Comparison of contrast-enhanced ultrasonography and MRI results obtained by expert and novice radiologists indicating short-term response after transarterial chemoembolisation for hepatocellular carcinoma.

AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.

[Association between the ApoB/A1 ratio and the vulnerability of LMCA plaque in the patients with stable angina pectoris].

Objective: To investigate the relationship between ApoB/A1 ratio and the characteristics of tissue components of their left main coronary artery(LMCA)plaque. Methods: A total of 98 patients with stable angina pectoris who received chronic statin treatment underwentpercutaneous coronary intervention in the People's Hospital of Henan Province from June 2010 to June 2016 were included.We prospectively performed intravascular ultrasound virtualhistology (IVUS-VH) to their LMCA and evaluated the tissue characteristics, and the blood level of total cholesterol (TC) and low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), triglyceride(TG), LDL-C/HDL-C ratio, ApoB, ApoA1, ApoB/A1 ratio were measured, then the association of the tissue characteristics with the aboved lipids values were analyzed. Results: According to the median value of their ApoB/A1ratios (0.80), they were divided into 2 groups [high ApoB/A1 ratio (>0.80) (n=49) and low ApoB/A1 ratio (≤0.80) (n=49)]. The patients with a high ApoB/A1 ratio had alarger fibrolipid volume and a smaller fibrous volume compared to patients with a low ApoB/A1 ratio ( 17.5%±1.2% vs 9.0%±1.0%, P=0.03 and 55.1%±2.1% vs 63.9%±1.8%, P<0.01). Using multivariate linear regression analysis after adjustment for the above-mentioned confounding factors, the ApoB/A1 ratio had a significantly positive correlation with fibrolipid volume (r=0.445, ß=0.29, P=0.010)and had a negative correlation with fibrous volume (r=-0.567, ß=-0.32, P=0.011), suggesting that the ApoB/A1 ratio was associated with the vulnerability of the LMCA plaque. Conclusion: For the patients with stable angina pectoris and chronic treatment of statins, a high ApoB/A1 ratio is associated with a high percentage of fibrolipid volume and a low percentage of fibrous volume in LMCA lesions, suggesting that the ApoB/A1 ratios could predict the vulnerability of the LMCA plaque.

Aberrant IKKα and IKKß cooperatively activate NF-κB and induce EGFR/AP1 signaling to promote survival and migration of head and neck cancer.

The inhibitor-κB kinase-nuclear factor-κB (IKK-NF-κB) and epidermal growth factor receptor-activator protein-1 (EGFR-AP1) pathways are often co-activated and promote malignant behavior, but the underlying basis for this relationship is unclear. Resistance to inhibitors of IKKß or EGFR is observed in head and neck squamous cell carcinomas (HNSCC). Here, we reveal that both IKKα and ß contribute to nuclear activation of canonical and alternate NF-κB/REL family transcription factors, and overexpression of signal components that enhance co-activation of the EGFR-AP1 pathway. We observed that IKKα and IKKß exhibit increased protein expression, nuclear localization, and phosphorylation in HNSCC tissues and cell lines. Individually, IKK activity varied among different cell lines, but overexpression of both IKKs induced the strongest NF-κB activation. Conversely, siRNA knock down of both IKKs significantly decreased nuclear localization and phosphorylation of canonical RELA and IκBα and alternative p52 and RELB subunits. Knock down of both IKKs more effectively inhibited NF-κB activation, broadly modulated gene expression and suppressed cell proliferation and migration. Global expression profiling revealed that NF-κB, cytokine, inflammatory response and growth factor signaling are among the top pathways and networks regulated by IKKs. Importantly, IKKα and IKKß together promoted the expression and activity of transforming growth factor α, EGFR and AP1 transcription factors cJun, JunB and Fra1. Knock down of AP1 subunits individually decreased 8/15 (53%) of IKK-targeted genes sampled and similarly inhibited cell proliferation and migration. Mutations of NF-κB and AP1-binding sites abolished or decreased IKK-induced interleukin-8 (IL-8) promoter activity. Compounds such as wedelactone with dual IKK inhibitory activity and geldanomycins that block IKKα/ß and EGFR pathways were more active than IKKß-specific inhibitors in suppressing NF-κB activation and proliferation and inducing cell death. We conclude that IKKα and IKKß cooperatively activate NF-κB and EGFR/AP1 networks of signaling pathways and contribute to the malignant phenotype and the intrinsic or acquired therapeutic resistance of HNSCC.

An informational stair climbing intervention with greater effects in overweight pedestrians.

Previous interventions have successfully increased levels of stair climbing in public-access settings (e.g. malls). This study used robust methods to establish the magnitude of intervention effects among a specific target group-the overweight. Ascending stair/escalator users (N = 20 807) were observed in a mall. A 2-week baseline was followed by a 5-week intervention in which message banners, promoting stair climbing, were attached to the stair risers. Standardized silhouettes were used to code individuals as normal/overweight. Logistic regression analyses were conducted with stair/escalator choice as the outcome variable and weight status entered as a moderator alongside condition, gender, ethnicity and 'pedestrian traffic volume'. Overall, the intervention significantly increased the rate of stair climbing [odds ratio (OR) = 1.28, 95% confidence intervals (CI) = 1.08-1.53], with the effects sustained over 5 weeks. There were differential effects between weight categories, with greater increases in overweight (OR = 1.95, CI = 1.34-2.83) versus normal weight individuals (OR = 1.29, CI = 1.09-1.53). In conclusion, message prompts produced larger effects among overweight individuals, who could benefit most from stair climbing. The public health value of these interventions may, therefore, be greater than realized. The heightened effects among the overweight were likely due to the salience of the current message, which linked stair climbing with the target of weight control.

IRF-3-dependent and augmented target genes during viral infection.

Activation of the transcription factor interferon regulatory factor-3 (IRF-3) is an essential event in the innate immune response to viral infection. To understand the contribution of IRF-3 to host defense, we used a systems biology approach to analyze global gene expression dependent on IRF-3. Comparison of expression profiles in cells from IRF-3 knockout animals or wild-type siblings following viral infection revealed three sets of induced genes, those that are strictly dependent on IRF-3, augmented with IRF-3, or not responsive to IRF-3. Products of identified IRF-3 target genes are involved in innate or acquired immunity, or in the regulation of cell cycle, apoptosis and proliferation. These results reveal the global effects of one transcription factor in the immune response and provide information to evaluate the integrated response to viral infection.

Expression of the serine protease, matriptase, in breast ductal carcinoma of Chinese women: correlation with clinicopathological parameters.

Matriptase is a serine protease expressed by cells of surface epithelial origin, including epithelial breast tumor cells. Matriptase cleaves and activates proteins implicated in the progression of cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine matriptase expression in breast tumors of Chinese women and to identify its clinicopathological correlations. Immunohistochemical analysis of matriptase was performed in tissue microarrays of 251 breast tumors including 30 fibroadenomas, 59 ductal carcinomas in situ (DCIS), 38 grade I invasive ductal carcinomas (IDC), 79 grade II IDC, and 45 grade III IDC. The matriptase scores were significantly higher in the tumors than their non-tumor counterparts (178+/-12 for fibroadenoma; 275+/-11 for DCIS; 299+/-10 for grade I IDC; 251+/-10 for grade II IDC; and 314+/-11 for grade III IDC). In cases of IDC, matriptase scores were significantly correlated with tumor staging and nodal staging. Our findings demonstrate that matriptase is over-expressed in breast ductal carcinoma of Chinese women. It therefore may be a good biomarker for diagnosis and treatment of malignant breast tumors.

Radiofrequency catheter ablation of septal accessory pathways within the triangle of Koch: importance of energy titration testing other than the local electrogram characteristics for identifying the successful target site.

Radiofrequency (RF) catheter ablation of accessory atrioventricular (AV) connections in the proximity of His bundle or AV node is at high risk of developing complete heart block. A safe and effective protocol has not been well established. Nineteen consecutive patients with 19 septal accessory pathways within the triangle of Koch underwent a protocol with power-titrated RF energy testing to identify the target site for successful catheter ablation. At every potential target site preselected by local electrogram characteristics, RF energy was started at 5 W for 10 seconds, with an increment of 5 W (duration remained at 10 s) until maximally 30 W or the observation of transient interruption of accessory pathway conduction. By this stepwise RF energy testing, we successfully localized and ablated 18 (94.7%) of the 19 septal accessory pathways, 10 close to His bundle (zone I) and 8 away from it (zone II). The test-effective RF power was 20 W or less in 9 of all 11 septal accessory pathways in zone I, and 5 of the 8 in zone II (P = 0.68). Meanwhile, the final RF power for successful ablation was 30 W or less in 9 of the 10 zone I and 6 of the 8 zone II septal accessory pathways (P = 0.83). One patient with an accessory pathway in zone I was complicated with complete AV block after final ablation at 30 W. None of the local electrogram characteristics except continuous electrical activity during retrograde mapping was helpful in the prediction of ablation outcome. Careful RF energy titration testing could effectively help identify the target site for successful RF catheter ablation of septal accessory pathways within the triangle of Koch. The dependence on local electrogram manifestations could be frustrated by a low probability of success.

Perinodal slow potential as a local guide for transcatheter radiofrequency ablation of atrioventricular nodal reentrant tachycardia: therapeutic efficacy and electrophysiological mechanisms of success.

BACKGROUND: A specific local indicator in the Koch's triangle could be critical to the complication-free treatment of atrioventricular nodal reentrant tachycardia by transcatheter radiofrequency ablation. Recording of perinodal slow potential reflects a slow conduction area, and probably indicates the location of the slow pathway component of the circuit. Specific ablation of the slow pathway would carry the least risk of atrioventricular block. METHOD AND RESULTS: Guided by the mapped perinodal slow potential, atrioventricular nodal reentrant tachycardia was successfully eliminated in all of 55 consecutive patients in one session. Fifty two patients (94.5%) had confirmed slow potential at the final success sites. Despite the good result, the underlying electrophysiological mechanisms of early success from slow-potential-guiding catheter ablation were heterogeneous: selective slow pathway eradication in 31 patients (56.4%, group A), selective slow pathway modification in 18 patients (32.7%, group B), inadvertent fast pathway damage in six patients (10.9%, group C). Group B patients had the preservation of dual atrioventricular nodal pathways, adequate atrio-Hisian delay, fast pathway facilitation, and a higher frequency of inducible, single non-conducted nodal echo (15/18, 83.3% v 6/31, 19.4% in group A, P << 0.001). The upper communicating path of the circuit was implicated as another site of radiofrequency destruction. Three recurrences were documented in follow up study. However, reablation by the same approach caused complete atrioventricular block in one patient (1.7%, 1/58 procedures). None of the local characteristics of ablation sites was an independent predictor of procedure outcome. CONCLUSIONS: Perinodal slow potential is not a specific slow pathway indicator in transcatheter radiofrequency ablation of atrioventricular nodal reentrant tachycardia. Multiple strategic sites of the reentry circuit may be damaged through similar local signals.

Value of local electrogram characteristics predicting successful catheter ablation of left-versus right-sided accessory atrioventricular pathways by radiofrequency current.

Despite similar guidance by local electrogram criteria, catheter ablation of right-sided accessory atrioventricular (AV) pathways by radiofrequency current has been less effective than that of left-sided ones. In order to elucidate the possible diversities in local electrosignal criteria, we systematically analyzed the morphological and timing characteristics of 215 bipolar local electrograms from catheter ablation sites of 65 left-sided accessory AV pathways and of 356 from those of 37 right-sided ones in 92 consecutive patients with Wolff-Parkinson-White syndrome or AV reentrant tachycardia incorporating concealed accessory AV pathways. After stepwise multivariate analysis, we selected the presence of a possible accessory pathway potential, local ventricular activation preceding QRS complex for 20 ms or more during ventricular insertion mapping, and the local retrograde ventriculoatrial (VA) continuity, local retrograde VA interval < or = 50 ms, electrogram stability (left-sided targets only), retrograde accessory pathway potential (right-sided targets only) during atrial insertion mapping, as independent local electrogram predictors for successful ablation of left- and right-sided accessory AV pathways. Combination of all local electrogram predictors could have moderate chance of success (80 and 51%) for the ventricular and atrial insertion ablation of left-sided accessory AV pathways, but only low probability of success (40% in ventricular insertion ablation) or very low sensitivity (12.5% in atrial insertion ablation) for right-sided ones. In conclusion, with the present approach, successful catheter ablation of right-sided accessory AV pathways, compared to left-sided ones, still necessitate a breakthrough in the precision mapping and the efficiency of energy delivery.