrospective study, 254 patients (IMSPDM/DE: 129; IDC:125) were enrolled between January 2018 and December 2020 as a training cohort to develop the classification models. The radiomics features were extracted from the GSUS and CEUS images. The least absolute shrinkage and selection operator (LASSO) regression model was employed to select the corresponding features. Based on these selected features, logistic regression analysis was used to aid the construction of these three radiomics signatures (GSUS, CEUS and GSCEUS radiomics signature). In addition, 80 patients (IMSPDM/DE:40; IDC:40) were recruited between January 2021 and November 2021 and were used as the validation cohort. The best radiomics signature was selected. Based on the clinical parameters and the radiomics signature, a classification model was built. Finally, the classification model was assessed using nomogram and decision curve analyses. Results: Three radiomics signatures were able to differentiate IMSPDM/DE from IDC. The GSCEUS radiomics signature outperformed the other two radiomics signatures and the AUC, sensitivity, specificity, and accuracy were estimated to be 0.876, 0.756, 0.804, and 0.798 in the training cohort and 0.796, 0.675, 0.838 and 0.763 in the validation cohort, respectively. The lower patient age (p<0.001), higher neutrophil count (p<0.001), lack of pausimenia (p=0.023) and GSCEUS radiomics features (p<0.001) were independent risk factors of IMSPDM/DE. The classification model that included the clinical factors and the GSCEUS radiomics signature outperformed the GSCEUS radiomics signature alone (the AUC values of the training and validation cohorts were 0.962 and 0.891, respectively). The nomogram was applied to the validation cohort, reaching optimal discrimination, with an AUC value of 0.891, a sensitivity of 0.888, and a specificity of 0.750. Conclusions: The present study combined the clinical parameters with the GSCEUS radiomics signature and developed a nomogram. This GSCEUS radiomics-based classification model could be used to differentiate IMSPDM/DE from IDC in a non-invasive manner.

Value of conventional ultrasound and shear wave elastography in assessing disease activity and prognosis in female patients with Sjögren's syndrome.

OBJECTIVES: This study aimed to assess the diagnostic value of labial salivary gland changes in female patients with Sjögren's syndrome (SS) having different European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and serological markers using conventional ultrasound and shear wave elastography (SWE). METHODS: A total of 82 female inpatients diagnosed with SS were retrospectively examined at the First Affiliated Hospital of Soochow University from July 2020 to December 2021. The patients were divided into two groups based on the ESSDAI score: remission group (ESSDAI <5) and active group (ESSDAI ≥5). The prognosis of patients was assessed using serological markers. The ultrasound examination of bilateral labial glands was performed in all patients to analyse the quantity and area of the largest single labial gland per unit detection range (Smax). The SWE of labial glands was performed in different groups. RESULTS: The Smax and quantity of labial glands on both sides were correlated with patient age in 82 female patients with SS. Emin, Emean and Emax of the remission group based on ESSDAI were significantly lower than the active group (p<0.001), and the areas under the receiver operating characteristic (ROC) curve for these three in diagnosing were 0.720, 0.728 and 0.734, respectively. The differences in Emean, Emin and Emax values of labial glands between the two groups of immunoglobulin G (IgG) <16g/L and IgG ≥16g/L were statistically significant (p<0.05), and the area under the ROC curve (AUC) for the three values were 0.825, 0.830, and 0.815, respectively. There were statistically significant differences (p<0.05) in Emin, Emean, and Emax of labial glands between the hypocomplementaemic and non-hypocomplementaemic groups, and the AUC for the three values were 0.840, 0.843, and 0.819, respectively. CONCLUSIONS: Conventional ultrasound and SWE of the labial gland can reflect the disease activity and prognosis of patients with SS, and more conveniently assess the progression in the patients and provide imaging evidence.

Development of an ultrasound-based radiomics nomogram to preoperatively predict Ki-67 expression level in patients with breast cancer.

Objective: To develop and validate a radiomics nomogram that could incorporate clinicopathological characteristics and ultrasound (US)-based radiomics signature to non-invasively predict Ki-67 expression level in patients with breast cancer (BC) preoperatively. Methods: A total of 328 breast lesions from 324 patients with BC who were pathologically confirmed in our hospital from June 2019 to October 2020 were included, and they were divided into high Ki-67 expression level group and low Ki-67 expression level group. Routine US and shear wave elastography (SWE) were performed for each lesion, and the ipsilateral axillary lymph nodes (ALNs) were scanned for abnormal changes. The datasets were randomly divided into training and validation cohorts with a ratio of 7:3. Correlation analysis and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomics features obtained from gray-scale US images of BC patients, and each radiomics score (Rad-score) was calculated. Afterwards, multivariate logistic regression analysis was used to establish a radiomics nomogram based on the radiomics signature and clinicopathological characteristics. The prediction performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC), the calibration curve, and decision curve analysis (DCA) using the results of immunohistochemistry as the gold standard. Results: The radiomics signature, consisted of eight selected radiomics features, achieved a nearly moderate prediction efficacy with AUC of 0.821 (95% CI:0.764-0.880) and 0.713 (95% CI:0.612-0.814) in the training and validation cohorts, respectively. The radiomics nomogram, incorporating maximum diameter of lesions, stiff rim sign, US-reported ALN status, and radiomics signature showed a promising performance for prediction of Ki-67 expression level, with AUC of 0.904 (95% CI:0.860-0.948) and 0.890 (95% CI:0.817-0.964) in the training and validation cohorts, respectively. The calibration curve and DCA indicated promising consistency and clinical applicability. Conclusion: The proposed US-based radiomics nomogram could be used to non-invasively predict Ki-67 expression level in BC patients preoperatively, and to assist clinicians in making reliable clinical decisions.

Matrix Regeneration Ability In Situ Induced by a Silk Fibroin Small-Caliber Artificial Blood Vessel In Vivo.

The success of a small-caliber artificial vascular graft in the host in order to obtain functional tissue regeneration and remodeling remains a great challenge in clinical application. In our previous work, a silk-based, small-caliber tubular scaffold (SFTS) showed excellent mechanical properties, long-term patency and rapid endothelialization capabilities. On this basis, the aim of the present study was to evaluate the vascular reconstruction process after implantation to replace the common carotid artery in rabbits. The new tissue on both sides of the SFTSs at 1 month was clearly observed. Inside the SFTSs, the extracellular matrix (ECM) was deposited on the pore wall at 1 month and continued to increase during the follow-up period. The self-assembled collagen fibers and elastic fibers were clearly visible in a circumferential arrangement at 6 months and were similar to autologous blood vessels. The positive expression rate of Lysyl oxidase-1 (LOXL-1) was positively correlated with the formation and maturity of collagen fibers and elastic fibers. In summary, the findings of the tissue regeneration processes indicated that the bionic SFTSs induced in situ angiogenesis in defects.

Machine Learning-Based Ultrasound Radiomics for Evaluating the Function of Transplanted Kidneys.

The aim of the study described here was to investigate the value of different machine learning models based on the clinical and radiomic features of 2-D ultrasound images to evaluate post-transplant renal function (pTRF). We included 233 patients who underwent ultrasound examination after renal transplantation and divided them into the normal pTRF group (group 1) and the abnormal pTRF group (group 2) based on their estimated glomerular filtration rates. The patients with abnormal pTRF were further subdivided into the non-severe renal function impairment group (group 2A) and the severe impairment group (group 2B). The radiomic features were extracted from the 2-D ultrasound images of each case. The clinical and ultrasound image features as well as radiomic features from the training set were selected, and then five machine learning algorithms were used to construct models for evaluating pTRF. Receiver operating characteristic curves were used to evaluate the discriminatory ability of each model. A total of 19 radiomic features and one clinical feature (age) were retained for discriminating group 1 from group 2. The area under the receiver operating characteristic curve (AUC) values of the models ranged from 0.788 to 0.839 in the test set, and no significant differences were found between the models (all p values >0.05). A total of 17 radiomic features and 1 ultrasound image feature (thickness) were retained for discriminating group 2A from group 2B. The AUC values of the models ranged from 0.689 to 0.772, and no significant differences were found between the models (all p values >0.05). Machine learning models based on clinical and ultrasound image features, as well as radiomics features, from 2-D ultrasound images can be used to evaluate pTRF.

Combining contrast-enhanced ultrasound and blood cell analysis to improve diagnostic accuracy of plasma cell mastitis.

Plasma cell mastitis is a benign suppurative disease of the breast, lack of specific clinical manifestations, which is easy to be misdiagnosed and mistreated, often confused with mastitis, breast cancer (BC), and other diseases. Thus, we aimed to establish a combined model of promoting diagnostic accuracy of plasma cell mastitis by contrast-enhanced ultrasound (CEUS) patterns and routine blood cell analysis. Eighty-eight plasma cell mastitis, 91 breast cancer, and 152 other benign breast diseases' patients grouped according to pathological diagnosis underwent CEUS and blood cell analysis examination; 100 healthy female donors were involved. All the plasma cell mastitis and breast cancer patients presented hyperenhancement of CEUS breast lesions compared with others. The majority of plasma cell mastitis (65/88) showed perfusion defect of CEUS patterns with smooth edge (56/65) and multiple lesions (49/65); in contrast, fewer breast cancer patients (30/91) displayed perfusion defect. White blood cell count (WBC), neutrophils, and neutrophils/lymphocytes ratio of blood cell analysis in plasma cell mastitis patients increased significantly compared with other patients (P < 0.0001). Combining perfusion defect of CEUS patterns and WBC yielded an area under the receiver operating characteristic curve of 0.831, higher than single 0.720 and 0.774, respectively. The cut-off value of WBC (7.28 × 109/L) helped remaining 65.2% (15/23) atypical cases to be correctly diagnosed as plasma cell mastitis, not misdiagnosed as breast cancer. In conclusion, CEUS presented a clear perfusion defect pattern of plasma cell mastitis lesion for the first time. A precise WBC by routine blood cell analysis test can assist CEUS examination in the differential diagnosis of plasma cell mastitis and breast cancer. It is a promised combination for laboratory diagnostic of PCM.