Super-resolution ultrasound and microvasculomics: a consensus statement.

This is a summary of a consensus statement on the introduction of "Ultrasound microvasculomics" produced by The Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound. The evaluation of microvessels is a very important part for the assessment of diseases. Super-resolution ultrasound (SRUS) microvascular imaging surpasses traditional ultrasound imaging in the morphological and functional analysis of microcirculation. SRUS microvascular imaging relies on contrast microbubbles to gain sensitivity to microvessels and improves the spatial resolution of ultrasound blood flow imaging for a more detailed depiction of vascular structures and hemodynamics. This method has been applied in preclinical animal models and pilot clinical studies, involving areas including neurology, oncology, nephrology, and cardiology. However, the current quantitative parameters of SRUS images are not enough for precise evaluation of microvessels. Therefore, by employing omics methods, more quantification indicators can be obtained, enabling a more precise and personalized assessment of microvascular status. Ultrasound microvasculomics - a high-throughput extraction of image features from SRUS images - is one novel approach that holds great promise but needs further validation in both bench and clinical settings. CLINICAL RELEVANCE STATEMENT: Super-resolution Ultrasound (SRUS) blood flow imaging improves spatial resolution. Ultrasound microvasculomics is possible to acquire high-throughput information of features from SRUS images. It provides more precise and abundant micro-blood flow information in clinical medicine. KEY POINTS: This consensus statement reviews the development and application of super-resolution ultrasound (SRUS). The shortcomings of the current quantification indicators of SRUS and strengths of the omics methodology are addressed. "Ultrasound microvasculomics" is introduced for a high-throughput extraction of image features from SRUS images.

Ultrasound Viscosity Imaging in Breast Lesions: A Multicenter Prospective Study.

RATIONALE AND OBJECTIVES: To explore and validate the clinical value of ultrasound (US) viscosity imaging in differentiating breast lesions by combining with BI-RADS, and then comparing the diagnostic performances with BI-RADS alone. MATERIALS AND METHODS: This multicenter, prospective study enrolled participants with breast lesions from June 2021 to November 2022. A development cohort (DC) and validation cohort (VC) were established. Using histological results as reference standard, the viscosity-related parameter with the highest area under the receiver operating curve (AUC) was selected as the optimal one. Then the original BI-RADS would upgrade or not based on the value of this parameter. Finally, the results were validated in the VC and total cohorts. In the DC, VC and total cohorts, all breast lesions were divided into the large lesion, small lesion and overall groups respectively. RESULTS: A total of 639 participants (mean age, 46 years ± 14) with 639 breast lesions (372 benign and 267 malignant lesions) were finally enrolled in this study including 392 participants in the DC and 247 in the VC. In the DC, the optimal viscosity-related parameter in differentiating breast lesions was calculated to be A'-S2-Vmax, with the AUC of 0.88 (95% CI: 0.84, 0.91). Using > 9.97 Pa.s as the cutoff value, the BI-RADS was then modified. The AUC of modified BI-RADS significantly increased from 0.85 (95% CI: 0.81, 0.88) to 0.91 (95% CI: 0.87, 0.93), 0.85 (95% CI: 0.80, 0.89) to 0.90 (95% CI: 0.85, 0.93) and 0.85 (95% CI: 0.82, 0.87) to 0.90 (95% CI: 0.88, 0.92) in the DC, VC and total cohorts respectively (P < .05 for all). CONCLUSION: The quantitative viscous parameters evaluated by US viscosity imaging contribute to breast cancer diagnosis when combined with BI-RADS.

Performance of large language models on benign prostatic hyperplasia frequently asked questions.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition, yet it is challenging for the average BPH patient to find credible and accurate information about BPH. Our goal is to evaluate and compare the accuracy and reproducibility of large language models (LLMs), including ChatGPT-3.5, ChatGPT-4, and the New Bing Chat in responding to a BPH frequently asked questions (FAQs) questionnaire. METHODS: A total of 45 questions related to BPH were categorized into basic and professional knowledge. Three LLM-ChatGPT-3.5, ChatGPT-4, and New Bing Chat-were utilized to generate responses to these questions. Responses were graded as comprehensive, correct but inadequate, mixed with incorrect/outdated data, or completely incorrect. Reproducibility was assessed by generating two responses for each question. All responses were reviewed and judged by experienced urologists. RESULTS: All three LLMs exhibited high accuracy in generating responses to questions, with accuracy rates ranging from 86.7% to 100%. However, there was no statistically significant difference in response accuracy among the three (p > 0.017 for all comparisons). Additionally, the accuracy of the LLMs' responses to the basic knowledge questions was roughly equivalent to that of the specialized knowledge questions, showing a difference of less than 3.5% (GPT-3.5: 90% vs. 86.7%; GPT-4: 96.7% vs. 95.6%; New Bing: 96.7% vs. 93.3%). Furthermore, all three LLMs demonstrated high reproducibility, with rates ranging from 93.3% to 97.8%. CONCLUSIONS: ChatGPT-3.5, ChatGPT-4, and New Bing Chat offer accurate and reproducible responses to BPH-related questions, establishing them as valuable resources for enhancing health literacy and supporting BPH patients in conjunction with healthcare professionals.

Transforming free-text radiology reports into structured reports using ChatGPT: A study on thyroid ultrasonography.

PURPOSE: The importance of structured radiology reports has been fully recognized, as they facilitate efficient data extraction and promote collaboration among healthcare professionals. Our purpose is to assess the accuracy and reproducibility of ChatGPT, a large language model, in generating structured thyroid ultrasound reports. METHODS: This is a retrospective study that includes 184 nodules in 136 thyroid ultrasound reports from 136 patients. ChatGPT-3.5 and ChatGPT-4.0 were used to structure the reports based on ACR-TIRADS guidelines. Two radiologists evaluated the responses for quality, nodule categorization accuracy, and management recommendations. Each text was submitted twice to assess the consistency of the nodule classification and management recommendations. RESULTS: On 136 ultrasound reports from 136 patients (mean age, 52 years ± 12 [SD]; 61 male), ChatGPT-3.5 generated 202 satisfactory structured reports, while ChatGPT-4.0 only produced 69 satisfactory structured reports (74.3 % vs. 25.4 %, odds ratio (OR) = 8.490, 95 %CI: 5.775-12.481, p < 0.001). ChatGPT-4.0 outperformed ChatGPT-3.5 in categorizing thyroid nodules, with an accuracy of 69.3 % compared to 34.5 % (OR = 4.282, 95 %CI: 3.145-5.831, p < 0.001). ChatGPT-4.0 also provided more comprehensive or correct management recommendations than ChatGPT-3.5 (OR = 1.791, 95 %CI: 1.297-2.473, p < 0.001). Finally, ChatGPT-4.0 exhibits higher consistency in categorizing nodules compared to ChatGPT-3.5 (ICC = 0.732 vs. ICC = 0.429), and both exhibited moderate consistency in management recommendations (ICC = 0.549 vs ICC = 0.575). CONCLUSIONS: Our study demonstrates the potential of ChatGPT in transforming free-text thyroid ultrasound reports into structured formats. ChatGPT-3.5 excels in generating structured reports, while ChatGPT-4.0 shows superior accuracy in nodule categorization and management recommendations.

Comparison of the efficacy and safety of ultrasound-guided radiofrequency ablation and microwave ablation for the treatment of unifocal papillary thyroid microcarcinoma: a retrospective study.

PURPOSE: This study aimed to compare the efficacy and safety of ultrasound-guided RFA and MWA in the treatment of unifocal PTMC. METHODS: This retrospective study included 512 patients with 512 unifocal papillary thyroid microcarcinomas (PTMCs) who underwent RFA (n = 346) and MWA (n = 166) between January 2021 and December 2021. The volumes of the ablation areas were measured during follow-up, and the volume reduction rates were evaluated. The ablation duration, volume of hydrodissection, and ablation-related complications were also compared between the groups. RESULTS: All lesions received complete ablation and no local or distant recurrences were observed in the two groups. A larger volume of isolation liquid was used for RFA than for MWA (p = 0.000). Hoarseness occurred in seven patients who underwent RFA (p = 0.102). At the 1-week follow-up, the mean volume of the areas ablated by RFA was smaller than that of the areas ablated by MWA (p = 0.049). During follow-ups at months 3, 9, 12, 15, and 18, the mean volumes of the ablated areas were larger in the RFA group than in the MWA group (all, p < 0.05). The mean volume of the ablated lesions increased slightly at the 1-week follow-up and then decreased at 1 month after ablation in both groups. The absorption curve of the ablated lesions in the RFA group was similar to that in the MWA group. CONCLUSIONS: RFA and MWA are both efficient and safe methods for treating unifocal PTMC. They may be alternative techniques for patients who are not eligible or are unwilling to undergo surgery.

Volume reduction rate of radiofrequency ablation in ≤ 2 cm Bethesda IV thyroid nodules.

OBJECTIVE: This prospective observational study aimed to evaluate the efficacy of radiofrequency ablation (RFA) in treating ≤ 2 cm thyroid nodules with Bethesda IV cytology and C-TIRADS 4A categorization. Additionally, the factors influencing the completed absorption of ablation (CAA) were examined. METHODS: A total of 62 cases with 62 nodules underwent ultrasound-guided RFA and were included in the study. The volume reduction rate (VRR), CAA, and incomplete absorption of ablation (IAA) were assessed at the 1st, 3rd, 6th, and subsequent 6-month follow-ups. Clinical and ultrasound features were compared between the CAA and IAA groups at the 12th month follow-up. RESULTS: The average VRR at the 1st, 3rd, 6th, 12th month, and last follow-up were -88.6%, 16.0%, 59.7%, 82.0%, and 98.2%, respectively. More than half of the nodules achieved a 90% VRR after 1 year of RFA, with 88.7% demonstrating CAA at the end of the study (follow-up duration of 14 to 63 months). Nodules with grade 3 vascularity and those associated with chronic thyroiditis showed delayed CAA at the 12th month follow-up (p = 0.036 and 0.003, respectively). CONCLUSION: RFA is an effective technique for treating ≤ 2 cm thyroid nodules with Bethesda IV cytology and C-TIRADS 4A categorization. Nodules with grade 3 blood supply and patients with chronic thyroiditis exhibited an impact on the completed absorption following RFA. CLINICAL RELEVANCE STATEMENT: Our study has shown that radiofrequency ablation is an effective treatment for ≤ 2 cm thyroid nodules classified as Bethesda IV cytology. However, we identified that high vascularity of the nodule and chronic thyroiditis are adverse factors affecting the completed absorption of the ablation. KEY POINTS: •Radiofrequency ablation (RFA) is an effective technique for treatment of ≤ 2 cm Bethesda IV category thyroid nodules. •Higher blood supply and chronic thyroiditis influence the completed absorption after RFA.

The emerging role of snoRNAs in human disease.

Small nucleolar RNAs (snoRNAs) play critical roles in various biological processes. The aberrant expression or depletion of snoRNAs is related to various diseases. In previous research, most of the snoRNAs were categorized as C/D box snoRNAs and H/ACA box snoRNAs, whose typical functions were thought of as regulation of 2'-O-ribose methylation and pseudouridylation of ribosome RNAs, respectively. However, in the past two decades, studies have revealed an increasing number of snoRNAs without specific targets or determined cell functions. These findings indicated that some potential roles of snoRNAs are still unknown. Numerous studies have indicated the correlation of snoRNAs with human diseases. SnoRNAs play various roles in abundant biological processes, and they have great potential in controlling human diseases. This new and rising field could benefit from investigations of the disease pathogenesis, biomarker identification, and the determination of novel therapeutic targets. This review summarized the reports on snoRNAs and the regulation of different diseases in recent years.

Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor-Specific and Ferroptosis-Augmented Sonodynamic Therapy.

Covalent organic frameworks (COFs) have attracted increasing attention for biomedical applications. COFs-based nanosensitizers with uniform nanoscale morphology and tumor-specific curative effects are in high demand; however, their synthesis is yet challenging. In this study, distinct COF nanobowls are synthesized in a controlled manner and engineered as activatable nanosensitizers with tumor-specific sonodynamic activity. High crystallinity ensures an ordered porous structure of COF nanobowls for the efficient loading of the small-molecule sonosensitizer rose bengal (RB). To circumvent non-specific damage to normal tissues, the sonosensitization effect is specifically inhibited by the in situ growth of manganese oxide (MnOx ) on RB-loaded COFs. Upon reaction with tumor-overexpressed glutathione (GSH), the "gatekeeper" MnOx is rapidly decomposed to recover the reactive oxygen species (ROS) generation capability of the COF nanosensitizers under ultrasound irradiation. Increased intracellular ROS stress and GSH consumption concomitantly induce ferroptosis to improve sonodynamic efficacy. Additionally, the unconventional bowl-shaped morphology renders the nanosensitizers with enhanced tumor accumulation and retention. The combination of tumor-specific sonodynamic therapy and ferroptosis achieves high efficacy in killing cancer cells and inhibiting tumor growth. This study paves the way for the development of COF nanosensitizers with unconventional morphologies for biomedicine, offering a paradigm to realize activatable and ferroptosis-augmented sonodynamic tumor therapy.

Native top-down mass spectrometry for higher-order structural characterization of proteins and complexes.

Progress in structural biology research has led to a high demand for powerful and yet complementary analytical tools for structural characterization of proteins and protein complexes. This demand has significantly increased interest in native mass spectrometry (nMS), particularly native top-down mass spectrometry (nTDMS) in the past decade. This review highlights recent advances in nTDMS for structural research of biological assemblies, with a particular focus on the extra multi-layers of information enabled by TDMS. We include a short introduction of sample preparation and ionization to nMS, tandem fragmentation techniques as well as mass analyzers and software/analysis pipelines used for nTDMS. We highlight unique structural information offered by nTDMS and examples of its broad range of applications in proteins, protein-ligand interactions (metal, cofactor/drug, DNA/RNA, and protein), therapeutic antibodies and antigen-antibody complexes, membrane proteins, macromolecular machineries (ribosome, nucleosome, proteosome, and viruses), to endogenous protein complexes. The challenges, potential, along with perspectives of nTDMS methods for the analysis of proteins and protein assemblies in recombinant and biological samples are discussed.

Deep learning algorithm using bispectrum analysis energy feature maps based on ultrasound radiofrequency signals to detect breast cancer.

Background: Ultrasonography is an important imaging method for clinical breast cancer screening. As the original echo signals of ultrasonography, ultrasound radiofrequency (RF) signals provide abundant tissue macroscopic and microscopic information and have important development and utilization value in breast cancer detection. Methods: In this study, we proposed a deep learning method based on bispectrum analysis feature maps to process RF signals and realize breast cancer detection. The bispectrum analysis energy feature maps with frequency subdivision were first proposed and applied to breast cancer detection in this study. Our deep learning network was based on a weight sharing network framework for the input of multiple feature maps. A feature map attention module was designed for multiple feature maps input of the network to adaptively learn both feature maps and features that were conducive to classification. We also designed a similarity constraint factor, learning the similarity and difference between feature maps by cosine distance. Results: The experiment results showed that the areas under the receiver operating characteristic curves of our proposed method in the validation set and two independent test sets for benign and malignant breast tumor classification were 0.913, 0.900, and 0.885, respectively. The performance of the model combining four ultrasound bispectrum analysis energy feature maps in breast cancer detection was superior to that of the model using an ultrasound grayscale image and the model using a single bispectrum analysis energy feature map in this study. Conclusion: The combination of deep learning technology and our proposed ultrasound bispectrum analysis energy feature maps effectively realized breast cancer detection and was an efficient method of feature extraction and utilization of ultrasound RF signals.

Noninvasive Assessment of Liver Fibrosis and Inflammation in Chronic Hepatitis B: A Dual-task Convolutional Neural Network (DtCNN) Model Based on Ultrasound Shear Wave Elastography.

Background and Aims: Liver stiffness (LS) measured by shear wave elastography (SWE) is often influenced by hepatic inflammation. The aim was to develop a dual-task convolutional neural network (DtCNN) model for the simultaneous staging of liver fibrosis and inflammation activity using 2D-SWE. Methods: A total of 532 patients with chronic hepatitis B (CHB) were included to develop and validate the DtCNN model. An additional 180 consecutive patients between December 2019 and April 2021 were prospectively included for further validation. All patients underwent 2D-SWE examination and serum biomarker assessment. A DtCNN model containing two pathways for the staging of fibrosis and inflammation was used to improve the classification of significant fibrosis (≥F2), advanced fibrosis (≥F3) as well as cirrhosis (F4). Results: Both fibrosis and inflammation affected LS measurements by 2D-SWE. The proposed DtCNN performed the best among all the classification models for fibrosis stage [significant fibrosis AUC=0.89 (95% CI: 0.87-0.92), advanced fibrosis AUC=0.87 (95% CI: 0.84-0.90), liver cirrhosis AUC=0.85 (95% CI: 0.81-0.89)]. The DtCNN-based prediction of inflammation activity achieved AUCs of 0.82 (95% CI: 0.78-0.86) for grade ≥A1, 0.88 (95% CI: 0.85-0.90) grade ≥A2 and 0.78 (95% CI: 0.75-0.81) for grade ≥A3, which were significantly higher than the AUCs of the single-task groups. Similar findings were observed in the prospective study. Conclusions: The proposed DtCNN improved diagnostic performance compared with existing fibrosis staging models by including inflammation in the model, which supports its potential clinical application.

A new visual quantitative assessment of ultrasound attenuation parameters for the mild liver steatosis.

Background: Controlled attenuation parameter (CAP) without the guidance of the grey scale sonogram was a classic method in the quantitative evaluation of liver steatosis, it is recommended by international guidelines. Our study aimed to compare the diagnostic efficiency of a new real-time visual liver steatosis analysis (LiSA) versus CAP in chronic hepatitis B patients with liver steatosis. Methods: Patients were enrolled who underwent liver biopsy and received both LiSA (Hepatus, Mindray, probe LFP5-1U/s, China) and CAP (FibroScan502, Echosens, probe M, France) measurement simultaneously in our hospital from November 2018 to December 2019. The obtained values were both expressed as dB/m. Based on the liver fat content validated by liver biopsy, these patients were divided into the S0 group (fat content <5%) and S1 group (fat content ≥5%). The efficiency of the LiSA and CAP value in the diagnosis of liver steatosis was evaluated. Independent factors influencing the LiSA value were predicted by correlation analysis and multiple linear regression analysis. Results: A total of 151 patients were included in the analysis according to the exclusion criteria from 304 enrolled liver biopsy chronic hepatitis B (CHB) patients. Both LiSA and CAP successfully differentiated the S0 group from the S1 group. Receiver operating characteristic (ROC) curves showed that both LiSA and CAP had good diagnostic performance [area under the ROC curve area under the curve (AUC) >0.7] in evaluating liver steatosis, while there was no significant difference between the 2 methods (AUC 0.825 vs. 0.798, P=0.067). Using the optimal cutoff point, the specificity and sensitivity of LiSA in diagnosing liver steatosis were 89.18% and 79.16%, respectively. The specificity and sensitivity of CAP in diagnosing liver steatosis were 87.20% and 76.31%, respectively. Conclusions: Both LiSA and CAP are efficient for evaluating liver steatosis noninvasively.

Sublethal heat treatment promotes breast cancer metastasis and its molecular mechanism revealed by quantitative proteomic analysis.

Radiofrequency ablation (RFA) is a frequently used thermal ablation technique for breast tumors. The study aimed to identify the effect of sublethal heat treatment on biological function of breast cancer cells and reveal its potential molecular mechanism. The expression profile of dysregulated proteins in sublethal heat treated breast cancer cells was analyzed by quantitative proteomic analysis. The differentially expressed proteins in the sublethal heat treated breast cancer were identified. The potential biological functions of these proteins were evaluated. The proliferation and invasion ability of breast cancer cells were enhanced after sublethal heat treatment. The expression profile of proteins in sublethal heat treated breast cancer cells was abundant, and most of which were newly discovered. A total of 206 differentially expressed proteins were identified. Among them, 101 proteins were downregulated while 105 proteins were upregulated. GO and KEGG analysis indicated that various systems were involved in the process of sublethal heat treatment including cancer, immune system, et al. Immunohistochemistry staining showed that the expression of Heat shock protein 1B, NOB1 and CRIP1 was highly expressed while the expression of BCLAF1 was lower in sublethal heat treated group. The proliferation and invasion ability of breast cancer cells were enhanced after sublethal heat treatment. Sublethal heat treatment caused gene alterations in cancer and immune system. Heat shock protein 1B, NOB1 and CRIP1 were upregulated while BCLAF1 was downregulated in breast cancer after sublethal heat treatment.

Evaluation of Microwave Ablation in 4T1 Breast Tumor by a Novel VEFGR2 Targeted Ultrasound Contrast Agents.

OBJECTIVES: A novel ultrasound contrast agent (UCA) VEGFR2-targeting iron-doped silica (SiO2) hollow nanoparticles (VEGFR2-PEG-HSNs-Fe NPs) was prepared and applied in microwave ablation for breast cancer to investigate its value in the evaluation of effectiveness after tumor ablation. METHODS: VEGFR2-PEG-HSNs-Fe NPs were prepared by using nano-SiO2, which was regarded as a substrate and etched by ferrous acetate, and then modified with anti-VEGFR2 antibody. Laser confocal microscope and flow cytometry were used to observe its main physicochemical properties, and biological safety was also investigated. After the xenograft tumor was treated with microwave ablation, the extent of perfusion defect was evaluated by ultrasound by injecting VEGFR2-PEG-HSNs-Fe NPs. RESULTS: The average particle size of VEGFR2-PEG-HSNs-Fe was 276.64 ± 30.31 nm, and the surface potential was -13.46 ± 2.83 mV. In vitro, the intensity of ultrasound signal increased with UCA concentration. Good biosafety was performed in in vivo and in vitro experiments. The enhanced ultrasound signal was detected in tumors after injection of VEGFR2-PEG-HSNs-Fe NPs, covering the whole tumor. The lesions, which were incompletely ablated, presented as contrast agent perfusion at the periphery of the tumor, and contrast enhanced ultrasound (CEUS) was performed again after complementary ablation. It was confirmed that all the lesions were completely ablated. CONCLUSION: Nano-targeted UCAs VEGFR2-PEG-HSNs-Fe NPs had good biosafety and ability of specific imaging, which might be used as a contrast agent in CEUS to evaluate the efficacy of tumor ablation.

Ultrasound-Guided Fine-Needle Aspiration Versus Fine-Needle Capillary Sampling in Evaluation of Lymph Node Metastasis of Thyroid Cancer.

BACKGROUND: To compare the sampling adequacy and diagnostic efficiency of ultrasound-guided fine-needle aspiration with 22-, 25-gauge needles and capillary sampling with 22-gauge needle in the biopsy of cervical lymph node. METHODS: A total of 130 cervical lymph nodes from 103 patients were consecutively included in the prospective study. Each suspected lymph node was aspirated with a 22-gauge needle, capillary sampled with a 22-gauge needle and aspirated with a 25-gauge needle. The adequacy rates and nondiagnostic rates of obtained specimen were calculated. RESULTS: Of the 130 suspected lymph nodes, there were 77 lymph nodes<6.0 mm and 53 lymph nodes≥6.0mm in the smallest dimension. Both FNA22G and FNC22G got significantly higher sampling adequacy than FNA25G for the total lymph nodes. For lymph nodes<6.0 mm, the sampling adequacy was significantly higher with FNA22G than with FNA25G for each parameter and the cumulative score (all P<0.05), while no difference were seen between FNA22G and FNC22G, and between FNC22G and FNA25G. There were higher nondiagnostic rates for FNA25G compared with FNA22G and FNC22G in all lymph nodes and in each size subgroups. FNA25G yielded more diagnostically inadequate specimens than FNA22G and FNC22G did in the total lymph nodes (P=0.002), in lymph nodes<6.0 mm (P=0.014), and in those ≥ 6.0 mm (P=0.000). CONCLUSIONS: FNA22G and FNC22G obtained more diagnostically adequate specimens than FNA25G in cervical lymph nodes. FNA22G and FNC22G may be more suitable than FNA25G in diagnosing cervical lymph nodes. FNA22G and FNC22G may yield specimens with similar quality.

Diagnostic Performance of Shear Wave Elastography in the Noninvasive Evaluation of Liver Inflammation of Chronic Hepatitis B Patients.

ABSTRACT: In the current study, we sought to delineate the elastographic characteristics and further compare the diagnostic performance of various shear wave elastography modalities in hepatitis B virus patients whose liver fibrosis stage was less than F2 by liver biopsy. We retrospectively studied the clinical and imaging data of chronic hepatitis B virus patients who underwent liver biopsy at our hospital between January 2017 and October 2017. Totally, 102 patients were eligible for the study. The mean Young modulus of sound touch elastography (STE) and sound touch quantify (STQ) gradually increased as inflammation grade of the liver rose from G0 to G3. Spearman rank correlation analysis revealed that the mean Young modulus of STE and STQ significantly correlated with hepatic inflammation grade (r = 0.341, P < 0.05). The area under the receiver operating characteristic curve (AUC) was the highest for the mean Young modulus of STE (AUC = 0.740; P = 0.015) followed by that of STQ (AUC = 0.684; P = 0.063) for G ≥ 2 hepatic inflammation and the AUC was the highest for the mean Young modulus of STE (AUC = 0.920; P = 0.000) followed by that of STQ (AUC = 0.910; P = 0.000) for G ≥ 3 hepatic inflammation. The current study demonstrated that the mean Young modulus of STE and STQ could serve as a useful diagnostic marker for hepatic inflammation of hepatitis B virus patients with no apparent liver fibrosis.

Drug loading techniques for exosome-based drug delivery systems.

Exosomes are bilayer membrane-coated extracellular vesicles measuring between 40 and 100 nm in diameter. As a natural carrier, exosomes have the advantages of low immunogenicity, high stability in blood, and direct delivery of drugs to cells. Exosomes can be transported between cells and thus are conducive to the exchange of substances and information between cells. They change the functional state of recipient cells by loading exogenous drugs (e.g., small-molecule drugs, transmembrane proteins, and nucleic acid drugs). The key to using exosomes as drug carriers is the effective loading of exogenous drugs into exosomes; however, this task poses a challenge in studying the functionalization of exosomes as drug carriers. Currently, sonication, electroporation, transfection, incubation, extrusion, saponin-assisted loading, transgenesis, freeze-thaw cycles, thermal shock, pH gradient method, and hypotonic dialysis have been applied to load these drugs into exosomes. This review aims to provide an overview of the advantages and disadvantages of various drug loading technologies for exosomes.

Analysis of liver steatosis analysis and controlled attenuation parameter for grading liver steatosis in patients with chronic hepatitis B.

BACKGROUND: Chronic hepatitis B is the most common chronic liver disease in China. For patients with chronic hepatitis B, steatosis increases the risk of cirrhosis and hepatocellular carcinoma. This study aimed to analyze and compare the clinical value of a newly developed ultrasound attenuation parameter, liver steatosis analysis (LiSA), acquired by Hepatus (Mindray, China), and controlled attenuation parameter (CAP), a widely used ultrasound attenuation parameter acquired by FibroScan (Echosens, France), for grading liver steatosis in patients with chronic hepatitis B infection. METHODS: A total of 203 patients were divided into two groups according to liver fat content validated by liver biopsy: group 1 (liver fat content <10%) and group 2 (liver fat content ≥10%). All patients underwent LiSA and CAP examinations. Receiver operating characteristic (ROC) curves were calculated for the two ultrasound attenuation tools. RESULTS: Both LiSA and CAP successfully discriminated between patients in group 1 and group 2. ROC curves showed that both tools had good diagnostic ability (AUC: >0.7) for steatosis ≥10%, and the performance of LiSA was significantly better than CAP (AUC: 0.859 vs. 0.801, P=0.048). Using optimal cut-off points, LiSA had specificity and sensitivity of 96.23% and 76.08%, respectively, for the diagnosis of steatosis ≥10%, compared to 91.53% and 72.10%, respectively, for CAP. CONCLUSIONS: LiSA and CAP are extremely efficient tools for assessing liver steatosis, even at a low grade. Both parameters are non-invasive, inexpensive, and easy to use, and can provide immediate results with high sensitivity.

A New Visual Transient Elastography Technique for Grading Liver Fibrosis in Patients With Chronic Hepatitis B.

ABSTRACT: Liver fibrosis is evaluated to assess the prognosis and guide the treatment of chronic hepatitis B (CHB). To compare the efficiency of 2 transient elastography techniques for grading liver fibrosis in CHB: visual transient elastography (ViTE) with real-time image guidance and FibroScan (FS) with no image guidance. All of the CHB patients in this study underwent both FS and ViTE examinations. The final diagnosis was based on the histological findings of a liver biopsy. According to the severity of liver fibrosis (based on the Scheuer criteria), the area under the receiver operating characteristic curve values for diagnostic efficiency were calculated for the 2 elastography techniques. This study enrolled 227 patients (79 [39.1%] women; mean age, 45.8 ± 16.8 years). The ViTE and FS liver elasticity measurements were highly correlated with liver fibrosis stage (r = 0.852 and r = 0.813, respectively). The area under the receiver operating characteristic curve value was larger for ViTE compared with FS, with respect to differentiating liver fibrosis stage, but not significantly (P > 0.05). The ViTE and FS can be used to detect and stage liver fibrosis. ViTE, easier and quicker to perform with superior interoperator reproducibility, is a stable and reliable elastography technique that benefits from real-time visual guidance.

A study of spleen shear-wave elastography in indirect prediction of liver fibrosis in patients with chronic hepatitis B.

PURPOSE: To evaluate the value of spleen shear-wave elastography (sound touch elastography [STE], sound touch quantification [STQ]) in indirect prediction of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: The Young's modulus (kPa) of spleen STE, STQ and liver FibroScan were measured in 112 patients with CHB. The final diagnosis was according to histological results from liver biopsy based on Scheure G/S scoring system and liver FibroScan was considered as a reference index of prediction efficiency. Grouped by the stage of liver fibrosis, data were analyzed by Spearman correlation analysis, Mann-Whitney test and receiver operating characteristic curve (ROC). RESULTS: Spleen STE was positively correlated with the degree of liver fibrosis, but spleen STQ was not. STEmean and STEmax of spleen were statistically different between the groups categorized by S = 2, S = 3 and S = 4 (all p < 0.05), respectively. Spleen STEmean had the best predicting performance on staging liver fibrosis. The areas under the ROC (AUC) for spleen STEmean were 0.66 (95% confidence interval [CI], 0.56-0.76) for stage S = 2 or higher, 0.72 (95% CI, 0.60-0.83) for S = 3 or higher, 0.83 (95% CI, 0.74-0.92) for S = 4 (all P < 0.01). The differences between the AUC for spleen STEmean and liver FibroScan in liver fibrosis staging were not statistically significant when the groups categorized by S = 2 and S = 4 (P = 0.146 and P = 0.052). But when categorized by S = 3, the evaluating performance of liver FibroScan was better (P = 0.004). CONCLUSION: STEmean of spleen is applicable in indirect predicting fibrosis stage in patients with CHB.