Repurposing cyclovirobuxine D as a novel inhibitor of colorectal cancer progression via modulating the CCT3/YAP axis.

BACKGROUND AND PURPOSE: Colorectal cancer (CRC) ranks second in mortality worldwide and requires effective and affordable remedies. Cyclovirobuxine D (CVB-D) is the main effective component of Huangyangning tablet, an approved traditional patent medicine, which is mainly used for cardiovascular treatment. As a multibioactive natural compound, CVB-D possesses underlying anticancer activities. EXPERIMENTAL APPROACH: Cell viability and clone-forming ability were determined in human CRC lines. Western blot, immunofluorescence assay, transmission electron microscopy and senescence-associated ß-galactosidase (SA-ß-Gal) staining were utilized to investigate cell autophagy and senescence. The molecular mechanisms were explored by virtual prediction and experimental validation. Patient-derived xenograft (PDX), dextran sulfate sodium salt (DSS), and azomethane (AOM)/DSS mouse models were employed for in vivo studies. KEY RESULTS: CVB-D inhibited the growth and development of advanced CRC cells / mice by inducing autophagic and senescent activities through the chaperonin containing TCP1 subunit 3 (CCT3)/yes-associated protein (YAP) axis. CVB-D acted as a promising inhibitor of CCT3 by interacting with its ATP site. In PDX tumours, CVB-D showed potential therapeutic effects by targeting CCT3. Treatment with CVB-D alleviated the mouse model of colitis induced by DSS and attenuated AOM/DSS-induced formation of adenomatous polyps by its action on CCT3. CONCLUSIONS AND IMPLICATIONS: Our study has provided a scientific basis for the suggestion that CVB-D may be recognized as a prospective drug candidate for the therapy of CRC in patients.

Identification of proteins related to SIS3 by iTRAQ and PRM-based comparative proteomic analysis in cisplatin-induced acute kidney injury.

Background: Cisplatin is a commonly used nephrotoxic drug and can cause acute kidney injury (AKI). In the present study, isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM)-based comparative proteomics were used to analyze differentially expressed proteins (DEPs) to determine the key molecular mechanism in mice with cisplatin-induced AKI in the presence or absence of SIS3, a specific p-smad3 inhibitor, intervention. Methods: The cisplatin-induced AKI mouse model was established and treated with SIS3. We used iTRAQ to search for DEPs, PRM to verify key DEPs and combined Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for bioinformatics analysis. We then assessed lipid deposition, malondialdehyde (MDA) and reactive oxygen species (ROS) and detected the expression of SREBF1, SCD1, CPT1A, PPARα and NDRG1 in vitro. Results: Proteomic analysis showed that the identified DEPs were mainly enriched in energy metabolism pathways, especially in lipid metabolism. When SIS3 was applied to inhibit the phosphorylation of Smad3, the expression of NDRG1 and fatty acid oxidation key proteins CPT1A and PPARα increased, the expression of lipid synthesis related proteins SREBF1 and SCD1 decreased and the production of lipid droplets, MDA and ROS decreased. Conclusion: SIS3 alleviates oxidative stress, reduces lipid accumulation and promotes fatty acid oxidation through NDRG1 in cisplatin-induced AKI. Our study provides a new candidate protein for elucidating the molecular mechanisms of fatty acid metabolism disorders in cisplatin-induced acute kidney injury.

Comparison contrast-enhanced CT with contrast-enhanced US in diagnosing combined hepatocellular-cholangiocarcinoma: a propensity score-matched study.

OBJECTIVES: To develop and compare noninvasive models for differentiating between combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and HCC based on serum tumor markers, contrast-enhanced ultrasound (CEUS), and computed tomography (CECT). METHODS: From January 2010 to December 2021, patients with pathologically confirmed cHCC-CCA or HCC who underwent both preoperative CEUS and CECT were retrospectively enrolled. Propensity scores were calculated to match cHCC-CCA and HCC patients with a near-neighbor ratio of 1:2. Two predicted models, a CEUS-predominant (CEUS features plus tumor markers) and a CECT-predominant model (CECT features plus tumor markers), were constructed using logistic regression analyses. Model performance was evaluated by the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: A total of 135 patients (mean age, 51.3 years ± 10.9; 122 men) with 135 tumors (45 cHCC-CCA and 90 HCC) were included. By logistic regression analysis, unclear boundary in the intratumoral nonenhanced area, partial washout on CEUS, CA 19-9 > 100 U/mL, lack of cirrhosis, incomplete tumor capsule, and nonrim arterial phase hyperenhancement (APHE) volume < 50% on CECT were independent factors for a diagnosis of cHCC-CCA. The CECT-predominant model showed almost perfect sensitivity for cHCC-CCA, unlike the CEUS-predominant model (93.3% vs. 55.6%, p < 0.001). The CEUS-predominant model showed higher diagnostic specificity than the CECT-predominant model (80.0% vs. 63.3%; p = 0.020), especially in the ≤ 5 cm subgroup (92.0% vs. 70.0%; p = 0.013). CONCLUSIONS: The CECT-predominant model provides higher diagnostic sensitivity than the CEUS-predominant model for CHCC-CCA. Combining CECT features with serum CA 19-9 > 100 U/mL shows excellent sensitivity. CRITICAL RELEVANCE STATEMENT: Combining lack of cirrhosis, incomplete tumor capsule, and nonrim arterial phase hyperenhancement (APHE) volume < 50% on CECT with serum CA 19-9 > 100 U/mL shows excellent sensitivity in differentiating cHCC-CCA from HCC. KEY POINTS: 1. Accurate differentiation between cHCC-CCA and HCC is essential for treatment decisions. 2. The CECT-predominant model provides higher accuracy than the CEUS-predominant model for CHCC-CCA. 3. Combining CECT features and CA 19-9 levels shows a sensitivity of 93.3% in diagnosing cHCC-CCA.

Sono-activated materials for enhancing focused ultrasound ablation: Design and application in biomedicine.

The ablation effect of focused ultrasound (FUS) has played an increasingly important role in the biomedical field over the past decades, and its non-invasive features have great advantages, especially for clinical diseases where surgical treatment is not available or appropriate. Recently, rapid advances in the adjustable morphology, enzyme-mimetic activity, and biostability of sono-activated materials have significantly promoted the medical application of FUS ablation. However, a systematic review of sono-activated materials based on FUS ablation is not yet available. This progress review focuses on the recent design, fundamental principles, and applications of sono-activated materials in the FUS ablation biomedical field. First, the different ablation mechanisms and the key factors affecting ablation are carefully determined. Then, the design of sono-activated materials with high FUS ablation efficiencies is comprehensively discussed. Subsequently, the representative biological applications are summarized in detail. Finally, the primary challenges and future perspectives are also outlined. We believe this timely review will provide key information and insights for further exploration of focused ultrasound ablation and new inspiration for designing future sono-activated materials. STATEMENT OF SIGNIFICANCE: The ablation effect of focused ultrasound (FUS) has played an increasingly important role in the biomedical field over the past decades. However, there are also some challenges of FUS ablation, such as skin burns, tumour recurrence after thermal ablation, and difficulty in controlling cavitation ablation. The rapid advance in adjustable morphology, enzyme-mimetic activity, and biostability of sono-activated materials has significantly promoted the medical application of FUS ablation. However, the systematic review of sono-activated materials based on FUS ablation is not yet available. This progress review focuses on the recent design, fundamental principles, and applications in the FUS ablation biomedical field of sono-activated materials. We believe this timely review will provide key information and insights for further exploration of FUS ablation.

A nomogram based on ultrasonographic features and clinical indicators for differentiating mass-forming intrahepatic cholangiocarcinoma and liver metastatic colorectal adenocarcinoma.

Objective: This study aimed to develop and validate a nomogram based on ultrasonographic features and clinical indicators to differentiate mass-forming intrahepatic cholangiocarcinoma (MF-ICC) from hepatic metastatic colorectal adenocarcinoma. Materials and methods: A total of 343 patients with pathologically confirmed MF-ICC or metastatic colorectal adenocarcinoma were enrolled between October 2018 and July 2022. Patients were randomly assigned to training and validation sets at a ratio of 7:3. Preoperative ultrasound features and clinical indicators were retrieved. Univariate logistic regression analysis was employed to select relevant features. Multivariate logistic regression analysis was used to establish a predictive model, which was presented as a nomogram in training sets. The model's performance was assessed in terms of discrimination, calibration, and clinical usefulness. Results: The study included 169 patients with MF-ICC and 174 with liver metastatic colorectal adenocarcinoma, assigned to training (n=238) and validation (n=105) cohorts. The nomogram incorporated ultrasound features (tumor size, lesion number, echogenicity, tumor necrosis, and rim arterial phase hyperenhancement) and clinical information (serum levels of CEA, CA19-9, CA125). The nomogram demonstrated promising performance in differentiating these two entities in both training and validation sets, with an AUC value of 0.937 (95%CI: 0.907,0.969) and 0.916 (95%CI: 0.863,0.968), respectively. The Hosmer-Lemeshow test and calibration curves confirmed good consistency between predictions and observations. Additionally, decision curve analysis confirmed the nomogram's high clinical practicability. Conclusion: The nomogram based on ultrasound features and clinical indicators demonstrated good discrimination performance in differentiating MF-ICC from metastatic colorectal adenocarcinoma, which may enhance clinical decision-making process in managing these challenging diagnostic scenarios.

Photosensitive small extracellular vesicles regulate the immune microenvironment of triple negative breast cancer.

Currently, the treatment of triple-negative breast cancer (TNBC) is limited by the special pathological characteristics of this disease. In recent years, photodynamic therapy (PDT) has created new hope for the treatment of TNBC. Moreover, PDT can induce immunogenic cell death (ICD) and improve tumor immunogenicity. However, even though PDT can improve the immunogenicity of TNBC, the inhibitory immune microenvironment of TNBC still weakens the antitumor immune response. Therefore, we used the neutral sphingomyelinase inhibitor GW4869 to inhibit the secretion of small extracellular vesicles (sEVs) by TNBC cells to improve the tumor immune microenvironment and enhance antitumor immunity. In addition, bone mesenchymal stem cell (BMSC)-derived sEVs have good biological safety and a strong drug loading capacity, which can effectively improve the efficiency of drug delivery. In this study, we first obtained primary BMSCs and sEVs, and then the photosensitizers Ce6 and GW4869 were loaded into the sEVs by electroporation to produce immunomodulatory photosensitive nanovesicles (Ce6-GW4869/sEVs). When administered to TNBC cells or orthotopic TNBC models, these photosensitive sEVs could specifically target TNBC and improve the tumor immune microenvironment. Moreover, PDT combined with GW4869-based therapy showed a potent synergistic antitumor effect mediated by direct killing of TNBC and activation of antitumor immunity. Here, we designed photosensitive sEVs that could target TNBC and regulate the tumor immune microenvironment, providing a potential approach for improving the effectiveness of TNBC treatment. STATEMENT OF SIGNIFICANCE: We designed an immunomodulatory photosensitive nanovesicle (Ce6-GW4869/sEVs) with the photosensitizer Ce6 to achieve photodynamic therapy and the neutral sphingomyelinase inhibitor GW4869 to inhibit the secretion of small extracellular vesicles (sEVs) by triple-negative breast cancer (TNBC) cells to improve the tumor immune microenvironment and enhance antitumor immunity. In this study, the immunomodulatory photosensitive nanovesicle could target TNBC cells and regulate the tumor immune microenvironment, thus providing a potential approach for improving the treatment effect in TNBC. We found that the reduction in tumor sEVs secretion induced by GW4869 improved the tumor-suppressive immune microenvironment. Moreover, similar therapeutic strategies can also be applied in other kinds of tumors, especially immunosuppressive tumors, which is of great value for the clinical translation of tumor immunotherapy.

Non-invasive evaluation of liver steatosis with imaging modalities: New techniques and applications.

In the world, nonalcoholic fatty liver disease (NAFLD) accounts for majority of diffuse hepatic diseases. Notably, substantial liver fat accumulation can trigger and accelerate hepatic fibrosis, thus contributing to disease progression. Moreover, the presence of NAFLD not only puts adverse influences for liver but is also associated with an increased risk of type 2 diabetes and cardiovascular diseases. Therefore, early detection and quantified measurement of hepatic fat content are of great importance. Liver biopsy is currently the most accurate method for the evaluation of hepatic steatosis. However, liver biopsy has several limitations, namely, its invasiveness, sampling error, high cost and moderate intraobserver and interobserver reproducibility. Recently, various quantitative imaging techniques have been developed for the diagnosis and quantified measurement of hepatic fat content, including ultrasound- or magnetic resonance-based methods. These quantitative imaging techniques can provide objective continuous metrics associated with liver fat content and be recorded for comparison when patients receive check-ups to evaluate changes in liver fat content, which is useful for longitudinal follow-up. In this review, we introduce several imaging techniques and describe their diagnostic performance for the diagnosis and quantified measurement of hepatic fat content.

Head-to-head comparison of Sonazoid and SonoVue in the diagnosis of hepatocellular carcinoma for patients at high risk.

Objectives: To compare the diagnostic efficacy of SonoVue-enhanced and Sonazoid-enhanced ultrasound (US) for hepatocellular carcinoma (HCC) in patients at high risk. Methods: Between August 2021 and February 2022, participants at high risk for HCC with focal liver lesions were enrolled and underwent both SonoVue- and Sonazoid-enhanced US. Vascular-phase and Kupffer phase (KP) imaging features of contrast-enhanced US (CEUS) were analyzed. The diagnostic performance of both contrast agent-enhanced US according to the CEUS liver imaging reporting and data system (LI-RADS) and the modified criteria (using KP defect instead of late and mild washout) were compared. Histopathology and contrast-enhanced MRI/CT were used as reference standards. Results: In total, 62 nodules, namely, 55 HCCs, 3 non-HCC malignancies and 4 hemangiomas, from 59 participants were included. SonoVue-enhanced US had comparable sensitivity to Sonazoid-enhanced US for diagnosing HCC [80% (95% confidential interval (CI): 67%, 89.6%) versus 74.6% (95% CI: 61%, 85.3%), p = 0.25]. Both SonoVue and Sonazoid-enhanced US achieved a specificity of 100%. Compared with CEUS LI-RADS, the modified criteria with Sonazoid did not improve sensitivity for HCC diagnosis [74.6% (95% CI: 61%, 85.3%) versus 76.4% (95% CI: 63%, 86.8%), p = 0.99]. Conclusions: Sonazoid-enhanced US had comparable diagnostic performance to SonoVue-enhanced US for patients with HCC risk. KP did not considerably improve the diagnostic efficacy, whereas KP defects in atypical hemangioma may be pitfalls in diagnosing HCC. Further studies with larger sample sizes are needed to further validate the conclusions in the present study.

Active compounds and potential targets of Shuganning injection in the treatment of hepatocellular carcinoma by network pharmacology and in vitro validation.

Shuganning injection (SGNI), a TCM (traditional Chinese medicine) injection with good hepatoprotective effects, exerted therapeutic effects on hepatocellular carcinoma (HCC). However, the active compounds and effects of SGNI on HCC remain unclear. The objective of this study was to investigate the active compounds and potential targets of SGNI in the treatment of HCC, and explore the molecular mechanisms of main compounds. Network pharmacology was applied to predict the active compounds and targets of SGNI on cancer. The interactions between active compounds and target proteins were validated by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and pull-down assay. The in vitro test of the effects and mechanism of vanillin and baicalein was elucidated by MTT, western blot, immunofluorescence, and apoptosis analysis. According to compound characteristics, targets, etc., two typical active ingredients (vanillin and baicalein) were selected as representatives to explore the effects on HCC. Vanillin (an important food additive) bound to NF-κB1 and baicalein (a bioactive flavonoid) bound to FLT3 (FMS-like tyrosine kinase 3) were confirmed in this study. Vanillin and baicalein both inhibited cell viability and promoted apoptosis of Hep3B and Huh7 cells. In addition, both vanillin and baicalein could enhance the activation of the p38/MAPK (mitogen-activated protein kinase) signaling pathway, which may partially explain the anti-apoptosis effects of the two compounds. In conclusion, two active compounds of SGNI, vanillin and baicalein, promoted apoptosis of HCC cells via binding with NF-κB1 or FLT3, and regulating the p38/MAPK pathway. Baicalein and vanillin may be good candidates for HCC treatment on drug development.

Adult-type rhabdomyoma of the thyroid: A case report.

Adult-type rhabdomyoma (AR) is a benign myogenous neoplasm. It is rarely located in the thyroid. We present a case of a 61-year-old man, presenting with complaints of a mass found in his left neck for three years. Ultrasonography and computed tomography showed a mass in the left lobe of the thyroid. Subsequently, a fine-needle aspiration biopsy showed that the lesion was suspected to be an oncocytic neoplasm, and the patient underwent surgery. Finally, the lesion was confirmed to be an AR of the thyroid by postoperative pathological diagnosis. In conclusion, AR that occurs in the thyroid is remarkably rare. No case reports to date have described in detail the imaging findings of AR in the thyroid. This study demonstrates the imaging characteristics of a patient with AR of the thyroid, in order to provide more extensive insights to consider the differential diagnosis of thyroid lesions.

Angiopep-2 Modified Exosomes Load Rifampicin with Potential for Treating Central Nervous System Tuberculosis.

Background: Central nervous system tuberculosis (CNS-TB) is the most devastating form of extrapulmonary tuberculosis. Rifampin (RIF) is a first-line antimicrobial agent with potent bactericidal action. Nonetheless, the blood-brain barrier (BBB) limits the therapeutic effects on CNS-TB. Exosomes, however, can facilitate drug movements across the BBB. In addition, exosomes show high biocompatibility and drug-loading capacity. They can also be modified to increase drug delivery efficacy. In this study, we loaded RIF into exosomes and modified the exosomes with a brain-targeting peptide to improve BBB permeability of RIF; we named these exosomes ANG-Exo-RIF. Methods: Exosomes were isolated from the culture medium of BMSCs by differential ultracentrifugation and loaded RIF by electroporation and modified ANG by chemical reaction. To characterize ANG-Exo-RIF, Western blot (WB), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were performed. Bend.3 cells were incubated with DiI labeled ANG-Exo-RIF and then fluorescent microscopy and flow cytometry were used to evaluate the targeting ability of ANG-Exo-RIF in vitro. Fluorescence imaging and frozen section were used to evaluate the targeting ability of ANG-Exo-RIF in vivo. MIC and MBC were determined through microplate alamar blue assay (MABA). Results: A novel exosome-based nanoparticle was developed. Compared with untargeted exosomes, the targeted exosomes exhibited high targeting capacity and permeability in vitro and in vivo. The MIC and MBC of ANG-Exo-RIF were 0.25 µg/mL, which were sufficient to meet the clinical needs. Conclusion: In summary, excellent targeting ability, high antitubercular activity and biocompatibility endow ANG-Exo-RIF with potential for use in future translation-aimed research and provide hope for an effective CNS-TB treatment.

Contrast-enhanced ultrasound and contrast-enhanced computed tomography for differentiating mass-forming pancreatitis from pancreatic ductal adenocarcinoma: a meta-analysis.

BACKGROUND: Patients with mass-forming pancreatitis (MFP) or pancreatic ductal adenocarcinoma (PDAC) presented similar clinical symptoms, but required different treatment approaches and had different survival outcomes. This meta-analysis aimed to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) in differentiating MFP from PDAC. METHODS: A literature search was performed in the PubMed, EMBASE (Ovid), Cochrane Library (CENTRAL), China National Knowledge Infrastructure (CNKI), Weipu (VIP), and WanFang databases to identify original studies published from inception to August 20, 2021. Studies reporting the diagnostic performances of CEUS and CECT for differentiating MFP from PDAC were included. The meta-analysis was performed with Stata 15.0 software. The outcomes included the pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves of CEUS and CECT. Meta-regression was conducted to investigate heterogeneity. Bayesian network meta-analysis was conducted to indirectly compare the overall diagnostic performance. RESULTS: Twenty-six studies with 2115 pancreatic masses were included. The pooled sensitivity and specificity of CEUS for MFP were 82% (95% confidence interval [CI], 73%-88%; I2  = 0.00%) and 95% (95% CI, 90%-97%; I2  = 63.44%), respectively; the overall +LR, -LR, and DOR values were 15.12 (95% CI, 7.61-30.01), 0.19 (95% CI, 0.13-0.29), and 78.91 (95% CI, 30.94-201.27), respectively; and the area under the SROC curve (AUC) was 0.90 (95% CI, 0.87-92). However, the overall sensitivity and specificity of CECT were 81% (95% CI, 75-85%; I2  = 66.37%) and 94% (95% CI, 90-96%; I2  = 74.87%); the overall +LR, -LR, and DOR values were 12.91 (95% CI, 7.86-21.20), 0.21 (95% CI, 0.16-0.27), and 62.53 (95% CI, 34.45-113.51), respectively; and, the SROC AUC was 0.92 (95% CI, 0.90-0.94). The overall diagnostic accuracy of CEUS was comparable to that of CECT for the differential diagnosis of MFP and PDAC (relative DOR 1.26, 95% CI [0.42-3.83], P  > 0.05). CONCLUSIONS: CEUS and CECT have comparable diagnostic performance for differentiating MFP from PDAC, and should be considered as mutually complementary diagnostic tools for suspected focal pancreatic lesions.

An Oxygen-Sufficient Nanoplatform for Enhanced Imaging-Guided Microwave Dynamic Therapy Against Hypoxic Tumors.

Background: Microwave dynamic therapy (MDT) as a novel reactive oxygen species (ROS)-based therapeutic modality has been explored as a promising modality for cancer treatment. However, the intrinsic hypoxic tumor microenvironment (TME) restricted the effectiveness of the MDT. The aim of this study is to develop an oxygen-sufficient nanoplatform with multi-modal imaging capability for enhanced MDT against hypoxic tumors. Methods and Materials: The liquid perfluorocarbon-based nanoplatform PFP@IR780@O2 was constructed by the phospholipid hydration and sonication method. Then, the characteristics, intracellular uptake process, and subcellular localization of PFP@IR780@O2 were verified. Additionally, the abilities of ROS generation, the anti-hypoxia capability, multi-mode imaging capabilities, and MDT efficacy of the nanoplatform were evaluated via in vitro and in vivo experiments. Finally, the in vivo biocompatibility and toxicity were also evaluated. Results: The prepared nanoparticles PFP@IR780@O2 exhibited suitable size, improved stability, elevated dissolved oxygen level, enhanced cellular uptake, and mitochondria targeting capacity. Additionally, PFP@IR780@O2 demonstrated in vitro and in vivo multimodal imaging capabilities involving ultrasound, fluorescence, and photoacoustic imaging. In vivo studies also indicated that nanoparticles were safe and capable of accumulating in the tumor site after intravenous injection. Furthermore, the PFP@IR780@O2 nanoplatform mediated MDT could effectively alleviate the hypoxic TME, and elevate ROS concentration, thereby resulting in significant tumor growth inhibition. Conclusion: Overall, the oxygen-sufficient nanoplatform with multi-bimodal imaging capability demonstrated improved MDT efficiency, indicating a promising strategy for treating hypoxic tumors.

Differentiating malignant and benign focal liver lesions in children using CEUS LI-RADS combined with serum alpha-fetoprotein.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) can be used to diagnose focal liver lesions (FLLs) in children. The America College of Radiology developed the CEUS liver imaging reporting and data system (LI-RADS) for standardizing CEUS diagnosis of FLLs in adult patients. Until now, no similar consensus or guidelines have existed for pediatric patients to improve imaging interpretation as adults. AIM: To evaluate the performance of CEUS LI-RADS combined with alpha-fetoprotein (AFP) in differentiating benign and malignant FLLs in pediatric patients. METHODS: Between January 2011 and January 2021, patients ≤ 18 years old who underwent CEUS for FLLs were retrospectively evaluated. The following criteria for diagnosing malignancy were proposed: Criterion I considered LR-4, LR-5, or LR-M lesions as malignancies; criterion II regarded LR-4, LR-5 or LR-M lesions with simultaneously elevated AFP (≥ 20 ng/mL) as malignancies; criterion III took LR-4 Lesions with elevated AFP or LR-5 or LR-M lesions as malignancies. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) were calculated to determine the diagnostic value of the aforementioned criteria. RESULTS: The study included 63 nodules in 60 patients (mean age, 11.0 ± 5.2 years; 26 male). There were no statistically significant differences between the specificity, accuracy, or AUC of criterion II and criterion III (95.1% vs 80.5%, 84.1% vs 87.3%, and 0.794 vs 0.902; all P > 0.017). Notably, criterion III showed a higher diagnostic sensitivity than criterion II (100% vs 63.6%; P < 0.017). However, both the specificity and accuracy of criterion I was inferior to those of criterion II and criterion III (all P < 0.017). For pediatric patients more than 5 years old, the performance of the three criteria was overall similar when patients were subcategorized by age when compared to all patients in aggregate. CONCLUSION: CEUS LI-RADS combined with AFP may be a powerful diagnostic tool in pediatric patients. LR-4 with elevated AFP, LR-5 or LR-M lesions is highly suggestive of malignant tumors.

Profiling hepatocellular carcinoma aggressiveness with contrast-enhanced ultrasound and gadoxetate disodium-enhanced MRI: An intra-individual comparative study based on the Liver Imaging Reporting and Data System.

PURPOSE: Contrast-enhanced ultrasound (CEUS) and gadoxetate disodium-enhanced MRI (EOB-MRI) may synergize in profiling hepatocellular carcinoma (HCC) aggressiveness considering distinct imaging traits. This study aimed to intra-individually compare CEUS and EOB-MRI with Liver Imaging Reporting and Data System (LI-RADS) in assessing HCC aggressiveness. METHOD: From January 2015 to November 2020, consecutive at-risk patients with surgically-confirmed HCC who underwent both preoperative CEUS and EOB-MRI examinations were retrospectively enrolled. Image analyses were conducted independently by two masked radiologists for CEUS and EOB-MRI, respectively. The diagnostic performance of each modality for macrovascular invasion against pathology was evaluated and compared with the McNemar's test, while Edmondson-Steiner grade and the presence of microvascular invasion (MVI) were compared between patients with and without LR-M features on each modality. RESULTS: A total of 140 patients (mean age, 51.9 years ± 11.0; 116 men) were included. Inter-modality agreement was poor (κ = -0.087 âˆ¼ 0.139) for major LI-RADS features and moderate (κ = 0.449) for overall LI-RADS categorization, and LR-TIV and LR-M were the top sources of inter-modality variations. Although CEUS demonstrated significantly higher specificity for diagnosing macrovascular invasion (96% vs. 89%, P =.02), LR-M features on EOB-MRI were more effective in identifying higher Edmondson-Steiner grades (P =.01) and MVI (P =.02). CONCLUSIONS: Marked discrepancies were found between CEUS and EOB-MRI in evaluating LI-RADS features and categories. Whereas CEUS showed superior diagnostic specificity for macrovascular invasion, LR-M features on EOB-MRI provided more information regarding tumor grade and MVI status in HCC patients.

Development and validation of an ultrasound-based prediction model for differentiating between malignant and benign solid pancreatic lesions.

OBJECTIVE: To identify the diagnostic ability of precontrast and contrast-enhanced ultrasound (CEUS) in differentiating between malignant and benign solid pancreatic lesions (MSPLs and BSPLs) and to develop an easy-to-use diagnostic nomogram. MATERIALS AND METHODS: This study was approved by the institutional review board. Patients with pathologically confirmed solid pancreatic lesions were enrolled from one tertiary medical centre from March 2011 to June 2021 and in two tertiary institutions between January 2015 and June 2021. A prediction nomogram model was established in the training set by using precontrast US and CEUS imaging features that were independently associated with MSPLs. The performance of the prediction model was further externally validated. RESULTS: A total of 155 patients (mean age, 55 ± 14.6 years, M/F = 84/71) and 78 patients (mean age, 59 ± 13.4 years, M/F = 36/42) were included in the training and validation cohorts, respectively. In the training set, an ill-defined border and dilated main pancreatic duct on precontrast ultrasound, CEUS patterns of hypoenhancement in both the arterial and venous phases of CEUS, and hyperenhancement/isoenhancement followed by washout were independently associated with MSPLs. The prediction nomogram model developed with the aforementioned variables showed good performance in differentiating MSPLs from BSPLs with an area under the curve (AUC) of 0.938 in the training set and 0.906 in the validation set. CONCLUSION: Hypoenhancement in all phases, hyperenhancement/isoenhancement followed by washout on CEUS, an ill-defined border, and a dilated main pancreatic duct were independent risk factors for MSPLs. The nomogram constructed based on these predictors can be used to diagnose MSPLs. KEY POINTS: • An ill-defined border and dilated main pancreatic duct on precontrast ultrasound, hypoenhancement in all phases of CEUS, and hyperenhancement/isoenhancement followed by washout were independently associated with MSPLs. • The ultrasound-based prediction model showed good performance in differentiating MSPLs from BSPLs with an AUC of 0.938 in the training set and 0.906 in the external validation set. • An ultrasound-based nomogram is an easy-to-use tool to differentiate between MSPLs and BSPLs with high efficacy.

Quantitative and qualitative characterization of retinal dystrophies in canine models of inherited retinal diseases using spectral domain optical coherence tomography (SD-OCT).

The purpose of this study was to establish spectral domain optical coherence tomography (SD-OCT) assessment data in well-established canine models of inherited retinal dystrophies: PDE6B-rod-cone dysplasia 1 (RCD1: early onset retinitis pigmentosa), PRCD-progressive rod-cone degeneration (PRCD: late onset retinitis pigmentosa), CNGB3-achromatopsia, and RPE65-Leber congenital amaurosis (LCA). High resolution SD-OCT images of the retina were acquired from both eyes in 5 planes: temporal; superotemporal; superior; nasal; and inferior in adult dogs with: RCD1 (n = 4 dogs, median age: 1.5 yrs); PRCD (n = 2, 4.3 yrs); LCA (n = 3, 5.2 yrs); achromatopsia (n = 3, 4.2 yrs); and wild types (wt, n = 6, 5.5 yrs). Total, inner and outer retinal thicknesses and ellipsoid zone were analyzed. In selected animals, histomorphometric evaluations were performed. In dogs with RCD1, PRCD, and LCA, the thickness of the outer retina was, compared to wt, significantly decreased (p ≤ 0.02) in all OCT imaging planes, and in superotemporal and inferior imaging planes in dogs with achromatopsia. No significant thinning was observed in inner retina thickness in any disease model except in the inferior imaging plane in dogs with RCD1. Dogs with RCD1, PRCD, and LCA had significantly more areas with disrupted ellipsoid zone in the presumed area centralis than wt (p ≤ 0.001). OCT findings provide baseline information for research of retinal dystrophies using these canine models.

Contrast-enhanced ultrasound manifestations of synchronous combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma: A case report.

BACKGROUND: Synchronous combined hepatocellular-cholangiocarcinoma (CHC) and hepatocellular carcinoma (HCC) is very rare, with few literature reports and poor clinical outcomes associated with the disorder. Surgical resection is the main treatment, which makes the preoperative diagnosis very important. However, due to imaging manifestations overlapping with HCC, diagnosis of this type of synchronous cancer is challenging and it tends to be misdiagnosed as multiple HCC. Herein, we report the contrast-enhanced ultrasound (CEUS) manifestations of a case of synchronous CHC and HCC, aiming at adding to the understanding of this disease. CEUS displayed exquisite vascularity and tissue perfusion in real time with good spatial and temporal resolution and more accurately reflect tumor washin and washout times than contrast-enhanced computed tomography (CT) in this case. CASE SUMMARY: The patient was a 69-year-old female with a 20-year history of chronic hepatitis B. Due to months of epigastric pain and anorexia, she reffered to our hospital for treatment. Five days before hospitalization, abdominal magnetic resonance imaging performed at another hospital detected a space-occupying lesion in the liver. After her hospitalization, laboratory tests showed elevated alpha-fetoprotein and carbohydrate antigen 19-9 level. Two suspicious liver lesions located in S4 and S6, respectively, were identified in a cirrhotic background by abdominal contrast-enhanced CT (CECT). Furthermore, the lesion in S4 and S6 were detected by CEUS and assigned to CEUS LI-RADS 5 and M categories, respectively. The patient underwent tumor radical resections. Post-operative pathology confirmed the S4 and S6 lesions to be HCC and CHC, respectively. A newly-found suspicious liver nodule with potential malignancy was detected in liver S1 by both CEUS and CECT 7 mo after operation. CONCLUSION: The CEUS characteristics of CHC and HCC are different. CEUS features in combination with clinical information could help in effective diagnosis, clinical decision-making and better prognosis.

Stachydrine hydrochloride inhibits hepatocellular carcinoma progression via LIF/AMPK axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is not only one of the four highest malignancies, but also the principal reason of cancer-related death worldwide, yet no effective medication for anti-HCC is available. Stachydrine hydrochloride (SH), an alkaloid component in Panzeria alaschanica Kupr, exhibits potent antitumor activity in breast cancer. However, the anti-HCC effects of SH remain unknown. PURPOSE: Our study assessed the therapeutic effect of SH on HCC and tried to clarify the mechanisms by which it ameliorates HCC. No studies involving using SH for anti-HCC activity and molecular mechanism have been reported yet. STUDY DESIGN/METHODS: We examined the cell viability of SH on HCC cells by MTT assay. The effect of SH on cell autophagy in HCC cells was verified by Western blot and Immunofluorescence test. Flow cytometry was performed to assess cell-cycle arrest effects. Cell senescence was detected using ß-Gal staining and Western blot, respectively. An inhibitor or siRNA of autophagy, i.e., CQ and si LC-3B, were applied to confirm the role of autophagy acted in the anti-cancer function of SH. Protein expression in signaling pathways was detected by Western blot. Besides, molecular docking combined with cellular thermal shift assay (CETSA) was used for analysis. Patient-derived xenograft (PDX) model were built to explore the inhibitory effect of SH in HCC in vivo. RESULTS: In vitro studies showed that SH possessed an anti-HCC effect by inducing autophagy, cell-cycle arrest and promoting cell senescence. Specifically, SH induced autophagy with p62 and LC-3B expression. Flow cytometry analysis revealed that SH caused an obvious cell-cycle arrest, accompanied by the decrease and increase in Cyclin D1 and p27 levels, respectively. Additionally, SH induced cell senescence with the induction of p21 in HCC cell lines. Mechanistically, SH treatment down-regulated the LIF and up-regulated p-AMPK. Moreover, PDX model in NSG mice was conducted to support the results in vitro. CONCLUSION: This study is the first to report the inhibitory function of SH in HCC, which may be due to the induction of autophagy and senescence. This study provides novel insights into the anti-HCC efficacy of SH and it might be a potential lead compound for further development of drug candidates for HCC.

Cavernous hemangioma of an intrapancreatic accessory spleen mimicking a pancreatic tumor: A case report.

BACKGROUND: Intrapancreatic accessory spleen (IPAS) is an uncommon condition, with the majority of cases presenting as solid lesions. Thus, this condition is frequently misdiagnosed as pancreatic solid neoplasm. Moreover, splenic cavernous hemangioma is a rare disorder, whereas lesions with a cystic appearance arising from IPAS have not been reported. CASE SUMMARY: Herein, we present a case involving a 32-year-old male who had a complex cystic lesion in the tail of the pancreas revealed by conventional ultrasound. The lesion was misdiagnosed as a pancreatic cystadenoma because of its confusing anatomic location, as well as due to its peripheral nodular and internal septal enhancement patterns on contrast-enhanced ultrasound. After multidisciplinary discussion, the patient finally underwent laparoscopic pancreatic body and tail resections. Postoperative pathology demonstrated the lesion to be a cavernous hemangioma arising from the IPAS. CONCLUSION: Cavernous hemangioma in the intrapancreatic accessory spleen may mimic pancreatic cystadenoma, which is a condition with the potential to be malignant. Imaging follow-ups or surgical interventions may be helpful for the exclusion of malignant risks in complicated cystic lesions, especially those with parietal and septal enhancements.