RRAGB-mediated suppression of PI3K/AKT exerts anti-cancer role in glioblastoma.

Glioblastoma (GBM) has a high degree of invasiveness, which is largely attributed to the invalidation of current therapy and the unclear tumor growth mechanism. Ras related GTP binding B (RRAGB) is a family member of the Ras-homologous GTPases. The effect of RRAGB on tumor growth has been recognized, but its influences on GBM progression are ill-defined. Here, in our research, a significantly decreased expression of RRAGB in GBM tissues by using TCGA databases and glioma samples is observed. According to Kaplan-Meier (KM) analysis, RRAGB low expression leads to a significant decrease of overall survival rate of patients, and is associated with the classification of WHO grade, histological type and age increase. Functional enrichment analysis reveals that the pathway of enrichment includes cell cycle arrest, extracellular matrix (ECM) processes and PI3K/AKT signal. Thereafter, our cell experiments confirm an obvious decrease of RRAGB in several GBM cell lines. It should be noted that RRAGB promotion strongly reduces the proliferation, migration and invasion of GBM cells and induces cell cycle arrest in G0/G1 phase. RRAGB up-regulation significantly decreases the expression of PI3K, phosphorylated AKT, mTOR and S6K in GBM cell lines. Surprisingly, we further find that RRAGB-restrained proliferative, migratory and invasive properties of GBM cells are markedly offset after promoting AKT activation, accompanied with restored phosphorylation of mTOR and S6K, elucidating that AKT signaling blockage is partially indispensable for RRAGB to play its anti-cancer role in GBM. Animal studies confirmed that RRAGB over-expression obviously inhibits the tumor growth both in the xenograft and orthotopic mouse glioma models, along with improved overall survival rates. In short, we provide evidence that RRAGB is a potential therapeutic target and prognostic marker for GBM treatment.

HCC treated with immune checkpoint inhibitors: a hyper-enhanced rim on Sonazoid-CEUS Kupffer phase images is a predictor of tumor response.

OBJECTIVES: We aimed to evaluate the efficacy of anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibody therapy by assessing the hyper-enhanced rim phenomenon of hepatocellular carcinoma (HCC) on Sonazoid-contrast-enhanced ultrasound (CEUS) Kupffer phase images. METHODS: This retrospective study included 61 patients with HCC who received anti-PD-1/PD-L1 antibody therapy from August 1, 2020, to January 31, 2022. We compared the progression-free survival (PFS) of patients with hyper-enhanced rim+ and hyper-enhanced rim-nodules and the time to nodule progression (TTnP) of hyper-enhanced rim+ and hyper-enhanced rim- nodules. RESULTS: Thirty-nine patients received postoperative therapy, and 22 patients had unresectable HCC. The mean PFS was 11.8 months (95% confidence interval [CI]: 8.7-14.9) for patients with hyper-enhanced rim+ HCC nodules and 16.5 months (95% CI: 14.9-18.1) for patients with hyper-enhanced rim- HCC nodules in the surgery group (p = 0.017). The mean PFS was 9.2 months (95% CI: 3.6-14.8) for patients with hyper-enhanced rim+ HCC nodules and 17.8 months (95% CI: 14.9-20.6) for patients with hyper-enhanced rim- HCC nodules in the non-surgery group (p = 0.015). For hyper-enhanced rim+ HCC nodules, TTnP for each nodule exceeding the specified threshold was 10.1 months, whereas that for hyper-enhanced rim- HCC nodules was 17.6 months (p = 0 .018). The disease control rate was 42.9% (3/7) for hyper-enhanced rim+ HCC nodules and 85.7% (21/24) for hyper-enhanced rim- HCC nodules (p = 0.013). CONCLUSIONS: The presence of hyper-enhanced rim on the Kupffer phase images obtained via the non-invasive Sonazoid-CEUS is a promising imaging biomarker for predicting unfavorable response with anti-PD-1/PD-L1 therapy in patients with HCC. KEY POINTS: • The mean progression-free survival was 11.8 months for patients with hyper-enhanced rim+ HCC nodules and 16.5 months for patients with hyper-enhanced rim- HCC nodules in the surgery group. • The mean progression-free survival was 9.2 months for patients with hyper-enhanced rim+ HCC nodules and 17.8 months for patients with hyper-enhanced rim- HCC nodules in the non-surgery group. • The disease control rate was 42.9% for hyper-enhanced rim+ HCC nodules and 85.7% for hyper-enhanced rim- HCC nodules (p = 0.013).

Analysis of Sonazoid contrast-enhanced ultrasound for predicting the risk of microvascular invasion in hepatocellular carcinoma: a prospective multicenter study.

OBJECTIVES: The aim of this study was to evaluate the potential of Sonazoid contrast-enhanced ultrasound (SNZ-CEUS) as an imaging biomarker for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: From August 2020 to March 2021, we conducted a prospective multicenter study on the clinical application of Sonazoid in liver tumor; a MVI prediction model was developed and validated by integrating clinical and imaging variables. Multivariate logistic regression analysis was used to establish the MVI prediction model; three models were developed: a clinical model, a SNZ-CEUS model, and a combined model and conduct external validation. We conducted subgroup analysis to investigate the performance of the SNZ-CEUS model in non-invasive prediction of MVI. RESULTS: Overall, 211 patients were evaluated. All patients were split into derivation (n = 170) and external validation (n = 41) cohorts. Patients who had MVI accounted for 89 of 211 (42.2%) patients. Multivariate analysis revealed that tumor size (> 49.2 mm), pathology differentiation, arterial phase heterogeneous enhancement pattern, non-single nodular gross morphology, washout time (< 90 s), and gray value ratio (≤ 0.50) were significantly associated with MVI. Combining these factors, the area under the receiver operating characteristic (AUROC) of the combined model in the derivation and external validation cohorts was 0.859 (95% confidence interval (CI): 0.803-0.914) and 0.812 (95% CI: 0.691-0.915), respectively. In subgroup analysis, the AUROC of the SNZ-CEUS model in diameter ≤ 30 mm and ˃ 30 mm cohorts were 0.819 (95% CI: 0.698-0.941) and 0.747 (95% CI: 0.670-0.824). CONCLUSIONS: Our model predicted the risk of MVI in HCC patients with high accuracy preoperatively. CLINICAL RELEVANCE STATEMENT: Sonazoid, a novel second-generation ultrasound contrast agent, can accumulate in the endothelial network and form a unique Kupffer phase in liver imaging. The preoperative non-invasive prediction model based on Sonazoid for MVI is helpful for clinicians to make individualized treatment decisions. KEY POINTS: • This is the first prospective multicenter study to analyze the possibility of SNZ-CEUS preoperatively predicting MVI. • The model established by combining SNZ-CEUS image features and clinical features has high predictive performance in both derivation cohort and external validation cohort. • The findings can help clinicians predict MVI in HCC patients before surgery and provide a basis for optimizing surgical management and monitoring strategies for HCC patients.

Evaluation of contrast-enhanced ultrasound LI-RADS version 2017: application on 271 liver nodules in individuals with non-alcoholic steatohepatitis.

OBJECTIVES: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) version 2017 in a population with non-alcoholic steatohepatitis (NASH). METHODS: Between January 2013 and December 2020, consecutive patients diagnosed with NASH with untreated liver nodules were enrolled in this retrospective study. A prospective evaluation was performed between January 2021 and August 2021 as a validation set. Diagnostic performance was assessed. RESULTS: We included 217 nodules in 211 patients (mean age, 49.7 ± 21.7 years; male, 156) in the retrospective study. The positive predictive value (PPV) of CEUS LR-5 in the diagnosis of hepatocellular carcinoma (HCC) was 70.8% (56/79). In total, 28 of 217 (12.9%) nodules were classified as LR-M, of which 12 showed arterial phase hyper-enhancement, early washout, and absence of a punched-out appearance within 5 min; 10 of the 12 (83%) were HCC. When these nodules were reclassified as LR-5, the specificity of LR-M as a predictor of non-HCC malignancy increased from 91.0 (181/199) to 96.5% (192/199) (p = .023). Despite the reclassification, LR-5 specificity and PPV remained high (80.6% and 72.5%, respectively). Following reclassification, LR-M specificity increased from 90.0 (45/50) to 100% (50/50) (p = .022) in the validation set. CONCLUSION: CEUS LI-RADS category LR-5 is effective in predicting the presence of HCC. In NASH patients, diagnostic performance can be further improved by reclassifying LR-M nodules with arterial phase hyper-enhancement, early washout, and punched-out appearance as LR-5. KEY POINTS: • The LI-RADS classification of CEUS has a high application value for differentiation of HCC in NASH patients. • When LR-M nodules with arterial phase hyperenhancement and early washout but not punched-out appearance at < 5 min are reclassified as LR-5; the modification of LI-RADS has a better performance. • The PPV of modified LR-5 in the non-cirrhotic group was better than that of LR-5. The PPV of modified CEUS LR-5 in the non-cirrhotic group was comparable to that in the cirrhotic group (p both = 0.065).

[Effect of Rehmanniae Radix on depression-like behavior and hippocampal monoamine neurotransmitters of chronic unpredictable mild stress model rats].

To investigate the effect of Rehmanniae Radix on depression-like behavior and monoamine neurotransmitters of chronic unpredictable mild stress(CUMS) model rats. CUMS combined with isolated feeding was used to induce the depression model of rats. The depression-like behavior of rats was evaluated by sucrose preference test, open field test, and forced swim test. Hematoxylin-Eosin(HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS) was used to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), 3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), norepinephrine(NE), and 3-methoxy-4-hydroxyphenyl glycol(MHPG) in rats. Western blot was used to detect the protein expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), and monoamine oxidase A(MAO-A) in the hippocampus of rats. Compared with the normal group, depressive-like behavior of rats was obvious in the model group. The arrangements of neurons in the CA1 and CA3 area of hippocampus were loose and disorderly. The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in the hippocampal area were decreased(P<0.01). The protein expression of TPH2 was decreased(P<0.01), but those of SERT and MAO-A were increased(P<0.01). In the Rehmanniae Radix groups with 1.8 g·kg~(-1) and 7.2 g·kg~(-1), the depression-like behavior of CUMS rats and pathological changes of neurons in CA1, CA3 area of hippocampus were improved. The protein expression of TPH2(P<0.05, P<0.01) was increased, and those of SERT and MAO-A were down-regulated(P<0.05, P<0.01). The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in hippocampus were increased(P<0.05, P<0.01). The changes in DA, DOPAC, HVA, DA/(DOPAC +HVA), NE, DHPG, and NE/DHPG were not statistically significant. The results suggested that Rehmanniae Radix improved depression-like behavior of CUMS rats, and the mechanism might be related to the regulation of synthesis, transportation, and metabolism of 5-HT neurotransmitter in the hippocampus.

Ultrasound contrast agent Sonazoid for the diagnosis of hepatic epithelioid angiomyolipoma: a case report.

BACKGROUND: An angiomyolipoma usually occurs in the kidneys and rarely in the liver. Hepatic epithelioid angiomyolipoma (HEAML), a rare variant of angiomyolipoma, possesses malignant potential and mimics the imaging features of hepatocellular carcinoma. Sonazoid® (perfluorobutane microbubbles), a new contrast agent that facilitates hepatic parenchyma-specific Kupffer phase imaging on contrast-enhanced ultrasonography (CEUS), is useful for the detection and characterization of focal liver lesions. CASE PRESENTATION: A 30-year-old man with HEAML underwent CEUS using Sonazoid®, in which new concepts for ultrasonography-based differentiation between HEAML and hepatocellular carcinoma were applied. CONCLUSIONS: This case report provides clinicians and radiologists with a reference for distinguishing HEAML from hepatocellular carcinoma based on CEUS using Sonazoid®.

Long-term outcomes of ultrasound-guided percutaneous microwave ablation versus resection for colorectal cancer liver metastases: a propensity-score matched study.

BACKGROUND AND AIMS: Many previous studies comparing liver resection versus thermal ablation for colorectal cancer liver metastases (CRCLM) are subject to severe selection bias. This study aimed to compare the long-term clinical efficacy of ultrasonography-guided percutaneous microwave ablation (PMWA) with resection for CRCLM using propensity score analysis to reduce confounding by indication. METHODS: This retrospective study included 184 patients with CRCLM from January 2012 to June 2017. Treatment effect was estimated after propensity score matching, Descriptive, regression and survival statistics were applied. RESULTS: A lower American Society of Anesthesiologists classification score and higher performance status were found positively associated with resection (p < 0.05). After propensity score matching, the 1-, 2-, and 3-year local tumor progression free survival rates were found to be 60.3%, 19.1%, and 17.6% in the PMWA group, and 72.1%, 35.3%, 26.5% in the resection group, respectively (p = 0.049). The 1-, 3-, 5-, and 7-year overall survival rates in two groups were similar (p = 0.943). In the PMWA group and resection group, the median hospital stay was 1 (0-12) days and 7 (1-27) days (p = 0.005), respectively; major complications occurred in two patients (2%) and 11 patients (12.9%) (p = 0.009), respectively. CONCLUSIONS: After adjusting for factors known to affect treatment choice, no significant difference in overall survival rates was shown after ultrasound-guided PMWA versus resection for CRCLM. The LTPFS rate of the resection group were better than those of the ultrasound-guided PMWA group. However, the ultrasound-guided PMWA group had fewer complications and shorter hospital stay.

[Study on protective effect of total flavonoids from Rosa multiflora on HUVEC induced by ox-LDL].

The aim of this paper was to study the protective effect of total flavonoids from Rosa multiflora(TF-RM) on the injury of HUVEC induced by oxidized low density lipoprotein(ox-LDL). SPF male SD rats were randomly divided into blank group, simvastatin group(1.8 mg·kg~(-1)·d~(-1)) and TF-RM group(2.5 g·kg~(-1)·d~(-1)), with 10 rats in each group. They were intragastrically administered with drugs for 7 days, and then blood was collected from the abdominal aorta to prepare drug-containing serum. The HUVEC injury model was established through ox-LDL induction, and added with 15% simvastatin, 5% TF-RM, 10% TF-RM, 15% TF-RM drug-containing serum and blank serum, respectively. Reactive oxygen species(ROS) was determined by flow cytometry. Nitric oxide(NO) content was determined by nitrate reductase method. The contents of ET-1, P-selectin, E-selectin, ICAM-1, VCAM-1, IL-1ß, IL-6 and TNF-α were determined by ELISA. The expression of Lox-1 protein was determined by Western blot. Compared with the blank group, ROS level in HUVEC and the contents of ET-1, P-selectin, E-selectin, ICAM-1, VCAM-1 and IL-1ß in HUVEC were significantly increased(P<0.05), NO decreased significantly(P<0.01),Lox-1 protein expression increased significantly(P<0.05), and TNF-α and IL-6 showed an increasing trend. Compared with the model group, TF-RM significantly reduced ROS level in HUVEC and ET-1, P-selectin, E-selectin, ICAM-1, TNF-α, IL-1ß content in supernatant(P<0.05), significantly increased NO content(P<0.01), and inhibited Lox-1 protein expression(P<0.05). VCAM-1, IL-6 contents showed a decreasing trend. Serum containing TF-RM acts on lectin-like oxidized low-density lipoprotein receptors, and exerts a protective effect on vascular endothelial cells by reducing cell oxidative damage, regulating vasoactive substances, and reducing adhesion molecules and inflammatory cascades.

[Guanxin Zhitong Capsules attenuate human endothelial cell damage induced by palmitic acid via MAPK signaling pathway].

The present study observed the effect of Guanxin Zhitong Capsules(GXZT) on the lipotoxicity of vascular endothelial cells and investigated the mechanism of GXZT in atherosclerosis treatment. The lipotoxicity model in human umbilical vein endothelial cells(HUVECs) was induced by palmitic acid(PA) stimulation. These cells were divided into a normal control group(NC, 15% normal serum), a model group(PA, 0.6 mmol·L~(-1) PA+15% normal serum), a high-dose GXZT group(GXZT-H, 0.6 mmol·L~(-1) PA+15% GXZT-medicated serum), a medium-dose GXZT group(GXZT-M, 0.6 mmol·L~(-1) PA+10% GXZT-medicated serum+5% normal serum) and a low-dose GXZT group(GXZT-L, 0.6 mmol·L~(-1) PA+5% GXZT-medicated serum+10% normal serum). HUVECs were detected for cell viability by cell counting kit-8(CCK-8) assay, apoptosis by flow cytometry, mitochondrial membrane potential(MMP) by JC-1 labeled laser scanning confocal microscopy, and total and phosphorylated proteins of p38, ERK1/2, and JNK1/2 in the mitogen-activated protein kinases(MAPK) signaling pathway by Western blot. The phosphorylated level was calcula-ted. Compared with the NC group, the PA group showed decreased cell viability and MMP(P<0.01, P<0.01), elevated apoptosis(P<0.01), and up-regulated phosphorylated levels of p38, ERK1/2, and JNK1/2(P<0.01, P<0.01, P<0.01). Compared with the PA group, the GXZT-H, GXZT-M, and GXZT-L groups showed increased cell viability and MMP(P<0.01, P<0.01, P<0.01), reduced apoptosis(P<0.01), and down-regulated protein expression and phosphorylated levels of p38, ERK1/2 and JNK1/2 in the MAPK signaling pathway(P<0.01, P<0.01, P<0.01). In conclusion, the results suggest that GXZT functions via blocking MAPK signaling pathway to relieve the damage of HUVECs induced by PA.

[Protective effect of serum containing ginseng and Moutan Cortex on HUVEC injured by H_2O_2].

This study aimed to investigate the effect of serum containing ginseng and Moutan Cortex on human umbilical vein endothelial cells(HUVEC) injured with hydrogen peroxide(H_2O_2). HUVEC injured with H_2O_2 were divided into 6 groups, namely blank group, model group, ginsenoside(TGG) group, total glucosides of Moutan Cortex(TGM) group, paeonol(P) group and TGG+TGM+P group. After 24 hours of co-culture with H_2O_2, the activities of succinate dehydrogenase(SDH) and Ca~(2+)-Mg~(2+)-ATP were detected by microenzyme labeling. The apoptosis rate, intracellular Ca~(2+) concentration, reactive oxygen species(ROS) and mitochondrial membrane potential(JC-1) were detected by flow cytometry. The expressions of mitochondrial apoptosis pathway-related proteins Bax, Bcl-2, cytochrome C, caspase-3 and caspase-9 were detected by Western blot. The results showed that H_2O_2 could significantly damage HUVEC, decrease the activity of SDH and Ca~(2+)-Mg~(2+)-ATP(P<0.01), while could increase the apoptosis+necrosis rate, JC-1 decline rate, ROS increase rate and Ca~(2+) concentration increase rate(P<0.01). Serum containing ginseng and Moutan Cortex could increase the activities of SDH and Ca~(2+)-Mg~(2+)-ATP to different degrees, decrease the apoptosis+necrosis rate, JC-1 decline rate, ROS increase rate and Ca~(2+) concentration increase rate(P<0.05 or P<0.01), and down-regulate the protein expressions of Bax, caspase-3, caspase-9, cytochrome C, and up-regulate the protein expression of Bcl-2. The results showed that serum containing ginseng and Moutan Cortex has a protective effect on vascular endothelial cell injury induced by ROS, and its mechanism may be related to the improvement of mitochondrial function and the inhibition of the activation of mitochondrial apoptosis pathway.

Dexamethasone prevents the Epstein-Barr virus induced epithelial-mesenchymal transition in A549 cells.

Clinical data have shown that pulmonary interstitial fibrosis is likely to occur in the later stages of viral pneumonia. While viral infections are thought to cause chronic pulmonary interstitial inflammation and pulmonary fibrosis, it remains unclear if they promote pulmonary fibrosis by epithelial-mesenchymal transition (EMT). In this study, human epithelial cell line A549 has been used to model the infection of the Epstein-Barr virus (EBV) and the respiratory syncytial virus (RSV). Their differences were compared and the possible infection mechanisms analyzed by randomly assigning cells to one of five treatments. Exposure of the LMP1 is thought to be the key gene during EBV-induced EMT in the A549 cells. Enzyme-linked immunosorbent assay analysis revealed that the EBV infection was associated with the induction of a number of cytokines (interleukin-8 [IL-8], IL-13, tumor necrosis factor-α, and transforming growth factor-ß) and dexamethasone (DXM) could significantly prevent the phenotypic changes, and partly the mechanisms related with the IL-13 pathway. Surprisingly, different results were seen with the RSV infection as the A549 cells still displayed an epithelial morphology but the levels of E-cadherin, α-SMA, vimentin, and fibronectin did not change. This is the first study demonstrating the different reactions induced by different viruses, and the protective effects of DXM on the EBV-induced EMT in the A549 cells by partially inhibiting the IL-13 pathway. These findings suggest a novel mechanism, by which DXM or anti-IL-13 may delay the progression of pulmonary fibrosis by preventing the progress of EBV-induced EMT.

Predictors of fatality including radiographic findings in adults with COVID-19.

BACKGROUND: Older age and elevated d-dimer are reported risk factors for coronavirus disease 2019 (COVID-19). However, whether early radiographic change is a predictor of fatality remains unknown. METHODS: We retrospectively reviewed records of all laboratory-confirmed patients admitted to a quarantine unit at Tongji Hospital, a large regional hospital in Wuhan, China, between January 31 and March 5, 2020. Confirmed cases were defined by positive RT-PCR detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in throat-swab specimens. Chest CT images were reviewed independently by two radiologists. The Tongji Hospital ethics committee approved this study. RESULTS: A total of 102 patients were confirmed to have SARS-CoV-2 infection. As of March 25, 85 confirmed patients were discharged, 15 died, and 2 remained hospitalized. When compared with survivors, non-survivors were older (median age, 69 [interquartile range, 58-77] vs. 55 [44-66], p = 0.003), and more likely to have decreased lymphocyte count (0.5 vs. 0.9 ×  109/L, p = 0.006), elevated lactate dehydrogenase (LDH) (569.0 vs. 272.0 U/L, p < 0.001), elevated d-dimer (> 1 µg/mL, 86% vs. 37%, p = 0.002) on admission. Older age and elevated LDH were independent risk factors for fatality in a multivariate regression model included the above variables. In a subset of patients with CT images within the first week, higher total severity score, and more involved lung lobes (5 involved lobes) in CT images within the first week were significantly associated with fatality. Moreover, in this subset of patients, higher total severity score was the only independent risk factor in a multivariate analysis incorporating the above mentioned variables. CONCLUSIONS: Older age, elevated LDH on admission, and higher severity score of CT images within the first week are potential predictors of fatality in adults with COVID-19. These predictors may help clinicians identify patients with a poor prognosis at an early stage.

Hepatic Angiomyolipoma: Clinical Features and Imaging Findings of Quantitative Contrast-Enhanced Ultrasound Perfusion Analysis and Magnetic Resonance Imaging.

OBJECTIVES: To investigate whether quantitative contrast-enhanced ultrasound (CEUS) analysis and magnetic resonance imaging (MRI) can differentiate hepatic angiomyolipoma (AML) from hepatocellular carcinoma (HCC) and hepatic epithelial angiomyolipoma (EAML) from nonepithelial AML. METHODS: Retrospective analysis of 26 CEUS lesions pathologically confirmed as AML and 60 patients with confirmed HCC. Clinical and ultrasound (US) features of AML versus HCC and EAML versus nonepithelial AML were analyzed. Quantitative parameters, including arrival time, ascending slope, time to peak, peak intensity (PI), fall time (FT), and mean transit time (MTT), were analyzed. Diagnostic performance of MRI and CEUS was compared. RESULTS: Angiomyolipoma was significantly different from HCC in US findings of solitary tumor (P < .001), well-defined border (P = .025), and hyperechogenicity (P < .001). Tumor types were significantly different in US findings of centripetal filling pattern (P < .001), less hypoenhancement in the CEUS delayed phase (P = .04), high PI (P = .007) and ascending slope (P = .006), and short FT (P = .001) and MTT (P < .05). The sensitivity and specificity of quantitative parameters were 61.5% to 96.2% and 55.0% to 71.7% (area under the curve, 0.642-0.773). An early draining vein and tumor vessels, intratumor fat, absence of pseudocapsules, mild signal intensity on diffusion-weighted imaging, and hypointensity in the MRI delayed phase were helpful for differentiation of AML from HCC (P < .05). The positive predictive values of CEUS and MRI were 46.3% to 100% and 42.9% to 75%, with no significant difference (P > .05). Epithelial AML was more likely to be hypoechoic with a centripetal filling pattern than nonepithelial AML (P < .05). The MTT and FT of EAML were shorter than those of nonepithelial AML (P < .05). The PI of EAML was significantly stronger than that of nonepithelial AML (P < .01). The sensitivity and specificity of quantitative parameters were 68.7% to 100.0% and 60.0% to 100.0% (area under the curve, 0.825-0.941). Less intratumor fat was helpful for differentiation of EAML from nonepithelial AML (P < .05). The positive predictive values of CEUS and MRI were 77.8% to 100% and 85.7%, with a significant difference (P < .05). CONCLUSIONS: Quantitative CEUS findings could be valuable in differentiating EAML from HCC.

Evaluation of Scoliosis With a Commercially Available Ultrasound System.

OBJECTIVES: Currently, radiography with measurement of the Cobb angle is still considered the reference standard for diagnosing scoliosis. However, the ionizing radiation hazard is drawing wide attention. Can 3-dimensional (3D) ultrasound (US) be an alternative modality for diagnosing and monitoring patients with scoliosis? The aim of our study was to assess the reliability and validity of 3D US imaging in the evaluation of scoliosis. METHODS: A commercially available ultrasound system with a magnetic tracking system was selected for long-distance 3D US imaging. Straight phantoms and curved phantoms were scanned with the imaging system to evaluate the stability of the system for curvature measurements. Eight healthy adult volunteers and 28 patients with scoliosis were recruited for long-distance 3D US imaging. The intraclass correlation coefficient was used to test the reproducibility of the interobserver and intraobserver measurements for both the healthy adults and patients with scoliosis. A linear regression analysis and Bland-Altman plot were used to analyze the correlation and to determine the extent of agreement between the angles measured on US images and the Cobb angles measured on conventional radiographs. RESULTS: The 28 patients with scoliosis included 10 male and 18 female patients aged 8 to 37 years (mean age ± SD, 17.7 ± 1.4 years; body mass index, <25 kg/m2 ). In the phantom study, there was no statistically significant difference between the angles measured by the 3D US imaging system and those measured by an angle gauge (P > 0.05). In the clinical study, there was very good interobserver and intraobserver reliability (intraclass correlation coefficients, >0.90) for the US imaging system, with a high correlation (r2 = 0.92) and agreement between the US and radiographic methods. CONCLUSIONS: The long-distance 3D US imaging system offers a viable modality for diagnosing and monitoring scoliosis without radiation.

Contrast-enhanced ultrasonography of intraluminal inferior vena cava leiomyosarcoma: A case report.

Primary leiomyosarcoma of the inferior vena cava (IVC) is a rare and fatal disease. Imaging is the main diagnostic method. CT and MRI images of IVC leiomyosarcoma have been published, but ultrasonographic features have been scarcely described, especially with contrast-enhancement. We report the case of a patient in whom ultrasonography incidentally revealed a mass in the IVC. Contrast-enhanced ultrasonography showed heterogeneous enhancement in the arterial phase with some irregular non-enhanced areas, and mild clearance in the venous phase. The location and nature of the lesion as shown by ultrasonography were confirmed by CT and MRI.

[Long-term outcomes of percutaneous microwave ablation versus repeat hepatectomy for treatment of late recurrent small hepatocellular carcinoma: a retrospective study].

OBJECTIVE: To compare the effectiveness of percutaneous microwave ablation with those of repeat hepatectomy in the treatment of late recurrent small hepatocellular carcinoma measuring ≤ 5 cm (interval of recurrence from initial hepatectomy was > 12 months). METHODS: 66 patients who underwent initial hepatectomy for primary liver cancer in April 1998 to December 2010, and subsequent initial recurrent hepatocellular carcinoma treated with percutaneous microwave ablation or repeat hepatectomy, were enrolled in the study. Among these patients 39 were treated with percutaneous microwave ablation and 27 were treated with repeat hepatectomy. Technique effectiveness was evaluated by means of contrast enhanced techniques one month after ablation. The overall survival and disease-free survival were evaluated by using the Kaplan-Meier method. RESULTS: The technique effectiveness rate determined one month after ablation was 94.9%. The 1, 3, and 5 year overall survival rates were 86.2%, 73.3%, and 62.2%, respectively, for the microwave ablation group and 96.2%, 76.9%, and 61.2%, respectively, for the repeat hepatectomy group (P = 0.471). The corresponding recurrence-free survival rates were 65.8%, 28.0%, and 14.0%, respectively, for the microwave ablation group and 66.7%, 50.7%, and 43.4%, respectively, for the repeat hepatectomy group (P = 0.323). CONCLUSIONS: In patients with late recurrent small hepatocellular carcinoma, Percutaneous microwave ablation was efficient, and showed similar long-term survival and recurrence-free survival compared with repeat hepatectomy.

CEUS in prediction of early recurrence of hepatocellular carcinoma after curative resection and to stratify the risk of early recurrence: a retrospective observational study.

PURPOSE: Early recurrence (ER) after surgery is related to early death in patients with hepatocellular carcinoma (HCC) after radical resection. To explore the role of preoperative contrast-enhanced ultrasound (CEUS) in predicting ER of HCC after curative resection and to stratify the risk of ER. MATERIALS AND METHODS: This study evaluated consecutive 556 patients with HCC who were examined by CEUS during the 2 weeks before curative resection between January 2011 and December 2018. ER was defined as intrahepatic and/or extrahepatic recurrence within 2 year after resection of HCC. Univariate and logistic regression analyses were performed to identify independent risk factors for ER after surgical resection of HCC. Recurrence-free time (RFS) rates were analyzed and compared by log-rank test. RESULTS: ER occurred in 307 (55.2%) of the 556 patients. Univariate and multivariate analyses revealed that a tumor size ≥ 30 mm and satellite nodules seen on CEUS, DL(deep learning) radiomics reoccurrence score based on the frame of image with the maximum intensity of CEUS and an elevated alpha-fetoprotein level were significantly associated with ER (P < .05). Based on the number of predictors present, patients with CEUS LR-5 HCC were stratified into three risk subgroups: risk group 3 (high-risk patients, 4 predictors), risk group 2 (medium-risk patients, 2-3 predictors), and risk group 1 (low-risk patients, 0-1 predictor). The 2-year RFS rate was 19.4% in risk group 3, 40.9% in risk group 2, and 48.1% in risk group 1; the corresponding mean RFS times were 14.0 ± 2.9 months, 43.7 ± 6.6 months, and 55.5 ± 2.8 months, respectively (P < .001). CONCLUSIONS: Tumor size ≥ 30 mm and satellite nodules seen on CEUS, DL radiomics reoccurrence score based on the frame of image with the maximum intensity of CEUS and an elevated alpha-fetoprotein level can predict ER of HCC.

Comparison of Sonazoid-Contrast­Enhanced Ultrasound and Gd­EOB­DTPA­Enhanced MRI for Predicting Microvascular Invasion in Hepatocellular Carcinoma.

OBJECTIVE: This study aims to evaluate and compare the predictive accuracy of Sonazoid-contrast-enhanced ultrasound (CEUS) and Gd-EOB-DTPA-enhanced MRI for detecting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: In this single-center prospective study, we included 64 patients with histopathologically confirmed single HCC lesions. Based on post-operative pathologic data, patients were categorized into two groups: those with MVI (n = 21) and those without MVI (n = 43). The diagnostic efficacy of CEUS was compared with that of MRI in predicting MVI. RESULTS: Multifactorial analysis revealed that US features (tumor size > 4.35 cm, peritumoral enhancement, post-vascular ring enhancement, peak energy in the arterial phase of the difference between the margin area of HCC and distal liver parenchyma <-1.0 × 106 a.u), MRI features (rim enhancement, irregular tumor margin, and the halo sign) were all independent predictors of MVI (p < 0.05). The sensitivity and specificity of CEUS features in predicting MVI ranged from 61.9% to 86.4% and from 42.9% to 71.4%, respectively. For MRI features, the sensitivity and specificity ranged from 33.3% to 76.3% and from 54.7% to 90.5%, respectively. No statistically significant differences were observed in the area under the curve between CEUS and MRI (p > 0.05). Notably, peak energy of the difference showed the highest sensitivity at 86.4%, while the halo sign in MRI exhibited the highest specificity at 90.5%. CONCLUSION: Sonazoid-CEUS and Gd-EOB-DTPA-enhanced MRI demonstrate potential in predicting MVI in HCC lesions. Notably, CEUS showed higher sensitivity, whereas MRI displayed greater specificity in predicting MVI.

Unified Multi-Modal Image Synthesis for Missing Modality Imputation.

Multi-modal medical images provide complementary soft-tissue characteristics that aid in the screening and diagnosis of diseases. However, limited scanning time, image corruption and various imaging protocols often result in incomplete multi-modal images, thus limiting the usage of multi-modal data for clinical purposes. To address this issue, in this paper, we propose a novel unified multi-modal image synthesis method for missing modality imputation. Our method overall takes a generative adversarial architecture, which aims to synthesize missing modalities from any combination of available ones with a single model. To this end, we specifically design a Commonality- and Discrepancy-Sensitive Encoder for the generator to exploit both modality-invariant and specific information contained in input modalities. The incorporation of both types of information facilitates the generation of images with consistent anatomy and realistic details of the desired distribution. Besides, we propose a Dynamic Feature Unification Module to integrate information from a varying number of available modalities, which enables the network to be robust to random missing modalities. The module performs both hard integration and soft integration, ensuring the effectiveness of feature combination while avoiding information loss. Verified on two public multi-modal magnetic resonance datasets, the proposed method is effective in handling various synthesis tasks and shows superior performance compared to previous methods.

Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE. METHODS: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-a-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to assess the biologic function of RhoA. An enzyme-linked immunoassay (ELISA) measured C-X-C motif chemokine ligand 10 (CXCL10) protein expression. RESULTS: Our studies demonstrate that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than in healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2'-5'-oligoadenylate synthetase 1 (OAS1). Finally, we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in the PBMCs of SLE patients. CONCLUSION: Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.