Glycosylated AIE-active Red Light-triggered Photocage with Precisely Tumor Targeting Capability for Synergistic Type I Photodynamic Therapy and CPT Chemotherapy.

Photocaging is an emerging protocol for precisely manipulating spatial and temporal behaviors over biological activity. However, the red/near-infrared light-triggered photolysis process of current photocage is largely singlet oxygen (1O2)-dependent and lack of compatibility with other reactive oxygen species (ROS)-activated techniques, which has proven to be the major bottleneck in achieving efficient and precise treatment. Herein, we reported a lactosylated photocage BT-LRC by covalently incorporating camptothecin (CPT) into hybrid BODIPY-TPE fluorophore via the superoxide anion radical (O2-•)-cleavable thioketal bond for type I photodynamic therapy (PDT) and anticancer drug release. Amphiphilic BT-LRC could be self-assembled into aggregation-induced emission (AIE)-active nanoparticles (BT-LRCs) owing to the regulation of carbohydrate-carbohydrate interactions (CCIs) among neighboring lactose units in the nanoaggregates. BT-LRCs could simultaneously generate abundant O2-• through the aggregation modulated by lactose interactions, and DNA-damaging agent CPT was subsequently and effectively released. Notably, the type I PDT and CPT chemotherapy collaboratively amplified the therapeutic efficacy in HepG2 cells and tumor-bearing mice. Furthermore, the inherent AIE property of BT-LRCs endowed the photocaged prodrug with superior bioimaging capability, which provided a powerful tool for real-time tracking and finely tuning the PDT and photoactivated drug release behavior in tumor therapy.

Whole-Genome Resequencing of Worldwide Wild and Domestic Sheep Elucidates Genetic Diversity, Introgression, and Agronomically Important Loci.

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.

Malignant transformation of rectal endometriosis: Preoperative diagnosis by endorectal ultrasound guided biopsy.

The prevalence of malignant transformation of endometriotic lesions is estimated between 0.3% and 1%. Malignant transformations of endometriosis occur in the colorectum is rarer, accounting for 0.25%. Because the malignant transformation of colorectal endometriosis rarely involves mucosa, it is difficult to obtain abnormal tissue by routine endoscopic biopsy. In this case, we evaluated a patient with a rectal mass by endorectal ultrasound (ERUS) and performed endorectal ultrasound-guided biopsy (EGB). Malignant transformations of endometriosis were confirmed by histological result. For patients with rectal tumors but with negative findings on colonoscopy and biopsy, ERUS and EGB contribute to preoperative diagnosis.

In Situ Self-Assembled J-Aggregate Nanofibers of Glycosylated Aza-BODIPY for Synergetic Cell Membrane Disruption and Type†I Photodynamic Therapy.

The in situ self-assembly of exogenous molecules is a powerful strategy for manipulating cellular behavior. However, the direct self-assembly of photochemically inert constituents into supramolecular nano-photosensitizers (PSs) within cancer cells for precise photodynamic therapy (PDT) remains a challenge. Herein, we developed a glycosylated Aza-BODIPY compound (LMBP) capable of self-assembling into J-aggregate nanofibers in situ for cell membrane destruction and type I PDT. LMBP selectively entered human hepatocellular carcinoma HepG2 cells and subsequently self-assembled into intracellular J-aggregate nanovesicles and nanofibers through supramolecular interactions. Detailed studies revealed that these J-aggregate nanostructures generated superoxide radicals (O2 - ⋅) exclusively through photoinduced electron transfer, thus enabling effective PDT. Furthermore, the intracellular nanofibers exhibited an aggregation-induced retention effect, which resulted in selective toxicity to HepG2 cells by disrupting their cellular membranes and synergizing with PDT for powerful tumor suppression efficacy in vivo.

Contrast-Enhanced Ultrasound Imaging Features of Focal Chemotherapy-Induced Sinusoidal Injury in Patients With Colorectal Cancer: Initial Experience.

OBJECTIVES: Increasing studies have reported focal chemotherapy-induced sinusoidal injury (CSI) mimicking colorectal liver metastasis (CRLM) on imaging studies, resulting in unnecessary lobectomy. This study aimed to investigate the contrast-enhanced ultrasound (CEUS) imaging features of focal CSI. METHODS: We retrospectively evaluated 16 patients who had a pathologic diagnosis of focal CSI and underwent CEUS between January 2013 and January 2019. The images were compared with those obtained from 27 patients with CRLM. RESULTS: On CEUS, 14 (87.5%) focal CSIs showed heterogeneous isoenhancement, 1 (6.3%) peripheral hyperenhancement, and 1 (6.3%) homogeneous hyperenhancement during the arterial phase. Compared with the adjacent liver parenchyma, the initial enhancement time of focal CSI was earlier in 2 (12.5%), simultaneous in 9 (56.3%), and later in 5 (31.3%) patients. In the portal and late phases, all of the focal CSI cases showed hypoenhancement compared with the adjacent liver parenchyma. Focal CSI had the following CEUS findings, which were different from those of CRLM: (1) heterogeneous isoenhancement in the arterial phase (87.5% versus 0%; P < .001); (2) an initial enhancement time later than that of the liver parenchyma (mean ± SD, 0.5 ± 1.5 versus -1.5 ± 1.9; P < .001); (3) a longer time to peak (30.5 ± 5.6 versus 22.5 ± 4.4 seconds; P < .001); and (4) a later time to wash-out (51.0 ± 12.5 versus 35.0 ± 6.2 seconds; P = .002). CONCLUSIONS: Focal CSI usually shows heterogeneous isoenhancement in arterial phase and hypoenhancement in portal and late phases on CEUS, with slow contrast wash-in and wash-out, which can be helpful in the differential diagnosis with CRLM.

Multiparametric ultrasomics of significant liver fibrosis: A machine learning-based analysis.

OBJECTIVE: To assess significant liver fibrosis by multiparametric ultrasomics data using machine learning. MATERIALS AND METHODS: This prospective study consisted of 144 patients with chronic hepatitis B. Ultrasomics-high-throughput quantitative data from ultrasound imaging of liver fibrosis-were generated using conventional radiomics, original radiofrequency (ORF) and contrast-enhanced micro-flow (CEMF) features. Three categories of features were explored using pairwise correlation and hierarchical clustering. Features were selected using diagnostic tests for fibrosis, activity and steatosis stage, with the histopathological results as the reference. The fibrosis staging performance of ultrasomics models with combinations of the selected features was evaluated with machine-learning algorithms by calculating the area under the receiver-operator characteristic curve (AUC). RESULTS: ORF and CEMF features had better predictive power than conventional radiomics for liver fibrosis stage (both p < 0.01). CEMF features exhibited the highest diagnostic value for activity stage (both p < 0.05), and ORF had the best diagnostic value for steatosis stage (both p < 0.01). The machine-learning classifiers of adaptive boosting, random forest and support vector machine were found to be optimal algorithms with better (all mean AUCs = 0.85) and more stable performance (coefficient of variation = 0.01-0.02) for fibrosis staging than decision tree, logistic regression and neural network (mean AUC = 0.61-0.72, CV = 0.07-0.08). The multiparametric ultrasomics model achieved much better performance (mean AUC values of 0.78-0.85) than the features from a single modality in discriminating significant fibrosis (≥ F2). CONCLUSION: Machine-learning-based analysis of multiparametric ultrasomics can help improve the discrimination of significant fibrosis compared with mono or dual modalities. KEY POINTS: • Multiparametric ultrasomics has achieved much better performance in the discrimination of significant fibrosis (≥ F2) than the single modality of conventional radiomics, original radiofrequency and contrast-enhanced micro-flow. • Adaptive boosting, random forest and support vector machine are the optimal algorithms for machine learning.

The local efficacy and influencing factors of ultrasound-guided percutaneous microwave ablation in colorectal liver metastases: a review of a 4-year experience at a single center.

PURPOSE: To investigate the clinical effectiveness and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for colorectal liver metastasis (CRLM) and evaluate the influencing factors of local efficacy. METHODS: From January 2013 to January 2017, 137 CRLM patients accepting US-guided percutaneous MWA were included. The 2450-MHz microwave ablation system and a cooled-shaft antenna were used. All patients were regularly followed up for at least 6 months. Technical success, complete ablation, local tumor progression (LTP), complications and side effects were assessed. Logistic regression analysis was used to identify the independent prognostic factors for LTP. RESULTS: In total, 411 lesions (mean diameter 15.4 ± 7.2 mm, range 5-67 mm) were treated. Complete ablation was achieved in 99.27% (408/411) of lesions and 97.81% (134/137) of patients. LTP occurred in 5.35% (22/411) of lesions and 16.06% (22/137) of patients. LTP was more likely to occur in lesions larger than 3 cm in diameter (OR: 14.71; p < .001; 95% CI: 3.7 3-57.92), near a large vascular structure (OR: 7.04; p < .001; 95% CI: 2.41-20.60), near the diaphragm (OR: 4.02; p = .049; 95% CI: 1.05-16.11) and in patients with no response to chemotherapy before MWA (OR: 3.25; p = .032; 95% CI: 1.14-15.30). MWA was well tolerated, with a major complication rate of 3.65%, a minor complication rate of 8.03% and a mortality rate of 0%. Fever and pain were the most common side effects after MWA. CONCLUSIONS: US-guided percutaneous MWA of CRLM is a safe and effective method that is expected to become a routine treatment for local tumor control of CRLM.

Whole-Genome Sequencing of Native Sheep Provides Insights into Rapid Adaptations to Extreme Environments.

Global climate change has a significant effect on extreme environments and a profound influence on species survival. However, little is known of the genome-wide pattern of livestock adaptations to extreme environments over a short time frame following domestication. Sheep (Ovis aries) have become well adapted to a diverse range of agroecological zones, including certain extreme environments (e.g., plateaus and deserts), during their post-domestication (approximately 8-9 kya) migration and differentiation. Here, we generated whole-genome sequences from 77 native sheep, with an average effective sequencing depth of ∼5× for 75 samples and ∼42× for 2 samples. Comparative genomic analyses among sheep in contrasting environments, that is, plateau (>4,000 m above sea level) versus lowland (<100 m), high-altitude region (>1500 m) versus low-altitude region (<1300 m), desert (<10 mm average annual precipitation) versus highly humid region (>600 mm), and arid zone (<400 mm) versus humid zone (>400 mm), detected a novel set of candidate genes as well as pathways and GO categories that are putatively associated with hypoxia responses at high altitudes and water reabsorption in arid environments. In addition, candidate genes and GO terms functionally related to energy metabolism and body size variations were identified. This study offers novel insights into rapid genomic adaptations to extreme environments in sheep and other animals, and provides a valuable resource for future research on livestock breeding in response to climate change.

Maternal IGF1 and IGF1R polymorphisms and the risk of spontaneous preterm birth.

BACKGROUND: The insulin-like growth factor (IGF) pathway was involved in the occurrence of spontaneous preterm birth (SPTB), but little is known regarding the relationship between genetic variations in IGF pathway and the risk of SPTB. We aimed to investigate the associations of IGF1 rs972936 and IGF1 receptor (IGF1R) rs2229765 polymorphisms with SPTB risk in a Chinese population. METHOD: A total of 114 cases of SPTB and 250 controls of term delivery were included from Guangzhou Women and Children's Medical Center, China. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated using multivariate logistic regression. RESULTS: We found that the GA and GA/AA genotypes of IGF1 rs972936 were associated with an increased risk of SPTB, and the adjusted ORs (95% CI) were 1.74 (1.01-3.02) and 1.75 (1.04-2.93) respectively. Women carrying GA and GA/AA genotypes of IGF1R rs2229765 had a reduced risk compared to those with the GG genotype (0.60 [0.37-0.98] and 0.64 [0.40-1.00] respectively). There were significant interactions between IGF1 rs972936 and GDM status (P for interaction=.02), as well as between IGF1R rs2229765 and pre-pregnancy BMI (P for interaction <.001) on the risk of SPTB. CONCLUSION: Our findings suggest that polymorphisms of IGF1 rs972936 and IGF1R rs2229765 were associated with the risk of SPTB in Chinese pregnant women and these effects depend on the maternal metabolic status.

Assessment of liver fibrosis in chronic hepatitis B using acoustic structure quantification: quantitative morphological ultrasound.

OBJECTIVES: To prospectively investigate the usefulness of acoustic structure quantification (ASQ) for noninvasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: Consecutive patients with CHB scheduled for liver biopsy or partial liver resection underwent standardized ASQ examinations. The ASQ parameter, named focal disturbance (FD) ratio, were compared with METAVIR scores. The analysis was based on receiver operating characteristic (ROC) curves and multiple regression analysis. RESULTS: A total of 114 patients were enrolled in the final analysis. The area under the ROC curve for the FD ratio was 0.84 for significant fibrosis (≥ F2), 0.86 for severe fibrosis (≥ F3), and 0.83 for cirrhosis (= F4). The optimal cutoff values for the FD ratio were 0.25, 0.30 and 0.50 for fibrosis stages ≥ F2, ≥ F3 and = F4, respectively. The prevalence of a difference of at least two stages between the FD ratio and the histological stage was 12.3 % (14 of 114). The fibrosis stage (P < 0.001), degree of steatosis (P < 0.001) were independent factors associated with the FD ratio. CONCLUSIONS: FD ratio should be an effective noninvasive imaging biomarker for the assessment of liver fibrosis in patients with CHB. KEY POINTS: • Focal disturbance (FD) ratio increased with the increasing histological fibrosis stages. • FD ratio showed promising diagnostic accuracy in assessing liver fibrosis. • Degree of fibrosis and steatosis were independent factors associated with FD ratio.

Differentiation of Atypical Hepatocellular Carcinoma from Focal Nodular Hyperplasia: Diagnostic Performance of Contrast-enhanced US and Microflow Imaging.

PURPOSE: To evaluate diagnostic performance of contrast-enhanced (CE) ultrasonography (US) and microflow (MF) imaging in differentiation of atypical hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH). MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived. A total of 103 patients (mean age, 43.9 years; age range, 17-75 years) were included; 38 patients with HCC and 65 with FNH underwent CE US, and vascular architecture pattern (VAP) and arrival time parametric (ATP) images were analyzed. Resident and staff radiologists independently and retrospectively reviewed CE US, VAP, and ATP images. χ(2) test and logistic regression analysis were applied to identify specific features of FNH or HCC on CE US and MF images. To compare diagnostic performance of CE US with or without MF imaging, four sets of criteria were assigned: (a) routine CE US alone, (b) VAP and CE US, (c) ATP imaging and CE US, and (d) all three methods in combination. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of resident and staff radiologists were analyzed. Cohen κ statistic was used to assess agreement of CE US and MF imaging features between staff and resident radiologists. RESULTS: MF imaging offered significant improvements over most detection rates achieved with routine CE US signs in both groups. For staff radiologists, AUCs from criteria sets 3 (AUC = 0.873, P < .05) and 4 (AUC = 0.887, P < .05) were significantly higher than AUC from criteria set 1 (AUC = 0.835). For resident radiologists, specificity (71% and 69% vs 25%, P < .01) and accuracy (78% and 79% vs 50%, P < .01) of criteria sets 3 and 4 were significantly higher than those of criteria set 1. Moreover, AUCs for criteria sets 2 (AUC = 0.728, P < .05), 3 (AUC = 0.823, P < .01), and 4 (AUC = 0.857, P < .01) were significantly higher than those for criteria set 1 (AUC = 0.667). CONCLUSION: When compared with routine CE US, MF imaging can more effectively depict specific features and offers improved diagnostic performance in the differentiation of atypical HCC from FNH, especially when used by resident radiologists. Online supplemental material is available for this article.

Diagnostic accuracy of two-dimensional shear wave elastography for the non-invasive staging of hepatic fibrosis in chronic hepatitis B: a cohort study with internal validation.

OBJECTIVES: To determine the accuracy of two-dimensional shear wave elastography (2D-SWE) for noninvasive staging of hepatic fibrosis in chronic hepatitis B (CHB). METHODS: Patients with CHB infection who underwent liver biopsy were consecutively included. Receiver-operating characteristic (ROC) curves were constructed to assess the overall accuracy and identify optimal cutoff values. RESULTS: Three hundred three patients were analysed. The diagnostic performance characteristics were determined for the first 202 patients (the index cohort) and were validated on the next 101 patients (validation cohort). The areas under the ROC curves for significant fibrosis, severe fibrosis and cirrhosis were all greater than 0.90 and did not differ significantly between the index and validation cohorts. Using the cutoff values generated from the index cohort, the validation cohort 2D-SWE had negative predictive values of 82.6 % (95 % confidence interval [CI]: 68.4 % - 92.3 %) for significant fibrosis, 95.1 % (95 % CI: 86.3 % - 99.0 %) for severe fibrosis and 97.4 % (95 % CI: 90.8 % - 99.7 %) for cirrhosis. The positive predictive values were 83.6 % (95 % CI: 71.2 % - 92.2 %), 65.0 % (95 % CI: 48.1 - 79.5 %) and 60.0 % (95 % CI: 38.7 % - 78.9 %), respectively. CONCLUSION: The 2D-SWE showed good diagnostic accuracy in staging liver fibrosis in patients with CHB infection and assisted in excluding liver fibrosis and cirrhosis. KEY POINTS: • Two-dimensional shear wave elastography showed good diagnostic accuracy in assessing liver fibrosis. • Diagnostic performance did not differ significantly between the index and validation cohorts. • Two-dimensional shear wave elastography assisted in excluding liver fibrosis and cirrhosis.

Preliminary experience of a new perspective view technology for the detection of portal vein thrombus in hepatocellular carcinoma patients.

OBJECTIVE: To assess the feasibility and efficiency of a perspective view technology (Fly Thru) for the detection of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients. METHODS: Fly Thru was performed in 79 HCC patients. The images were reviewed off-site for evaluation of the imaging quality and diagnosis. Pathology and/or contrast-enhanced CT was used as the reference standard for PVTT. The diagnostic quality of the images, presences of PVTT, and patency of the target vessels were recorded by two-dimensional ultrasound (2DUS) and Fly Thru image. The diagnostic performances of resident and staff radiologists were compared between 2DUS with or without off-line Fly Thru. RESULTS: Fly Thru was performed successfully in 43 of 79 patients (54.4%). The Fly Thru Imaging quality was good in 30/43 patients (69.8%), suboptimal but diagnostic in 10/43 (23.2%), and non-diagnostic in the remaining 3/43 (7.0%). PVTTs were detected in 31 patients according to the reference standard, with 8 in the main portal vein, 15 in the first branch, and 8 in the second branch of the portal vein. The agreement was good between conventional 2DUS and Fly Thru (κ = 0.783, p = 0.000). There was a significant association between the quality and the ability of Fly Thru in the detection of PVTTs (p = 0.001). The diagnostic performance for both readers between 2DUS with or without Fly Thru showed no statistically significant differences, except for the sensitivity for resident radiologist. The sensitivity of 2DUS (71.0%, 22/31) for resident radiologists was lower than that of Fly Thru as an adjunctive diagnostic tool (90.3%, 28/31) (p = 0.041). CONCLUSION: Fly Thru is of diagnostic quality and can provide useful information for the detection of PVTT in HCC patients.

Percutaneous radiofrequency ablation of malignant liver tumors with ultrasound and CT fusion imaging guidance.

BACKGROUND: To evaluate the feasibility, accuracy, and utility of sonography (US) and CT fusion imaging guidance for radiofrequency ablation (RFA) of malignant liver tumors not visualized on conventional US. METHODS: Seventy-seven patients with hepatocellular carcinoma and 15 patients with metastatic liver cancer with a total of 136 lesions underwent RFA with US and CT fusion imaging guidance. The mean number of punctures, success rate of a single ablation session, local tumor progression rates, and long-term outcome were evaluated. Treatment efficacy was evaluated by dynamic CT and contrast-enhanced US 1 month after RFA. RESULTS: RFA was technically feasible in all patients, and no major complications occurred. The mean ± SD time needed to synchronize US and CT images was 13.9 ± 11.9 minutes (range, 5-55 minutes). The success rate of a single ablation session was 83.8% (114/136), and tumor residue was present in 7.4% of lesions (10/136). The mean number of treatment sessions was 1.2 ± 0.5 sessions. During follow-up, local tumor progression was observed for 15 (11.9%) lesions. Distant tumor recurrence was found in 51 (55.4%) patients. CONCLUSIONS: US and CT fusion-assisted RFA is a safe and efficacious treatment for patients with hepatocellular carcinoma and metastatic liver cancer.

Recent advances in sugar-based AIE luminogens and their applications in sensing and imaging.

Most fluorogens with aggregation-induced emission (AIE) characteristics are hydrophobic and most common sugars are hydrophilic and naturally nontoxic. The combination of AIEgens and sugars can construct glycosyl AIEgens with the advantages of good water-solubility, low fluorescent background and satisfactory biocompatibility. Based on the specific reaction or binding with analytes to change the conjugate system or restrict intramolecular motions, glycosyl AIEgens can be used as powerful tools for detecting bioactive molecules or imaging living cells. In this feature article, we summarize recent advances in sugar-based AIE luminogens and their applications in biosensing and imaging. The sugar units could significantly increase the solubility, biocompatibility, target activity, and chemical modifying capacity and often decrease the background fluorescence of the AIE probes. Corresponding studies not only expand the application fields of AIEgens but also provide effective tools for broad carbohydrate research.

Numerical study on the characteristics of roadway failure and instability in coal seam with rock parting.

In order to explore the mechanism of rockburst in coal seam with rock parting, a combination of on-site and numerical experiment is used to study the failure and instability process, crack propagation mechanism, and influencing factors. The following four points were addressed: (1) the instability is a process that roadway in coal seam with rock parting go through from stable locking in the initial stress unloading stage to slipping unlocking, and then to spatter ejection in slipping dynamic load disturbance stage. (2) The fracture development caused by unloading excavation of coal seam with rock parting will change from shear crack to tensile crack. In this process, coal-rock contact surface slip and coal-rock fracture are coupled with each other. (3) The greater the mining depth is, the greater the lateral pressure coefficient is, and the higher the rockburst risk is. On the contrary, the lower the risk of rockburst. (4) When choosing the support form of roadway in coal seam with rock parting, the two supporting forms of bolting (cable) and supplementary masonry support should be preferred. The results enrich the theory of the dynamics of surrounding rock fracture in coal mine, further clarify the potential dangers to mining-area roadways and working faces, and provide technical information to ensure the safe and efficient mining of bifurcated coal seam.

Contrast-enhanced ultrasound features of histologically proven focal nodular hyperplasia: diagnostic performance compared with contrast-enhanced CT.

OBJECTIVES: To investigate and compare contrast-enhanced ultrasound (CEUS) in the characterisation of histologically proven focal nodular hyperplasia (FNH) with contrast-enhanced computed tomography (CECT). METHODS: CEUS was performed in 85 patients with 85 histologically proven FNHs. Enhancement, centrifugal filling, spoke-wheel arteries, feeding artery and central scarring were reviewed and correlated with lesion size or liver background. Independent factors for predicting FNH from other focal liver lesions (FLLs) were evaluated. Forty-seven FLLs with CECT were randomly selected for comparison of diagnostic performance with CEUS. RESULTS: Centrifugal filling was more common (P = 0.002) and the significant predictor (P = 0.003) in FNHs ≤3 cm. Lesion size or liver background has no significant influence on the detection rate of the spoke-wheel arteries and feeding artery (P > 0.05). Central scarring was found in 42.6 % of FNHs ≥3 cm (P = 0.000). The area under the ROC curve, sensitivity and specificity showed no significant differences between CEUS and CECT (P > 0.05), except that the sensitivity of CEUS was better for reader 1 (P = 0.041). CONCLUSION: CEUS is valuable in characterising centrifugal filling signs or spoke wheels in small FNHs and should be employed as the first-line imaging technique for diagnosis of FNH. KEY POINTS: • The confident diagnosis of focal nodular hyperplasia is important in liver imaging. • The centrifugal filling sign is useful for diagnosis of FNHs ≤3 cm. • Contrast-enhanced ultrasound and contrast-enhanced CT have similar diagnostic performance for FNH. • CEUS should be the first-line imaging technique for the diagnosis of FNH.

Sorafenib suppresses the rapid progress of hepatocellular carcinoma after insufficient radiofrequency ablation therapy: an experiment in vivo.

BACKGROUND: Radiofrequency ablation (RFA) is a widely applied treatment for hepatocellular carcinoma (HCC), but insufficient RFA can promote rapid progression of the residual tumor through the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) pathway. Although sorafenib has been successfully applied to advanced HCC, the use of sorafenib in residual tumor cells after RFA has rarely been tested. PURPOSE: To evaluate the potential role of sorafenib as an adjunct to RFA to reduce the recurrence rate after insufficient RFA. MATERIAL AND METHODS: Xenograft tumors of SMMC 7721 were created by subcutaneously inoculating nude mice with hepatoma cells (5 × 10(6) cells per mouse). Fourteen days after inoculation, all mice were divided into three groups (control group [sham puncture], RFA group, and RFA combined with sorafenib treatment group) with six mice in each group. Each group was given a different treatment procedure. After treatment, the volume of the tumors was calculated from the resected specimens. The mRNA and protein expression of HIF-1α and VEGFA was quantified by real-time PCR and immunohistochemistry analysis. The micro-vessel density (MVD) was determined by CD34 immunohistochemistry. RESULTS: Real-time PCR and immunohistochemistry analysis showed that, compared to the RFA group, HIF-1α and VEGFA expression were significantly decreased in the group that received RFA combined with sorafenib treatment (P < 0.05). By comparing the control group with the RFA group, we found that insufficient RFA promoted HIF-1α and VEGFA expression (P < 0.05). Similar results were obtained for MVD expression. Additionally, the combination of RFA with sorafenib therapy resulted in a synergistic reduction in tumor growth compared to insufficient RFA and sham puncture (P < 0.05). CONCLUSION: Sorafenib was able to inhibit the expression of HIF-1α and VEGFA, and sorafenib was able to increase time to recurrence when used as an adjunct to RFA.

Evaluation of the vascular architecture of focal liver lesions using micro flow imaging.

OBJECTIVES: To identify the vascular architecture of focal liver lesions using micro flow imaging and compare it with characteristics on contrast harmonic imaging during the arterial phase. METHODS: Micro flow imaging and contrast harmonic imaging were performed in 118 patients with various focal liver lesions: hepatocellular carcinoma (n = 70), metastasis(n = 19), intrahepatic cholangiocarcinoma (n = 3), lymphoma (n = 1), hemangioma (n = 17), and focal nodular hyperplasia (n = 8). The vascular architecture of the lesions on micro flow imaging was evaluated by 2 investigators independently to reveal 6 patterns (types IVI). Enhancement characteristics on contrast harmonic imaging were also evaluated. RESULTS: Inter-reader agreement for delineating the vascular architecture was higher on contrast harmonic imaging (κ= 0.856) than micro flow imaging (κ= 0.613). On micro flow imaging, the vascular patterns of hepatocellular carcinomas were types I (28.6%), II (65.7%), and III (5.7%). On contrast harmonic imaging, 44 of 70 (62.9%) hepatocellular carcinomas showed chaotic vessels, of which 40 were type II and 4 were type II. The vascular patterns of metastases were types IV (78.9%), I (10.5%), and II (10.5%). Typical rim enhancement was identified in 57.9% of metastases on contrast harmonic imaging, and all were type IV. The vascular patterns of focal nodular hyperplasia were types VI (87.5%) and I (12.5%). Typical spoked wheel arteries were identified on contrast harmonic imaging in 2 focal nodular hyperplasia cases. The vascular patterns of hemangiomas were types V (94.1%) and II (5.9%). Typical peripheral nodular enhancement was identified in 88.2% of hemangiomas on contrast harmonic imaging, and all were type V. The χ(2) test revealed that differences in vascular architecture between the lesions were significant on micro flow imaging (P < .001). CONCLUSIONS: Micro flow imaging permitted detailed delineation of the vascular architecture of focal liver lesions. Hepatocellular carcinoma, metastasis, focal nodular hyperplasia, and hemangioma showed characteristic vascular architecture.

A unilateral brachiocephalic vein thrombosis: cause of a rare, transient ischemic attack, a case report and review of the literature.

The purpose of this report is to inform medical professionals of a case in which brachiocephalic vein thrombosis caused a transient ischemic attack (TIA). A brain computerized tomography (CT) scan, magnetic resonance imaging, digital subtraction angiography, head and lung CT angiography, jugular venography, cardiac color Doppler ultrasound scan, color Doppler ultrasound scan of the neck and lower vascular extremities and 24-hour, continuous electrocardiogram monitoring were performed. A 50-year-old male experienced a total of 31 onsets of weakness in the right side of his body, speech impairment and numbness in the right side of his body during a period of 20 days. Imaging results did not reveal evidence of a cerebral infarction. The potential of a TIA with an arterial origin and other causes were ruled out, and a left brachiocephalic vein thrombosis and left jugular vein congestion were discovered. Thus, the brachiocephalic vein thrombosis was considered to be the cause of the TIA. The patient received anticoagulant and antiplatelet aggregation treatment. On the following day after the termination of the TIA, a color Doppler ultrasound scan detected the opening of the jugular venous arch, but the blood flow that returned to the superior vena cava via the left brachiocephalic vein did not significantly increase. A brachiocephalic vein thrombosis can be the cause of a TIA. In addition to the anticoagulant and antiplatelet aggregation treatment, the opening of the collateral of veins, including that of the jugular venous arch, may play an important role in reducing venous congestion and in terminating TIAs.